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Conserved domains on  [gi|1907123492|ref|XP_036016352|]
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pleckstrin homology domain-containing family H member 2 isoform X1 [Mus musculus]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
FERM_F1_PLEKHH2 cd17179
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in pleckstrin ...
 1168-1270 6.33e-73

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in pleckstrin homology domain-containing family H member 2 (PLEKHH2); PLEKHH2 is a novel podocyte protein downregulated in human focal segmental glomerulosclerosis. It is highly enriched in renal glomerular podocytes, and acts as a novel, important component of the podocyte foot processes. PLEKHH2 contains a putative alpha-helical coiled-coil segment within the N-terminal half, and two Pleckstrin homology (PH) domains, a MyTH4 domain, and a FERM (Band 4.1, ezrin, radixin, moesin) domain within the C-terminal half. The FERM domain is made up of three sub-domains, F1, F2, and F3. The family corresponds to F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). PLEKHH2 is involved in matrix adhesion and actin dynamics. It directly interacts through its FERM domain with the focal adhesion protein Hic-5 and actin.


:

Pssm-ID: 340699  Cd Length: 103  Bit Score: 237.56  E-value: 6.33e-73
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492 1168 PFSIPVHFMNGLYQVVGFDASTTVEEFLNTLNQDTGMRKPAQSGFALFTDDPSGRDLEHCLQGNIKICDIISKWEQASKE 1247
Cdd:cd17179      1 PFSIPVHFMNGTYQVVGFDASTTVEEFLNTLNQDTGMRKPGQSGFALFTDDPSGKDLEHCLQGNIKICDIISKWEQASKE 80

                           90       100
                   ....*....|....*....|...
gi 1907123492 1248 QQPGKCEGSRTVRLTYKNRLYFS 1270
Cdd:cd17179     81 QHPGKCEGTRTVRLTYKNRLYFS 103
FERM_C-lobe_PLEKHH1_PLEKHH2 cd13206
FERM domain C-lobe of Pleckstrin homology domain-containing family H; PLEKHH1 and PLEKHH2 ...
 1398-1496 1.72e-58

FERM domain C-lobe of Pleckstrin homology domain-containing family H; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.


:

Pssm-ID: 241360  Cd Length: 100  Bit Score: 196.11  E-value: 1.72e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492 1398 GAKLFFAKPIAPSSLGNNCVWLAVHENGLSILEYTSMRLVTSYMYKGLMTFGGYQEDFMVVVSTQS-KDRPTEKLLFAMA 1476
Cdd:cd13206      1 GAKLFAAKPKTPSSLENTVVWLAVNEDGISILDYNTMRLVVTYPYSSVMTFGGCQDDFMLVVNSIKdKKKPTEKLLFAMA 80

                           90       100
                   ....*....|....*....|
gi 1907123492 1477 KHKILEITLLIASYINSFHQ 1496
Cdd:cd13206     81 KPKILEITLLIASYINAFHQ 100
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
 754-849 3.63e-50

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


:

Pssm-ID: 241436  Cd Length: 96  Bit Score: 172.48  E-value: 3.63e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDVIRKPQGHIELSASCSILRGDNKQTVQLATEKHTYYLTADSPNIL 833
Cdd:cd13282      1 KAGYLTKLGGKVKTWKRRWFVLKNGELFYYKSPNDVIRKPQGQIALDGSCEIARAEGAQTFEIVTEKRTYYLTADSENDL 80

                           90
                   ....*....|....*.
gi 1907123492  834 EEWIKVLQSVLRVQAA 849
Cdd:cd13282     81 DEWIRVIQNVLRRQAS 96
MyTH4 smart00139
Domain in Myosin and Kinesin Tails; Domain present twice in myosin-VIIa, and also present in 3 ...
 1003-1158 2.44e-45

Domain in Myosin and Kinesin Tails; Domain present twice in myosin-VIIa, and also present in 3 other myosins.


:

Pssm-ID: 214535  Cd Length: 152  Bit Score: 160.60  E-value: 2.44e-45
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  1003 HSKEGILSPLTTLPSEALQTEAIKLFKTCQLFINAaVDSPAIDYHISLAQSALQVCLTHPELQNEICCQLIKQTRRRqlQ 1082
Cdd:smart00139    1 YTKDPIKTSLLKLESDELQKEAVKIFKAILKFMGD-IPLPRPDSHLDLVQFILQKGLDHPELRDEIYCQLIKQLTDN--P 77

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907123492  1083 NQPGPLQGWQLLALCVGLFLPHHPFLWLLQLHLQRNADSRTeFGKYAIYCQRCVERTQQNGDREARPSRMEILSTL 1158
Cdd:smart00139   78 SRQSEERGWQLLYLCTSLFPPSERLLPYLLQFLSRRADPGS-EQGLAKYCLYRLERTLKNGARKQPPSRLELEAIL 152
B41 smart00295
Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in ...
 1171-1402 1.65e-22

Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in myosins, ezrin, radixin, moesin, protein tyrosine phosphatases. Plasma membrane-binding domain. These proteins play structural and regulatory roles in the assembly and stabilization of specialized plasmamembrane domains. Some PDZ domain containing proteins bind one or more of this family. Now includes JAKs.


:

Pssm-ID: 214604 [Multi-domain]  Cd Length: 201  Bit Score: 96.98  E-value: 1.65e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  1171 IPVHFMNGLYQVVGFDASTTVEEFLNTLNQDTGMRkpAQSGFALFTDDPSGrDLEHCLQGNIKICDIISKWEqaskeqqp 1250
Cdd:smart00295    2 LKVYLLDGTTLEFEVDSSTTAEELLETVCRKLGIR--ESEYFGLQFEDPDE-DLRHWLDPAKTLLDQDVKSE-------- 70

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  1251 gkcegsrTVRLTYKNRLYFSVQARGETDREKTLLLY-QTNDQIINGLFPLNKDLALEMAALLAQVDIGDFERPFSTPAGP 1329
Cdd:smart00295   71 -------PLTLYFRVKFYPPDPNQLKEDPTRLNLLYlQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDEELHDLRGE 143

                           170       180       190       200       210       220       230
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907123492  1330 VtnqckanqtlkqVIERFYPKRYREgcsEEQLRQLYQRLSTKWMALRGHSAADCIRIYLTVARKWPFFGAKLF 1402
Cdd:smart00295  144 L------------SLKRFLPKQLLD---SRKLKEWRERIVELHKELIGLSPEEAKLKYLELARKLPTYGVELF 201
COG4372 COG4372
Uncharacterized protein, contains DUF3084 domain [Function unknown];
91-221 7.66e-08

Uncharacterized protein, contains DUF3084 domain [Function unknown];


:

Pssm-ID: 443500 [Multi-domain]  Cd Length: 370  Bit Score: 56.45  E-value: 7.66e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   91 MQQLERQVIDAERQAEKAFQEVQVMEEKLKAANIQTSESETRLYKKCQDLESVMQEKDDIIQNLALRLEEQKQVRIQEAK 170
Cdd:COG4372     40 LDKLQEELEQLREELEQAREELEQLEEELEQARSELEQLEEELEELNEQLQAAQAELAQAQEELESLQEEAEELQEELEE 119

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1907123492  171 IIEEKAAKIKEwvtvkLNELEVENQNLRFINQTQTEEIRAIQSKLQELQEK 221
Cdd:COG4372    120 LQKERQDLEQQ-----RKQLEAQIAELQSEIAEREEELKELEEQLESLQEE 165
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
 852-965 4.06e-05

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.


The actual alignment was detected with superfamily member cd13288:

Pssm-ID: 473070 [Multi-domain]  Cd Length: 120  Bit Score: 44.54  E-value: 4.06e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  852 LCLQPEGKpavKGLLTK---VKHGYSKRvWCMLVGKVLYYFRNQEDKFPLGQLKLWEAKVEevdrSCDSDEDYetrgCYL 928
Cdd:cd13288      3 TCNSPVDK---EGYLWKkgeRNTSYQKR-WFVLKGNLLFYFEKKGDREPLGVIVLEGCTVE----LAEDAEPY----AFA 70

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1907123492  929 LSTHytiivhpkdqGP---TYLLIGSKHEK-EAWLYHLTVA 965
Cdd:cd13288     71 IRFD----------GPgarSYVLAAENQEDmESWMKALSRA 101
DMP1 super family cl25845
Dentin matrix protein 1 (DMP1); This family consists of several mammalian dentin matrix ...
 257-453 1.32e-03

Dentin matrix protein 1 (DMP1); This family consists of several mammalian dentin matrix protein 1 (DMP1) sequences. The dentin matrix acidic phosphoprotein 1 (DMP1) gene has been mapped to human chromosome 4q21. DMP1 is a bone and teeth specific protein initially identified from mineralized dentin. DMP1 is primarily localized in the nuclear compartment of undifferentiated osteoblasts. In the nucleus, DMP1 acts as a transcriptional component for activation of osteoblast-specific genes like osteocalcin. During the early phase of osteoblast maturation, Ca(2+) surges into the nucleus from the cytoplasm, triggering the phosphorylation of DMP1 by a nuclear isoform of casein kinase II. This phosphorylated DMP1 is then exported out into the extracellular matrix, where it regulates nucleation of hydroxyapatite. DMP1 is a unique molecule that initiates osteoblast differentiation by transcription in the nucleus and orchestrates mineralized matrix formation extracellularly, at later stages of osteoblast maturation. The DMP1 gene has been found to be ectopically expressed in lung cancer although the reason for this is unknown.


The actual alignment was detected with superfamily member pfam07263:

Pssm-ID: 462128 [Multi-domain]  Cd Length: 519  Bit Score: 43.38  E-value: 1.32e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  257 EEV---SKMASNEPEITEGRCVEEM--EIAEKPADNQVQENSRsqrklHETSCSSEQNQKTRASFAMDGGTSQNSGV--- 328
Cdd:pfam07263  288 EEVksdSTESTSSKEAGLSQSREDSksESQEDSEESQSQEDSQ-----NSQDPSSESSQEADLPSQESSSESQEEVVses 362

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  329 ----PVSDWSSDEDDGSKGRSKSRCTSTLSSHTSEEGGQCGRLGSEAYLTASDDSssifEEETFDGNRPEQKKLCSWQQK 404
Cdd:pfam07263  363 rgdnPDNTSSSEEDQEDSDSSEEDSLSTFSSSESESREEQADSESNESLRSSEES----PESSEDENSSSQEGLQSHSAS 438

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1907123492  405 APWKAQGNLAKGRSQSGVKEQDSSSDELNKKFHSQRLDYTSSSSEANTP 453
Cdd:pfam07263  439 TESQSEESQSEQDSQSEEDDESDSQDSSRSKEDSNSTESTSSSEEDGQS 487
 
Name Accession Description Interval E-value
FERM_F1_PLEKHH2 cd17179
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in pleckstrin ...
 1168-1270 6.33e-73

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in pleckstrin homology domain-containing family H member 2 (PLEKHH2); PLEKHH2 is a novel podocyte protein downregulated in human focal segmental glomerulosclerosis. It is highly enriched in renal glomerular podocytes, and acts as a novel, important component of the podocyte foot processes. PLEKHH2 contains a putative alpha-helical coiled-coil segment within the N-terminal half, and two Pleckstrin homology (PH) domains, a MyTH4 domain, and a FERM (Band 4.1, ezrin, radixin, moesin) domain within the C-terminal half. The FERM domain is made up of three sub-domains, F1, F2, and F3. The family corresponds to F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). PLEKHH2 is involved in matrix adhesion and actin dynamics. It directly interacts through its FERM domain with the focal adhesion protein Hic-5 and actin.


Pssm-ID: 340699  Cd Length: 103  Bit Score: 237.56  E-value: 6.33e-73
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492 1168 PFSIPVHFMNGLYQVVGFDASTTVEEFLNTLNQDTGMRKPAQSGFALFTDDPSGRDLEHCLQGNIKICDIISKWEQASKE 1247
Cdd:cd17179      1 PFSIPVHFMNGTYQVVGFDASTTVEEFLNTLNQDTGMRKPGQSGFALFTDDPSGKDLEHCLQGNIKICDIISKWEQASKE 80

                           90       100
                   ....*....|....*....|...
gi 1907123492 1248 QQPGKCEGSRTVRLTYKNRLYFS 1270
Cdd:cd17179     81 QHPGKCEGTRTVRLTYKNRLYFS 103
FERM_C-lobe_PLEKHH1_PLEKHH2 cd13206
FERM domain C-lobe of Pleckstrin homology domain-containing family H; PLEKHH1 and PLEKHH2 ...
 1398-1496 1.72e-58

FERM domain C-lobe of Pleckstrin homology domain-containing family H; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.


Pssm-ID: 241360  Cd Length: 100  Bit Score: 196.11  E-value: 1.72e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492 1398 GAKLFFAKPIAPSSLGNNCVWLAVHENGLSILEYTSMRLVTSYMYKGLMTFGGYQEDFMVVVSTQS-KDRPTEKLLFAMA 1476
Cdd:cd13206      1 GAKLFAAKPKTPSSLENTVVWLAVNEDGISILDYNTMRLVVTYPYSSVMTFGGCQDDFMLVVNSIKdKKKPTEKLLFAMA 80

                           90       100
                   ....*....|....*....|
gi 1907123492 1477 KHKILEITLLIASYINSFHQ 1496
Cdd:cd13206     81 KPKILEITLLIASYINAFHQ 100
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
 754-849 3.63e-50

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241436  Cd Length: 96  Bit Score: 172.48  E-value: 3.63e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDVIRKPQGHIELSASCSILRGDNKQTVQLATEKHTYYLTADSPNIL 833
Cdd:cd13282      1 KAGYLTKLGGKVKTWKRRWFVLKNGELFYYKSPNDVIRKPQGQIALDGSCEIARAEGAQTFEIVTEKRTYYLTADSENDL 80

                           90
                   ....*....|....*.
gi 1907123492  834 EEWIKVLQSVLRVQAA 849
Cdd:cd13282     81 DEWIRVIQNVLRRQAS 96
MyTH4 smart00139
Domain in Myosin and Kinesin Tails; Domain present twice in myosin-VIIa, and also present in 3 ...
 1003-1158 2.44e-45

Domain in Myosin and Kinesin Tails; Domain present twice in myosin-VIIa, and also present in 3 other myosins.


Pssm-ID: 214535  Cd Length: 152  Bit Score: 160.60  E-value: 2.44e-45
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  1003 HSKEGILSPLTTLPSEALQTEAIKLFKTCQLFINAaVDSPAIDYHISLAQSALQVCLTHPELQNEICCQLIKQTRRRqlQ 1082
Cdd:smart00139    1 YTKDPIKTSLLKLESDELQKEAVKIFKAILKFMGD-IPLPRPDSHLDLVQFILQKGLDHPELRDEIYCQLIKQLTDN--P 77

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907123492  1083 NQPGPLQGWQLLALCVGLFLPHHPFLWLLQLHLQRNADSRTeFGKYAIYCQRCVERTQQNGDREARPSRMEILSTL 1158
Cdd:smart00139   78 SRQSEERGWQLLYLCTSLFPPSERLLPYLLQFLSRRADPGS-EQGLAKYCLYRLERTLKNGARKQPPSRLELEAIL 152
MyTH4 pfam00784
MyTH4 domain; Domain in myosin and kinesin tails, present twice in myosin-VIIa, and also ...
 1051-1156 2.52e-37

MyTH4 domain; Domain in myosin and kinesin tails, present twice in myosin-VIIa, and also present in 3 other myosins.


Pssm-ID: 459939  Cd Length: 105  Bit Score: 135.78  E-value: 2.52e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492 1051 AQSALQVCLTHPELQNEICCQLIKQTRRRQlqNQPGPLQGWQLLALCVGLFLPHHPFLWLLQLHLQRNADSR-TEFGKYA 1129
Cdd:pfam00784    1 AQNILQKGLKRPELRDEIYCQLIKQTTNNP--KPESLLRGWQLLALCLGTFPPSKKLLKYLLKFLKRHADDPsREVGKYA 78

                           90       100
                   ....*....|....*....|....*..
gi 1907123492 1130 IYCQRCVERTQQNGDREARPSRMEILS 1156
Cdd:pfam00784   79 QFCLKRLKRTLKNGGRKYPPSREEIEA 105
B41 smart00295
Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in ...
 1171-1402 1.65e-22

Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in myosins, ezrin, radixin, moesin, protein tyrosine phosphatases. Plasma membrane-binding domain. These proteins play structural and regulatory roles in the assembly and stabilization of specialized plasmamembrane domains. Some PDZ domain containing proteins bind one or more of this family. Now includes JAKs.


Pssm-ID: 214604 [Multi-domain]  Cd Length: 201  Bit Score: 96.98  E-value: 1.65e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  1171 IPVHFMNGLYQVVGFDASTTVEEFLNTLNQDTGMRkpAQSGFALFTDDPSGrDLEHCLQGNIKICDIISKWEqaskeqqp 1250
Cdd:smart00295    2 LKVYLLDGTTLEFEVDSSTTAEELLETVCRKLGIR--ESEYFGLQFEDPDE-DLRHWLDPAKTLLDQDVKSE-------- 70

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  1251 gkcegsrTVRLTYKNRLYFSVQARGETDREKTLLLY-QTNDQIINGLFPLNKDLALEMAALLAQVDIGDFERPFSTPAGP 1329
Cdd:smart00295   71 -------PLTLYFRVKFYPPDPNQLKEDPTRLNLLYlQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDEELHDLRGE 143

                           170       180       190       200       210       220       230
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907123492  1330 VtnqckanqtlkqVIERFYPKRYREgcsEEQLRQLYQRLSTKWMALRGHSAADCIRIYLTVARKWPFFGAKLF 1402
Cdd:smart00295  144 L------------SLKRFLPKQLLD---SRKLKEWRERIVELHKELIGLSPEEAKLKYLELARKLPTYGVELF 201
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 752-845 3.03e-15

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 72.98  E-value: 3.03e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  752 LEKSGYLLKMS-VRVKTWKRRWFVLKGGELLYYKSPSDVI-RKPQGHIELSASCSILRGDNKQT---------VQLATEK 820
Cdd:pfam00169    1 VVKEGWLLKKGgGKKKSWKKRYFVLFDGSLLYYKDDKSGKsKEPKGSISLSGCEVVEVVASDSPkrkfcfelrTGERTGK 80

                           90       100
                   ....*....|....*....|....*
gi 1907123492  821 HTYYLTADSPNILEEWIKVLQSVLR 845
Cdd:pfam00169   81 RTYLLQAESEEERKDWIKAIQSAIR 105
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 752-845 5.18e-15

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 72.20  E-value: 5.18e-15
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   752 LEKSGYLLKMS-VRVKTWKRRWFVLKGGELLYYKSPSDV-IRKPQGHIELSaSCSI------LRGDNKQTVQLAT-EKHT 822
Cdd:smart00233    1 VIKEGWLYKKSgGGKKSWKKRYFVLFNSTLLYYKSKKDKkSYKPKGSIDLS-GCTVreapdpDSSKKPHCFEIKTsDRKT 79

                            90       100
                    ....*....|....*....|...
gi 1907123492   823 YYLTADSPNILEEWIKVLQSVLR 845
Cdd:smart00233   80 LLLQAESEEEREKWVEALRKAIA 102
FERM_M pfam00373
FERM central domain; This domain is the central structural domain of the FERM domain.
 1276-1402 8.87e-11

FERM central domain; This domain is the central structural domain of the FERM domain.


Pssm-ID: 459788 [Multi-domain]  Cd Length: 117  Bit Score: 60.75  E-value: 8.87e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492 1276 ETDREKTLLLYQTNDQIINGLFPLNKDLALEMAALLAQVDIGDFerpfstpagpvtnQCKANQTLKQVIERFYPKRYreg 1355
Cdd:pfam00373    7 QDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGDY-------------QPSSHTSEYLSLESFLPKQL--- 70

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1907123492 1356 CSEEQLRQLYQRLSTKWMALRGHSAADCIRIYLTVARKWPFFGAKLF 1402
Cdd:pfam00373   71 LRKMKSKELEKRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 117
COG4372 COG4372
Uncharacterized protein, contains DUF3084 domain [Function unknown];
91-221 7.66e-08

Uncharacterized protein, contains DUF3084 domain [Function unknown];


Pssm-ID: 443500 [Multi-domain]  Cd Length: 370  Bit Score: 56.45  E-value: 7.66e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   91 MQQLERQVIDAERQAEKAFQEVQVMEEKLKAANIQTSESETRLYKKCQDLESVMQEKDDIIQNLALRLEEQKQVRIQEAK 170
Cdd:COG4372     40 LDKLQEELEQLREELEQAREELEQLEEELEQARSELEQLEEELEELNEQLQAAQAELAQAQEELESLQEEAEELQEELEE 119

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1907123492  171 IIEEKAAKIKEwvtvkLNELEVENQNLRFINQTQTEEIRAIQSKLQELQEK 221
Cdd:COG4372    120 LQKERQDLEQQ-----RKQLEAQIAELQSEIAEREEELKELEEQLESLQEE 165
SMC_prok_A TIGR02169
chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of ...
 85-224 7.77e-07

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274009 [Multi-domain]  Cd Length: 1164  Bit Score: 54.30  E-value: 7.77e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   85 ASAKHHMQQLERQVIDAERQAEKAFQEVQVMEEKLKAANIQTSESETRLYKKCQDLESVMQEKDDIIQNLALRLEEQKQV 164
Cdd:TIGR02169  698 RRIENRLDELSQELSDASRKIGEIEKEIEQLEQEEEKLKERLEELEEDLSSLEQEIENVKSELKELEARIEELEEDLHKL 777

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907123492  165 RIQEAKI-----------IEEKAAKIKEWVT---VKLNELEVENQNLRFINQTQTEEIRAIQSKLQELQEKKIS 224
Cdd:TIGR02169  778 EEALNDLearlshsripeIQAELSKLEEEVSrieARLREIEQKLNRLTLEKEYLEKEIQELQEQRIDLKEQIKS 851
FERM_B-lobe cd14473
FERM domain B-lobe; The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C ...
 1284-1394 4.66e-06

FERM domain B-lobe; The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases, the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains and consequently is capable of binding to both peptides and phospholipids at different sites.


Pssm-ID: 271216  Cd Length: 99  Bit Score: 46.47  E-value: 4.66e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492 1284 LLY-QTNDQIINGLFPLNKDLALEMAALLAQVDIGDFERPFSTPagpvtnqckanqtLKQVIERFYPKRYREGCSEEQLR 1362
Cdd:cd14473      4 LLYlQVKRDILEGRLPCSEETAALLAALALQAEYGDYDPSEHKP-------------KYLSLKRFLPKQLLKQRKPEEWE 70

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1907123492 1363 qlyQRLSTKWMALRGHSAADCIRIYLTVARKW 1394
Cdd:cd14473     71 ---KRIVELHKKLRGLSPAEAKLKYLKIARKL 99
CENP-F_leu_zip pfam10473
Leucine-rich repeats of kinetochore protein Cenp-F/LEK1; Cenp-F, a centromeric kinetochore, ...
 80-220 2.65e-05

Leucine-rich repeats of kinetochore protein Cenp-F/LEK1; Cenp-F, a centromeric kinetochore, microtubule-binding protein consisting of two 1,600-amino acid-long coils, is essential for the full functioning of the mitotic checkpoint pathway. There are several leucine-rich repeats along the sequence of LEK1 that are considered to be zippers, though they do not appear to be binding DNA directly in this instance.


Pssm-ID: 463102 [Multi-domain]  Cd Length: 140  Bit Score: 45.75  E-value: 2.65e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   80 SSHRSASAKHHMQQLERQVIDAE-------RQAEKAFQEVQVMEEKLKAANIQTSESEtrlykkcQDLESVMQEKDDIIQ 152
Cdd:pfam10473   15 SERKADSLKDKVENLERELEMSEenqelaiLEAENSKAEVETLKAEIEEMAQNLRDLE-------LDLVTLRSEKENLTK 87

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907123492  153 NLalrleEQKQVRIQEAKIIEEKAAKIkewvtvkLNELEVENqnlRFINQTQTEEIRAIQSKLQELQE 220
Cdd:pfam10473   88 EL-----QKKQERVSELESLNSSLENL-------LEEKEQEK---VQMKEESKTAVEMLQTQLKELNE 140
PRK03918 PRK03918
DNA double-strand break repair ATPase Rad50;
95-222 3.11e-05

DNA double-strand break repair ATPase Rad50;


Pssm-ID: 235175 [Multi-domain]  Cd Length: 880  Bit Score: 48.91  E-value: 3.11e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   95 ERQVIDAERQAEKAFQEVQVMEEKLKAANIQTSESETRLYKkcqdLESVMQEKDDIIQNLALRLEEQKQvRIQEAKIIEE 174
Cdd:PRK03918   216 LPELREELEKLEKEVKELEELKEEIEELEKELESLEGSKRK----LEEKIRELEERIEELKKEIEELEE-KVKELKELKE 290

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1907123492  175 KA------AKIKEWVTVKLNELEVENQNLRfinqtqtEEIRAIQSKLQELQEKK 222
Cdd:PRK03918   291 KAeeyiklSEFYEEYLDELREIEKRLSRLE-------EEINGIEERIKELEEKE 337
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
 852-965 4.06e-05

Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 mammalian members: Ses1 and Ses2, which are also callled 7 kDa inositol polyphosphate phosphatase-interacting protein 1 and 2. They play a role in endocytic trafficking and are required for receptor recycling from endosomes, both to the trans-Golgi network and the plasma membrane. Members of this family form homodimers and heterodimers. Sesquipedalian interacts with inositol polyphosphate 5-phosphatase OCRL-1 (INPP5F) also known as Lowe oculocerebrorenal syndrome protein, a phosphatase enzyme that is involved in actin polymerization and is found in the trans-Golgi network and INPP5B. Sesquipedalian contains a single PH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270105 [Multi-domain]  Cd Length: 120  Bit Score: 44.54  E-value: 4.06e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  852 LCLQPEGKpavKGLLTK---VKHGYSKRvWCMLVGKVLYYFRNQEDKFPLGQLKLWEAKVEevdrSCDSDEDYetrgCYL 928
Cdd:cd13288      3 TCNSPVDK---EGYLWKkgeRNTSYQKR-WFVLKGNLLFYFEKKGDREPLGVIVLEGCTVE----LAEDAEPY----AFA 70

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1907123492  929 LSTHytiivhpkdqGP---TYLLIGSKHEK-EAWLYHLTVA 965
Cdd:cd13288     71 IRFD----------GPgarSYVLAAENQEDmESWMKALSRA 101
DMP1 pfam07263
Dentin matrix protein 1 (DMP1); This family consists of several mammalian dentin matrix ...
 257-453 1.32e-03

Dentin matrix protein 1 (DMP1); This family consists of several mammalian dentin matrix protein 1 (DMP1) sequences. The dentin matrix acidic phosphoprotein 1 (DMP1) gene has been mapped to human chromosome 4q21. DMP1 is a bone and teeth specific protein initially identified from mineralized dentin. DMP1 is primarily localized in the nuclear compartment of undifferentiated osteoblasts. In the nucleus, DMP1 acts as a transcriptional component for activation of osteoblast-specific genes like osteocalcin. During the early phase of osteoblast maturation, Ca(2+) surges into the nucleus from the cytoplasm, triggering the phosphorylation of DMP1 by a nuclear isoform of casein kinase II. This phosphorylated DMP1 is then exported out into the extracellular matrix, where it regulates nucleation of hydroxyapatite. DMP1 is a unique molecule that initiates osteoblast differentiation by transcription in the nucleus and orchestrates mineralized matrix formation extracellularly, at later stages of osteoblast maturation. The DMP1 gene has been found to be ectopically expressed in lung cancer although the reason for this is unknown.


Pssm-ID: 462128 [Multi-domain]  Cd Length: 519  Bit Score: 43.38  E-value: 1.32e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  257 EEV---SKMASNEPEITEGRCVEEM--EIAEKPADNQVQENSRsqrklHETSCSSEQNQKTRASFAMDGGTSQNSGV--- 328
Cdd:pfam07263  288 EEVksdSTESTSSKEAGLSQSREDSksESQEDSEESQSQEDSQ-----NSQDPSSESSQEADLPSQESSSESQEEVVses 362

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  329 ----PVSDWSSDEDDGSKGRSKSRCTSTLSSHTSEEGGQCGRLGSEAYLTASDDSssifEEETFDGNRPEQKKLCSWQQK 404
Cdd:pfam07263  363 rgdnPDNTSSSEEDQEDSDSSEEDSLSTFSSSESESREEQADSESNESLRSSEES----PESSEDENSSSQEGLQSHSAS 438

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1907123492  405 APWKAQGNLAKGRSQSGVKEQDSSSDELNKKFHSQRLDYTSSSSEANTP 453
Cdd:pfam07263  439 TESQSEESQSEQDSQSEEDDESDSQDSSRSKEDSNSTESTSSSEEDGQS 487
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 863-962 1.60e-03

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 39.47  E-value: 1.60e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  863 KGLLTKVKHGYS---KRVWCMLVGKVLYYFRNQ---EDKFPLGQLKLWEAKVEEVDRSCDSDEDYetrgcyllstHYTII 936
Cdd:pfam00169    4 EGWLLKKGGGKKkswKKRYFVLFDGSLLYYKDDksgKSKEPKGSISLSGCEVVEVVASDSPKRKF----------CFELR 73

                           90       100
                   ....*....|....*....|....*..
gi 1907123492  937 VHPKDQGPTYLLI-GSKHEKEAWLYHL 962
Cdd:pfam00169   74 TGERTGKRTYLLQaESEEERKDWIKAI 100
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 863-962 2.32e-03

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 39.07  E-value: 2.32e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   863 KGLLTKVKHGYS---KRVWCMLVGKVLYYFRN---QEDKFPLGQLKLWEAKVEEVDRSCDSDEDyetrgcyllsthYTII 936
Cdd:smart00233    4 EGWLYKKSGGGKkswKKRYFVLFNSTLLYYKSkkdKKSYKPKGSIDLSGCTVREAPDPDSSKKP------------HCFE 71

                            90       100
                    ....*....|....*....|....*.
gi 1907123492   937 VHPKDQGPTYLLIGSKHEKEAWLYHL 962
Cdd:smart00233   72 IKTSDRKTLLLQAESEEEREKWVEAL 97
 
Name Accession Description Interval E-value
FERM_F1_PLEKHH2 cd17179
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in pleckstrin ...
 1168-1270 6.33e-73

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in pleckstrin homology domain-containing family H member 2 (PLEKHH2); PLEKHH2 is a novel podocyte protein downregulated in human focal segmental glomerulosclerosis. It is highly enriched in renal glomerular podocytes, and acts as a novel, important component of the podocyte foot processes. PLEKHH2 contains a putative alpha-helical coiled-coil segment within the N-terminal half, and two Pleckstrin homology (PH) domains, a MyTH4 domain, and a FERM (Band 4.1, ezrin, radixin, moesin) domain within the C-terminal half. The FERM domain is made up of three sub-domains, F1, F2, and F3. The family corresponds to F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). PLEKHH2 is involved in matrix adhesion and actin dynamics. It directly interacts through its FERM domain with the focal adhesion protein Hic-5 and actin.


Pssm-ID: 340699  Cd Length: 103  Bit Score: 237.56  E-value: 6.33e-73
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492 1168 PFSIPVHFMNGLYQVVGFDASTTVEEFLNTLNQDTGMRKPAQSGFALFTDDPSGRDLEHCLQGNIKICDIISKWEQASKE 1247
Cdd:cd17179      1 PFSIPVHFMNGTYQVVGFDASTTVEEFLNTLNQDTGMRKPGQSGFALFTDDPSGKDLEHCLQGNIKICDIISKWEQASKE 80

                           90       100
                   ....*....|....*....|...
gi 1907123492 1248 QQPGKCEGSRTVRLTYKNRLYFS 1270
Cdd:cd17179     81 QHPGKCEGTRTVRLTYKNRLYFS 103
FERM_F1_PLEKHH1 cd17178
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in pleckstrin ...
 1168-1273 1.47e-65

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in pleckstrin homology domain-containing family H member 1 (PLEKHH1); PLEKHH1 is a homolog of Caenorhabditis elegans MAX-1 that has been implicated in motor neuron axon guidance. PLEKHH1 is critical in vascular patterning in vertebrate species through acting upstream of the ephrin pathway. PLEKHH1 contains a putative alpha-helical coiled-coil segment within the N-terminal half, and two Pleckstrin homology (PH) domains, a MyTH4 domain, and a FERM (Band 4.1, ezrin, radixin, moesin) domain within the C-terminal half. The FERM domain is made up of three sub-domains, F1, F2, and F3. The family corresponds to F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).


Pssm-ID: 340698  Cd Length: 106  Bit Score: 216.75  E-value: 1.47e-65
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492 1168 PFSIPVHFMNGLYQVVGFDASTTVEEFLNTLNQDTGMRKPAQSGFALFTDDPSGRDLEHCLQGNIKICDIISKWEQASKE 1247
Cdd:cd17178      1 PFSIPVHFMNGTYQVVGFDGSTTVDEFLQTLNQETGMRKPSHSGFALFTDDPSGKDLEHCLQGSVKICDVISKWEQALKE 80

                           90       100
                   ....*....|....*....|....*.
gi 1907123492 1248 QQPGKCEGSRTVRLTYKNRLYFSVQA 1273
Cdd:cd17178     81 LHPGKYEGTRTVRLTYKSRLYFRAQA 106
FERM_F1_Max1_like cd17094
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in Caenorhabditis ...
 1168-1269 7.23e-61

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in Caenorhabditis elegans max-1 and its homologs PLEKHH1 and PLEKHH2; Caenorhabditis elegans max-1 is expressed and functions in motor neurons. MAX-1 protein plays a possible role in netrin-induced axon repulsion by modulating the UNC-5 receptor signaling pathway. PLEKHH1 is critically required in vascular patterning in vertebrate species through acting upstream of the ephrin pathway. PLEKHH2 is highly enriched in renal glomerular podocytes, and acts as a novel, important component of the podocyte foot processes. It is involved in matrix adhesion and actin dynamics. Members in this family all contain two Pleckstrin homology (PH) domains, a MyTH4 domain, and a FERM (Band 4.1, ezrin, radixin, moesin) domain within the C-terminal half. The FERM domain is made up of three sub-domains, F1, F2, and F3. The family corresponds to F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).


Pssm-ID: 340614  Cd Length: 102  Bit Score: 203.24  E-value: 7.23e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492 1168 PFSIPVHFMNGLYQVVGFDASTTVEEFLNTLNQDTGMRKPAQSGFALFTDDPSGRDLEHCLQGNIKICDIISKWEQASKE 1247
Cdd:cd17094      1 PISIPVHLPNGTYQVVGFDGSTTVEEFLQTLNLELGIRPPSQSGFALFSDDPIGKDIEHCLQPSVKICDVISKWERASRE 80

                           90       100
                   ....*....|....*....|..
gi 1907123492 1248 QQPGKCEGSRTVRLTYKNRLYF 1269
Cdd:cd17094     81 AHSGKVDSSRVIRLTYKNRLYF 102
FERM_C-lobe_PLEKHH1_PLEKHH2 cd13206
FERM domain C-lobe of Pleckstrin homology domain-containing family H; PLEKHH1 and PLEKHH2 ...
 1398-1496 1.72e-58

FERM domain C-lobe of Pleckstrin homology domain-containing family H; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.


Pssm-ID: 241360  Cd Length: 100  Bit Score: 196.11  E-value: 1.72e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492 1398 GAKLFFAKPIAPSSLGNNCVWLAVHENGLSILEYTSMRLVTSYMYKGLMTFGGYQEDFMVVVSTQS-KDRPTEKLLFAMA 1476
Cdd:cd13206      1 GAKLFAAKPKTPSSLENTVVWLAVNEDGISILDYNTMRLVVTYPYSSVMTFGGCQDDFMLVVNSIKdKKKPTEKLLFAMA 80

                           90       100
                   ....*....|....*....|
gi 1907123492 1477 KHKILEITLLIASYINSFHQ 1496
Cdd:cd13206     81 KPKILEITLLIASYINAFHQ 100
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
 754-849 3.63e-50

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241436  Cd Length: 96  Bit Score: 172.48  E-value: 3.63e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDVIRKPQGHIELSASCSILRGDNKQTVQLATEKHTYYLTADSPNIL 833
Cdd:cd13282      1 KAGYLTKLGGKVKTWKRRWFVLKNGELFYYKSPNDVIRKPQGQIALDGSCEIARAEGAQTFEIVTEKRTYYLTADSENDL 80

                           90
                   ....*....|....*.
gi 1907123492  834 EEWIKVLQSVLRVQAA 849
Cdd:cd13282     81 DEWIRVIQNVLRRQAS 96
MyTH4 smart00139
Domain in Myosin and Kinesin Tails; Domain present twice in myosin-VIIa, and also present in 3 ...
 1003-1158 2.44e-45

Domain in Myosin and Kinesin Tails; Domain present twice in myosin-VIIa, and also present in 3 other myosins.


Pssm-ID: 214535  Cd Length: 152  Bit Score: 160.60  E-value: 2.44e-45
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  1003 HSKEGILSPLTTLPSEALQTEAIKLFKTCQLFINAaVDSPAIDYHISLAQSALQVCLTHPELQNEICCQLIKQTRRRqlQ 1082
Cdd:smart00139    1 YTKDPIKTSLLKLESDELQKEAVKIFKAILKFMGD-IPLPRPDSHLDLVQFILQKGLDHPELRDEIYCQLIKQLTDN--P 77

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907123492  1083 NQPGPLQGWQLLALCVGLFLPHHPFLWLLQLHLQRNADSRTeFGKYAIYCQRCVERTQQNGDREARPSRMEILSTL 1158
Cdd:smart00139   78 SRQSEERGWQLLYLCTSLFPPSERLLPYLLQFLSRRADPGS-EQGLAKYCLYRLERTLKNGARKQPPSRLELEAIL 152
MyTH4 pfam00784
MyTH4 domain; Domain in myosin and kinesin tails, present twice in myosin-VIIa, and also ...
 1051-1156 2.52e-37

MyTH4 domain; Domain in myosin and kinesin tails, present twice in myosin-VIIa, and also present in 3 other myosins.


Pssm-ID: 459939  Cd Length: 105  Bit Score: 135.78  E-value: 2.52e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492 1051 AQSALQVCLTHPELQNEICCQLIKQTRRRQlqNQPGPLQGWQLLALCVGLFLPHHPFLWLLQLHLQRNADSR-TEFGKYA 1129
Cdd:pfam00784    1 AQNILQKGLKRPELRDEIYCQLIKQTTNNP--KPESLLRGWQLLALCLGTFPPSKKLLKYLLKFLKRHADDPsREVGKYA 78

                           90       100
                   ....*....|....*....|....*..
gi 1907123492 1130 IYCQRCVERTQQNGDREARPSRMEILS 1156
Cdd:pfam00784   79 QFCLKRLKRTLKNGGRKYPPSREEIEA 105
B41 smart00295
Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in ...
 1171-1402 1.65e-22

Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in myosins, ezrin, radixin, moesin, protein tyrosine phosphatases. Plasma membrane-binding domain. These proteins play structural and regulatory roles in the assembly and stabilization of specialized plasmamembrane domains. Some PDZ domain containing proteins bind one or more of this family. Now includes JAKs.


Pssm-ID: 214604 [Multi-domain]  Cd Length: 201  Bit Score: 96.98  E-value: 1.65e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  1171 IPVHFMNGLYQVVGFDASTTVEEFLNTLNQDTGMRkpAQSGFALFTDDPSGrDLEHCLQGNIKICDIISKWEqaskeqqp 1250
Cdd:smart00295    2 LKVYLLDGTTLEFEVDSSTTAEELLETVCRKLGIR--ESEYFGLQFEDPDE-DLRHWLDPAKTLLDQDVKSE-------- 70

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  1251 gkcegsrTVRLTYKNRLYFSVQARGETDREKTLLLY-QTNDQIINGLFPLNKDLALEMAALLAQVDIGDFERPFSTPAGP 1329
Cdd:smart00295   71 -------PLTLYFRVKFYPPDPNQLKEDPTRLNLLYlQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDEELHDLRGE 143

                           170       180       190       200       210       220       230
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907123492  1330 VtnqckanqtlkqVIERFYPKRYREgcsEEQLRQLYQRLSTKWMALRGHSAADCIRIYLTVARKWPFFGAKLF 1402
Cdd:smart00295  144 L------------SLKRFLPKQLLD---SRKLKEWRERIVELHKELIGLSPEEAKLKYLELARKLPTYGVELF 201
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 754-840 3.53e-19

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 83.75  E-value: 3.53e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKMS-VRVKTWKRRWFVLKGGELLYYKSPSDVIRKPQGHIELSASCSI---LRGDNKQTVQLATEKH-TYYLTAD 828
Cdd:cd00821      1 KEGYLLKRGgGGLKSWKKRWFVLFEGVLLYYKSKKDSSYKPKGSIPLSGILEVeevSPKERPHCFELVTPDGrTYYLQAD 80

                           90
                   ....*....|..
gi 1907123492  829 SPNILEEWIKVL 840
Cdd:cd00821     81 SEEERQEWLKAL 92
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
 754-843 2.01e-17

Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, repeat 1; ATG26 (also called UGT51/UDP-glycosyltransferase 51), a member of the glycosyltransferase 28 family, resulting in the biosynthesis of sterol glucoside. ATG26 in decane metabolism and autophagy. There are 32 known autophagy-related (ATG) proteins, 17 are components of the core autophagic machinery essential for all autophagy-related pathways and 15 are the additional components required only for certain pathways or species. The core autophagic machinery includes 1) the ATG9 cycling system (ATG1, ATG2, ATG9, ATG13, ATG18, and ATG27), 2) the phosphatidylinositol 3-kinase complex (ATG6/VPS30, ATG14, VPS15, and ATG34), and 3) the ubiquitin-like protein system (ATG3, ATG4, ATG5, ATG7, ATG8, ATG10, ATG12, and ATG16). Less is known about how the core machinery is adapted or modulated with additional components to accommodate the nonselective sequestration of bulk cytosol (autophagosome formation) or selective sequestration of specific cargos (Cvt vesicle, pexophagosome, or bacteria-containing autophagosome formation). The pexophagosome-specific additions include the ATG30-ATG11-ATG17 receptor-adaptors complex, the coiled-coil protein ATG25, and the sterol glucosyltransferase ATG26. ATG26 is necessary for the degradation of medium peroxisomes. It contains 2 GRAM domains and a single PH domain. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275402  Cd Length: 116  Bit Score: 79.59  E-value: 2.01e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDvIRKPQGHIEL----SASCSILRGDNKQTVQLATEKHTYYLTADS 829
Cdd:cd13215     23 KSGYLSKRSKRTLRYTRYWFVLKGDTLSWYNSSTD-LYFPAGTIDLryatSIELSKSNGEATTSFKIVTNSRTYKFKADS 101

                           90
                   ....*....|....
gi 1907123492  830 PNILEEWIKVLQSV 843
Cdd:cd13215    102 ETSADEWVKALKKQ 115
PH_TAAP2-like cd13255
Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 ...
 747-840 7.61e-17

Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP2 contains two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. The members here are most sequence similar to TAPP2 proteins, but may not be actual TAPP2 proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270075  Cd Length: 110  Bit Score: 77.84  E-value: 7.61e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  747 GKNEPLEKSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSD--VIRK-PQGHIELSASCSILRGDNkqTVQLATEKHTY 823
Cdd:cd13255      1 MISEAVLKAGYLEKKGERRKTWKKRWFVLRPTKLAYYKNDKEyrLLRLiDLTDIHTCTEVQLKKHDN--TFGIVTPARTF 78

                           90
                   ....*....|....*..
gi 1907123492  824 YLTADSPNILEEWIKVL 840
Cdd:cd13255     79 YVQADSKAEMESWISAI 95
FERM_F1_DdMyo7_like cd17208
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in Dictyostelium ...
 1166-1269 2.06e-16

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in Dictyostelium discoideum Myosin-VIIa (DdMyo7) and similar proteins; DdMyo7, also termed Myosin-I heavy chain, or class VII unconventional myosin, or M7, plays a role in adhesion in Dictyostelium where it is a component of a complex of proteins that serve to link membrane receptors to the underlying actin cytoskeleton. It interacts with talinA, an actin-binding protein with a known role in cell-substrate adhesion. DdMyo7 is required for phagocytosis. It is also essential for the extension of filopodia, plasma membrane protrusions filled with parallel bundles of F-actin. Members in this family contain a myosin motor domain, two MyTH4 domains, two FERM (Band 4.1, ezrin, radixin, moesin) domains, and two Pleckstrin homology (PH) domains. Some family members contain an extra SH3 domain. Each FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).


Pssm-ID: 340728  Cd Length: 98  Bit Score: 76.14  E-value: 2.06e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492 1166 SRPFSIPVHFMNGLYQVVGFDASTTVEEFLNTLNQDTGMRKPAQsGFALFTDDPsgrDLEHCLQGNIKICDIISKWEQAS 1245
Cdd:cd17208      1 RRPIVARFYFLDGQFKALEFDSAATAAEVLEQLKQKIGLRSTAD-GFALYEVFG---GIERAILPEEKVADVLSKWEKLQ 76

                           90       100
                   ....*....|....*....|....
gi 1907123492 1246 KEQqpGKCEGSRTVRLTYKNRLYF 1269
Cdd:cd17208     77 RTM--ASCAAQQAVKFVFKKRLFF 98
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
 754-837 6.11e-16

Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all plant tissue and is proposed to be the plant homolog of human pleckstrin. Pleckstrin consists of two PH domains separated by a linker region, while AtPH has a single PH domain with a short N-terminal extension. AtPH1 binds PtdIns3P specifically and is thought to be an adaptor molecule since it has no obvious catalytic functions. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270095  Cd Length: 106  Bit Score: 75.05  E-value: 6.11e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPsDVIR--KPQGHIELSaSCSILRGD----NKQ-TVQLATEKHTYYLT 826
Cdd:cd13276      1 KAGWLEKQGEFIKTWRRRWFVLKQGKLFWFKEP-DVTPysKPRGVIDLS-KCLTVKSAedatNKEnAFELSTPEETFYFI 78

                           90
                   ....*....|.
gi 1907123492  827 ADSPNILEEWI 837
Cdd:cd13276     79 ADNEKEKEEWI 89
PH_DAPP1 cd10573
Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; ...
 754-844 2.09e-15

Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; DAPP1 (also known as PHISH/3' phosphoinositide-interacting SH2 domain-containing protein or Bam32) plays a role in B-cell activation and has potential roles in T-cell and mast cell function. DAPP1 promotes B cell receptor (BCR) induced activation of Rho GTPases Rac1 and Cdc42, which feed into mitogen-activated protein kinases (MAPK) activation pathways and affect cytoskeletal rearrangement. DAPP1can also regulate BCR-induced activation of extracellular signal-regulated kinase (ERK), and c-jun NH2-terminal kinase (JNK). DAPP1 contains an N-terminal SH2 domain and a C-terminal pleckstrin homology (PH) domain with a single tyrosine phosphorylation site located centrally. DAPP1 binds strongly to both PtdIns(3,4,5)P3 and PtdIns(3,4)P2. The PH domain is essential for plasma membrane recruitment of PI3K upon cell activation. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269977 [Multi-domain]  Cd Length: 96  Bit Score: 73.13  E-value: 2.09e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDVirKPQGHIELSASCSILRGDNKQTV---QLATEKHTYYLTADSP 830
Cdd:cd10573      5 KEGYLTKLGGIVKNWKTRWFVLRRNELKYFKTRGDT--KPIRVLDLRECSSVQRDYSQGKVncfCLVFPERTFYMYANTE 82

                           90
                   ....*....|....
gi 1907123492  831 NILEEWIKVLQSVL 844
Cdd:cd10573     83 EEADEWVKLLKWKL 96
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
 749-841 2.36e-15

Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 mammalian members: Ses1 and Ses2, which are also callled 7 kDa inositol polyphosphate phosphatase-interacting protein 1 and 2. They play a role in endocytic trafficking and are required for receptor recycling from endosomes, both to the trans-Golgi network and the plasma membrane. Members of this family form homodimers and heterodimers. Sesquipedalian interacts with inositol polyphosphate 5-phosphatase OCRL-1 (INPP5F) also known as Lowe oculocerebrorenal syndrome protein, a phosphatase enzyme that is involved in actin polymerization and is found in the trans-Golgi network and INPP5B. Sesquipedalian contains a single PH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270105 [Multi-domain]  Cd Length: 120  Bit Score: 73.81  E-value: 2.36e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  749 NEPLEKSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDviRKPQGHIELsASCSILRGDNKQTVQLATEKH-----TY 823
Cdd:cd13288      5 NSPVDKEGYLWKKGERNTSYQKRWFVLKGNLLFYFEKKGD--REPLGVIVL-EGCTVELAEDAEPYAFAIRFDgpgarSY 81

                           90
                   ....*....|....*...
gi 1907123492  824 YLTADSPNILEEWIKVLQ 841
Cdd:cd13288     82 VLAAENQEDMESWMKALS 99
PH2_MyoX cd13296
Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular ...
 754-845 2.72e-15

Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular motor that has crucial functions in the transport and/or tethering of integrins in the actin-based extensions known as filopodia, microtubule binding, and in netrin-mediated axon guidance. It functions as a dimer. MyoX walks on bundles of actin, rather than single filaments, unlike the other unconventional myosins. MyoX is present in organisms ranging from humans to choanoflagellates, but not in Drosophila and Caenorhabditis elegans.MyoX consists of a N-terminal motor/head region, a neck made of 3 IQ motifs, and a tail consisting of a coiled-coil domain, a PEST region, 3 PH domains, a myosin tail homology 4 (MyTH4), and a FERM domain at its very C-terminus. The first PH domain in the MyoX tail is a split-PH domain, interupted by the second PH domain such that PH 1a and PH 1b flanks PH 2. The third PH domain (PH 3) follows the PH 1b domain. This cd contains the second PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270108  Cd Length: 103  Bit Score: 72.88  E-value: 2.72e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLK----MS-VRVKTWKRRWFVLKGGELLYYKSPSDViRKPQGHIELSASCSILRGDNKQT-VQLATEKHTYYLTA 827
Cdd:cd13296      1 KSGWLTKkgggSStLSRRNWKSRWFVLRDTVLKYYENDQEG-EKLLGTIDIRSAKEIVDNDPKENrLSITTEERTYHLVA 79

                           90
                   ....*....|....*...
gi 1907123492  828 DSPNILEEWIKVLQSVLR 845
Cdd:cd13296     80 ESPEDASQWVNVLTRVIS 97
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 752-845 3.03e-15

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 72.98  E-value: 3.03e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  752 LEKSGYLLKMS-VRVKTWKRRWFVLKGGELLYYKSPSDVI-RKPQGHIELSASCSILRGDNKQT---------VQLATEK 820
Cdd:pfam00169    1 VVKEGWLLKKGgGKKKSWKKRYFVLFDGSLLYYKDDKSGKsKEPKGSISLSGCEVVEVVASDSPkrkfcfelrTGERTGK 80

                           90       100
                   ....*....|....*....|....*
gi 1907123492  821 HTYYLTADSPNILEEWIKVLQSVLR 845
Cdd:pfam00169   81 RTYLLQAESEEERKDWIKAIQSAIR 105
PH_RhoGap25-like cd13263
Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; ...
 754-844 3.74e-15

Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; RhoGAP25 (also called ArhGap25) like other RhoGaps are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. This hierarchy contains RhoGAP22, RhoGAP24, and RhoGAP25. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270083  Cd Length: 114  Bit Score: 73.19  E-value: 3.74e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDVirKPQGHIELSASC----------------SILRGDNKQtvQLA 817
Cdd:cd13263      5 KSGWLKKQGSIVKNWQQRWFVLRGDQLYYYKDEDDT--KPQGTIPLPGNKvkevpfnpeepgkflfEIIPGGGGD--RMT 80

                           90       100
                   ....*....|....*....|....*..
gi 1907123492  818 TEKHTYYLTADSPNILEEWIKVLQSVL 844
Cdd:cd13263     81 SNHDSYLLMANSQAEMEEWVKVIRRVI 107
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 752-845 5.18e-15

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 72.20  E-value: 5.18e-15
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   752 LEKSGYLLKMS-VRVKTWKRRWFVLKGGELLYYKSPSDV-IRKPQGHIELSaSCSI------LRGDNKQTVQLAT-EKHT 822
Cdd:smart00233    1 VIKEGWLYKKSgGGKKSWKKRYFVLFNSTLLYYKSKKDKkSYKPKGSIDLS-GCTVreapdpDSSKKPHCFEIKTsDRKT 79

                            90       100
                    ....*....|....*....|...
gi 1907123492   823 YYLTADSPNILEEWIKVLQSVLR 845
Cdd:smart00233   80 LLLQAESEEEREKWVEALRKAIA 102
PH_SWAP-70 cd13273
Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called ...
 754-847 3.49e-14

Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called Differentially expressed in FDCP 6/DEF-6 or IRF4-binding protein) functions in cellular signal transduction pathways (in conjunction with Rac), regulates cell motility through actin rearrangement, and contributes to the transformation and invasion activity of mouse embryo fibroblasts. Metazoan SWAP-70 is found in B lymphocytes, mast cells, and in a variety of organs. Metazoan SWAP-70 contains an N-terminal EF-hand motif, a centrally located PH domain, and a C-terminal coiled-coil domain. The PH domain of Metazoan SWAP-70 contains a phosphoinositide-binding site and a nuclear localization signal (NLS), which localize SWAP-70 to the plasma membrane and nucleus, respectively. The NLS is a sequence of four Lys residues located at the N-terminus of the C-terminal a-helix; this is a unique characteristic of the Metazoan SWAP-70 PH domain. The SWAP-70 PH domain binds PtdIns(3,4,5)P3 and PtdIns(4,5)P2 embedded in lipid bilayer vesicles. There are additional plant SWAP70 proteins, but these are not included in this hierarchy. Rice SWAP70 (OsSWAP70) exhibits GEF activity toward the its Rho GTPase, OsRac1, and regulates chitin-induced production of reactive oxygen species and defense gene expression in rice. Arabidopsis SWAP70 (AtSWAP70) plays a role in both PAMP- and effector-triggered immunity. Plant SWAP70 contains both DH and PH domains, but their arrangement is the reverse of that in typical DH-PH-type Rho GEFs, wherein the DH domain is flanked by a C-terminal PH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270092  Cd Length: 110  Bit Score: 70.02  E-value: 3.49e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDviRKPQGHIELSASCSI----LRGDNKQTVQLATEKHTYYLTADS 829
Cdd:cd13273     10 KKGYLWKKGHLLPTWTERWFVLKPNSLSYYKSEDL--KEKKGEIALDSNCCVeslpDREGKKCRFLVKTPDKTYELSASD 87

                           90
                   ....*....|....*...
gi 1907123492  830 PNILEEWIKVLQSVLRVQ 847
Cdd:cd13273     88 HKTRQEWIAAIQTAIRLS 105
FERM_C-lobe cd00836
FERM domain C-lobe; The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N ...
 1398-1495 4.83e-14

FERM domain C-lobe; The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.


Pssm-ID: 275389  Cd Length: 93  Bit Score: 69.33  E-value: 4.83e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492 1398 GAKLFFAKPiapSSLGNNCVWLAVHENGLSILEYTSMRLVTSYMYK--GLMTFGGyQEDFMVVVSTQSKDRpteKLLFAM 1475
Cdd:cd00836      1 GVEFFPVKD---KSKKGSPIILGVNPEGISVYDELTGQPLVLFPWPniKKISFSG-AKKFTIVVADEDKQS---KLLFQT 73

                           90       100
                   ....*....|....*....|
gi 1907123492 1476 AKHKILEITLLIASYINSFH 1495
Cdd:cd00836     74 PSRQAKEIWKLIVGYHRFLL 93
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
 749-840 6.04e-14

Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; PEPP1 (also called PLEKHA4/PH domain-containing family A member 4 and RHOXF1/Rhox homeobox family member 1), and related homologs PEPP2 (also called PLEKHA5/PH domain-containing family A member 5) and PEPP3 (also called PLEKHA6/PH domain-containing family A member 6), have PH domains that interact specifically with PtdIns(3,4)P3. Other proteins that bind PtdIns(3,4)P3 specifically are: TAPP1 (tandem PH-domain-containing protein-1) and TAPP2], PtdIns3P AtPH1, and Ptd- Ins(3,5)P2 (centaurin-beta2). All of these proteins contain at least 5 of the 6 conserved amino acids that make up the putative phosphatidylinositol 3,4,5- trisphosphate-binding motif (PPBM) located at their N-terminus. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270068  Cd Length: 104  Bit Score: 69.22  E-value: 6.04e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  749 NEPLEKSGYLLKM-SVRVKTWKRRWFVLKGGELLYYKSPSDviRKPQGHIEL-SASCSILRGDNKQTVQLA-----TEKH 821
Cdd:cd13248      4 NAPVVMSGWLHKQgGSGLKNWRKRWFVLKDNCLYYYKDPEE--EKALGSILLpSYTISPAPPSDEISRKFAfkaehANMR 81

                           90
                   ....*....|....*....
gi 1907123492  822 TYYLTADSPNILEEWIKVL 840
Cdd:cd13248     82 TYYFAADTAEEMEQWMNAM 100
PH_Sbf1_hMTMR5 cd01235
Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a ...
 756-844 3.46e-13

Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a myotubularin-related pseudo-phosphatase. Both Sbf1 and myotubularin interact with the SET domains of Hrx and other epigenetic regulatory proteins, but Sbf1 lacks phosphatase activity due to several amino acid changes in its structurally preserved catalytic pocket. It contains pleckstrin (PH), GEF, and myotubularin homology domains that are thought to be responsible for signaling and growth control. Sbf1 functions as an inhibitor of cellular growth. The N-terminal GEF homology domain serves to inhibit the transforming effects of Sbf1. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269941  Cd Length: 106  Bit Score: 66.97  E-value: 3.46e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  756 GYLLKMSVRVKTWKRRWFVLKGG--ELLYYKSPSDviRKPQGHIELSASCSI----------LRGDNKQTVQLATEKHTY 823
Cdd:cd01235      7 GYLYKRGALLKGWKQRWFVLDSTkhQLRYYESRED--TKCKGFIDLAEVESVtpatpiigapKRADEGAFFDLKTNKRVY 84

                           90       100
                   ....*....|....*....|.
gi 1907123492  824 YLTADSPNILEEWIKVLQSVL 844
Cdd:cd01235     85 NFCAFDAESAQQWIEKIQSCL 105
PH_GRP1-like cd01252
General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 ...
 753-844 4.23e-13

General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 and the related proteins ARNO (ARF nucleotide-binding site opener)/cytohesin-2 and cytohesin-1 are ARF exchange factors that contain a pleckstrin homology (PH) domain thought to target these proteins to cell membranes through binding polyphosphoinositides. The PH domains of all three proteins exhibit relatively high affinity for PtdIns(3,4,5)P3. Within the Grp1 family, diglycine (2G) and triglycine (3G) splice variants, differing only in the number of glycine residues in the PH domain, strongly influence the affinity and specificity for phosphoinositides. The 2G variants selectively bind PtdIns(3,4,5)P3 with high affinity,the 3G variants bind PtdIns(3,4,5)P3 with about 30-fold lower affinity and require the polybasic region for plasma membrane targeting. These ARF-GEFs share a common, tripartite structure consisting of an N-terminal coiled-coil domain, a central domain with homology to the yeast protein Sec7, a PH domain, and a C-terminal polybasic region. The Sec7 domain is autoinhibited by conserved elements proximal to the PH domain. GRP1 binds to the DNA binding domain of certain nuclear receptors (TRalpha, TRbeta, AR, ER, but not RXR), and can repress thyroid hormone receptor (TR)-mediated transactivation by decreasing TR-complex formation on thyroid hormone response elements. ARNO promotes sequential activation of Arf6, Cdc42 and Rac1 and insulin secretion. Cytohesin acts as a PI 3-kinase effector mediating biological responses including cell spreading and adhesion, chemotaxis, protein trafficking, and cytoskeletal rearrangements, only some of which appear to depend on their ability to activate ARFs. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269954  Cd Length: 119  Bit Score: 67.34  E-value: 4.23e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  753 EKSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDviRKPQGHIELS------------ASCSILRGD-NKQTVQ---- 815
Cdd:cd01252      4 DREGWLLKLGGRVKSWKRRWFILTDNCLYYFEYTTD--KEPRGIIPLEnlsvrevedkkkPFCFELYSPsNGQVIKackt 81

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1907123492  816 -----LATEKHT-YYLTADSPNILEEWIKVLQSVL 844
Cdd:cd01252     82 dsdgkVVEGNHTvYRISAASEEERDEWIKSIKASI 116
PH_RASA1 cd13260
RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 ...
 751-841 4.35e-13

RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 (also called RasGap1 or p120) is a member of the RasGAP family of GTPase-activating proteins. RASA1 contains N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Splice variants lack the N-terminal domains. It is a cytosolic vertebrate protein that acts as a suppressor of RAS via its C-terminal GAP domain function, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. Additionally, it is involved in mitogenic signal transmission towards downstream interacting partners through its N-terminal SH2-SH3-SH2 domains. RASA1 interacts with a number of proteins including: G3BP1, SOCS3, ANXA6, Huntingtin, KHDRBS1, Src, EPHB3, EPH receptor B2, Insulin-like growth factor 1 receptor, PTK2B, DOK1, PDGFRB, HCK, Caveolin 2, DNAJA3, HRAS, GNB2L1 and NCK1. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270080  Cd Length: 103  Bit Score: 66.60  E-value: 4.35e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  751 PLEKSGYLLKMSVRVKTWKRRWFVLKGGE--LLYYKSPSDVirKPQGHIELSaSCSIL--------RGDNKQTVQLATEK 820
Cdd:cd13260      2 GIDKKGYLLKKGGKNKKWKNLYFVLEGKEqhLYFFDNEKRT--KPKGLIDLS-YCSLYpvhdslfgRPNCFQIVVRALNE 78

                           90       100
                   ....*....|....*....|..
gi 1907123492  821 HT-YYLTADSPNILEEWIKVLQ 841
Cdd:cd13260     79 STiTYLCADTAELAQEWMRALR 100
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
 754-845 5.08e-13

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270110  Cd Length: 106  Bit Score: 66.50  E-value: 5.08e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDviRKPQGHIELS--ASCSILRGDNKQTV-QLATEKHTYYLTADSP 830
Cdd:cd13298      8 KSGYLLKRSRKTKNWKKRWVVLRPCQLSYYKDEKE--YKLRRVINLSelLAVAPLKDKKRKNVfGIYTPSKNLHFRATSE 85

                           90
                   ....*....|....*
gi 1907123492  831 NILEEWIKVLQSVLR 845
Cdd:cd13298     86 KDANEWVEALREEFR 100
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
 754-843 7.27e-13

ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP (also called centaurin beta) functions both as a Rab35 effector and as an Arf6-GTPase-activating protein (GAP) by which it controls actin remodeling and membrane trafficking. ACAP contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain, a phospholipid-binding domain, a PH domain, a GAP domain, and four ankyrin repeats. The AZAPs constitute a family of Arf GAPs that are characterized by an NH2-terminal pleckstrin homology (PH) domain and a central Arf GAP domain followed by two or more ankyrin repeats. On the basis of sequence and domain organization, the AZAP family is further subdivided into four subfamilies: 1) the ACAPs contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain (a phospholipid-binding domain that is thought to sense membrane curvature), a single PH domain followed by the GAP domain, and four ankyrin repeats; 2) the ASAPs also contain an NH2-terminal BAR domain, the tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 domain; 3) the AGAPs contain an NH2-terminal GTPase-like domain (GLD), a split PH domain, and the GAP domain followed by four ankyrin repeats; and 4) the ARAPs contain both an Arf GAP domain and a Rho GAP domain, as well as an NH2-terminal sterile-a motif (SAM), a proline-rich region, a GTPase-binding domain, and five PH domains. PMID 18003747 and 19055940 Centaurin can bind to phosphatidlyinositol (3,4,5)P3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270070  Cd Length: 98  Bit Score: 66.09  E-value: 7.27e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKMSV-RVKTWKRRWFVLKGGELLYYKspsdvirKPQGHIELSASCSILRGdnkqTVQLATEKH----------- 821
Cdd:cd13250      1 KEGYLFKRSSnAFKTWKRRWFSLQNGQLYYQK-------RDKKDEPTVMVEDLRLC----TVKPTEDSDrrfcfevispt 69

                           90       100
                   ....*....|....*....|...
gi 1907123492  822 -TYYLTADSPNILEEWIKVLQSV 843
Cdd:cd13250     70 kSYMLQAESEEDRQAWIQAIQSA 92
PH_TBC1D2A cd01265
TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1 ...
 755-842 1.65e-12

TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1/Prostate antigen recognized and identified by SEREX 1 and ARMUS) contains a PH domain and a TBC-type GTPase catalytic domain. TBC1D2A integrates signaling between Arf6, Rac1, and Rab7 during junction disassembly. Activated Rac1 recruits TBC1D2A to locally inactivate Rab7 via its C-terminal TBC/RabGAP domain and facilitate E-cadherin degradation in lysosomes. The TBC1D2A PH domain mediates localization at cell-cell contacts and coprecipitates with cadherin complexes. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269966  Cd Length: 102  Bit Score: 65.04  E-value: 1.65e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  755 SGYLLKMSVR---VKTWKRRWFVLKGG--ELLYYKSPSDVirKPQGHIELS-ASCSILRGDNKQTVQLATEKHTYYLTAD 828
Cdd:cd01265      3 CGYLNKLETRglgLKGWKRRWFVLDESkcQLYYYRSPQDA--TPLGSIDLSgAAFSYDPEAEPGQFEIHTPGRVHILKAS 80

                           90
                   ....*....|....
gi 1907123492  829 SPNILEEWIKVLQS 842
Cdd:cd01265     81 TRQAMLYWLQALQS 94
PH_RhoGAP2 cd13378
Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 ...
 750-844 4.33e-12

Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 or ArhGap22) are involved in cell polarity, cell morphology and cytoskeletal organization. They activate a GTPase belonging to the RAS superfamily of small GTP-binding proteins. The encoded protein is insulin-responsive, is dependent on the kinase Akt, and requires the Akt-dependent 14-3-3 binding protein which binds sequentially to two serine residues resulting in regulation of cell motility. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241529  Cd Length: 116  Bit Score: 64.58  E-value: 4.33e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  750 EPLEKSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDVirKPQGHIELSAS----------------CSILRGDNKQT 813
Cdd:cd13378      1 EGVLKAGWLKKQRSIMKNWQQRWFVLRGDQLFYYKDEEET--KPQGCISLQGSqvnelppnpeepgkhlFEILPGGAGDR 78

                           90       100       110
                   ....*....|....*....|....*....|.
gi 1907123492  814 VQLATEKHTYYLTADSPNILEEWIKVLQSVL 844
Cdd:cd13378     79 EKVPMNHEAFLLMANSQSDMEDWVKAIRRVI 109
PH_ORP3_ORP6_ORP7 cd13287
Human Oxysterol binding protein related proteins 3, 6, and 7 Pleckstrin homology (PH) domain; ...
 748-841 2.68e-11

Human Oxysterol binding protein related proteins 3, 6, and 7 Pleckstrin homology (PH) domain; Human ORP3 is proposed to function in regulating the cell-matrix and cell-cell adhesion. A proposed specific function for Human ORP6 was not found at present. Human ORP7is proposed to function in negatively regulating the Golgi soluble NSF attachment protein receptor (SNARE) of 28kDa (GS28) protein stability via sequestration of Golgi-associated ATPase enhancer of 16 kDa (GATE-16). ORP3 has 2 isoforms: the longer ORP3(1) and the shorter ORP3(2). ORP3(1), ORP6, and ORP7 all contain a N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. The shorter ORP3(2) is missing the C-terminal portion of its OSBP-related domain. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270104  Cd Length: 123  Bit Score: 62.35  E-value: 2.68e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  748 KNEPLEKSGYLLKMSVR-VKTWKRRWFVLKGGELLYYKSPSDVIR-KPQGHIELSASC-SILRgdNKQTVQLATEKHTYY 824
Cdd:cd13287     18 VQEPGKQEGYLLKKRKWpLKGWHKRFFVLEKGILKYAKSPLDIAKgKLHGSIDVGLSVmSIKK--KARRIDLDTEEFIYH 95

                           90
                   ....*....|....*..
gi 1907123492  825 LTADSPNILEEWIKVLQ 841
Cdd:cd13287     96 LKVKSQDLFDSWVAKLR 112
FERM_M pfam00373
FERM central domain; This domain is the central structural domain of the FERM domain.
 1276-1402 8.87e-11

FERM central domain; This domain is the central structural domain of the FERM domain.


Pssm-ID: 459788 [Multi-domain]  Cd Length: 117  Bit Score: 60.75  E-value: 8.87e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492 1276 ETDREKTLLLYQTNDQIINGLFPLNKDLALEMAALLAQVDIGDFerpfstpagpvtnQCKANQTLKQVIERFYPKRYreg 1355
Cdd:pfam00373    7 QDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGDY-------------QPSSHTSEYLSLESFLPKQL--- 70

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1907123492 1356 CSEEQLRQLYQRLSTKWMALRGHSAADCIRIYLTVARKWPFFGAKLF 1402
Cdd:pfam00373   71 LRKMKSKELEKRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 117
PH_RhoGap24 cd13379
Rho GTPase activating protein 24 Pleckstrin homology (PH) domain; RhoGap24 (also called ...
 754-844 6.68e-10

Rho GTPase activating protein 24 Pleckstrin homology (PH) domain; RhoGap24 (also called ARHGAP24, p73RhoGAp, and Filamin-A-associated RhoGAP) like other RhoGAPs are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241530  Cd Length: 114  Bit Score: 58.06  E-value: 6.68e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDVirKPQGHIELSAS------CS----------ILRGDNKQtvQLA 817
Cdd:cd13379      5 KCGWLRKQGGFVKTWHTRWFVLKGDQLYYFKDEDET--KPLGTIFLPGNrvtehpCNeeepgkflfeVVPGGDRE--RMT 80

                           90       100
                   ....*....|....*....|....*..
gi 1907123492  818 TEKHTYYLTADSPNILEEWIKVLQSVL 844
Cdd:cd13379     81 ANHETYLLMASTQNDMEDWVKSIRRVI 107
PH_evt cd13265
Evectin Pleckstrin homology (PH) domain; There are 2 members of the evectin family (also ...
 750-807 2.14e-09

Evectin Pleckstrin homology (PH) domain; There are 2 members of the evectin family (also called pleckstrin homology domain containing, family B): evt-1 (also called PLEKHB1) and evt-2 (also called PLEKHB2). evt-1 is specific to the nervous system, where it is expressed in photoreceptors and myelinating glia. evt-2 is widely expressed in both neural and nonneural tissues. Evectins possess a single N-terminal PH domain and a C-terminal hydrophobic region. evt-1 is thought to function as a mediator of post-Golgi trafficking in cells that produce large membrane-rich organelles. It is a candidate gene for the inherited human retinopathy autosomal dominant familial exudative vitreoretinopathy and a susceptibility gene for multiple sclerosis. evt-2 is essential for retrograde endosomal membrane transport from the plasma membrane (PM) to the Golgi. Two membrane trafficking pathways pass through recycling endosomes: a recycling pathway and a retrograde pathway that links the PM to the Golgi/ER. Its PH domain that is unique in that it specifically recognizes phosphatidylserine (PS), but not polyphosphoinositides. PS is an anionic phospholipid class in eukaryotic biomembranes, is highly enriched in the PM, and plays key roles in various physiological processes such as the coagulation cascade, recruitment and activation of signaling molecules, and clearance of apoptotic cells. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270085  Cd Length: 108  Bit Score: 56.54  E-value: 2.14e-09
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1907123492  750 EPLEKSGYLLKMSVRVKTWKRRWFVLKG-GELLYYKSPSDviRKPQGHIELSASCSILR 807
Cdd:cd13265      1 MALVKSGWLLRQSTILKRWKKNWFVLYGdGNLVYYEDETR--REVEGRINMPRECRNIR 57
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
 753-847 3.73e-09

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 1; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the first PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270073  Cd Length: 94  Bit Score: 55.09  E-value: 3.73e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  753 EKSGYLLKMSVR--VKTWKRRWFVLKGGELLYYKSPSDVIRKpqGHIELSA-SCSILRGDNKqtVQLATEKHTYYLTADS 829
Cdd:cd13253      1 IKSGYLDKQGGQgnNKGFQKRWVVFDGLSLRYFDSEKDAYSK--RIIPLSAiSTVRAVGDNK--FELVTTNRTFVFRAES 76

                           90
                   ....*....|....*...
gi 1907123492  830 PNILEEWIKVLQSVLRVQ 847
Cdd:cd13253     77 DDERNLWCSTLQAAISEY 94
PH1_Pleckstrin_2 cd13301
Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in ...
 754-838 7.08e-09

Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in platelets. This name is derived from platelet and leukocyte C kinase substrate and the KSTR string of amino acids. Pleckstrin 2 contains two PH domains and a DEP (dishvelled, egl-10, and pleckstrin) domain. Unlike pleckstrin 1, pleckstrin 2 does not contain obvious sites of PKC phosphorylation. Pleckstrin 2 plays a role in actin rearrangement, large lamellipodia and peripheral ruffle formation, and may help orchestrate cytoskeletal arrangement. The PH domains of pleckstrin 2 are thought to contribute to lamellipodia formation. This cd contains the first PH domain repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270113  Cd Length: 108  Bit Score: 55.07  E-value: 7.08e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDviRKPQGHIEL---SASCSILRGDNKQTV-QLATEK-HTYYLTAD 828
Cdd:cd13301      5 KEGYLVKKGHVVNNWKARWFVLKEDGLEYYKKKTD--SSPKGMIPLkgcTITSPCLEYGKRPLVfKLTTAKgQEHFFQAC 82

                           90
                   ....*....|
gi 1907123492  829 SPNILEEWIK 838
Cdd:cd13301     83 SREERDAWAK 92
PH_Boi cd13316
Boi family Pleckstrin homology domain; Yeast Boi proteins Boi1 and Boi2 are functionally ...
 755-840 1.13e-08

Boi family Pleckstrin homology domain; Yeast Boi proteins Boi1 and Boi2 are functionally redundant and important for cell growth with Boi mutants displaying defects in bud formation and in the maintenance of cell polarity.They appear to be linked to Rho-type GTPase, Cdc42 and Rho3. Boi1 and Boi2 display two-hybrid interactions with the GTP-bound ("active") form of Cdc42, while Rho3 can suppress of the lethality caused by deletion of Boi1 and Boi2. These findings suggest that Boi1 and Boi2 are targets of Cdc42 that promote cell growth in a manner that is regulated by Rho3. Boi proteins contain a N-terminal SH3 domain, followed by a SAM (sterile alpha motif) domain, a proline-rich region, which mediates binding to the second SH3 domain of Bem1, and C-terminal PH domain. The PH domain is essential for its function in cell growth and is important for localization to the bud, while the SH3 domain is needed for localization to the neck. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270126  Cd Length: 97  Bit Score: 53.92  E-value: 1.13e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  755 SGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDVIRKpqGHIELSAScSILRGDN------KQTVQL--ATEKHTYYLT 826
Cdd:cd13316      3 SGWMKKRGERYGTWKTRYFVLKGTRLYYLKSENDDKEK--GLIDLTGH-RVVPDDSnspfrgSYGFKLvpPAVPKVHYFA 79

                           90
                   ....*....|....
gi 1907123492  827 ADSPNILEEWIKVL 840
Cdd:cd13316     80 VDEKEELREWMKAL 93
PH_3BP2 cd13308
SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes ...
 754-840 1.22e-08

SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes the adaptor protein 3BP2), HD, ITU, IT10C3, and ADD1 are located near the Huntington's Disease Gene on Human Chromosome 4pl6.3. SH3BP2 lies in a region that is often missing in individuals with Wolf-Hirschhorn syndrome (WHS). Gain of function mutations in SH3BP2 causes enhanced B-cell antigen receptor (BCR)-mediated activation of nuclear factor of activated T cells (NFAT), resulting in a rare, genetic disorder called cherubism. This results in an increase in the signaling complex formation with Syk, phospholipase C-gamma2 (PLC-gamma2), and Vav1. It was recently discovered that Tankyrase regulates 3BP2 stability through ADP-ribosylation and ubiquitylation by the E3-ubiquitin ligase. Cherubism mutations uncouple 3BP2 from Tankyrase-mediated protein destruction, which results in its stabilization and subsequent hyperactivation of the Src, Syk, and Vav signaling pathways. SH3BP2 is also a potential negative regulator of the abl oncogene. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270118  Cd Length: 113  Bit Score: 54.33  E-value: 1.22e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKMSVRVKT---WKRRWFVLKGGELLYYKSPSDVirKPQGHIELS-ASCSI---LRGDNK---QTVQLATEKHTY 823
Cdd:cd13308     11 HSGTLTKKGGSQKTlqnWQLRYVIIHQGCVYYYKNDQSA--KPKGVFSLNgYNRRAaeeRTSKLKfvfKIIHLSPDHRTW 88

                           90
                   ....*....|....*..
gi 1907123492  824 YLTADSPNILEEWIKVL 840
Cdd:cd13308     89 YFAAKSEDEMSEWMEYI 105
PH_M-RIP cd13275
Myosin phosphatase-RhoA Interacting Protein Pleckstrin homology (PH) domain; M-RIP is proposed ...
 754-843 1.91e-08

Myosin phosphatase-RhoA Interacting Protein Pleckstrin homology (PH) domain; M-RIP is proposed to play a role in myosin phosphatase regulation by RhoA. M-RIP contains 2 PH domains followed by a Rho binding domain (Rho-BD), and a C-terminal myosin binding subunit (MBS) binding domain (MBS-BD). The amino terminus of M-RIP with its adjacent PH domains and polyproline motifs mediates binding to both actin and Galpha. M-RIP brings RhoA and MBS into close proximity where M-RIP can target RhoA to the myosin phosphatase complex to regulate the myosin phosphorylation state. M-RIP does this via its C-terminal coiled-coil domain which interacts with the MBS leucine zipper domain of myosin phosphatase, while its Rho-BD, directly binds RhoA in a nucleotide-independent manner. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270094  Cd Length: 104  Bit Score: 53.49  E-value: 1.91e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDVIRK-PQGHIELS--ASCSILRGDNKQTVQLAT-EKHTYYLTADS 829
Cdd:cd13275      1 KKGWLMKQGSRQGEWSKHWFVLRGAALKYYRDPSAEEAGeLDGVIDLSscTEVTELPVSRNYGFQVKTwDGKVYVLSAMT 80

                           90
                   ....*....|....
gi 1907123492  830 PNILEEWIKVLQSV 843
Cdd:cd13275     81 SGIRTNWIQALRKA 94
PH_IRS cd01257
Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate ...
 754-845 2.04e-08

Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate (IRS) molecules are mediators in insulin signaling and play a role in maintaining basic cellular functions such as growth and metabolism. They act as docking proteins between the insulin receptor and a complex network of intracellular signaling molecules containing Src homology 2 (SH2) domains. Four members (IRS-1, IRS-2, IRS-3, IRS-4) of this family have been identified that differ as to tissue distribution, subcellular localization, developmental expression, binding to the insulin receptor, and interaction with SH2 domain-containing proteins. IRS molecules have an N-terminal PH domain, followed by an IRS-like PTB domain which has a PH-like fold. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.cytoskeletal associated molecules, and in lipid associated enzymes.


Pssm-ID: 269959  Cd Length: 106  Bit Score: 53.45  E-value: 2.04e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKmsvrVKTWKRRWFVLKGGE------LLYYKSPSDVIRK--PQGHIELSASCSILR---GDNKQTVQLATEKHT 822
Cdd:cd01257      5 KSGYLKK----LKTMRKRYFVLRAEShggparLEYYENEKKFRRNaePKRVIPLSSCFNINKradAKHKHLIALYTKDEC 80

                           90       100
                   ....*....|....*....|...
gi 1907123492  823 YYLTADSPNILEEWIKVLQSVLR 845
Cdd:cd01257     81 FGLVAESEEEQDEWYQALLELQR 103
PH2_ADAP cd01251
ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called ...
 754-844 2.44e-08

ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called centaurin alpha) is a phophatidlyinositide binding protein consisting of an N-terminal ArfGAP domain and two PH domains. In response to growth factor activation, PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 1 is recruited to the plasma membrane following growth factor stimulation by specific binding of its PH domain to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 2 is constitutively bound to the plasma membrane since it binds phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate with equal affinity. This cd contains the second PH domain repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241282  Cd Length: 105  Bit Score: 53.36  E-value: 2.44e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKMSVRVKT-WKRRWFVLKGGELLYYKSPSDVIRKPQ---GHIELSASCSI-----LRGDNKQTVQLATEKHTYY 824
Cdd:cd01251      4 KEGYLEKTGPKQTDgFRKRWFTLDDRRLMYFKDPLDAFPKGEifiGSKEEGYSVREglppgIKGHWGFGFTLVTPDRTFL 83

                           90       100
                   ....*....|....*....|
gi 1907123492  825 LTADSPNILEEWIKVLQSVL 844
Cdd:cd01251     84 LSAETEEERREWITAIQKVL 103
PH_OSBP_ORP4 cd13284
Human Oxysterol binding protein and OSBP-related protein 4 Pleckstrin homology (PH) domain; ...
 754-841 4.23e-08

Human Oxysterol binding protein and OSBP-related protein 4 Pleckstrin homology (PH) domain; Human OSBP is proposed to function is sterol-dependent regulation of ERK dephosphorylation and sphingomyelin synthesis as well as modulation of insulin signaling and hepatic lipogenesis. It contains a N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. OSBPs and Osh1p PH domains specifically localize to the Golgi apparatus in a PtdIns4P-dependent manner. ORP4 is proposed to function in Vimentin-dependent sterol transport and/or signaling. Human ORP4 has 2 forms, a long (ORP4L) and a short (ORP4S). ORP4L contains a N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. ORP4S is truncated and contains only an OSBP-related domain. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270101  Cd Length: 99  Bit Score: 52.38  E-value: 4.23e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDVIRKPQGHIELSASCsILRGDNKQTVQLATEKHTYYLTADSPNIL 833
Cdd:cd13284      1 MKGWLLKWTNYIKGYQRRWFVLSNGLLSYYRNQAEMAHTCRGTINLAGAE-IHTEDSCNFVISNGGTQTFHLKASSEVER 79


                   ....*...
gi 1907123492  834 EEWIKVLQ 841
Cdd:cd13284     80 QRWVTALE 87
PH_Osh1p_Osh2p_yeast cd13292
Yeast oxysterol binding protein homologs 1 and 2 Pleckstrin homology (PH) domain; Yeast Osh1p ...
 751-845 4.56e-08

Yeast oxysterol binding protein homologs 1 and 2 Pleckstrin homology (PH) domain; Yeast Osh1p is proposed to function in postsynthetic sterol regulation, piecemeal microautophagy of the nucleus, and cell polarity establishment. Yeast Osh2p is proposed to function in sterol metabolism and cell polarity establishment. Both Osh1p and Osh2p contain 3 N-terminal ankyrin repeats, a PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. OSBP andOsh1p PH domains specifically localize to the Golgi apparatus in a PtdIns4P-dependent manner. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241446  Cd Length: 103  Bit Score: 52.31  E-value: 4.56e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  751 PLEKSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDVIRKPQGHIELSAscSILRGDNKQTVQL-------ATEKhtY 823
Cdd:cd13292      1 PPTMKGYLKKWTNYAKGYKTRWFVLEDGVLSYYRHQDDEGSACRGSINMKN--ARLVSDPSEKLRFevssktsGSPK--W 76

                           90       100
                   ....*....|....*....|..
gi 1907123492  824 YLTADSPNILEEWIKVLQSVLR 845
Cdd:cd13292     77 YLKANHPVEAARWIQALQKAIE 98
PH_FAPP1_FAPP2 cd01247
Four phosphate adaptor protein 1 and 2 Pleckstrin homology (PH) domain; Human FAPP1 (also ...
 756-842 5.08e-08

Four phosphate adaptor protein 1 and 2 Pleckstrin homology (PH) domain; Human FAPP1 (also called PLEKHA3/Pleckstrin homology domain-containing, family A member 3) regulates secretory transport from the trans-Golgi network to the plasma membrane. It is recruited through binding of PH domain to phosphatidylinositol 4-phosphate (PtdIns(4)P) and a small GTPase ADP-ribosylation factor 1 (ARF1). These two binding sites have little overlap the FAPP1 PH domain to associate with both ligands simultaneously and independently. FAPP1 has a N-terminal PH domain followed by a short proline-rich region. FAPP1 is a member of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), and Goodpasture antigen binding protein (GPBP). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. FAPP2 (also called PLEKHA8/Pleckstrin homology domain-containing, family A member 8), a member of the Glycolipid lipid transfer protein(GLTP) family has an N-terminal PH domain that targets the TGN and C-terminal GLTP domain. FAPP2 functions to traffic glucosylceramide (GlcCer) which is made in the Golgi. It's interaction with vesicle-associated membrane protein-associated protein (VAP) could be a means of regulation. Some FAPP2s share the FFAT-like motifs found in GLTP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269951  Cd Length: 100  Bit Score: 52.41  E-value: 5.08e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  756 GYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDVIRKPQGHIELSAsCSILRGDNKQT---VQLATEKHtYYLTADSPNI 832
Cdd:cd01247      3 GVLWKWTNYLSGWQPRWFVLDDGVLSYYKSQEEVNQGCKGSVKMSV-CEIIVHPTDPTrmdLIIPGEQH-FYLKASSAAE 80

                           90
                   ....*....|
gi 1907123492  833 LEEWIKVLQS 842
Cdd:cd01247     81 RQRWLVALGS 90
PH_GPBP cd13283
Goodpasture antigen binding protein Pleckstrin homology (PH) domain; The GPBP (also called ...
 754-842 5.96e-08

Goodpasture antigen binding protein Pleckstrin homology (PH) domain; The GPBP (also called Collagen type IV alpha-3-binding protein/hCERT; START domain-containing protein 11/StARD11; StAR-related lipid transfer protein 11) is a kinase that phosphorylates an N-terminal region of the alpha 3 chain of type IV collagen, which is commonly known as the goodpasture antigen. Its splice variant the ceramide transporter (CERT) mediates the cytosolic transport of ceramide. There have been additional splice variants identified, but all of them function as ceramide transport proteins. GPBP and CERT both contain an N-terminal PH domain, followed by a serine rich domain, and a C-terminal START domain. However, GPBP has an additional serine rich domain just upstream of its START domain. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270100 [Multi-domain]  Cd Length: 100  Bit Score: 51.90  E-value: 5.96e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDVIRKPQGHIELSaSCSI-------LRGDnkqtvqLATEKHTYYLT 826
Cdd:cd13283      1 LRGVLSKWTNYIHGWQDRYFVLKDGTLSYYKSESEKEYGCRGSISLS-KAVIkphefdeCRFD------VSVNDSVWYLR 73

                           90
                   ....*....|....*.
gi 1907123492  827 ADSPNILEEWIKVLQS 842
Cdd:cd13283     74 AESPEERQRWIDALES 89
COG4372 COG4372
Uncharacterized protein, contains DUF3084 domain [Function unknown];
91-221 7.66e-08

Uncharacterized protein, contains DUF3084 domain [Function unknown];


Pssm-ID: 443500 [Multi-domain]  Cd Length: 370  Bit Score: 56.45  E-value: 7.66e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   91 MQQLERQVIDAERQAEKAFQEVQVMEEKLKAANIQTSESETRLYKKCQDLESVMQEKDDIIQNLALRLEEQKQVRIQEAK 170
Cdd:COG4372     40 LDKLQEELEQLREELEQAREELEQLEEELEQARSELEQLEEELEELNEQLQAAQAELAQAQEELESLQEEAEELQEELEE 119

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1907123492  171 IIEEKAAKIKEwvtvkLNELEVENQNLRFINQTQTEEIRAIQSKLQELQEK 221
Cdd:COG4372    120 LQKERQDLEQQ-----RKQLEAQIAELQSEIAEREEELKELEEQLESLQEE 165
PH2_TAPP1_2 cd13271
Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal ...
 754-843 9.92e-08

Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal repeat; The binding of TAPP1 (also called PLEKHA1/pleckstrin homology domain containing, family A (phosphoinositide binding specific) member 1) and TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP1 and TAPP2 contain two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270090  Cd Length: 114  Bit Score: 51.97  E-value: 9.92e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDviRKPQGHIEL-----SASC---SILRGDNkqTVQLATEKHTYYL 825
Cdd:cd13271     10 KSGYCVKQGAVRKNWKRRFFILDDNTISYYKSETD--KEPLRTIPLrevlkVHEClvkSLLMRDN--LFEIITTSRTFYI 85

                           90
                   ....*....|....*...
gi 1907123492  826 TADSPNILEEWIKVLQSV 843
Cdd:cd13271     86 QADSPEEMHSWIKAISGA 103
PH3_MyoX-like cd13297
Myosin X-like Pleckstrin homology (PH) domain, repeat 3; MyoX, a MyTH-FERM myosin, is a ...
 769-844 1.80e-07

Myosin X-like Pleckstrin homology (PH) domain, repeat 3; MyoX, a MyTH-FERM myosin, is a molecular motor that has crucial functions in the transport and/or tethering of integrins in the actin-based extensions known as filopodia, microtubule binding, and in netrin-mediated axon guidance. It functions as a dimer. MyoX walks on bundles of actin, rather than single filaments, unlike the other unconventional myosins. MyoX is present in organisms ranging from humans to choanoflagellates, but not in Drosophila and Caenorhabditis elegans.MyoX consists of a N-terminal motor/head region, a neck made of 3 IQ motifs, and a tail consisting of a coiled-coil domain, a PEST region, 3 PH domains, a myosin tail homology 4 (MyTH4), and a FERM domain at its very C-terminus. The first PH domain in the MyoX tail is a split-PH domain, interupted by the second PH domain such that PH 1a and PH 1b flanks PH 2. The third PH domain (PH 3) follows the PH 1b domain. This cd contains the third MyoX PH repeat. PLEKHH3/Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) member 3 is also part of this CD and like MyoX contains a FERM domain, a MyTH4 domain, and a single PH domain. Not much is known about the function of PLEKHH3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270109  Cd Length: 126  Bit Score: 51.28  E-value: 1.80e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  769 KRRWFVLKGGELLYYKSPSDVIRKpQGHIELSASCSILRGDNKQ-------TVQLATEKHTYYLTADSPNILEEWIKVLQ 841
Cdd:cd13297     35 KKRWFVLTGNSLDYYKSSEKNSLK-LGTLVLNSLCSVVPPDEKMaketgywTFTVHGRKHSFRLYTKLQEEAMRWVNAIQ 113


                   ...
gi 1907123492  842 SVL 844
Cdd:cd13297    114 DVI 116
PH_DGK_type2 cd13274
Type 2 Diacylglycerol kinase Pleckstrin homology (PH) domain; DGK (also called DAGK) catalyzes ...
 754-843 3.42e-07

Type 2 Diacylglycerol kinase Pleckstrin homology (PH) domain; DGK (also called DAGK) catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA) utilizing ATP as a source of the phosphate. In non-stimulated cells, DGK activity is low and DAG is used for glycerophospholipid biosynthesis. Upon receptor activation of the phosphoinositide pathway, DGK activity increases which drives the conversion of DAG to PA. DGK acts as a switch by terminating the signalling of one lipid while simultaneously activating signalling by another. There are 9 mammalian DGK isoforms all with conserved catalytic domains and two cysteine rich domains. These are further classified into 5 groups according to the presence of additional functional domains and substrate specificity: Type 1 - DGK-alpha, DGK-beta, DGK-gamma - contain EF-hand motifs and a recoverin homology domain; Type 2 - DGK-delta, DGK-eta, and DGK-kappa- contain a pleckstrin homology domain, two cysteine-rich zinc finger-like structures, and a separated catalytic region; Type 3 - DGK-epsilon - has specificity for arachidonate-containing DAG; Type 4 - DGK-zeta, DGK-iota- contain a MARCKS homology domain, ankyrin repeats, a C-terminal nuclear localization signal, and a PDZ-binding motif; Type 5 - DGK-theta - contains a third cysteine-rich domain, a pleckstrin homology domain and a proline rich region. The type 2 DGKs are present as part of this Metazoan DGK hierarchy. They have a N-terminal PH domain, two cysteine rich domains, followed by bipartite catalytic domains, and a C-terminal SAM domain. Their catalytic domains and perhaps other DGK catalytic domains may function as two independent units in a coordinated fashion. They may also require other motifs for maximal activity because several DGK catalytic domains have very little DAG kinase activity when expressed as isolated subunits. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270093  Cd Length: 97  Bit Score: 49.70  E-value: 3.42e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDVIRKpqgHIELS----ASCSILRGDNkqTVQLATEKHTYYLTADS 829
Cdd:cd13274      2 KEGPLLKQTSSFQRWKRRYFKLKGRKLYYAKDSKSLIFE---EIDLSdasvAECSTKNVNN--SFTVITPFRKLILCAES 76

                           90
                   ....*....|....
gi 1907123492  830 PNILEEWIKVLQSV 843
Cdd:cd13274     77 RKEMEEWISALKTV 90
PH2_Pleckstrin_2 cd13302
Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 2; Pleckstrin is a protein found in ...
 754-843 4.14e-07

Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 2; Pleckstrin is a protein found in platelets. This name is derived from platelet and leukocyte C kinase substrate and the KSTR string of amino acids. Pleckstrin 2 contains two PH domains and a DEP (dishvelled, egl-10, and pleckstrin) domain. Unlike pleckstrin 1, pleckstrin 2 does not contain obvious sites of PKC phosphorylation. Pleckstrin 2 plays a role in actin rearrangement, large lamellipodia and peripheral ruffle formation, and may help orchestrate cytoskeletal arrangement. The PH domains of pleckstrin 2 are thought to contribute to lamellipodia formation. This cd contains the second PH domain repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270114  Cd Length: 109  Bit Score: 49.82  E-value: 4.14e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKMSVRVKTWKRRWFVLKG--GELLYYKSPSDviRKPQGHIELSASCSILRGDN----KQTVQ-------LATEK 820
Cdd:cd13302      9 KQGCLLKQGHRRKNWKVRKFVLRDdpAYLHYYDPAKG--EDPLGAIHLRGCVVTAVEDNsnprKGSVEgnlfeiiTADEV 86

                           90       100
                   ....*....|....*....|...
gi 1907123492  821 HtYYLTADSPNILEEWIKVLQSV 843
Cdd:cd13302     87 H-YYLQAATPAERTEWIKAIQMA 108
COG4372 COG4372
Uncharacterized protein, contains DUF3084 domain [Function unknown];
91-224 4.78e-07

Uncharacterized protein, contains DUF3084 domain [Function unknown];


Pssm-ID: 443500 [Multi-domain]  Cd Length: 370  Bit Score: 53.75  E-value: 4.78e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   91 MQQLERQVIDAERQAEKAFQEVQVMEEKLKAANIQTSESETRLYKKCQDLESVMQEKDDIIQNLAlRLEEQKQVRIQEAK 170
Cdd:COG4372     54 LEQAREELEQLEEELEQARSELEQLEEELEELNEQLQAAQAELAQAQEELESLQEEAEELQEELE-ELQKERQDLEQQRK 132

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1907123492  171 IIEEKAAKIKEWVTVKLNELEVENQNLRFINqtqtEEIRAIQSKLQELQEKKIS 224
Cdd:COG4372    133 QLEAQIAELQSEIAEREEELKELEEQLESLQ----EELAALEQELQALSEAEAE 182
SMC_prok_A TIGR02169
chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of ...
 85-224 7.77e-07

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274009 [Multi-domain]  Cd Length: 1164  Bit Score: 54.30  E-value: 7.77e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   85 ASAKHHMQQLERQVIDAERQAEKAFQEVQVMEEKLKAANIQTSESETRLYKKCQDLESVMQEKDDIIQNLALRLEEQKQV 164
Cdd:TIGR02169  698 RRIENRLDELSQELSDASRKIGEIEKEIEQLEQEEEKLKERLEELEEDLSSLEQEIENVKSELKELEARIEELEEDLHKL 777

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907123492  165 RIQEAKI-----------IEEKAAKIKEWVT---VKLNELEVENQNLRFINQTQTEEIRAIQSKLQELQEKKIS 224
Cdd:TIGR02169  778 EEALNDLearlshsripeIQAELSKLEEEVSrieARLREIEQKLNRLTLEKEYLEKEIQELQEQRIDLKEQIKS 851
FERM1_F1_Myosin-VII cd17092
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain 1, F1 sub-domain, found in Myosin-VIIa, ...
 1168-1264 1.38e-06

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain 1, F1 sub-domain, found in Myosin-VIIa, Myosin-VIIb, and similar proteins; This family includes two nontraditional members of the myosin superfamily, myosin-VIIa and myosin-VIIb. Myosin-VIIa, also termed myosin-7a (Myo7a), has been implicated in the structural organization of hair bundles at the apex of sensory hair cells (SHCs) where it serves mechanotransduction in the process of hearing and balance. Mutations in the MYO7A gene may be associated with Usher Syndrome type 1B (USH1B) and nonsyndromic hearing loss (DFNB2, DFNA11). Myosin-VIIb, also termed myosin-7b (Myo7b), is a high duty ratio motor adapted for generating and maintaining tension. It associates with harmonin and ANKS4B to form a stable ternary complex for anchoring microvilli tip-link cadherins. Like other unconventional myosins, myosin-VII is composed of a conserved motor head, a neck region and a tail region containing two MyTH4 domains, a SH3 domain, and two FERM domains. The FERM domain is made up of three sub-domains, F1, F2, and F3. The family corresponds to the F1 sub-domain of the first FERM domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).


Pssm-ID: 340612  Cd Length: 99  Bit Score: 48.02  E-value: 1.38e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492 1168 PFSIPVHFMNGLYQVVGFDASTTVEEFLNTLNQDTGMRKpaQSGFALF---TDDPS--GRDLEHclqgnikICDIISKWE 1242
Cdd:cd17092      1 PIMLPVTFMDGSTKTVEVDSATTARELCRQLAEKLGLKD--TFGFSLYialFDKVSslGSGTDH-------VMDAISQCE 71

                           90       100
                   ....*....|....*....|..
gi 1907123492 1243 QASKEQqpGKCEGSRTVRLTYK 1264
Cdd:cd17092     72 QYAKEK--GAQEREAPWRLYFR 91
PH_Gab-like cd13324
Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are ...
 755-837 1.47e-06

Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. There are 3 families: Gab1, Gab2, and Gab3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270133  Cd Length: 112  Bit Score: 48.56  E-value: 1.47e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  755 SGYLLK----MSVRVKTWKRRWFVLKGGELL-------YYKspSDVIRKPQGHIEL--------SASCSILRGDNKQTVQ 815
Cdd:cd13324      4 EGWLTKsppeKKIWRAAWRRRWFVLRSGRLSggqdvleYYT--DDHCKKLKGIIDLdqceqvdaGLTFEKKKFKNQFIFD 81

                           90       100
                   ....*....|....*....|..
gi 1907123492  816 LATEKHTYYLTADSPNILEEWI 837
Cdd:cd13324     82 IRTPKRTYYLVAETEEEMNKWV 103
PH_anillin cd01263
Anillin Pleckstrin homology (PH) domain; Anillin (Rhotekin/RTKN; also called PLEKHK/Pleckstrin ...
 767-844 2.77e-06

Anillin Pleckstrin homology (PH) domain; Anillin (Rhotekin/RTKN; also called PLEKHK/Pleckstrin homology domain-containing family K) is an actin binding protein involved in cytokinesis. It interacts with GTP-bound Rho proteins and results in the inhibition of their GTPase activity. Dysregulation of the Rho signal transduction pathway has been implicated in many forms of cancer. Anillin proteins have a N-terminal HRI domain/ACC (anti-parallel coiled-coil) finger domain or Rho-binding domain binds small GTPases from the Rho family. The C-terminal PH domain helps target anillin to ectopic septin containing foci. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269964  Cd Length: 121  Bit Score: 48.04  E-value: 2.77e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  767 TWKRRWFVLKGGELLYYKSPSDVIRK-PQGHIELSA----------------------SCSILRGDNKQTVQLATEKHty 823
Cdd:cd01263     19 AWHRRWCVLRGGYLSFWKYPDDEEKKkPIGSIDLTKcitekvepaprelcarpntfllETLRPAEDDDRDDTNEKIRV-- 96

                           90       100
                   ....*....|....*....|.
gi 1907123492  824 YLTADSPNILEEWIKVLQSVL 844
Cdd:cd01263     97 LLSADTKEERIEWLSALNQTL 117
FERM_B-lobe cd14473
FERM domain B-lobe; The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C ...
 1284-1394 4.66e-06

FERM domain B-lobe; The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases, the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains and consequently is capable of binding to both peptides and phospholipids at different sites.


Pssm-ID: 271216  Cd Length: 99  Bit Score: 46.47  E-value: 4.66e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492 1284 LLY-QTNDQIINGLFPLNKDLALEMAALLAQVDIGDFERPFSTPagpvtnqckanqtLKQVIERFYPKRYREGCSEEQLR 1362
Cdd:cd14473      4 LLYlQVKRDILEGRLPCSEETAALLAALALQAEYGDYDPSEHKP-------------KYLSLKRFLPKQLLKQRKPEEWE 70

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1907123492 1363 qlyQRLSTKWMALRGHSAADCIRIYLTVARKW 1394
Cdd:cd14473     71 ---KRIVELHKKLRGLSPAEAKLKYLKIARKL 99
PH2_FGD5_FGD6 cd13237
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6 pleckstrin ...
 755-840 5.86e-06

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6 pleckstrin homology (PH) domain, C-terminus; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270057  Cd Length: 91  Bit Score: 46.25  E-value: 5.86e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  755 SGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDVIrkPQGHIELS--ASCSILRGDNKQT---VQLATEKHTYY-LTAD 828
Cdd:cd13237      2 SGYLQRRKKSKKSWKRLWFVLKDKVLYTYKASEDVV--ALESVPLLgfTVVTIDESFEEDEslvFQLLHKGQLPIiFRAD 79

                           90
                   ....*....|..
gi 1907123492  829 SPNILEEWIKVL 840
Cdd:cd13237     80 DAETAQRWIEAL 91
PH_PHLDB1_2 cd14673
Pleckstrin homology-like domain-containing family B member 2 pleckstrin homology (PH) domain; ...
 756-840 6.65e-06

Pleckstrin homology-like domain-containing family B member 2 pleckstrin homology (PH) domain; PHLDB2 (also called LL5beta) and PHLDB1 (also called LL5alpha) are cytoskeleton- and membrane-associated proteins. PHLDB2 has been identified as a key component of the synaptic podosomes that play an important role in in postsynaptic maturation. Both are large proteins containing an N-terminal pleckstrin (PH) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270192  Cd Length: 105  Bit Score: 46.41  E-value: 6.65e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  756 GYLLKMSVRVKTWKRRWFV--LKGGELLYYKSPSDviRKPQGHIELSASCSI----LRGDNKQ-----TVQLATEKHTYY 824
Cdd:cd14673      7 GFLTKMGGKIKTWKKRWFVfdRNKRTLSYYVDKHE--KKLKGVIYFQAIEEVyydhLRSAAKSpnpalTFCVKTHDRLYY 84

                           90
                   ....*....|....*.
gi 1907123492  825 LTADSPNILEEWIKVL 840
Cdd:cd14673     85 MVAPSPEAMRIWMDVI 100
COG4372 COG4372
Uncharacterized protein, contains DUF3084 domain [Function unknown];
85-224 7.12e-06

Uncharacterized protein, contains DUF3084 domain [Function unknown];


Pssm-ID: 443500 [Multi-domain]  Cd Length: 370  Bit Score: 50.29  E-value: 7.12e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   85 ASAKHHMQQLERQVIDAERQAEKAFQEVQVMEEKLKAANIQTSESETRLYKKCQDLESVMQEKDDIIQNLAlRLEEQKQV 164
Cdd:COG4372     69 EQARSELEQLEEELEELNEQLQAAQAELAQAQEELESLQEEAEELQEELEELQKERQDLEQQRKQLEAQIA-ELQSEIAE 147

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  165 RIQEAKIIEEKAAKIKEwvtvKLNELEVENQNLrfinqTQTEEIRAIQSKLQELQEKKIS 224
Cdd:COG4372    148 REEELKELEEQLESLQE----ELAALEQELQAL-----SEAEAEQALDELLKEANRNAEK 198
PH_Gab2_2 cd13384
Grb2-associated binding protein family pleckstrin homology (PH) domain; The Gab subfamily ...
 756-837 1.15e-05

Grb2-associated binding protein family pleckstrin homology (PH) domain; The Gab subfamily includes several Gab proteins, Drosophila DOS and C. elegans SOC-1. They are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. Members here include insect, nematodes, and crustacean Gab2s. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241535  Cd Length: 115  Bit Score: 45.90  E-value: 1.15e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  756 GYLLK----MSVRVKTWKRRWFVLKGGE------LLYYKspSDVIRKPQGHIELSaSC----SILRGDNKQTVQLA---- 817
Cdd:cd13384      7 GWLTKsppeKRIWRAKWRRRYFVLRQSEipgqyfLEYYT--DRTCRKLKGSIDLD-QCeqvdAGLTFETKNKLKDQhifd 83

                           90       100
                   ....*....|....*....|..
gi 1907123492  818 --TEKHTYYLTADSPNILEEWI 837
Cdd:cd13384     84 irTPKRTYYLVADTEDEMNKWV 105
PH2_FGD4_insect-like cd13238
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 4 pleckstrin homology (PH) ...
 755-840 1.52e-05

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 4 pleckstrin homology (PH) domain, C-terminus, in insect and related arthropods; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. This cd contains insects, crustaceans, and chelicerates. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270058  Cd Length: 97  Bit Score: 45.33  E-value: 1.52e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  755 SGYLLKMSVRVKTWKRRWFVLKGGELLY-YKSPSDVIRKPQGHI------ELSASCSILRGDNKQ---TVQLATEKHTYY 824
Cdd:cd13238      2 SGYLKLKTNGRKTWSRRWFALQPDFVLYsYKSQEDKLPLTATPVpgflvtLLEKGSAVDPLNDPKrprTFKMFHVKKSYY 81

                           90
                   ....*....|....*.
gi 1907123492  825 LTADSPNILEEWIKVL 840
Cdd:cd13238     82 FQANDGDEQKKWVLTL 97
PH_ORP_plant cd13294
Plant Oxysterol binding protein related protein Pleckstrin homology (PH) domain; Plant ORPs ...
 756-843 1.57e-05

Plant Oxysterol binding protein related protein Pleckstrin homology (PH) domain; Plant ORPs contain a N-terminal PH domain and a C-terminal OSBP-related domain. Not much is known about its specific function in plants to date. Members here include: Arabidopsis, spruce, and petunia. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241448  Cd Length: 100  Bit Score: 45.18  E-value: 1.57e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  756 GYLLKMSVRVKTWKRRWFVLKGGELLYYK--SPSDVirKPQGHIELS-ASCSILRGDNKQtVQLATEKHTYYLTADSPNI 832
Cdd:cd13294      3 GILYKWVNYGKGWRSRWFVLQDGVLSYYKvhGPDKV--KPSGEVHLKvSSIRESRSDDKK-FYIFTGTKTLHLRAESRED 79

                           90
                   ....*....|.
gi 1907123492  833 LEEWIKVLQSV 843
Cdd:cd13294     80 RAAWLEALQAA 90
PH_Bud4 cd13278
Bud4 Pleckstrin homology (PH) domain; Bud4 is an anillin-like yeast protein involved in the ...
 752-844 2.08e-05

Bud4 Pleckstrin homology (PH) domain; Bud4 is an anillin-like yeast protein involved in the formation and the disassembly of the double ring structure formed by the septins during cytokinesis. Bud4 acts with Bud3 and and in parallel with septin phosphorylation by the p21-activated kinase Cla4 and the septin-dependent kinase Gin4. Bud4 is regulated by the cyclin-dependent protein kinase Cdk1, the master regulator of cell cycle progression. Bud4 contains an anillin-like domain followed by a PH domain. In addition there are two consensus Cdk phosphorylation sites: one at the N-terminus and one right before the C-terminal PH domain. Anillins also have C-terminal PH domains. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241432  Cd Length: 139  Bit Score: 46.05  E-value: 2.08e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  752 LEKSGYLLKMSVRVKTWKRRWFVLKGGELLYYkspSDVIRKPQGHIELSASCSILrgDNKQTVQLATEKHTYY------- 824
Cdd:cd13278     19 ITKEGYLLQEGGDCEYWRRRFFKLQGTKLVAY---HEVTRKPRATINLLKVVDVV--DDDDARERTSSFKRNFtdlvlfe 93

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1907123492  825 --------------LTADSPNILEEWIKVLQSVL 844
Cdd:cd13278     94 ecfrlvfangevidFYADSKEEKADWYSKLKEVV 127
Smc COG1196
Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning]; ...
 89-221 2.08e-05

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 440809 [Multi-domain]  Cd Length: 983  Bit Score: 49.55  E-value: 2.08e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   89 HHMQQLERQVIDAERQAEKAFQEVQVMEEKLKAANIQTSESETRLYKKCQDLESVMQEKDDIIQNLALRLEEQKQVRIQE 168
Cdd:COG1196    284 EEAQAEEYELLAELARLEQDIARLEERRRELEERLEELEEELAELEEELEELEEELEELEEELEEAEEELEEAEAELAEA 363

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1907123492  169 AKIIEEKAAKIKEWVTVKLNELEVENQNLRFINQTQTEEIRAIQSKLQELQEK 221
Cdd:COG1196    364 EEALLEAEAELAEAEEELEELAEELLEALRAAAELAAQLEELEEAEEALLERL 416
PH_ASAP cd13251
ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs ...
 752-841 2.30e-05

ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs (ASAP1, ASAP2, and ASAP3) function as an Arf-specific GAPs, participates in rhodopsin trafficking, is associated with tumor cell metastasis, modulates phagocytosis, promotes cell proliferation, facilitates vesicle budding, Golgi exocytosis, and regulates vesicle coat assembly via a Bin/Amphiphysin/Rvs domain. ASAPs contain an NH2-terminal BAR domain, a tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 (SH3) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270071  Cd Length: 108  Bit Score: 45.05  E-value: 2.30e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  752 LEKSGYLLKMSVR--VKTWKRRWFVLKGGELLYYKSPSDvirKPQGHIELsASCSI-LRGDNKQTVQLATEKHTYYLTAD 828
Cdd:cd13251     10 TEKSGYLLKKSEGkiRKVWQKRRCSIKDGFLTISHADEN---KPPAKLNL-LTCQVkLVPEDKKCFDLISHNRTYHFQAE 85

                           90
                   ....*....|...
gi 1907123492  829 SPNILEEWIKVLQ 841
Cdd:cd13251     86 DENDANAWMSVLK 98
PH_Skap-hom_Skap2 cd13381
Src kinase-associated phosphoprotein homolog and Skap 2 Pleckstrin homology (PH) domain; ...
 754-845 2.38e-05

Src kinase-associated phosphoprotein homolog and Skap 2 Pleckstrin homology (PH) domain; Adaptor protein Skap-hom, a homolog of Skap55, which interacts with actin and with ADAP (adhesion and degranulation promoting adapter protein) undergoes tyrosine phosphorylation in response to plating of bone marrow-derived macrophages on fibronectin. Skap-hom has an N-terminal coiled-coil conformation that is involved in homodimer formation, a central PH domain and a C-terminal SH3 domain that associates with ADAP. The Skap-hom PH domain regulates intracellular targeting; its interaction with the DM domain inhibits Skap-hom actin-based ruffles in macrophages and its binding to 3'-phosphoinositides reverses this autoinhibition. The Skap-hom PH domain binds PI[3,4]P2 and PI[3,4,5]P3, but not to PI[3]P, PI[5]P, or PI[4,5]P2. Skap2 is a downstream target of Heat shock transcription factor 4 (HSF4) and functions in the regulation of actin reorganization during lens differentiation. It is thought that SKAP2 anchors the complex of tyrosine kinase adaptor protein 2 (NCK20/focal adhesion to fibroblast growth factor receptors at the lamellipodium in lens epithelial cells. Skap2 has an N-terminal coiled-coil conformation which interacts with the SH2 domain of NCK2, a central PH domain and a C-terminal SH3 domain that associates with ADAP (adhesion and degranulation promoting adapter protein)/FYB (the Fyn binding protein). Skap2 PH domain binds to membrane lipids. Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Src kinase-associated phosphoprotein of 55 kDa (Skap55)/Src kinase-associated phosphoprotein 1 (Skap1), Skap2, and Skap-hom have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270181  Cd Length: 106  Bit Score: 44.95  E-value: 2.38e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKM----SVRVKTWKRRWFVLKGGELLYYKSPSDVIRKPQGHIE--LSASCSILRGDNKQTV---QLATEKHTYY 824
Cdd:cd13381      3 KAGYLEKRrkdhSFFGFEWQKRWCALSNSVFYYYGSDKDKQQKGEFAIDgyDVKMNNTLRKDAKKDCcfeICAPDKRVYQ 82

                           90       100
                   ....*....|....*....|.
gi 1907123492  825 LTADSPNILEEWIKVLQSVLR 845
Cdd:cd13381     83 FTAASPKEAEEWVQQIKFILQ 103
CENP-F_leu_zip pfam10473
Leucine-rich repeats of kinetochore protein Cenp-F/LEK1; Cenp-F, a centromeric kinetochore, ...
 80-220 2.65e-05

Leucine-rich repeats of kinetochore protein Cenp-F/LEK1; Cenp-F, a centromeric kinetochore, microtubule-binding protein consisting of two 1,600-amino acid-long coils, is essential for the full functioning of the mitotic checkpoint pathway. There are several leucine-rich repeats along the sequence of LEK1 that are considered to be zippers, though they do not appear to be binding DNA directly in this instance.


Pssm-ID: 463102 [Multi-domain]  Cd Length: 140  Bit Score: 45.75  E-value: 2.65e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   80 SSHRSASAKHHMQQLERQVIDAE-------RQAEKAFQEVQVMEEKLKAANIQTSESEtrlykkcQDLESVMQEKDDIIQ 152
Cdd:pfam10473   15 SERKADSLKDKVENLERELEMSEenqelaiLEAENSKAEVETLKAEIEEMAQNLRDLE-------LDLVTLRSEKENLTK 87

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907123492  153 NLalrleEQKQVRIQEAKIIEEKAAKIkewvtvkLNELEVENqnlRFINQTQTEEIRAIQSKLQELQE 220
Cdd:pfam10473   88 EL-----QKKQERVSELESLNSSLENL-------LEEKEQEK---VQMKEESKTAVEMLQTQLKELNE 140
PH_KIFIA_KIFIB cd01233
KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA ...
 748-840 2.71e-05

KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA (Caenorhabditis elegans homolog unc-104) and KIFIB transport synaptic vesicle precursors that contain synaptic vesicle proteins, such as synaptophysin, synaptotagmin and the small GTPase RAB3A, but they do not transport organelles that contain plasma membrane proteins. They have a N-terminal motor domain, followed by a coiled-coil domain, and a C-terminal PH domain. KIF1A adopts a monomeric form in vitro, but acts as a processive dimer in vivo. KIF1B has alternatively spliced isoforms distinguished by the presence or absence of insertion sequences in the conserved amino-terminal region of the protein; this results in their different motor activities. KIF1A and KIF1B bind to RAB3 proteins through the adaptor protein mitogen-activated protein kinase (MAPK) -activating death domain (MADD; also calledDENN), which was first identified as a RAB3 guanine nucleotide exchange factor (GEF). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269939  Cd Length: 103  Bit Score: 44.51  E-value: 2.71e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  748 KNEPLEKSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSD-----VIRKPQGHIELSASCSILRGdNKQTVQLATEKHT 822
Cdd:cd01233      2 KSPVVSKRGYLLFLEDATDGWVRRWVVLRRPYLHIYSSEKDgdergVINLSTARVEYSPDQEALLG-RPNVFAVYTPTNS 80

                           90
                   ....*....|....*...
gi 1907123492  823 YYLTADSPNILEEWIKVL 840
Cdd:cd01233     81 YLLQARSEKEMQDWLYAI 98
PH_11 pfam15413
Pleckstrin homology domain; This Pleckstrin homology domain is found in some fungal species.
 754-841 3.00e-05

Pleckstrin homology domain; This Pleckstrin homology domain is found in some fungal species.


Pssm-ID: 405988  Cd Length: 105  Bit Score: 44.50  E-value: 3.00e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKMSVrvKTWKRRWF-VLKGGELLYYKSPSDVIRKPQGHIELSASC----SILRGDNkQTVQ------------- 815
Cdd:pfam15413    1 IEGYLKKKGP--KTWKHRWFaVLRNGVLFYYKSEKMKVVKHVIVLSNYIVGklgtDIISGAL-FKIDnirsetsddllle 77

                           90       100
                   ....*....|....*....|....*.
gi 1907123492  816 LATEKHTYYLTADSPNILEEWIKVLQ 841
Cdd:pfam15413   78 ISTETKIFFLYGDNNEETYEWVEALQ 103
PH_DOCK-D cd13267
Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also ...
 748-855 3.07e-05

Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also called Zizimin subfamily) consists of Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2. DOCK-D has a N-terminal DUF3398 domain, a PH-like domain, a Dock Homology Region 1, DHR1 (also called CZH1), a C2 domain, and a C-terminal DHR2 domain (also called CZH2). Zizimin1 is enriched in the brain, lung, and kidney; zizimin2 is found in B and T lymphocytes, and zizimin3 is enriched in brain, lung, spleen and thymus. Zizimin1 functions in autoinhibition and membrane targeting. Zizimin2 is an immune-related and age-regulated guanine nucleotide exchange factor, which facilitates filopodial formation through activation of Cdc42, which results in activation of cell migration. No function has been determined for Zizimin3 to date. The N-terminal half of zizimin1 binds to the GEF domain through three distinct areas, including CZH1, to inhibit the interaction with Cdc42. In addition its PH domain binds phosphoinositides and mediates zizimin1 membrane targeting. DOCK is a family of proteins involved in intracellular signalling networks. They act as guanine nucleotide exchange factors for small G proteins of the Rho family, such as Rac and Cdc42. There are 4 subfamilies of DOCK family proteins based on their sequence homology: A-D. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270087  Cd Length: 126  Bit Score: 45.01  E-value: 3.07e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  748 KNEPLEKSGYLLK---------MSVRVKTWKRRWFVLK----GGELL-YYKSpsDVIRKPQGHIELSaSCSILRgDNKQT 813
Cdd:cd13267      2 GESGITKEGYLYKgpenssdsfISLAMKSFKRRFFHLKqlvdGSYILeFYKD--EKKKEAKGTIFLD-SCTGVV-QNSKR 77

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1907123492  814 VQLATE-----KHTYYLTADSPNILEEWIKVLQSVLrvQAANPLCLQ 855
Cdd:cd13267     78 RKFCFElrmqdKKSYVLAAESEAEMDEWISKLNKIL--QSSKEQSIQ 122
PRK03918 PRK03918
DNA double-strand break repair ATPase Rad50;
95-222 3.11e-05

DNA double-strand break repair ATPase Rad50;


Pssm-ID: 235175 [Multi-domain]  Cd Length: 880  Bit Score: 48.91  E-value: 3.11e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   95 ERQVIDAERQAEKAFQEVQVMEEKLKAANIQTSESETRLYKkcqdLESVMQEKDDIIQNLALRLEEQKQvRIQEAKIIEE 174
Cdd:PRK03918   216 LPELREELEKLEKEVKELEELKEEIEELEKELESLEGSKRK----LEEKIRELEERIEELKKEIEELEE-KVKELKELKE 290

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1907123492  175 KA------AKIKEWVTVKLNELEVENQNLRfinqtqtEEIRAIQSKLQELQEKK 222
Cdd:PRK03918   291 KAeeyiklSEFYEEYLDELREIEKRLSRLE-------EEINGIEERIKELEEKE 337
PRK12704 PRK12704
phosphodiesterase; Provisional
 88-182 4.02e-05

phosphodiesterase; Provisional


Pssm-ID: 237177 [Multi-domain]  Cd Length: 520  Bit Score: 48.24  E-value: 4.02e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   88 KHHMQQLERQVIDAERQAEKAFQEVQVMEEKLKAANIQTSESETRLYKKCQDLESVMQEKDDIIQNLA-LRLEEQKQVRI 166
Cdd:PRK12704    81 RNELQKLEKRLLQKEENLDRKLELLEKREEELEKKEKELEQKQQELEKKEEELEELIEEQLQELERISgLTAEEAKEILL 160

                           90
                   ....*....|....*...
gi 1907123492  167 Q--EAKIIEEKAAKIKEW 182
Cdd:PRK12704   161 EkvEEEARHEAAVLIKEI 178
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
 852-965 4.06e-05

Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 mammalian members: Ses1 and Ses2, which are also callled 7 kDa inositol polyphosphate phosphatase-interacting protein 1 and 2. They play a role in endocytic trafficking and are required for receptor recycling from endosomes, both to the trans-Golgi network and the plasma membrane. Members of this family form homodimers and heterodimers. Sesquipedalian interacts with inositol polyphosphate 5-phosphatase OCRL-1 (INPP5F) also known as Lowe oculocerebrorenal syndrome protein, a phosphatase enzyme that is involved in actin polymerization and is found in the trans-Golgi network and INPP5B. Sesquipedalian contains a single PH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270105 [Multi-domain]  Cd Length: 120  Bit Score: 44.54  E-value: 4.06e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  852 LCLQPEGKpavKGLLTK---VKHGYSKRvWCMLVGKVLYYFRNQEDKFPLGQLKLWEAKVEevdrSCDSDEDYetrgCYL 928
Cdd:cd13288      3 TCNSPVDK---EGYLWKkgeRNTSYQKR-WFVLKGNLLFYFEKKGDREPLGVIVLEGCTVE----LAEDAEPY----AFA 70

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1907123492  929 LSTHytiivhpkdqGP---TYLLIGSKHEK-EAWLYHLTVA 965
Cdd:cd13288     71 IRFD----------GPgarSYVLAAENQEDmESWMKALSRA 101
PH_Bem3 cd13277
Bud emergence protein 3 (Bem3) Pleckstrin homology (PH) domain; Bud emergence in Saccharomyces ...
 754-844 4.39e-05

Bud emergence protein 3 (Bem3) Pleckstrin homology (PH) domain; Bud emergence in Saccharomyces cerevisiae involves cell cycle-regulated reorganizations of cortical cytoskeletal elements and requires the action of the Rho-type GTPase Cdc42. Bem3 contains a RhoGAP domain and a PH domain. Though Bem3 and Bem2 both contain a RhoGAP, but only Bem3 is able to stimulate the hydrolysis of GTP on Cdc42. Bem3 is thought to be the GAP for Cdc42. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270096  Cd Length: 111  Bit Score: 44.20  E-value: 4.39e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKMsvRVKT------WKRRWFVLKGGELLYYKSPSDVIrkpQGHIELSaSCSILR----GDNKQTVQ---LATEK 820
Cdd:cd13277      5 KEGYLLKR--RKKTlgstggWKLRYGVLDGNILELYESRGGQL---LESIKLR-NAQIERqpnlPDDKYGTRhgfLINEH 78

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1907123492  821 HT--------YYLTADSPNILEEWIKVLQSVL 844
Cdd:cd13277     79 KKsglssttkYYLCAETDKERDEWVSALSEYI 110
PH_PLEKHD1 cd13281
Pleckstrin homology (PH) domain containing, family D (with coiled-coil domains) member 1 PH ...
 753-846 4.59e-05

Pleckstrin homology (PH) domain containing, family D (with coiled-coil domains) member 1 PH domain; Human PLEKHD1 (also called UPF0639, pleckstrin homology domain containing, family D (with M protein repeats) member 1) is a single transcript and contains a single PH domain. PLEKHD1 is conserved in human, chimpanzee, , dog, cow, mouse, chicken, zebrafish, and Caenorhabditis elegans. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270099  Cd Length: 139  Bit Score: 45.01  E-value: 4.59e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  753 EKSGYLLKMSVRVKT--WKRRWFVLKGGELLYYkspSDVIRK-----------PQGHIELsASCSILRG-DNKQTVQLAT 818
Cdd:cd13281     13 QLHGILWKKPFGHQSakWSKRFFIIKEGFLLYY---SESEKKdfektrhfnihPKGVIPL-GGCSIEAVeDPGKPYAISI 88

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1907123492  819 EkHTYY-----LTADSPNILEEWIKVLQSVLRV 846
Cdd:cd13281     89 S-HSDFkgniiLAADSEFEQEKWLDMLRESGKI 120
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
 83-299 5.55e-05

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 48.13  E-value: 5.55e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   83 RSASAKHHMQQLERQVIDAERQAEKAFQEVQVMEEKLKAANIQ---TSESETRLYKKCQDLESVMQEKDDIIQNLALRLE 159
Cdd:TIGR02168  769 RLEEAEEELAEAEAEIEELEAQIEQLKEELKALREALDELRAEltlLNEEAANLRERLESLERRIAATERRLEDLEEQIE 848

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  160 EQKQVRIQEAKIIEE---KAAKIKEWVTVKLNELEVENQNLRFIN---QTQTEEIRAIQSKLQELQEKKISCvsspKTSE 233
Cdd:TIGR02168  849 ELSEDIESLAAEIEEleeLIEELESELEALLNERASLEEALALLRselEELSEELRELESKRSELRRELEEL----REKL 924

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907123492  234 GQRNLTfgcfLSRAKsppcvVRCEEVSKMASNEPEITEgrcvEEMEIAEKPADNQVQENSRSQRKL 299
Cdd:TIGR02168  925 AQLELR----LEGLE-----VRIDNLQERLSEEYSLTL----EEAEALENKIEDDEEEARRRLKRL 977
PH_Btk cd01238
Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of ...
 754-846 5.60e-05

Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of cytoplasmic protein tyrosine kinases that includes BMX, IL2-inducible T-cell kinase (Itk) and Tec. Btk plays a role in the maturation of B cells. Tec proteins general have an N-terminal PH domain, followed by a Tek homology (TH) domain, a SH3 domain, a SH2 domain and a kinase domain. The Btk PH domain binds phosphatidylinositol 3,4,5-trisphosphate and responds to signalling via phosphatidylinositol 3-kinase. The PH domain is also involved in membrane anchoring which is confirmed by the discovery of a mutation of a critical arginine residue in the BTK PH domain. This results in severe human immunodeficiency known as X-linked agammaglobulinemia (XLA) in humans and a related disorder is mice.PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269944 [Multi-domain]  Cd Length: 140  Bit Score: 44.53  E-value: 5.60e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKMSVRVKT-----WKRRWFVLKGGELLYYKSPSDVIRKPQGHIELS-----------ASCsilrgDNKQTVQLA 817
Cdd:cd01238      1 LEGLLVKRSQGKKRfgpvnYKERWFVLTKSSLSYYEGDGEKRGKEKGSIDLSkvrcveevkdeAFF-----ERKYPFQVV 75

                           90       100
                   ....*....|....*....|....*....
gi 1907123492  818 TEKHTYYLTADSPNILEEWIKVLQSVLRV 846
Cdd:cd01238     76 YDDYTLYVFAPSEEDRDEWIAALRKVCRN 104
SMC_prok_A TIGR02169
chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of ...
 93-228 7.83e-05

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274009 [Multi-domain]  Cd Length: 1164  Bit Score: 47.37  E-value: 7.83e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   93 QLERQVIDAERQAEKAFQEVQVMEEKLKAANIQTSESETRLYKKCQDLESVMQEKDDIIQNLALRLEEQKQVRiQEAKII 172
Cdd:TIGR02169  354 KLTEEYAELKEELEDLRAELEEVDKEFAETRDELKDYREKLEKLKREINELKRELDRLQEELQRLSEELADLN-AAIAGI 432

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1907123492  173 EEKAAKIKEWVTVKLNELEVENQNLRFINQ---TQTEEIRAIQSKLQELqEKKISCVSS 228
Cdd:TIGR02169  433 EAKINELEEEKEDKALEIKKQEWKLEQLAAdlsKYEQELYDLKEEYDRV-EKELSKLQR 490
Smc COG1196
Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning]; ...
 91-223 8.42e-05

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 440809 [Multi-domain]  Cd Length: 983  Bit Score: 47.24  E-value: 8.42e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   91 MQQLERQVIDAERQAEKA--FQEVQVMEEKLKA------------------ANIQTSESE-TRLYKKCQDLESVMQEKDD 149
Cdd:COG1196    195 LGELERQLEPLERQAEKAerYRELKEELKELEAellllklreleaeleeleAELEELEAElEELEAELAELEAELEELRL 274

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907123492  150 IIQNLALRLEE-QKQVRIQEAKIIEEKAAKIKEwvTVKLNELEVENQNLRFINQTQTEEIRAIQSKLQELQEKKI 223
Cdd:COG1196    275 ELEELELELEEaQAEEYELLAELARLEQDIARL--EERRRELEERLEELEEELAELEEELEELEEELEELEEELE 347
PH_Skap_family cd13266
Src kinase-associated phosphoprotein family Pleckstrin homology (PH) domain; Skap adaptor ...
 754-846 8.76e-05

Src kinase-associated phosphoprotein family Pleckstrin homology (PH) domain; Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Src kinase-associated phosphoprotein of 55 kDa (Skap55)/Src kinase-associated phosphoprotein 1 (Skap1), Skap2, and Skap-homology (Skap-hom) have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270086  Cd Length: 106  Bit Score: 43.28  E-value: 8.76e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKM----SVRVKTWKRRWFVLKGGELLYYKSPSDviRKPQGHIELSA----SCSILRGDNKQ--TVQL-ATEKHT 822
Cdd:cd13266      3 KAGYLEKRrkdhSFFGSEWQKRWCAISKNVFYYYGSDKD--KQQKGEFAINGydvrMNPTLRKDGKKdcCFELvCPDKRT 80

                           90       100
                   ....*....|....*....|....
gi 1907123492  823 YYLTADSPNILEEWIKVLQSVLRV 846
Cdd:cd13266     81 YQFTAASPEDAEDWVDQISFILQD 104
DR0291 COG1579
Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General ...
 73-222 9.86e-05

Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General function prediction only];


Pssm-ID: 441187 [Multi-domain]  Cd Length: 236  Bit Score: 45.69  E-value: 9.86e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   73 LSLQHLVSS-----HRSASAKHHMQQLERQVIDAERQAEKAFQEVQVMEEKLKAANIQTSESETRLYKKCQDLESVMQEK 147
Cdd:COG1579     10 LDLQELDSEldrleHRLKELPAELAELEDELAALEARLEAAKTELEDLEKEIKRLELEIEEVEARIKKYEEQLGNVRNNK 89

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907123492  148 DdiIQNLALRLEEQKQvRIQ--EAKIIE--EKAAKIKEWVTVKLNELEVENQNLRFINQTQTEEIRAIQSKLQELQEKK 222
Cdd:COG1579     90 E--YEALQKEIESLKR-RISdlEDEILElmERIEELEEELAELEAELAELEAELEEKKAELDEELAELEAELEELEAER 165
PH_GAP1-like cd01244
RAS p21 protein activator (GTPase activating protein) family pleckstrin homology (PH) domain; ...
 754-855 1.00e-04

RAS p21 protein activator (GTPase activating protein) family pleckstrin homology (PH) domain; RASAL1, GAP1(m), GAP1(IP4BP), and CAPRI are all members of the GAP1 family of GTPase-activating proteins. They contain N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. They act as a suppressor of RAS enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. PH domains share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269950  Cd Length: 107  Bit Score: 43.05  E-value: 1.00e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKMS------VRVKTWKRRWFVLKGGELLYYKSPSDvirKPQGHIELSASCSILRGDN-----KQTVQLATEKHT 822
Cdd:cd01244      1 KEGYLIKRAqgrkkkFGRKNFKKRYFRLTNEALSYSKSKGK---QPLCSIPLEDILAVERVEEesfkmKNMFQIVQPDRT 77

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1907123492  823 YYLTADSPNILEEWIKVLQSVLRVqaaNPLCLQ 855
Cdd:cd01244     78 LYLQAKNVVELNEWLSALRKVCLC---NPNRLP 107
PH_Gab1_Gab2 cd01266
Grb2-associated binding proteins 1 and 2 pleckstrin homology (PH) domain; The Gab subfamily ...
 755-838 1.20e-04

Grb2-associated binding proteins 1 and 2 pleckstrin homology (PH) domain; The Gab subfamily includes several Gab proteins, Drosophila DOS and C. elegans SOC-1. They are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. The members in this cd include the Gab1 and Gab2 proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241297  Cd Length: 123  Bit Score: 43.40  E-value: 1.20e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  755 SGYLLK----MSVRVKTWKRRWFVLKGGELL-------YYKspSDVIRKPQGHIELSASCSILRG--DNKQTVQ------ 815
Cdd:cd01266      7 SGWLRKsppeKKLRRYAWKKRWFVLRSGRLSgdpdvleYYK--NDHAKKPIRVIDLNLCEQVDAGltFNKKELEnsyifd 84

                           90       100
                   ....*....|....*....|...
gi 1907123492  816 LATEKHTYYLTADSPNILEEWIK 838
Cdd:cd01266     85 IKTIDRIFYLVAETEEDMNKWVR 107
PH_CNK_mammalian-like cd01260
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
 768-848 1.26e-04

Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; CNK family members function as protein scaffolds, regulating the activity and the subcellular localization of RAS activated RAF. There is a single CNK protein present in Drosophila and Caenorhabditis elegans in contrast to mammals which have 3 CNK proteins (CNK1, CNK2, and CNK3). All of the CNK members contain a sterile a motif (SAM), a conserved region in CNK (CRIC) domain, and a PSD-95/DLG-1/ZO-1 (PDZ) domain, and, with the exception of CNK3, a PH domain. A CNK2 splice variant CNK2A also has a PDZ domain-binding motif at its C terminus and Drosophila CNK (D-CNK) also has a domain known as the Raf-interacting region (RIR) that mediates binding of the Drosophila Raf kinase. This cd contains CNKs from mammals, chickens, amphibians, fish, and crustacea. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269962  Cd Length: 114  Bit Score: 43.17  E-value: 1.26e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  768 WKRRWFVLKGGELLYYKSPSDviRKPQGHIELSaSCSILRGDN--KQTVQLATEKH--TYYLTADSPNILEEWIKVLQSV 843
Cdd:cd01260     33 WKKYWFVLKGSSLYWYSNQQD--EKAEGFINLP-DFKIERASEckKKYAFKACHPKikTFYFAAENLDDMNKWLSKLNMA 109


                   ....*
gi 1907123492  844 LRVQA 848
Cdd:cd01260    110 INKYA 114
Smc COG1196
Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning]; ...
 73-220 1.29e-04

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 440809 [Multi-domain]  Cd Length: 983  Bit Score: 46.85  E-value: 1.29e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   73 LSLQHLVSSHRSASAKHHMQQLERQVIDAERQAEKAFQEVQVMEEKLKAANIQTSESETRLYKKCQDLESVMQEKDDIIQ 152
Cdd:COG1196    272 LRLELEELELELEEAQAEEYELLAELARLEQDIARLEERRRELEERLEELEEELAELEEELEELEEELEELEEELEEAEE 351

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907123492  153 NLALRLEEQKQVRIQEAKIIEEKAAKIKEWVTVKLNELEVENQNLRFINQtQTEEIRAIQSKLQELQE 220
Cdd:COG1196    352 ELEEAEAELAEAEEALLEAEAELAEAEEELEELAEELLEALRAAAELAAQ-LEELEEAEEALLERLER 418
PH_3 pfam14593
PH domain;
748-845 1.44e-04

PH domain;


Pssm-ID: 434057  Cd Length: 103  Bit Score: 42.61  E-value: 1.44e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  748 KNEPLEKSGYLLKmsvRVK-TWKRRWFVLKGGELLYYKSPSDVIRKpqGHIELSASCSIlRGDNKQTVQLATEKHTYYLT 826
Cdd:pfam14593    9 PGELILKQGLVKK---RKGlFAKKRQLILTDGPRLIYVDPVKMVLK--GEIPWSKELKV-EAKNFKTFFIHTPNRTYYLE 82

                           90
                   ....*....|....*....
gi 1907123492  827 aDSPNILEEWIKVLQSVLR 845
Cdd:pfam14593   83 -DPEGDALKWCKAIEDVRK 100
PH_RIP cd01236
Rho-Interacting Protein Pleckstrin homology (PH) domain; RIP1-RhoGDI2 was obtained in a screen ...
 762-841 1.62e-04

Rho-Interacting Protein Pleckstrin homology (PH) domain; RIP1-RhoGDI2 was obtained in a screen for proteins that bind to wild-type RhoA. RIP2, RIP3, and RIP4 were isolated from cDNA libraries with constitutively active V14RhoA (containing the C190R mutation). RIP2 represents a novel GDP/GTP exchange factor (RhoGEF), while RIP3 (p116Rip) and RIP4 are thought to be structural proteins. RhoGEF contains a Dbl(DH)/PH region, a a zinc finger motif, a leucine-rich domain, and a coiled-coil region. The last 2 domains are thought to be involved in mediating protein-protein interactions. RIP3 is a negative regulator of RhoA signaling that inhibits, either directly or indirectly, RhoA-stimulated actomyosin contractility. In plants RIP3 is localized at microtubules and interacts with the kinesin-13 family member AtKinesin-13A, suggesting a role for RIP3 in microtubule reorganization and a possible function in Rho proteins of plants (ROP)-regulated polar growth. It has a PH domain, two proline-rich regions which are putative binding sites for SH3 domains, and a COOH-terminal coiled-coil region which overlaps with the RhoA-binding region. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269942  Cd Length: 136  Bit Score: 43.19  E-value: 1.62e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  762 SVRVKTWKRRWFVL-KGGELLYY--KSPSDVirkPQGHIELSASCSILRGD----NKQTVQLATEKHTYYLTADSPNILE 834
Cdd:cd01236     48 SHRSKRWQRRWFVLyDDGELTYAldEMPDTL---PQGSIDMSQCTEVTDAEartgHPHSLAITTPERIHFVKADSKEEIR 124


                   ....*..
gi 1907123492  835 EWIKVLQ 841
Cdd:cd01236    125 WWLELLA 131
TPH pfam13868
Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of ...
 101-222 1.64e-04

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.


Pssm-ID: 464007 [Multi-domain]  Cd Length: 341  Bit Score: 45.68  E-value: 1.64e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  101 AERQAEKAFQEVQVMEEKLKAANIQTSES-----ETRLYKKCQDLESVMQEKDDIIQNLA-----------LRLEEQKQV 164
Cdd:pfam13868   49 MEEERERALEEEEEKEEERKEERKRYRQEleeqiEEREQKRQEEYEEKLQEREQMDEIVEriqeedqaeaeEKLEKQRQL 128

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1907123492  165 RiQEAKIIEEKAAKIKEWvtVKLNELEVENQNLRFINQtQTEEIRAIQSKLQELQEKK 222
Cdd:pfam13868  129 R-EEIDEFNEEQAEWKEL--EKEEEREEDERILEYLKE-KAEREEEREAEREEIEEEK 182
FERM_F1_Myo10_like cd17110
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in unconventional ...
 1167-1269 2.28e-04

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in unconventional myosin-X and similar proteins; Myosin-X, also termed myosin-10 (Myo10), is an untraditional member of myosin superfamily. It is an actin-based motor protein that plays a critical role in diverse cellular motile events, such as filopodia formation/extension, phagocytosis, cell migration, and mitotic spindle maintenance, as well as a number of disease states including cancer metastasis and pathogen infection. Myosin-X functions as an important regulator of cytoskeleton that modulates cell motilities in many different cellular contexts. It regulates neuronal radial migration through interacting with N-cadherin. Like other unconventional myosins, Myosin-X is composed of a conserved motor head, a neck region and a variable tail. The neck region consists of three IQ motifs (light chain-binding sites), and a predicted stalk of coiled coil. The tail contains three PEST regions, three PH domains, a MyTH4 domain, and a FERM domain. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). Amoebozoan Dictyostelium discoideum myosin VII (DdMyo7) and uncharacterized pleckstrin homology domain-containing family H member 3 (PLEKHH3) are also included in this family. Like metazoan Myo10, DdMyo7 is essential for the extension of filopodia, plasma membrane protrusions filled with parallel bundles of F-actin.


Pssm-ID: 340630  Cd Length: 97  Bit Score: 41.60  E-value: 2.28e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492 1167 RPFSIPVHFMNGLYQVVGFDASTTVEEFLNTLNQDTGMRKpAQSGFALFtdDPSGrDLEHCLQGNIKICDIISKWEqasK 1246
Cdd:cd17110      2 QELTVTVTCQGGRTCKVAIDSWTTCGEVSKDLARRLGLER-SRNGFALF--ETSG-DIERALEAKTRVVDVLSKWE---K 74

                           90       100
                   ....*....|....*....|...
gi 1907123492 1247 EQQPGKCEGSRTVRLTYKNRLYF 1269
Cdd:cd17110     75 LAATGSSPGDDGWKLLFKLYLFL 97
Myosin_tail_1 pfam01576
Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and ...
 87-221 2.34e-04

Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and four light chains it is a fundamental contractile protein found in all eukaryote cell types. This family consists of the coiled-coil myosin heavy chain tail region. The coiled-coil is composed of the tail from two molecules of myosin. These can then assemble into the macromolecular thick filament. The coiled-coil region provides the structural backbone the thick filament.


Pssm-ID: 460256 [Multi-domain]  Cd Length: 1081  Bit Score: 45.94  E-value: 2.34e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   87 AKHHMQQLERQVIDAERQAEKAFQEVQVMEEKLKAaniqtsesETRLYKKCQD----LESVMQEKDDIIQNLALRLEE-- 160
Cdd:pfam01576   17 VKERQQKAESELKELEKKHQQLCEEKNALQEQLQA--------ETELCAEAEEmrarLAARKQELEEILHELESRLEEee 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  161 -------------QKQVRIQEAKIIEEKAAKIK---EWVTV--KLNELE-----VENQNLRFINQTQ--TEEIRAIQSKL 215
Cdd:pfam01576   89 ersqqlqnekkkmQQHIQDLEEQLDEEEAARQKlqlEKVTTeaKIKKLEedillLEDQNSKLSKERKllEERISEFTSNL 168


                   ....*.
gi 1907123492  216 QELQEK 221
Cdd:pfam01576  169 AEEEEK 174
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
 74-302 2.47e-04

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 45.82  E-value: 2.47e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   74 SLQHLVSSHRSASAKHHMQQLERQVIDAERQAEKAFQEVQVMEEKLKAANIQTSESETRLYKKCQDLESVMQEKDDIIQN 153
Cdd:TIGR02168  224 ELELALLVLRLEELREELEELQEELKEAEEELEELTAELQELEEKLEELRLEVSELEEEIEELQKELYALANEISRLEQQ 303

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  154 LAL---RLE------EQKQVRIQEAKIIEEKAAKIKEWVTVKLNELEVENQNLRFINQTQTEEIRAIQSKLQELQEKkis 224
Cdd:TIGR02168  304 KQIlreRLAnlerqlEELEAQLEELESKLDELAEELAELEEKLEELKEELESLEAELEELEAELEELESRLEELEEQ--- 380

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907123492  225 cvsspktSEGQRNLTFgcflsraksppcvvrcEEVSKMASNEPEITEGRcvEEMEIAEKPADNQVQENSRSQRKLHET 302
Cdd:TIGR02168  381 -------LETLRSKVA----------------QLELQIASLNNEIERLE--ARLERLEDRRERLQQEIEELLKKLEEA 433
Smc COG1196
Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning]; ...
 85-222 2.64e-04

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 440809 [Multi-domain]  Cd Length: 983  Bit Score: 45.70  E-value: 2.64e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   85 ASAKHHMQQLERQVIDAERQAEKAFQEVQVMEEKLKAANIQTSESETRLYKKCQDLESVMQEKDDIIQNLAlRLEEQKQV 164
Cdd:COG1196    249 EELEAELEELEAELAELEAELEELRLELEELELELEEAQAEEYELLAELARLEQDIARLEERRRELEERLE-ELEEELAE 327

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1907123492  165 RIQEAKIIEEKAAKIKEWVTVKLNELEVENQNLRFINQTQTEEIRAIQSKLQELQEKK 222
Cdd:COG1196    328 LEEELEELEEELEELEEELEEAEEELEEAEAELAEAEEALLEAEAELAEAEEELEELA 385
EnvC COG4942
Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, ...
 73-222 2.77e-04

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 443969 [Multi-domain]  Cd Length: 377  Bit Score: 45.14  E-value: 2.77e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   73 LSLQHLVSSHRSASAKHHMQQLERQVIDAERQAEKAFQEVQVMEEKLKAANIQTSESETRLykkcQDLESVMQEKDDIIQ 152
Cdd:COG4942     11 LALAAAAQADAAAEAEAELEQLQQEIAELEKELAALKKEEKALLKQLAALERRIAALARRI----RALEQELAALEAELA 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  153 NLALRLEE-QKQVRIQEAKIIEEKAA--KIKEWVTVKL-------NELEVENQNLRFINQTQTEEIRAIQSKLQELQEKK 222
Cdd:COG4942     87 ELEKEIAElRAELEAQKEELAELLRAlyRLGRQPPLALllspedfLDAVRRLQYLKYLAPARREQAEELRADLAELAALR 166
PH2_FGD1-4 cd13236
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins pleckstrin homology (PH) ...
 766-840 5.44e-04

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins pleckstrin homology (PH) domain, C-terminus; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Not much is known about FGD2. FGD1 is the best characterized member of the group with mutations here leading to the X-linked disorder known as faciogenital dysplasia (FGDY). Both FGD1 and FGD3 are targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. However, FGD1 and FGD3 induced significantly different morphological changes in HeLa Tet-Off cells and while FGD1 induced long finger-like protrusions, FGD3 induced broad sheet-like protrusions when the level of GTP-bound Cdc42 was significantly increased by the inducible expression of FGD3. They also reciprocally regulated cell motility in inducibly expressed in HeLa Tet-Off cells, FGD1 stimulated cell migration while FGD3 inhibited it. FGD1 and FGD3 therefore play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway through SCF(FWD1/beta-TrCP). FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270056  Cd Length: 105  Bit Score: 40.80  E-value: 5.44e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  766 KTWKRRWFVLKGGE--LLY-YKSPSDVirKPQGHI-----ELSASCSILRGDNKQTVQLATEKHTYYLTADSPNILEEWI 837
Cdd:cd13236     21 KTWQKVWCVIPRTEplVLYlYGAPQDV--RAQRTIplpgcEVTVPPPEERLDGRHVFKLSQSKQSHYFSAESEELQQRWL 98


                   ...
gi 1907123492  838 KVL 840
Cdd:cd13236     99 EAL 101
Niban-like cd23949
Niban-like protein; Niban-like proteins contain an N-terminal Pleckstrin-Homology (PH) domain ...
 752-845 6.83e-04

Niban-like protein; Niban-like proteins contain an N-terminal Pleckstrin-Homology (PH) domain that may be involved in binding to specific ligands. Phosphatidylinositol (3)-phosphate (PI3P) was recognized as the innate ligand of the PH domain of MINERVA (melanoma invasion by ERK, also known as FAM129B) PH. Niban family proteins have been found to regulate phosphorylation of a number of proteins involved in the regularion of translation, such as EIF2A, EIF4EBP1 and RPS6KB1. They may also be involved in the endoplasmic reticulum stress response (FAM129A, Niban-like protein 1), suggested to play a role in apoptosis suppression in cancer cells, while Niban-like protein 2 (FAM129C) is a B-cell membrane protein that is overexpressed in chronic lymphocytic leukemia.


Pssm-ID: 469558 [Multi-domain]  Cd Length: 550  Bit Score: 44.21  E-value: 6.83e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  752 LEKSGYLLKMSVRVKTWKRRWFVLKG-GELLYYKSPSDVIR--KPQGHIELS----------------ASCSILRGDNKQ 812
Cdd:cd23949     62 VIFSGKLSKYGEDSKKWKERFCVVRGdYNLEYYESKEAYERgkKPKGSINLAgykvltspeeylelvdRKFPDLAGKSEK 141

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1907123492  813 TVQLATEKHT-------------YYLTADSPNILEEWIKVLQSVLR 845
Cdd:cd23949    142 ASVPFPERPPpftlelyhpyrrhYYFCFETEKEQEEWVAVLQDCIR 187
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
 94-222 9.16e-04

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 43.89  E-value: 9.16e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   94 LERQVIDAERQAEKAfqevqvmeEKLKAANIQTSESETRLYKKcqdlesVMQEKDDiiqnlalRLEEQKQVRIQEAKIIE 173
Cdd:TIGR02168  198 LERQLKSLERQAEKA--------ERYKELKAELRELELALLVL------RLEELRE-------ELEELQEELKEAEEELE 256

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1907123492  174 EKAAKIKEwVTVKLNELEVENQNLRfinqtqtEEIRAIQSKLQELQEKK 222
Cdd:TIGR02168  257 ELTAELQE-LEEKLEELRLEVSELE-------EEIEELQKELYALANEI 297
PH_ORP9 cd13290
Human Oxysterol binding protein related protein 9 Pleckstrin homology (PH) domain; Human ORP9 ...
 756-841 9.69e-04

Human Oxysterol binding protein related protein 9 Pleckstrin homology (PH) domain; Human ORP9 is proposed to function in regulation of Akt phosphorylation. ORP9 has 2 forms, a long (ORP9L) and a short (ORP9S). ORP9L contains an N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. ORP1S is truncated and contains a FFAT motif and an OSBP-related domain. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241444  Cd Length: 102  Bit Score: 40.12  E-value: 9.69e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  756 GYLLKMSVRVKTWKRRWFVL--KGGELLYYKSPSDVIRKPQ-GHIELSASCSILRGDNKQTVQLATEKHTYYLTADSPNI 832
Cdd:cd13290      3 GPLSKWTNVMKGWQYRWFVLddNAGLLSYYTSKEKMMRGSRrGCVRLKGAVVGIDDEDDSTFTITVDQKTFHFQARDAEE 82


                   ....*....
gi 1907123492  833 LEEWIKVLQ 841
Cdd:cd13290     83 RERWIRALE 91
PH_PKB cd01241
Protein Kinase B-like pleckstrin homology (PH) domain; PKB (also called Akt), a member of the ...
 754-843 1.04e-03

Protein Kinase B-like pleckstrin homology (PH) domain; PKB (also called Akt), a member of the AGC kinase family, is a phosphatidylinositol 3'-kinase (PI3K)-dependent Ser/Thr kinase which alters the activity of the targeted protein. The name AGC is based on the three proteins that it is most similar to cAMP-dependent protein kinase 1 (PKA; also known as PKAC), cGMP-dependent protein kinase (PKG; also known as CGK1) and protein kinase C (PKC). Human Akt has three isoforms derived for distinct genes: Akt1/PKBalpha, Akt2/PKBbeta, and Akt3/PKBgamma. All Akts have an N-terminal PH domain with an activating Thr phosphorylation site, a kinase domain, and a short C-terminal regulatory tail with an activating Ser phosphorylation site. The PH domain recruits Akt to the plasma membrane by binding to phosphoinositides (PtdIns-3,4-P2) and is required for activation. The phosphorylation of Akt at its Thr and Ser phosphorylation sites leads to increased Akt activity toward forkhead transcription factors, the mammalian target of rapamycin (mTOR), and the Bcl-xL/Bcl-2-associated death promoter (BAD), all of which possess a consensus motif R-X-R-XX-ST-B (X = amino acid, B = bulky hydrophobic residue) for Akt phosphorylation. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269947  Cd Length: 107  Bit Score: 40.31  E-value: 1.04e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKMSVRVKTWKRRWFVLKG-GELLYYKspsdviRKPQGHIELS-------ASCSILRGDNKQT-------VQLAT 818
Cdd:cd01241      5 KEGWLLKRGEYIKNWRPRYFVLKSdGSFIGYK------EKPKPNQDPPplnnfsvAECQLMKTEKPKPntfiircLQWTT 78

                           90       100
                   ....*....|....*....|....*.
gi 1907123492  819 E-KHTYYltADSPNILEEWIKVLQSV 843
Cdd:cd01241     79 ViERTFH--VESEEEREEWMKAIQGV 102
SMC_prok_A TIGR02169
chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of ...
 102-221 1.09e-03

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274009 [Multi-domain]  Cd Length: 1164  Bit Score: 43.90  E-value: 1.09e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  102 ERQAEKAFQEVQVMEEKLKAANIQTSESEtRLYKKcQDLESVMQEKDDIIQNLALRLEEQKQvRIQEAKI-IEEKAAKIK 180
Cdd:TIGR02169  795 EIQAELSKLEEEVSRIEARLREIEQKLNR-LTLEK-EYLEKEIQELQEQRIDLKEQIKSIEK-EIENLNGkKEELEEELE 871

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1907123492  181 EwVTVKLNELEVENQNLRFINQTQTEEIRAIQSKLQELQEK 221
Cdd:TIGR02169  872 E-LEAALRDLESRLGDLKKERDELEAQLRELERKIEELEAQ 911
DMP1 pfam07263
Dentin matrix protein 1 (DMP1); This family consists of several mammalian dentin matrix ...
 257-453 1.32e-03

Dentin matrix protein 1 (DMP1); This family consists of several mammalian dentin matrix protein 1 (DMP1) sequences. The dentin matrix acidic phosphoprotein 1 (DMP1) gene has been mapped to human chromosome 4q21. DMP1 is a bone and teeth specific protein initially identified from mineralized dentin. DMP1 is primarily localized in the nuclear compartment of undifferentiated osteoblasts. In the nucleus, DMP1 acts as a transcriptional component for activation of osteoblast-specific genes like osteocalcin. During the early phase of osteoblast maturation, Ca(2+) surges into the nucleus from the cytoplasm, triggering the phosphorylation of DMP1 by a nuclear isoform of casein kinase II. This phosphorylated DMP1 is then exported out into the extracellular matrix, where it regulates nucleation of hydroxyapatite. DMP1 is a unique molecule that initiates osteoblast differentiation by transcription in the nucleus and orchestrates mineralized matrix formation extracellularly, at later stages of osteoblast maturation. The DMP1 gene has been found to be ectopically expressed in lung cancer although the reason for this is unknown.


Pssm-ID: 462128 [Multi-domain]  Cd Length: 519  Bit Score: 43.38  E-value: 1.32e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  257 EEV---SKMASNEPEITEGRCVEEM--EIAEKPADNQVQENSRsqrklHETSCSSEQNQKTRASFAMDGGTSQNSGV--- 328
Cdd:pfam07263  288 EEVksdSTESTSSKEAGLSQSREDSksESQEDSEESQSQEDSQ-----NSQDPSSESSQEADLPSQESSSESQEEVVses 362

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  329 ----PVSDWSSDEDDGSKGRSKSRCTSTLSSHTSEEGGQCGRLGSEAYLTASDDSssifEEETFDGNRPEQKKLCSWQQK 404
Cdd:pfam07263  363 rgdnPDNTSSSEEDQEDSDSSEEDSLSTFSSSESESREEQADSESNESLRSSEES----PESSEDENSSSQEGLQSHSAS 438

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1907123492  405 APWKAQGNLAKGRSQSGVKEQDSSSDELNKKFHSQRLDYTSSSSEANTP 453
Cdd:pfam07263  439 TESQSEESQSEQDSQSEEDDESDSQDSSRSKEDSNSTESTSSSEEDGQS 487
PH_ORP10_ORP11 cd13291
Human Oxysterol binding protein (OSBP) related proteins 10 and 11 (ORP10 and ORP11) Pleckstrin ...
 756-843 1.42e-03

Human Oxysterol binding protein (OSBP) related proteins 10 and 11 (ORP10 and ORP11) Pleckstrin homology (PH) domain; Human ORP10 is involvedt in intracellular transport or organelle positioning and is proposed to function as a regulator of cellular lipid metabolism. Human ORP11 localizes at the Golgi-late endosome interface and is thought to form a dimer with ORP9 functioning as an intracellular lipid sensor or transporter. Both ORP10 and ORP11 contain a N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270106  Cd Length: 107  Bit Score: 39.58  E-value: 1.42e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  756 GYLLKMSVRVKTWKRRWFVL--KGGELLYYKSPSDVIRKPQGHIELSASCSILRGDNKQT--VQLATEKhTYYLTADSPN 831
Cdd:cd13291      3 GQLLKYTNVVKGWQNRWFVLdpDTGILEYFLSEESKNQKPRGSLSLAGAVISPSDEDSHTftVNAANGE-MYKLRAADAK 81

                           90
                   ....*....|..
gi 1907123492  832 ILEEWIKVLQSV 843
Cdd:cd13291     82 ERQEWVNRLRAV 93
COG4372 COG4372
Uncharacterized protein, contains DUF3084 domain [Function unknown];
94-237 1.56e-03

Uncharacterized protein, contains DUF3084 domain [Function unknown];


Pssm-ID: 443500 [Multi-domain]  Cd Length: 370  Bit Score: 42.58  E-value: 1.56e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   94 LERQVIDAERQAEKAFQEVQVMEEKLKAANIQTSESETRLYKKCQDLESVMQEKDDIIQNLALRLEEQKQVRiQEAKIIE 173
Cdd:COG4372     29 LSEQLRKALFELDKLQEELEQLREELEQAREELEQLEEELEQARSELEQLEEELEELNEQLQAAQAELAQAQ-EELESLQ 107

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907123492  174 EKAAKIKEwvtvKLNELEVENQNLrfinqtqteeiraiQSKLQELQEKKISCVSSPKTSEGQRN 237
Cdd:COG4372    108 EEAEELQE----ELEELQKERQDL--------------EQQRKQLEAQIAELQSEIAEREEELK 153
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 863-962 1.60e-03

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 39.47  E-value: 1.60e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  863 KGLLTKVKHGYS---KRVWCMLVGKVLYYFRNQ---EDKFPLGQLKLWEAKVEEVDRSCDSDEDYetrgcyllstHYTII 936
Cdd:pfam00169    4 EGWLLKKGGGKKkswKKRYFVLFDGSLLYYKDDksgKSKEPKGSISLSGCEVVEVVASDSPKRKF----------CFELR 73

                           90       100
                   ....*....|....*....|....*..
gi 1907123492  937 VHPKDQGPTYLLI-GSKHEKEAWLYHL 962
Cdd:pfam00169   74 TGERTGKRTYLLQaESEEERKDWIKAI 100
Smc COG1196
Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning]; ...
 75-224 1.78e-03

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 440809 [Multi-domain]  Cd Length: 983  Bit Score: 43.00  E-value: 1.78e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   75 LQHLVSSHRSASAKHHMQQLERQVIDAERQAEKAFQEVQVMEEKLKAANIQTSESETRLYKKCQDLESVMQEKDDIIQNL 154
Cdd:COG1196    225 LEAELLLLKLRELEAELEELEAELEELEAELEELEAELAELEAELEELRLELEELELELEEAQAEEYELLAELARLEQDI 304

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907123492  155 ALRLEEQK--QVRIQEAKI-IEEKAAKIKEwVTVKLNELEVENQNLRFINQTQTEEIRAIQSKLQELQEKKIS 224
Cdd:COG1196    305 ARLEERRRelEERLEELEEeLAELEEELEE-LEEELEELEEELEEAEEELEEAEAELAEAEEALLEAEAELAE 376
Tropomyosin pfam00261
Tropomyosin; Tropomyosin is an alpha-helical protein that forms a coiled-coil structure of 2 ...
 91-220 1.81e-03

Tropomyosin; Tropomyosin is an alpha-helical protein that forms a coiled-coil structure of 2 parallel helices containing 2 sets of 7 alternating actin binding sites. The protein is best known for its role in regulating the interaction between actin and myosin in muscle contraction, but is also involved in the organization and dynamics of the cytoskeleton in non-muscle cells. There are multiple cell-specific isoforms, expressed by alternative promoters and alternative RNA processing of at least four genes. Muscle isoforms of tropomyosin are characterized by having 284 amino acid residues and a highly conserved N-terminal region, whereas non-muscle forms are generally smaller and are heterogeneous in their N-terminal region.


Pssm-ID: 459736 [Multi-domain]  Cd Length: 235  Bit Score: 41.55  E-value: 1.81e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   91 MQQLERQVIDAERQAEKAFQEVQVMEEKLKAA---------NIQTSE-----SETRLYKKCQDLESVMQEKDD------I 150
Cdd:pfam00261    3 MQQIKEELDEAEERLKEAMKKLEEAEKRAEKAeaevaalnrRIQLLEeelerTEERLAEALEKLEEAEKAADEsergrkV 82

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907123492  151 IQNLALRLEE---QKQVRIQEAKIIEEKAAKIKEWVTVKLNELEVENQNLRfinqtqtEEIRAIQSKLQELQE 220
Cdd:pfam00261   83 LENRALKDEEkmeILEAQLKEAKEIAEEADRKYEEVARKLVVVEGDLERAE-------ERAELAESKIVELEE 148
SMC_prok_A TIGR02169
chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of ...
 96-315 1.86e-03

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274009 [Multi-domain]  Cd Length: 1164  Bit Score: 43.13  E-value: 1.86e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   96 RQVIDA-------ERQAEKAFQEVQVMEEKLKaaNIQTSESETRlykkcQDLESVMQEKDDIIQNLALRLEEQKqvriQE 168
Cdd:TIGR02169  156 RKIIDEiagvaefDRKKEKALEELEEVEENIE--RLDLIIDEKR-----QQLERLRREREKAERYQALLKEKRE----YE 224

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  169 AKII---EEKAAKIKEWVTVKLNELEVENQNLRFINQTQTEEIRAIQSKLQELqEKKIscvsSPKTSEGQRNLTfgcfls 245
Cdd:TIGR02169  225 GYELlkeKEALERQKEAIERQLASLEEELEKLTEEISELEKRLEEIEQLLEEL-NKKI----KDLGEEEQLRVK------ 293

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907123492  246 raksppcvvrceevSKMASNEPEITEGR-----CVEEMEIAEKPADNQVQENSRSQRKLHETSCSSEQNQKTRAS 315
Cdd:TIGR02169  294 --------------EKIGELEAEIASLErsiaeKERELEDAEERLAKLEAEIDKLLAEIEELEREIEEERKRRDK 354
ATG16 pfam08614
Autophagy protein 16 (ATG16); Autophagy is a ubiquitous intracellular degradation system for ...
 40-197 1.87e-03

Autophagy protein 16 (ATG16); Autophagy is a ubiquitous intracellular degradation system for eukaryotic cells. During autophagy, cytoplasmic components are enclosed in autophagosomes and delivered to lysosomes/vacuoles. ATG16 (also known as Apg16) has been shown to be bind to Apg5 and is required for the function of the Apg12p-Apg5p conjugate in the yeast autophagy pathway.


Pssm-ID: 462536 [Multi-domain]  Cd Length: 176  Bit Score: 41.07  E-value: 1.87e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   40 ASLNEVKIREDSRPMKCCKASYASTPPLSIDFYLSLQHLVSSHRS--ASAKHHMQQLERQVIDAErqaekafQEVQVMEE 117
Cdd:pfam08614   20 EAENAKLQSEPESVLPSTSSSKLSKASPQSASIQSLEQLLAQLREelAELYRSRGELAQRLVDLN-------EELQELEK 92

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  118 KLKAANIQTSESETR---LYKKCQDLESVMQEKDDIIQNL-----ALRLeeqkQVRIQEAkiieekaakikewvtvKLNE 189
Cdd:pfam08614   93 KLREDERRLAALEAEraqLEEKLKDREEELREKRKLNQDLqdelvALQL----QLNMAEE----------------KLRK 152


                   ....*...
gi 1907123492  190 LEVENQNL 197
Cdd:pfam08614  153 LEKENREL 160
RA_RASSF7_like cd16123
Ras-associating (RA) domain found in Ras-association domain family members, RASSF7, RASSF8, ...
 1171-1249 1.91e-03

Ras-associating (RA) domain found in Ras-association domain family members, RASSF7, RASSF8, RASSF9, and RASSF10; The RASSF family of proteins shares a conserved RalGDS/AF6 Ras association (RA) domain either in the C-terminus (RASSF1-6) or N-terminus (RASSF7-10). RASSF7-10 lacks a conserved SARAH (Salvador/RASSF/Hpo) motif adjacent to the RA domain that is found in members of the RASSF1-6 family. The structural differences between the C-terminus and N-terminus RASSF subgroups have led to the suggestion that they are two distinct families. RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub). Ras proteins are small GTPases that are involved in cellular signal transduction. The N-terminus RASSF proteins are potential Ras effectors that have been linked to key biological processes, including cell death, proliferation, microtubule stability, promoter methylation, vesicle trafficking and response to hypoxia.


Pssm-ID: 340540  Cd Length: 81  Bit Score: 38.77  E-value: 1.91e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492 1171 IPVhFMNGLYQVV-GFDASTTVEEFLNTLNQDTGMRKPAQSgFALFTddpSGRDLEHCLQGNIKICDIISKWEQASKEQQ 1249
Cdd:cd16123      2 LKV-WVDGEERVVsGVTERTTCQDVIYALAQATGQTNDTGR-YVLVE---RWRGIERPLPPRTRILKVWKAWGEEQSNVQ 76
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 863-962 2.32e-03

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 39.07  E-value: 2.32e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   863 KGLLTKVKHGYS---KRVWCMLVGKVLYYFRN---QEDKFPLGQLKLWEAKVEEVDRSCDSDEDyetrgcyllsthYTII 936
Cdd:smart00233    4 EGWLYKKSGGGKkswKKRYFVLFNSTLLYYKSkkdKKSYKPKGSIDLSGCTVREAPDPDSSKKP------------HCFE 71

                            90       100
                    ....*....|....*....|....*.
gi 1907123492   937 VHPKDQGPTYLLIGSKHEKEAWLYHL 962
Cdd:smart00233   72 IKTSDRKTLLLQAESEEEREKWVEAL 97
PH_CNK_mammalian-like cd01260
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
 858-966 2.72e-03

Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; CNK family members function as protein scaffolds, regulating the activity and the subcellular localization of RAS activated RAF. There is a single CNK protein present in Drosophila and Caenorhabditis elegans in contrast to mammals which have 3 CNK proteins (CNK1, CNK2, and CNK3). All of the CNK members contain a sterile a motif (SAM), a conserved region in CNK (CRIC) domain, and a PSD-95/DLG-1/ZO-1 (PDZ) domain, and, with the exception of CNK3, a PH domain. A CNK2 splice variant CNK2A also has a PDZ domain-binding motif at its C terminus and Drosophila CNK (D-CNK) also has a domain known as the Raf-interacting region (RIR) that mediates binding of the Drosophila Raf kinase. This cd contains CNKs from mammals, chickens, amphibians, fish, and crustacea. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269962  Cd Length: 114  Bit Score: 39.31  E-value: 2.72e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  858 GKPAVKGLLTKVKHGYS------KRVWCMLVGKVLYYFRNQEDKFPLGQLKLWEAKVEevdRSCDSDEDYETRGCyllst 931
Cdd:cd01260     11 GRGDCQGWLWKKKEAKSffgqkwKKYWFVLKGSSLYWYSNQQDEKAEGFINLPDFKIE---RASECKKKYAFKAC----- 82

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1907123492  932 hytiivHPKDQgPTYLLIGSKHEKEAWLYHLTVAA 966
Cdd:cd01260     83 ------HPKIK-TFYFAAENLDDMNKWLSKLNMAI 110
PH2_PH_fungal cd13299
Fungal proteins Pleckstrin homology (PH) domain, repeat 2; The functions of these fungal ...
 756-844 3.73e-03

Fungal proteins Pleckstrin homology (PH) domain, repeat 2; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the second PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270111  Cd Length: 102  Bit Score: 38.38  E-value: 3.73e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  756 GYLLKMSVR-VKTWKRRWFVLKGGELLYYKSPSDVirKPQGHIELSASCSI-----LRGDNKQTVQLATEKHTYYLTADS 829
Cdd:cd13299     10 GYLQVLKKKgVNQWKKYWLVLRNRSLSFYKDQSEY--SPVKIIPIDDIIDVveldpLSKSKKWCLQIITPEKRIRFCADD 87

                           90
                   ....*....|....*
gi 1907123492  830 PNILEEWIKVLQSVL 844
Cdd:cd13299     88 EESLIKWLGALKSLL 102
PH_RASAL1 cd13369
Ras-GTPase-activating-like protein pleckstrin homology (PH) domain; RASAL1 is a member of the ...
 754-860 3.86e-03

Ras-GTPase-activating-like protein pleckstrin homology (PH) domain; RASAL1 is a member of the GAP1 family of GTPase-activating proteins, along with GAP1(m), GAP1(IP4BP) and CAPRI. RASAL1 contains two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. RASAL1 contains two fully conserved C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Its catalytic GAP domain has dual RasGAP and RapGAP activities, while its C2 domains bind phospholipids in the presence of Ca2+. Both CAPRI and RASAL1 are calcium-activated RasGAPs that inactivate Ras at the plasma membrane. Thereby enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS and allowing control of cellular proliferation and differentiation. CAPRI and RASAL1 differ in that CAPRI is an amplitude sensor while RASAL1 senses calcium oscillations. This difference between them resides not in their C2 domains, but in their PH domains leading to speculation that this might reflect an association with either phosphoinositides and/or proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270175  Cd Length: 138  Bit Score: 39.46  E-value: 3.86e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKMS------VRVKTWKRRWFVLKGGELLYYKSPSDVIRKPqghIELSASCSILRGDN-----KQTVQLAT---- 818
Cdd:cd13369     17 KEGYLHKRKaegvglVTRFTFKKRYFWLSSETLSYSKSPDWQVRSS---IPVQRICAVERVDEnafqqPNVMQVVTqdge 93

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1907123492  819 -EKHTYYLTADSPNILEEWIKVLQsvlRVQAANPlCLQPEGKP 860
Cdd:cd13369     94 gQVHTTYIQCKNVNELNQWLSALR---KVSLSNE-RMLPACHP 132
PH_MELT_VEPH1 cd01264
Melted pleckstrin homology (PH) domain; The melted protein (also called Ventricular zone ...
 765-844 4.12e-03

Melted pleckstrin homology (PH) domain; The melted protein (also called Ventricular zone expressed PH domain-containing protein homolog 1) is expressed in the developing central nervous system of vertebrates. It contains a single C-terminal PH domain that is required for membrane targeting. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269965  Cd Length: 105  Bit Score: 38.59  E-value: 4.12e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  765 VKTWKRRWFVLKGGELLYYKSPSDVIRKPqghIELSA--SCSILRGDNK---QTVQLATEKHTYYLTADSPNILEEWIKV 839
Cdd:cd01264     18 FKRWRTRYFTLSGAQLSYRGGKSKPDAPP---IELSKirSVKVVRKKDRsipKAFEIFTDDKTYVLKAKDEKNAEEWLQC 94


                   ....*
gi 1907123492  840 LQSVL 844
Cdd:cd01264     95 LSIAV 99
FERM_C2_myosin_like cd13204
FERM domain C-lobe, repeat 2, of Myosin-like proteins; These myosin-like proteins are ...
 1417-1492 4.27e-03

FERM domain C-lobe, repeat 2, of Myosin-like proteins; These myosin-like proteins are unidentified though they are sequence similar to myosin 1/myo1, myosin 7/myoVII, and myosin 10/myoX. These myosin-like proteins contain an N-terminal motor/head region and a C-terminal tail consisting of two myosin tail homology 4 (MyTH4) and twos FERM domains. In myoX the FERM domain forms a supramodule with its MyTH4 domain which binds to the negatively charged E-hook region in the tails of alpha- and beta-tubulin forming a proposed motorized link between actin filaments and microtubules and a similar thing might happen in these myosins. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The second FERM_N repeat is present in this hierarchy. The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.


Pssm-ID: 270025  Cd Length: 93  Bit Score: 38.18  E-value: 4.27e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907123492 1417 VWLAVHENGLSILEYTSMRLVTSYMYKGLMTFGGYQEDFMVVVSTQSKDRPtekllFAMAKHKILEITLLIASYIN 1492
Cdd:cd13204     19 LWLAIDQSGVHLLERRTKEPLCSYDYSSIVSYSPSLNSLMIVTGSLTKGSK-----FIFNTNQAFQIANLIRDYTH 89
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
 92-222 5.26e-03

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 41.58  E-value: 5.26e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   92 QQLERQVIDAERQAEKAFQEVQVMEEKLKAANIQTSESETRLYKKCQDLESVMQEKDDIIQNLAlRLEEQKQVRIQEAKI 171
Cdd:TIGR02168  722 EELSRQISALRKDLARLEAEVEQLEERIAQLSKELTELEAEIEELEERLEEAEEELAEAEAEIE-ELEAQIEQLKEELKA 800

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1907123492  172 IEEKAAKIKEwvtvKLNELEVENQNLRFINQTQTEEIRAIQSKLQELQEKK 222
Cdd:TIGR02168  801 LREALDELRA----ELTLLNEEAANLRERLESLERRIAATERRLEDLEEQI 847
PH_Skap1 cd13380
Src kinase-associated phosphoprotein 1 Pleckstrin homology (PH) domain; Adaptor protein Skap1 ...
 754-845 5.44e-03

Src kinase-associated phosphoprotein 1 Pleckstrin homology (PH) domain; Adaptor protein Skap1 (also called Skap55/Src kinase-associated phosphoprotein of 55 kDa) and its partner, ADAP (adhesion and degranulation promoting adapter protein) help reorganize the cytoskeleton and/or promote integrin-mediated adhesion upon immunoreceptor activation. Skap1 is also involved in T Cell Receptor (TCR)-induced RapL-Rap1 complex formation and LFA-1 activation. Skap1 has an N-terminal coiled-coil conformation which is proposed to be involved in homodimer formation, a central PH domain and a C-terminal SH3 domain that associates with ADAP. The Skap1 PH domain plays a role in controlling integrin function via recruitment of ADAP-SKAP complexes to integrins as well as in controlling the ability of ADAP to interact with the CBM signalosome and regulate NF-kappaB. SKAP1 is necessary for RapL binding to membranes in a PH domain-dependent manner and the PI3K pathway. Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Skap55/Skap1, Skap2, and Skap-homology (Skap-hom) have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270180  Cd Length: 106  Bit Score: 38.30  E-value: 5.44e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  754 KSGYLLKMSVRVK----TWKRRWFVLKGGELLYYKSPSDviRKPQGHIeLSASCSI-----LRGDNKQT--VQLATE-KH 821
Cdd:cd13380      3 KQGYLEKRSKDHSffgsEWQKRWCVLTNRAFYYYASEKS--KQPKGGF-LIKGYSAqmaphLRKDSRRDscFELTTPgRR 79

                           90       100
                   ....*....|....*....|....
gi 1907123492  822 TYYLTADSPNILEEWIKVLQSVLR 845
Cdd:cd13380     80 TYQFTAASPSEARDWVDQIQFLLK 103
SMC_prok_A TIGR02169
chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of ...
 92-221 5.77e-03

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274009 [Multi-domain]  Cd Length: 1164  Bit Score: 41.59  E-value: 5.77e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   92 QQLERQVIDAERQAEKAFQEVQVMEEKLKAANIQTSESETRLYKKCQDLESVMQEK-----------DDIIQNLALRLEE 160
Cdd:TIGR02169  240 EAIERQLASLEEELEKLTEEISELEKRLEEIEQLLEELNKKIKDLGEEEQLRVKEKigeleaeiaslERSIAEKERELED 319

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907123492  161 -QKQVRIQEAKI------IEEKAAKIKEWvTVKLNELEVENQNLRfinqtqtEEIRAIQSKLQELQEK 221
Cdd:TIGR02169  320 aEERLAKLEAEIdkllaeIEELEREIEEE-RKRRDKLTEEYAELK-------EELEDLRAELEEVDKE 379
COG5022 COG5022
Myosin heavy chain [General function prediction only];
96-313 6.27e-03

Myosin heavy chain [General function prediction only];


Pssm-ID: 227355 [Multi-domain]  Cd Length: 1463  Bit Score: 41.22  E-value: 6.27e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   96 RQVIDAERQAEKAFQEVQvmeEKLKAANIQTSESETRLYKKCQDLESV------MQEKDDIIQNLALRLEEQKQVRIQEA 169
Cdd:COG5022    761 RRRYLQALKRIKKIQVIQ---HGFRLRRLVDYELKWRLFIKLQPLLSLlgsrkeYRSYLACIIKLQKTIKREKKLRETEE 837

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  170 KIIEEKAAKIKE--WVTVKLNELEVENQNLRFINQTQTEEiRAIQSKLQELQE--KKISCVSSPKTSEGQRNLTFGCFLS 245
Cdd:COG5022    838 VEFSLKAEVLIQkfGRSLKAKKRFSLLKKETIYLQSAQRV-ELAERQLQELKIdvKSISSLKLVNLELESEIIELKKSLS 916

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907123492  246 RAKSPPCVVRCEEVSKMASNepeitegrcVEEMEIAEkPADNQVQENSRSQrKLHETSCSSEQNQKTR 313
Cdd:COG5022    917 SDLIENLEFKTELIARLKKL---------LNNIDLEE-GPSIEYVKLPELN-KLHEVESKLKETSEEY 973
COG4372 COG4372
Uncharacterized protein, contains DUF3084 domain [Function unknown];
92-222 6.55e-03

Uncharacterized protein, contains DUF3084 domain [Function unknown];


Pssm-ID: 443500 [Multi-domain]  Cd Length: 370  Bit Score: 40.66  E-value: 6.55e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   92 QQLERQVIDAERQAEKAFQEVQVMEEKLKAANIQTSESETRLYKKCQDLESVMQEKDDIIQNLALRLEEQKQVRiQEAKI 171
Cdd:COG4372      6 EKVGKARLSLFGLRPKTGILIAALSEQLRKALFELDKLQEELEQLREELEQAREELEQLEEELEQARSELEQLE-EELEE 84

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1907123492  172 IEEKAAKIKEWVTVKLNELEVENQNLrfinQTQTEEIRAIQSKLQELQEKK 222
Cdd:COG4372     85 LNEQLQAAQAELAQAQEELESLQEEA----EELQEELEELQKERQDLEQQR 131
PH_rhotekin2 cd13249
Anillin Pleckstrin homology (PH) domain; Anillin (Rhotekin/RTKN; also called PLEKHK/Pleckstrin ...
 755-840 7.92e-03

Anillin Pleckstrin homology (PH) domain; Anillin (Rhotekin/RTKN; also called PLEKHK/Pleckstrin homology domain-containing family K) is an actin binding protein involved in cytokinesis. It interacts with GTP-bound Rho proteins and results in the inhibition of their GTPase activity. Dysregulation of the Rho signal transduction pathway has been implicated in many forms of cancer. Anillin proteins have a N-terminal HRI domain/ACC (anti-parallel coiled-coil) finger domain or Rho-binding domain binds small GTPases from the Rho family. The C-terminal PH domain helps target anillin to ectopic septin containing foci. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270069  Cd Length: 111  Bit Score: 37.75  E-value: 7.92e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  755 SGYL--LKMSVRVKTWKRRWFVLKGGELLYYKSPSDVirkpQGHIELSASCSIlrgdNKQTVQLATEKH----------- 821
Cdd:cd13249      5 SGYLsqQQSVEGLQSWTRLYCVLKGGNLLCYYSPEEI----EAKVEPLLTIPI----NKETRIRAVEKDskgrasslsii 76

                           90       100
                   ....*....|....*....|....*..
gi 1907123492  822 --------TYYLTADSPNILEEWIKVL 840
Cdd:cd13249     77 npysgeevTHVLSADSREELQKWMEAL 103
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 863-962 8.33e-03

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 37.14  E-value: 8.33e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  863 KGLLTKVKHGYS---KRVWCMLVGKVLYYFRNQED--KFPLGQLKLWeaKVEEVDRSCDSDEDyetrgcyllstHYTIIV 937
Cdd:cd00821      2 EGYLLKRGGGGLkswKKRWFVLFEGVLLYYKSKKDssYKPKGSIPLS--GILEVEEVSPKERP-----------HCFELV 68

                           90       100
                   ....*....|....*....|....*.
gi 1907123492  938 HPKDQgpTYLLIG-SKHEKEAWLYHL 962
Cdd:cd00821     69 TPDGR--TYYLQAdSEEERQEWLKAL 92
COG2433 COG2433
Possible nuclease of RNase H fold, RuvC/YqgF family [General function prediction only];
101-220 8.41e-03

Possible nuclease of RNase H fold, RuvC/YqgF family [General function prediction only];


Pssm-ID: 441980 [Multi-domain]  Cd Length: 644  Bit Score: 40.61  E-value: 8.41e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  101 AERQAEKAFQEVQVMEEKLKAAN--IQTSESETrlykkcQDLESVMQEKDDIIQNLALRLEEQKQVRIQEAKIIEEkaak 178
Cdd:COG2433    397 AEREKEHEERELTEEEEEIRRLEeqVERLEAEV------EELEAELEEKDERIERLERELSEARSEERREIRKDRE---- 466

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1907123492  179 ikewvtvkLNELEVENQNLRFINQTQTEEIRAIQSKLQELQE 220
Cdd:COG2433    467 --------ISRLDREIERLERELEEERERIEELKRKLERLKE 500
CALCOCO1 pfam07888
Calcium binding and coiled-coil domain (CALCOCO1) like; Proteins found in this family are ...
 88-324 9.12e-03

Calcium binding and coiled-coil domain (CALCOCO1) like; Proteins found in this family are similar to the coiled-coil transcriptional coactivator protein coexpressed by Mus musculus (CoCoA/CALCOCO1). This protein binds to a highly conserved N-terminal domain of p160 coactivators, such as GRIP1, and thus enhances transcriptional activation by a number of nuclear receptors. CALCOCO1 has a central coiled-coil region with three leucine zipper motifs, which is required for its interaction with GRIP1 and may regulate the autonomous transcriptional activation activity of the C-terminal region.


Pssm-ID: 462303 [Multi-domain]  Cd Length: 488  Bit Score: 40.26  E-value: 9.12e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492   88 KHHMQQLERQVIDAERQAEKAFQEVQVMEEKlkaaniqtsesetrlYKKCQDL-ESVMQEKDDIiqnlaLRLEEQKQVRI 166
Cdd:pfam07888   72 ERQRRELESRVAELKEELRQSREKHEELEEK---------------YKELSASsEELSEEKDAL-----LAQRAAHEARI 131

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  167 QEakiIEEKAAKIKEWVTVKLNELE-VENQNLRFINQTQTEEI--RAIQSKLQELQEKKISCVS---SPKTSEGQRNlTF 240
Cdd:pfam07888  132 RE---LEEDIKTLTQRVLERETELErMKERAKKAGAQRKEEEAerKQLQAKLQQTEEELRSLSKefqELRNSLAQRD-TQ 207

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123492  241 GCFLSRAKSPPCVVRCEEVSKMASNEPEITEGRCVEE-MEIAEKPAD-------NQVQENSRSQRKLHETSCSSEQ--NQ 310
Cdd:pfam07888  208 VLQLQDTITTLTQKLTTAHRKEAENEALLEELRSLQErLNASERKVEglgeelsSMAAQRDRTQAELHQARLQAAQltLQ 287

                          250
                   ....*....|....
gi 1907123492  311 KTRASFAMDGGTSQ 324
Cdd:pfam07888  288 LADASLALREGRAR 301
PH_Osh1p_Osh2p_yeast cd13292
Yeast oxysterol binding protein homologs 1 and 2 Pleckstrin homology (PH) domain; Yeast Osh1p ...
 860-908 9.62e-03

Yeast oxysterol binding protein homologs 1 and 2 Pleckstrin homology (PH) domain; Yeast Osh1p is proposed to function in postsynthetic sterol regulation, piecemeal microautophagy of the nucleus, and cell polarity establishment. Yeast Osh2p is proposed to function in sterol metabolism and cell polarity establishment. Both Osh1p and Osh2p contain 3 N-terminal ankyrin repeats, a PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. OSBP andOsh1p PH domains specifically localize to the Golgi apparatus in a PtdIns4P-dependent manner. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241446  Cd Length: 103  Bit Score: 37.29  E-value: 9.62e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1907123492  860 PAVKGLLTK---VKHGYSKRvWCMLVGKVLYYFRNQED--KFPLGQLKLWEAKV 908
Cdd:cd13292      2 PTMKGYLKKwtnYAKGYKTR-WFVLEDGVLSYYRHQDDegSACRGSINMKNARL 54
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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