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Conserved domains on  [gi|1924565257|ref|NP_001375345|]
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kalirin isoform 22 [Homo sapiens]

Protein Classification

RhoGEF and PH1_Kalirin_Trio_like domain-containing protein( domain architecture ID 10075262)

protein containing domains SPEC, RhoGEF, and PH1_Kalirin_Trio_like

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PH1_Kalirin_Trio_like cd13240
Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1; ...
 798-920 8.62e-68

Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1; RhoGEFs, Kalirin and Trio, the mammalian homologs of Drosophila Trio and Caenorhabditis elegans UNC-73 regulate a novel step in secretory granule maturation. Their signaling modulates the extent to which regulated cargo enter and remain in the regulated secretory pathway. This allows for fine tuning of peptides released by a single secretory cell type with impaired signaling leading to pathological states. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Kalirin and Trio are encoded by separate genes in mammals and by a single one in invertebrates. Kalirin and Trio share the same complex multidomain structure and display several splice variants. The longest Kalirin and Trio proteins have a Sec14 domain, a stretch of spectrin repeats, a RhoGEF(DH)/PH cassette (also called GEF1), an SH3 domain, a second RhoGEF(DH)/PH cassette (also called GEF2), a second SH3 domain, Ig/FNIII domains, and a kinase domain. The first RhoGEF(DH)/PH cassette catalyzes exchange on Rac1 and RhoG while the second RhoGEF(DH)/PH cassette is specific for RhoA. Kalirin and Trio are closely related to p63RhoGEF and have PH domains of similar function. 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.


:

Pssm-ID: 270060  Cd Length: 123  Bit Score: 222.26  E-value: 8.62e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  798 MLEGFDENLDVQGELILQDAFQVWDPKSLIRKGRERHLFLFEISLVFSKEIKDSSGHTKYVYKNKLLTSELGVTEHVEGD 877
Cdd:cd13240      1 LLEGCDEDLDSLGEVILQDSFQVWDPKQLIRKGRERHVFLFELCLVFSKEVKDSNGKSKYIYKSRLMTSEIGVTEHIEGD 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1924565257  878 PCKFALWSGRTPSSDNKTVLKASNIETKQEWIKNIREVIQERI 920
Cdd:cd13240     81 PCKFALWTGRVPTSDNKIVLKASSLEVKQTWVKKLREVIQERI 123
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 621-791 1.83e-43

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


:

Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 155.92  E-value: 1.83e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  621 FIMAELLQTEKAYVRDLHECLETYLWEMTSGVEEIPPgilNKEHIIFGNIQEIYDFHNnIFLKELEKY----EQLPEDVG 696
Cdd:cd00160      3 EVIKELLQTERNYVRDLKLLVEVFLKPLDKELLPLSP---EEVELLFGNIEEIYEFHR-IFLKSLEERveewDKSGPRIG 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  697 HCFVTWADKFQMYVTYCKNKPDSNQLILEHAG--TFFDEIQQRHGLAN---SISSYLIKPVQRITKYQLLLKELLTCCEE 771
Cdd:cd00160     79 DVFLKLAPFFKIYSEYCSNHPDALELLKKLKKfnKFFQEFLEKAESECgrlKLESLLLKPVQRLTKYPLLLKELLKHTPD 158

                          170       180
                   ....*....|....*....|...
gi 1924565257  772 G---KGELKDGLEVMLSVPKKAN 791
Cdd:cd00160    159 GhedREDLKKALEAIKEVASQVN 181
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 237-466 1.89e-16

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


:

Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 79.41  E-value: 1.89e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  237 QLRHLQAEVKQVLGWIRNGESMLnASLVNASSLSEAEQLQREHEQFQLAIEKTHQSALQVQQKAEVLLQAGHYDADAIRE 316
Cdd:cd00176      1 KLQQFLRDADELEAWLSEKEELL-SSTDYGDDLESVEALLKKHEALEAELAAHEERVEALNELGEQLIEEGHPDAEEIQE 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  317 CAEKVALHWQQLMLKMEDRLKLVNASVAFYKTSEQVCSVlesleqeyrrdEDWCGGRDKLGPAAEIDHVIPLISKHLEQK 396
Cdd:cd00176     80 RLEELNQRWEELRELAEERRQRLEEALDLQQFFRDADDL-----------EQWLEEKEAALASEDLGKDLESVEELLKKH 148

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  397 EAFLKACTlarrNAEVFLKYIHRNNVSMpsVASHTRGPEQQVKAILSELLQRENRVLHFWTLKKRRLDQC 466
Cdd:cd00176    149 KELEEELE----AHEPRLKSLNELAEEL--LEEGHPDADEEIEEKLEELNERWEELLELAEERQKKLEEA 212
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 129-343 1.20e-11

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


:

Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 65.16  E-value: 1.20e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  129 AELDAWNEDLLRQMNDFNT-EDLTLAEQRLQRHTERKLAMnnmtfeviqqgQDLHQYITEVQASGIELIcEKDIDLAAQV 207
Cdd:cd00176     10 DELEAWLSEKEELLSSTDYgDDLESVEALLKKHEALEAEL-----------AAHEERVEALNELGEQLI-EEGHPDAEEI 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  208 QELLEFLHEKQHELELNAEQTHKRLEQCLQLRHLQAEVKQVLGWIRNGESMLnASLVNASSLSEAEQLQREHEQFQLAIE 287
Cdd:cd00176     78 QERLEELNQRWEELRELAEERRQRLEEALDLQQFFRDADDLEQWLEEKEAAL-ASEDLGKDLESVEELLKKHKELEEELE 156

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1924565257  288 KTHQSALQVQQKAEVLLQAGHYDADA-IRECAEKVALHWQQLMLKMEDRLKLVNASV 343
Cdd:cd00176    157 AHEPRLKSLNELAEELLEEGHPDADEeIEEKLEELNERWEELLELAEERQKKLEEAL 213
SPEC smart00150
Spectrin repeats;
472-572 4.20e-03

Spectrin repeats;


:

Pssm-ID: 197544 [Multi-domain]  Cd Length: 101  Bit Score: 37.69  E-value: 4.20e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257   472 FERSAKQALDWIQETGEFYLSTHTSTGETTEETqeLLKEYGEFRVPAKQTKEKVKLLIQLADSFVEKGHIHATEIRKWVT 551
Cdd:smart00150    3 FLRDADELEAWLEEKEQLLASEDLGKDLESVEA--LLKKHEAFEAELEAHEERVEALNELGEQLIEEGHPDAEEIEERLE 80

                            90       100
                    ....*....|....*....|.
gi 1924565257   552 TVDKHYRDFSLRMGKYRYSLE 572
Cdd:smart00150   81 ELNERWEELKELAEERRQKLE 101
 
Name Accession Description Interval E-value
PH1_Kalirin_Trio_like cd13240
Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1; ...
 798-920 8.62e-68

Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1; RhoGEFs, Kalirin and Trio, the mammalian homologs of Drosophila Trio and Caenorhabditis elegans UNC-73 regulate a novel step in secretory granule maturation. Their signaling modulates the extent to which regulated cargo enter and remain in the regulated secretory pathway. This allows for fine tuning of peptides released by a single secretory cell type with impaired signaling leading to pathological states. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Kalirin and Trio are encoded by separate genes in mammals and by a single one in invertebrates. Kalirin and Trio share the same complex multidomain structure and display several splice variants. The longest Kalirin and Trio proteins have a Sec14 domain, a stretch of spectrin repeats, a RhoGEF(DH)/PH cassette (also called GEF1), an SH3 domain, a second RhoGEF(DH)/PH cassette (also called GEF2), a second SH3 domain, Ig/FNIII domains, and a kinase domain. The first RhoGEF(DH)/PH cassette catalyzes exchange on Rac1 and RhoG while the second RhoGEF(DH)/PH cassette is specific for RhoA. Kalirin and Trio are closely related to p63RhoGEF and have PH domains of similar function. 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.


Pssm-ID: 270060  Cd Length: 123  Bit Score: 222.26  E-value: 8.62e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  798 MLEGFDENLDVQGELILQDAFQVWDPKSLIRKGRERHLFLFEISLVFSKEIKDSSGHTKYVYKNKLLTSELGVTEHVEGD 877
Cdd:cd13240      1 LLEGCDEDLDSLGEVILQDSFQVWDPKQLIRKGRERHVFLFELCLVFSKEVKDSNGKSKYIYKSRLMTSEIGVTEHIEGD 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1924565257  878 PCKFALWSGRTPSSDNKTVLKASNIETKQEWIKNIREVIQERI 920
Cdd:cd13240     81 PCKFALWTGRVPTSDNKIVLKASSLEVKQTWVKKLREVIQERI 123
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 621-791 1.83e-43

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 155.92  E-value: 1.83e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  621 FIMAELLQTEKAYVRDLHECLETYLWEMTSGVEEIPPgilNKEHIIFGNIQEIYDFHNnIFLKELEKY----EQLPEDVG 696
Cdd:cd00160      3 EVIKELLQTERNYVRDLKLLVEVFLKPLDKELLPLSP---EEVELLFGNIEEIYEFHR-IFLKSLEERveewDKSGPRIG 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  697 HCFVTWADKFQMYVTYCKNKPDSNQLILEHAG--TFFDEIQQRHGLAN---SISSYLIKPVQRITKYQLLLKELLTCCEE 771
Cdd:cd00160     79 DVFLKLAPFFKIYSEYCSNHPDALELLKKLKKfnKFFQEFLEKAESECgrlKLESLLLKPVQRLTKYPLLLKELLKHTPD 158

                          170       180
                   ....*....|....*....|...
gi 1924565257  772 G---KGELKDGLEVMLSVPKKAN 791
Cdd:cd00160    159 GhedREDLKKALEAIKEVASQVN 181
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 622-792 3.77e-41

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 149.37  E-value: 3.77e-41
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257   622 IMAELLQTEKAYVRDLHECLETYLWEMTSGVEEIPPgilNKEHIIFGNIQEIYDFHNnIFLKELEKY----EQLPEDVGH 697
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKLLSP---NELETLFGNIEEIYEFHR-DFLDELEERieewDDSVERIGD 76

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257   698 CFVTWADKFQMYVTYCKNKPDSNQLI--LEHAGTFFDEIQQRHGLAN----SISSYLIKPVQRITKYQLLLKELLTCCEE 771
Cdd:smart00325   77 VFLKLEEFFKIYSEYCSNHPDALELLkkLKKNPRFQKFLKEIESSPQcrrlTLESLLLKPVQRLTKYPLLLKELLKHTPE 156

                           170       180
                    ....*....|....*....|....
gi 1924565257   772 G---KGELKDGLEVMLSVPKKAND 792
Cdd:smart00325  157 DhedREDLKKALKAIKELANQVNE 180
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 622-791 8.71e-41

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 148.22  E-value: 8.71e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  622 IMAELLQTEKAYVRDLHECLETYLWEMTSGVEEIPPGIlnkeHIIFGNIQEIYDFHNNIFLKELEKYEQLPEDVGHCFVT 701
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEI----KTIFSNIEEIYELHRQLLLEELLKEWISIQRIGDIFLK 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  702 WADKFQMYVTYCKNKPDSNQLI------LEHAGTFFDEIQQRHGLAN-SISSYLIKPVQRITKYQLLLKELLTCCEEG-- 772
Cdd:pfam00621   77 FAPGFKVYSTYCSNYPKALKLLkkllkkNPKFRAFLEELEANPECRGlDLNSFLIKPVQRIPRYPLLLKELLKHTPPDhp 156

                          170       180
                   ....*....|....*....|
gi 1924565257  773 -KGELKDGLEVMLSVPKKAN 791
Cdd:pfam00621  157 dYEDLKKALEAIKEVAKQIN 176
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 237-466 1.89e-16

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 79.41  E-value: 1.89e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  237 QLRHLQAEVKQVLGWIRNGESMLnASLVNASSLSEAEQLQREHEQFQLAIEKTHQSALQVQQKAEVLLQAGHYDADAIRE 316
Cdd:cd00176      1 KLQQFLRDADELEAWLSEKEELL-SSTDYGDDLESVEALLKKHEALEAELAAHEERVEALNELGEQLIEEGHPDAEEIQE 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  317 CAEKVALHWQQLMLKMEDRLKLVNASVAFYKTSEQVCSVlesleqeyrrdEDWCGGRDKLGPAAEIDHVIPLISKHLEQK 396
Cdd:cd00176     80 RLEELNQRWEELRELAEERRQRLEEALDLQQFFRDADDL-----------EQWLEEKEAALASEDLGKDLESVEELLKKH 148

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  397 EAFLKACTlarrNAEVFLKYIHRNNVSMpsVASHTRGPEQQVKAILSELLQRENRVLHFWTLKKRRLDQC 466
Cdd:cd00176    149 KELEEELE----AHEPRLKSLNELAEEL--LEEGHPDADEEIEEKLEELNERWEELLELAEERQKKLEEA 212
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 129-343 1.20e-11

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 65.16  E-value: 1.20e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  129 AELDAWNEDLLRQMNDFNT-EDLTLAEQRLQRHTERKLAMnnmtfeviqqgQDLHQYITEVQASGIELIcEKDIDLAAQV 207
Cdd:cd00176     10 DELEAWLSEKEELLSSTDYgDDLESVEALLKKHEALEAEL-----------AAHEERVEALNELGEQLI-EEGHPDAEEI 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  208 QELLEFLHEKQHELELNAEQTHKRLEQCLQLRHLQAEVKQVLGWIRNGESMLnASLVNASSLSEAEQLQREHEQFQLAIE 287
Cdd:cd00176     78 QERLEELNQRWEELRELAEERRQRLEEALDLQQFFRDADDLEQWLEEKEAAL-ASEDLGKDLESVEELLKKHKELEEELE 156

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1924565257  288 KTHQSALQVQQKAEVLLQAGHYDADA-IRECAEKVALHWQQLMLKMEDRLKLVNASV 343
Cdd:cd00176    157 AHEPRLKSLNELAEELLEEGHPDADEeIEEKLEELNERWEELLELAEERQKKLEEAL 213
SPEC smart00150
Spectrin repeats;
239-337 5.67e-11

Spectrin repeats;


Pssm-ID: 197544 [Multi-domain]  Cd Length: 101  Bit Score: 60.04  E-value: 5.67e-11
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257   239 RHLQAEVKQVLGWIRNGESMLnASLVNASSLSEAEQLQREHEQFQLAIEKTHQSALQVQQKAEVLLQAGHYDADAIRECA 318
Cdd:smart00150    1 QQFLRDADELEAWLEEKEQLL-ASEDLGKDLESVEALLKKHEAFEAELEAHEERVEALNELGEQLIEEGHPDAEEIEERL 79

                            90
                    ....*....|....*....
gi 1924565257   319 EKVALHWQQLMLKMEDRLK 337
Cdd:smart00150   80 EELNERWEELKELAEERRQ 98
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
 563-783 1.14e-07

RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms];


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 56.05  E-value: 1.14e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  563 RMGKYRYSLEKaLGVNTEDNKDLELDiipASLSDREVKLRDANHEVNEEKRKSARKKEFIMAELLQTEKAYVRDLhECLE 642
Cdd:COG5422    433 RLEQQARLHLK-LMGGLKRNSSLALD---KFDEEKNLWTLSVPKEVWESLPKQEIKRQEAIYEVIYTERDFVKDL-EYLR 507

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  643 TYlWEMTSGVEEIPPGILNKEHI--IFGNIQEIYDFhNNIFLKELEK---YEQLPEDVGHCFVTWADKFQMYVTYCKNKP 717
Cdd:COG5422    508 DT-WIKPLEESNIIPENARRNFIkhVFANINEIYAV-NSKLLKALTNrqcLSPIVNGIADIFLDYVPKFEPFIKYGASQP 585

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1924565257  718 DSNQLILEHAGT------FFDEIQ-----QRHGlansISSYLIKPVQRITKYQLLLKELLTCCEEGKGELKDGLEVM 783
Cdd:COG5422    586 YAKYEFEREKSVnpnfarFDHEVErldesRKLE----LDGYLTKPTTRLARYPLLLEEVLKFTDPDNPDTEDIPKVI 658
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 824-917 4.70e-06

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: 46.00  E-value: 4.70e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257   824 KSLIRKGRERHLFLFEISLVFSKeikDSSGHTKYVYKNKLLTSELGVTEHVEGD----PCKFALWSGrtpssDNKT-VLK 898
Cdd:smart00233   12 GGGKKSWKKRYFVLFNSTLLYYK---SKKDKKSYKPKGSIDLSGCTVREAPDPDsskkPHCFEIKTS-----DRKTlLLQ 83

                            90
                    ....*....|....*....
gi 1924565257   899 ASNIETKQEWIKNIREVIQ 917
Cdd:smart00233   84 AESEEEREKWVEALRKAIA 102
Spectrin pfam00435
Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in ...
 236-328 8.08e-06

Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in cytoskeletal structure. These include spectrin, alpha-actinin and dystrophin. The sequence repeat used in this family is taken from the structural repeat in reference. The spectrin domain- repeat forms a three helix bundle. The second helix is interrupted by proline in some sequences. The repeats are defined by a characteriztic tryptophan (W) residue at position 17 in helix A and a leucine (L) at 2 residues from the carboxyl end of helix C. Although the domain occurs in multiple repeats along sequences, the domains are actually stable on their own - ie they act, biophysically, like domains rather than repeats that along function when aggregated.


Pssm-ID: 395348 [Multi-domain]  Cd Length: 105  Bit Score: 45.39  E-value: 8.08e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  236 LQLRHLQAEVKQVLGWIRNGESMLnASLVNASSLSEAEQLQREHEQFQLAIEkTHQSALQ-VQQKAEVLLQAGHYDADAI 314
Cdd:pfam00435    1 LLLQQFFRDADDLESWIEEKEALL-SSEDYGKDLESVQALLKKHKALEAELA-AHQDRVEaLNELAEKLIDEGHYASEEI 78

                           90
                   ....*....|....
gi 1924565257  315 RECAEKVALHWQQL 328
Cdd:pfam00435   79 QERLEELNERWEQL 92
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 831-916 2.39e-05

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 44.09  E-value: 2.39e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  831 RERHLFLFEISLVFSKeikDSSGHTKYVYKNKLLTSELGVTEHVEGD----PCKFALWSGrTPSSDNKTVLKASNIETKQ 906
Cdd:pfam00169   19 KKRYFVLFDGSLLYYK---DDKSGKSKEPKGSISLSGCEVVEVVASDspkrKFCFELRTG-ERTGKRTYLLQAESEEERK 94

                           90
                   ....*....|
gi 1924565257  907 EWIKNIREVI 916
Cdd:pfam00169   95 DWIKAIQSAI 104
EnvC COG4942
Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, ...
 27-288 3.04e-03

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: 40.90  E-value: 3.04e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257   27 VCADSVDAVQELIKQFQQQqtatLDATLNVIKEGEDLIQQLRDSAVSnnktphsssishiesVLQQLDDAQVQMEELfhE 106
Cdd:COG4942     10 LLALAAAAQADAAAEAEAE----LEQLQQEIAELEKELAALKKEEKA---------------LLKQLAALERRIAAL--A 68

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  107 RKIKlDIFLQLRIFEQYTIEVTAELDAWNEDLLRQMNDFntEDLTLAEQRLQRHTERKLAMNNMTFEVIQQGQDLHQYIT 186
Cdd:COG4942     69 RRIR-ALEQELAALEAELAELEKEIAELRAELEAQKEEL--AELLRALYRLGRQPPLALLLSPEDFLDAVRRLQYLKYLA 145

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  187 EVQASGIELICEKDIDLAAQVQELLEFLHEKQhELELNAEQTHKRLEQclqlrhLQAEVKQVLGWIRNGESMLNASLvnA 266
Cdd:COG4942    146 PARREQAEELRADLAELAALRAELEAERAELE-ALLAELEEERAALEA------LKAERQKLLARLEKELAELAAEL--A 216

                          250       260
                   ....*....|....*....|..
gi 1924565257  267 SSLSEAEQLQREHEQFQLAIEK 288
Cdd:COG4942    217 ELQQEAEELEALIARLEAEAAA 238
SPEC smart00150
Spectrin repeats;
472-572 4.20e-03

Spectrin repeats;


Pssm-ID: 197544 [Multi-domain]  Cd Length: 101  Bit Score: 37.69  E-value: 4.20e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257   472 FERSAKQALDWIQETGEFYLSTHTSTGETTEETqeLLKEYGEFRVPAKQTKEKVKLLIQLADSFVEKGHIHATEIRKWVT 551
Cdd:smart00150    3 FLRDADELEAWLEEKEQLLASEDLGKDLESVEA--LLKKHEAFEAELEAHEERVEALNELGEQLIEEGHPDAEEIEERLE 80

                            90       100
                    ....*....|....*....|.
gi 1924565257   552 TVDKHYRDFSLRMGKYRYSLE 572
Cdd:smart00150   81 ELNERWEELKELAEERRQKLE 101
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 468-588 9.62e-03

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 38.58  E-value: 9.62e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  468 QYVVFERSAKQALDWIQETGEFYLSTHTSTGETTEETqeLLKEYGEFRVPAKQTKEKVKLLIQLADSFVEKGHIHATEIR 547
Cdd:cd00176      1 KLQQFLRDADELEAWLSEKEELLSSTDYGDDLESVEA--LLKKHEALEAELAAHEERVEALNELGEQLIEEGHPDAEEIQ 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1924565257  548 KWVTTVDKHYRDFSLRMGKYRYSLEKALGVNTEDNKDLELD 588
Cdd:cd00176     79 ERLEELNQRWEELRELAEERRQRLEEALDLQQFFRDADDLE 119
 
Name Accession Description Interval E-value
PH1_Kalirin_Trio_like cd13240
Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1; ...
 798-920 8.62e-68

Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1; RhoGEFs, Kalirin and Trio, the mammalian homologs of Drosophila Trio and Caenorhabditis elegans UNC-73 regulate a novel step in secretory granule maturation. Their signaling modulates the extent to which regulated cargo enter and remain in the regulated secretory pathway. This allows for fine tuning of peptides released by a single secretory cell type with impaired signaling leading to pathological states. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Kalirin and Trio are encoded by separate genes in mammals and by a single one in invertebrates. Kalirin and Trio share the same complex multidomain structure and display several splice variants. The longest Kalirin and Trio proteins have a Sec14 domain, a stretch of spectrin repeats, a RhoGEF(DH)/PH cassette (also called GEF1), an SH3 domain, a second RhoGEF(DH)/PH cassette (also called GEF2), a second SH3 domain, Ig/FNIII domains, and a kinase domain. The first RhoGEF(DH)/PH cassette catalyzes exchange on Rac1 and RhoG while the second RhoGEF(DH)/PH cassette is specific for RhoA. Kalirin and Trio are closely related to p63RhoGEF and have PH domains of similar function. 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.


Pssm-ID: 270060  Cd Length: 123  Bit Score: 222.26  E-value: 8.62e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  798 MLEGFDENLDVQGELILQDAFQVWDPKSLIRKGRERHLFLFEISLVFSKEIKDSSGHTKYVYKNKLLTSELGVTEHVEGD 877
Cdd:cd13240      1 LLEGCDEDLDSLGEVILQDSFQVWDPKQLIRKGRERHVFLFELCLVFSKEVKDSNGKSKYIYKSRLMTSEIGVTEHIEGD 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1924565257  878 PCKFALWSGRTPSSDNKTVLKASNIETKQEWIKNIREVIQERI 920
Cdd:cd13240     81 PCKFALWTGRVPTSDNKIVLKASSLEVKQTWVKKLREVIQERI 123
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 621-791 1.83e-43

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 155.92  E-value: 1.83e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  621 FIMAELLQTEKAYVRDLHECLETYLWEMTSGVEEIPPgilNKEHIIFGNIQEIYDFHNnIFLKELEKY----EQLPEDVG 696
Cdd:cd00160      3 EVIKELLQTERNYVRDLKLLVEVFLKPLDKELLPLSP---EEVELLFGNIEEIYEFHR-IFLKSLEERveewDKSGPRIG 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  697 HCFVTWADKFQMYVTYCKNKPDSNQLILEHAG--TFFDEIQQRHGLAN---SISSYLIKPVQRITKYQLLLKELLTCCEE 771
Cdd:cd00160     79 DVFLKLAPFFKIYSEYCSNHPDALELLKKLKKfnKFFQEFLEKAESECgrlKLESLLLKPVQRLTKYPLLLKELLKHTPD 158

                          170       180
                   ....*....|....*....|...
gi 1924565257  772 G---KGELKDGLEVMLSVPKKAN 791
Cdd:cd00160    159 GhedREDLKKALEAIKEVASQVN 181
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 622-792 3.77e-41

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 149.37  E-value: 3.77e-41
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257   622 IMAELLQTEKAYVRDLHECLETYLWEMTSGVEEIPPgilNKEHIIFGNIQEIYDFHNnIFLKELEKY----EQLPEDVGH 697
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKLLSP---NELETLFGNIEEIYEFHR-DFLDELEERieewDDSVERIGD 76

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257   698 CFVTWADKFQMYVTYCKNKPDSNQLI--LEHAGTFFDEIQQRHGLAN----SISSYLIKPVQRITKYQLLLKELLTCCEE 771
Cdd:smart00325   77 VFLKLEEFFKIYSEYCSNHPDALELLkkLKKNPRFQKFLKEIESSPQcrrlTLESLLLKPVQRLTKYPLLLKELLKHTPE 156

                           170       180
                    ....*....|....*....|....
gi 1924565257   772 G---KGELKDGLEVMLSVPKKAND 792
Cdd:smart00325  157 DhedREDLKKALKAIKELANQVNE 180
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 622-791 8.71e-41

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 148.22  E-value: 8.71e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  622 IMAELLQTEKAYVRDLHECLETYLWEMTSGVEEIPPGIlnkeHIIFGNIQEIYDFHNNIFLKELEKYEQLPEDVGHCFVT 701
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEI----KTIFSNIEEIYELHRQLLLEELLKEWISIQRIGDIFLK 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  702 WADKFQMYVTYCKNKPDSNQLI------LEHAGTFFDEIQQRHGLAN-SISSYLIKPVQRITKYQLLLKELLTCCEEG-- 772
Cdd:pfam00621   77 FAPGFKVYSTYCSNYPKALKLLkkllkkNPKFRAFLEELEANPECRGlDLNSFLIKPVQRIPRYPLLLKELLKHTPPDhp 156

                          170       180
                   ....*....|....*....|
gi 1924565257  773 -KGELKDGLEVMLSVPKKAN 791
Cdd:pfam00621  157 dYEDLKKALEAIKEVAKQIN 176
PH2_Kalirin_Trio_p63RhoGEF cd13241
p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor ...
 796-931 1.78e-28

p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor p63RhoGEF is an effector of the heterotrimeric G protein, Galphaq and linking Galphaq-coupled receptors (GPCRs) to the activation of RhoA. The Dbl(DH) and PH domains of p63RhoGEF interact with the effector-binding site and the C-terminal region of Galphaq and appear to relieve autoinhibition of the catalytic DH domain by the PH domain. Trio, Duet, and p63RhoGEF are shown to constitute a family of Galphaq effectors that appear to activate RhoA both in vitro and in intact cells. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. 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: 270061  Cd Length: 140  Bit Score: 111.58  E-value: 1.78e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  796 VSMLEGFDENLDVQGELILQDAFQVWDPKS-LIRKGRERHLFLFEISLVFSKEI--KDSSGHTKYVYKNKLLTSELGVTE 872
Cdd:cd13241      1 VGRLQGFDGKITAQGKLLLQGTLLVSEPSAgLLQKGKERRVFLFEQIIIFSEILgkKTQFSNPGYIYKNHIKVNKMSLEE 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  873 HVEGDPCKFALWSgRTPSSDNKT-VLKASNIETKQEWIKNIREVIQERIIHLKgALKEPL 931
Cdd:cd13241     81 NVDGDPLRFALKS-RDPNNPSETfILQAASPEVRQEWVDTINQILDTQRDFLK-ALQSPI 138
PH_puratrophin-1 cd13242
Puratrophin-1 pleckstrin homology (PH) domain; Puratrophin-1 (also called Purkinje cell ...
 791-924 4.72e-23

Puratrophin-1 pleckstrin homology (PH) domain; Puratrophin-1 (also called Purkinje cell atrophy-associated protein 1 or PLEKHG4/Pleckstrin homology domain-containing family G member 4) contains a spectrin repeat, a RhoGEF (DH) domain, and a PH domain. It is thought to function in intracellular signaling and cytoskeleton dynamics at the Golgi. Puratrophin-1 is expressed in kidney, Leydig cells in the testis, epithelial cells in the prostate gland and Langerhans islet in the pancreas. A single nucleotide substitution in the puratrophin-1 gene were once thought to result in autosomal dominant cerebellar ataxia (ADCA), but now it has been demonstrated that this ataxia is a result of defects in the BEAN gene. Puratrophin contains a domain architecture similar to that of Dbl family members Dbs and Trio. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a RhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. 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: 270062  Cd Length: 136  Bit Score: 95.82  E-value: 4.72e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  791 NDAMHVSMLEGFDENLDVQGELILQDAFQVWDPksliRKGRERHLFLFEISLVFSKEIKDSSGHTKYVYKNKLLTSELGV 870
Cdd:cd13242      8 NDLLAMDSIRGCDVNLKEQGQLLRQDEFLVWQG----RKKCLRHVFLFEDLILFSKPKKTPGGKDVYIYKHSIKTSDIGL 83

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1924565257  871 TEHVEGDPCKFALWSGRTPSSDNkTVLKASNIETKQEWIKNIREVIQERIIHLK 924
Cdd:cd13242     84 TENVGDSGLKFEIWFRRRKARDT-YILQATSPEIKQAWTSDIAKLLWKQAIRNR 136
PH_Dbs cd01227
DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming ...
 801-916 4.61e-20

DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming sequence-like protein 2) is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. 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: 269934 [Multi-domain]  Cd Length: 126  Bit Score: 86.87  E-value: 4.61e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  801 GFDENLDVQGELILQDAFQVW------DPKSLIR-KGRERHLFLFEISLVFSKEIKDSSGHTKYVYKNKLLTSELGVTEH 873
Cdd:cd01227      4 GYDGNLGDLGKLLMQGSFNVWtehkkgHTKKLARfKPMQRHIFLYEKAVLFCKKRGENGEAPSYSYKNSLNTTAVGLTEN 83

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1924565257  874 VEGDPCKFALW-SGRTpssdNKTVLKASNIETKQEWIKNIREVI 916
Cdd:cd01227     84 VKGDTKKFEIWlNGRE----EVFIIQAPTPEIKAAWVKAIRQVL 123
PH_Obscurin cd13239
Obscurin pleckstrin homology (PH) domain; Obscurin (also called Obscurin-RhoGEF; ...
 798-919 1.14e-16

Obscurin pleckstrin homology (PH) domain; Obscurin (also called Obscurin-RhoGEF; Obscurin-myosin light chain kinase/Obscurin-MLCK) is a giant muscle protein that is concentrated at the peripheries of Z-disks and M-lines. It binds small ankyrin I, a component of the sarcoplasmic reticulum (SR) membrane. It is associated with the contractile apparatus through binding with titin and sarcomeric myosin. It plays important roles in the organization and assembly of the myofibril and the SR. Obscurin has been observed as alternatively-spliced isoforms. The major isoform in sleletal muscle, approximately 800 kDa in size, is composed of many adhesion modules and signaling domains. It harbors 49 Ig and 2 FNIII repeats at the N-terminues, a complex middle region with additional Ig domains, an IQ motif, and a conserved SH3 domain near RhoGEF and PH domains, and a non-modular C-terminus with phosphorylation motifs. The obscurin gene also encodes two kinase domains, which are not part of the 800 kDa form of the protein, but is part of smaller spliced products that present in heart muscle. 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: 270059  Cd Length: 125  Bit Score: 77.20  E-value: 1.14e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  798 MLEGFDENLDVQGELILQDAFQVWDPKSLIR---KGRERHLFLFEISLVFSKEIKDSSGHTK-YVYKNKLLTSELGVTEH 873
Cdd:cd13239      1 LIENYPAPLQALGEPIRQGHFTVWEEAPEVKtssRGHHRHVFLFKNCVVICKPKRDSRTDTVtYVFKNKMKLSDIDVKDT 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1924565257  874 VEGDPCKFALWSGRTpSSDNKTVLKASNIETKQEWIKNIREvIQER 919
Cdd:cd13239     81 VEGDDRSFGLWHEHR-GSVRKYTLQARSAIIKSSWLKDLRD-LQQR 124
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 237-466 1.89e-16

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 79.41  E-value: 1.89e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  237 QLRHLQAEVKQVLGWIRNGESMLnASLVNASSLSEAEQLQREHEQFQLAIEKTHQSALQVQQKAEVLLQAGHYDADAIRE 316
Cdd:cd00176      1 KLQQFLRDADELEAWLSEKEELL-SSTDYGDDLESVEALLKKHEALEAELAAHEERVEALNELGEQLIEEGHPDAEEIQE 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  317 CAEKVALHWQQLMLKMEDRLKLVNASVAFYKTSEQVCSVlesleqeyrrdEDWCGGRDKLGPAAEIDHVIPLISKHLEQK 396
Cdd:cd00176     80 RLEELNQRWEELRELAEERRQRLEEALDLQQFFRDADDL-----------EQWLEEKEAALASEDLGKDLESVEELLKKH 148

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  397 EAFLKACTlarrNAEVFLKYIHRNNVSMpsVASHTRGPEQQVKAILSELLQRENRVLHFWTLKKRRLDQC 466
Cdd:cd00176    149 KELEEELE----AHEPRLKSLNELAEEL--LEEGHPDADEEIEEKLEELNERWEELLELAEERQKKLEEA 212
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 129-343 1.20e-11

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 65.16  E-value: 1.20e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  129 AELDAWNEDLLRQMNDFNT-EDLTLAEQRLQRHTERKLAMnnmtfeviqqgQDLHQYITEVQASGIELIcEKDIDLAAQV 207
Cdd:cd00176     10 DELEAWLSEKEELLSSTDYgDDLESVEALLKKHEALEAEL-----------AAHEERVEALNELGEQLI-EEGHPDAEEI 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  208 QELLEFLHEKQHELELNAEQTHKRLEQCLQLRHLQAEVKQVLGWIRNGESMLnASLVNASSLSEAEQLQREHEQFQLAIE 287
Cdd:cd00176     78 QERLEELNQRWEELRELAEERRQRLEEALDLQQFFRDADDLEQWLEEKEAAL-ASEDLGKDLESVEELLKKHKELEEELE 156

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1924565257  288 KTHQSALQVQQKAEVLLQAGHYDADA-IRECAEKVALHWQQLMLKMEDRLKLVNASV 343
Cdd:cd00176    157 AHEPRLKSLNELAEELLEEGHPDADEeIEEKLEELNERWEELLELAEERQKKLEEAL 213
SPEC smart00150
Spectrin repeats;
239-337 5.67e-11

Spectrin repeats;


Pssm-ID: 197544 [Multi-domain]  Cd Length: 101  Bit Score: 60.04  E-value: 5.67e-11
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257   239 RHLQAEVKQVLGWIRNGESMLnASLVNASSLSEAEQLQREHEQFQLAIEKTHQSALQVQQKAEVLLQAGHYDADAIRECA 318
Cdd:smart00150    1 QQFLRDADELEAWLEEKEQLL-ASEDLGKDLESVEALLKKHEAFEAELEAHEERVEALNELGEQLIEEGHPDAEEIEERL 79

                            90
                    ....*....|....*....
gi 1924565257   319 EKVALHWQQLMLKMEDRLK 337
Cdd:smart00150   80 EELNERWEELKELAEERRQ 98
PH_PLEKHG1_G2_G3 cd13243
Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) ...
 775-918 7.08e-10

Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) domain; PLEKHG1 (also called ARHGEF41), PLEKHG2 (also called ARHGEF42 or CLG/common-site lymphoma/leukemia guanine nucleotide exchange factor2), and PLEKHG3 (also called ARHGEF43) have RhoGEF DH/double-homology domains in tandem with a PH domain which is involved in phospholipid binding. They function as a guanine nucleotide exchange factor (GEF) and are involved in the regulation of Rho protein signal transduction. Mutations in PLEKHG1 have been associated panic disorder (PD), an anxiety disorder characterized by panic attacks and anticipatory anxiety. 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: 270063 [Multi-domain]  Cd Length: 147  Bit Score: 58.52  E-value: 7.08e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  775 ELKDGLEVMLSVPKKAND-------AMHV----SMLEGFDE-NLDVQGELILQDAFQVWdpksliRKGRERHLFLFEISL 842
Cdd:cd13243      3 VVEEALDTMTQVAWHINDmkrkhehAVRVqeiqSLLDGWEGpELTTYGDLVLEGTFRMA------GAKNERLLFLFDKML 76

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1924565257  843 VFSKEIKDSSghtkYVYKNKLLTSELGVTEHVEGDPCKFALWSGRTPssDNKTVLKASNIETKQEWIKNIREVIQE 918
Cdd:cd13243     77 LITKKREDGI----LQYKTHIMCSNLMLSESIPKEPLSFQVLPFDNP--KLQYTLQAKNQEQKRLWTQEIKRLILE 146
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
 563-783 1.14e-07

RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms];


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 56.05  E-value: 1.14e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  563 RMGKYRYSLEKaLGVNTEDNKDLELDiipASLSDREVKLRDANHEVNEEKRKSARKKEFIMAELLQTEKAYVRDLhECLE 642
Cdd:COG5422    433 RLEQQARLHLK-LMGGLKRNSSLALD---KFDEEKNLWTLSVPKEVWESLPKQEIKRQEAIYEVIYTERDFVKDL-EYLR 507

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  643 TYlWEMTSGVEEIPPGILNKEHI--IFGNIQEIYDFhNNIFLKELEK---YEQLPEDVGHCFVTWADKFQMYVTYCKNKP 717
Cdd:COG5422    508 DT-WIKPLEESNIIPENARRNFIkhVFANINEIYAV-NSKLLKALTNrqcLSPIVNGIADIFLDYVPKFEPFIKYGASQP 585

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1924565257  718 DSNQLILEHAGT------FFDEIQ-----QRHGlansISSYLIKPVQRITKYQLLLKELLTCCEEGKGELKDGLEVM 783
Cdd:COG5422    586 YAKYEFEREKSVnpnfarFDHEVErldesRKLE----LDGYLTKPTTRLARYPLLLEEVLKFTDPDNPDTEDIPKVI 658
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 824-917 4.70e-06

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: 46.00  E-value: 4.70e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257   824 KSLIRKGRERHLFLFEISLVFSKeikDSSGHTKYVYKNKLLTSELGVTEHVEGD----PCKFALWSGrtpssDNKT-VLK 898
Cdd:smart00233   12 GGGKKSWKKRYFVLFNSTLLYYK---SKKDKKSYKPKGSIDLSGCTVREAPDPDsskkPHCFEIKTS-----DRKTlLLQ 83

                            90
                    ....*....|....*....
gi 1924565257   899 ASNIETKQEWIKNIREVIQ 917
Cdd:smart00233   84 AESEEEREKWVEALRKAIA 102
PH_unc89 cd13325
unc89 pleckstrin homology (PH) domain; unc89 is a myofibrillar protein. unc89-B the largest ...
 810-918 5.70e-06

unc89 pleckstrin homology (PH) domain; unc89 is a myofibrillar protein. unc89-B the largest isoform is composed of 53 immunoglobulin (Ig) domains, 2 Fn3 domains, a triplet of SH3, DH and PH domains at its N-terminus, and 2 protein kinase domains (PK1 and PK2) at its C-terminus. unc-89 mutants display disorganization of muscle A-bands, and usually lack M-lines. The COOH-terminal region of obscurin, the human homolog of unc89, interacts via two specific Ig-like domains with the NH(2)-terminal Z-disk region of titin, a protein that connects the Z line to the M line in the sarcomere and contributes to the contraction of striated muscle. obscurin is also thought to be involved in Ca2+/calmodulin via its IQ domains, as well as G protein-coupled signal transduction in the sarcomere via its RhoGEF/DH domain. The DH-PH region of OBSCN and unc89, the C. elegans homolog, has exchange activity for RhoA and Rho-1 respectively, but not for the small GTPases homologous to Cdc42 or Rac. 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: 270134  Cd Length: 114  Bit Score: 46.19  E-value: 5.70e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  810 GELILQDAFQVWDPKSlirKGRERHLFLFEISLVFSKEIKDSSGHTKYVYKNKLLTSELGVTEHvEGDPCKFALWSGRTP 889
Cdd:cd13325      7 GRLLRHDWFTVTDGEG---KAKERYLFLFKSRILITKVRRISEDRSVFILKDIIRLPEVNVKQH-PDDERTFELQPKLPA 82

                           90       100
                   ....*....|....*....|....*....
gi 1924565257  890 SSDNKTVLKASNIETKQEWIKNIREVIQE 918
Cdd:cd13325     83 FGILPIDFKAHKDEIKDYWLNEIEEYAND 111
Spectrin pfam00435
Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in ...
 236-328 8.08e-06

Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in cytoskeletal structure. These include spectrin, alpha-actinin and dystrophin. The sequence repeat used in this family is taken from the structural repeat in reference. The spectrin domain- repeat forms a three helix bundle. The second helix is interrupted by proline in some sequences. The repeats are defined by a characteriztic tryptophan (W) residue at position 17 in helix A and a leucine (L) at 2 residues from the carboxyl end of helix C. Although the domain occurs in multiple repeats along sequences, the domains are actually stable on their own - ie they act, biophysically, like domains rather than repeats that along function when aggregated.


Pssm-ID: 395348 [Multi-domain]  Cd Length: 105  Bit Score: 45.39  E-value: 8.08e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  236 LQLRHLQAEVKQVLGWIRNGESMLnASLVNASSLSEAEQLQREHEQFQLAIEkTHQSALQ-VQQKAEVLLQAGHYDADAI 314
Cdd:pfam00435    1 LLLQQFFRDADDLESWIEEKEALL-SSEDYGKDLESVQALLKKHKALEAELA-AHQDRVEaLNELAEKLIDEGHYASEEI 78

                           90
                   ....*....|....
gi 1924565257  315 RECAEKVALHWQQL 328
Cdd:pfam00435   79 QERLEELNERWEQL 92
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 823-912 1.43e-05

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: 44.46  E-value: 1.43e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  823 PKSLIRKGRERHLFLFEISLVFSKEIKDSsghtKYVYKNKL-LTSELGVTEHVEGD-PCKFALWsgrtpSSDNKT-VLKA 899
Cdd:cd00821      9 GGGGLKSWKKRWFVLFEGVLLYYKSKKDS----SYKPKGSIpLSGILEVEEVSPKErPHCFELV-----TPDGRTyYLQA 79

                           90
                   ....*....|...
gi 1924565257  900 SNIETKQEWIKNI 912
Cdd:cd00821     80 DSEEERQEWLKAL 92
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 831-916 2.39e-05

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 44.09  E-value: 2.39e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  831 RERHLFLFEISLVFSKeikDSSGHTKYVYKNKLLTSELGVTEHVEGD----PCKFALWSGrTPSSDNKTVLKASNIETKQ 906
Cdd:pfam00169   19 KKRYFVLFDGSLLYYK---DDKSGKSKEPKGSISLSGCEVVEVVASDspkrKFCFELRTG-ERTGKRTYLLQAESEEERK 94

                           90
                   ....*....|
gi 1924565257  907 EWIKNIREVI 916
Cdd:pfam00169   95 DWIKAIQSAI 104
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 5-236 6.99e-05

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 45.13  E-value: 6.99e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257    5 FHTHTKELWTWMEDLQKEMLEDVCADSVDAVQELIKQFQQQQT---ATLDATLNVIKEGEDLIQQLRDSAVSNNKTphss 81
Cdd:cd00176      5 FLRDADELEAWLSEKEELLSSTDYGDDLESVEALLKKHEALEAelaAHEERVEALNELGEQLIEEGHPDAEEIQER---- 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257   82 sishiesvLQQLDDAQVQMEELFHERKIKLDifLQLRIFEQYtiEVTAELDAWNEDLLRQMN-DFNTEDLTLAEQRLQRH 160
Cdd:cd00176     81 --------LEELNQRWEELRELAEERRQRLE--EALDLQQFF--RDADDLEQWLEEKEAALAsEDLGKDLESVEELLKKH 148

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1924565257  161 TERKLAMNNmtfeviqqgqdLHQYITEVQASGIELICEKDIDLAAQVQELLEFLHEKQHELELNAEQTHKRLEQCL 236
Cdd:cd00176    149 KELEEELEA-----------HEPRLKSLNELAEELLEEGHPDADEEIEEKLEELNERWEELLELAEERQKKLEEAL 213
EnvC COG4942
Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, ...
 27-288 3.04e-03

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: 40.90  E-value: 3.04e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257   27 VCADSVDAVQELIKQFQQQqtatLDATLNVIKEGEDLIQQLRDSAVSnnktphsssishiesVLQQLDDAQVQMEELfhE 106
Cdd:COG4942     10 LLALAAAAQADAAAEAEAE----LEQLQQEIAELEKELAALKKEEKA---------------LLKQLAALERRIAAL--A 68

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  107 RKIKlDIFLQLRIFEQYTIEVTAELDAWNEDLLRQMNDFntEDLTLAEQRLQRHTERKLAMNNMTFEVIQQGQDLHQYIT 186
Cdd:COG4942     69 RRIR-ALEQELAALEAELAELEKEIAELRAELEAQKEEL--AELLRALYRLGRQPPLALLLSPEDFLDAVRRLQYLKYLA 145

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  187 EVQASGIELICEKDIDLAAQVQELLEFLHEKQhELELNAEQTHKRLEQclqlrhLQAEVKQVLGWIRNGESMLNASLvnA 266
Cdd:COG4942    146 PARREQAEELRADLAELAALRAELEAERAELE-ALLAELEEERAALEA------LKAERQKLLARLEKELAELAAEL--A 216

                          250       260
                   ....*....|....*....|..
gi 1924565257  267 SSLSEAEQLQREHEQFQLAIEK 288
Cdd:COG4942    217 ELQQEAEELEALIARLEAEAAA 238
SPEC smart00150
Spectrin repeats;
472-572 4.20e-03

Spectrin repeats;


Pssm-ID: 197544 [Multi-domain]  Cd Length: 101  Bit Score: 37.69  E-value: 4.20e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257   472 FERSAKQALDWIQETGEFYLSTHTSTGETTEETqeLLKEYGEFRVPAKQTKEKVKLLIQLADSFVEKGHIHATEIRKWVT 551
Cdd:smart00150    3 FLRDADELEAWLEEKEQLLASEDLGKDLESVEA--LLKKHEAFEAELEAHEERVEALNELGEQLIEEGHPDAEEIEERLE 80

                            90       100
                    ....*....|....*....|.
gi 1924565257   552 TVDKHYRDFSLRMGKYRYSLE 572
Cdd:smart00150   81 ELNERWEELKELAEERRQKLE 101
PH_Collybistin_ASEF cd01224
Collybistin/APC-stimulated guanine nucleotide exchange factor pleckstrin homology (PH) domain; ...
 827-919 4.64e-03

Collybistin/APC-stimulated guanine nucleotide exchange factor pleckstrin homology (PH) domain; Collybistin (also called PEM2) is homologous to the Dbl proteins ASEF (also called ARHGEF4/RhoGEF4) and SPATA13 (Spermatogenesis-associated protein 13; also called ASEF2). It activates CDC42 specifically and not any other Rho-family GTPases. Collybistin consists of an SH3 domain, followed by a RhoGEF/DH and PH domain. In Dbl proteins, the DH and PH domains catalyze the exchange of GDP for GTP in Rho GTPases, allowing them to signal to downstream effectors. It induces submembrane clustering of the receptor-associated peripheral membrane protein gephyrin, which is thought to form a scaffold underneath the postsynaptic membrane linking receptors to the cytoskeleton. It also acts as a tumor suppressor that links adenomatous polyposis coli (APC) protein, a negative regulator of the Wnt signaling pathway and promotes the phosphorylation and degradation of beta-catenin, to Cdc42. Autoinhibition of collybistin is accomplished by the binding of its SH3 domain with both the RhoGEF and PH domains to block access of Cdc42 to the GTPase-binding site. Inactivation promotes cancer progression. 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: 269931  Cd Length: 138  Bit Score: 38.39  E-value: 4.64e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  827 IRKGR--ERHLFLFEISLVFSKeiKDSSGHTKYVYKNKLLTSELGV------TEHVEGDPCKFALWSGRTpsSDNKT-VL 897
Cdd:cd01224     38 ISAGRaqERTFFLFDHQLVYCK--KDLLRRKNYIYKGRIDTDNMEIedlpdgKDDESGVTVKNAWKIYNA--SKNKWyVL 113

                           90       100
                   ....*....|....*....|..
gi 1924565257  898 KASNIETKQEWIKNIREviqER 919
Cdd:cd01224    114 CAKSAEEKQRWLEAFAE---ER 132
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 468-588 9.62e-03

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 38.58  E-value: 9.62e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  468 QYVVFERSAKQALDWIQETGEFYLSTHTSTGETTEETqeLLKEYGEFRVPAKQTKEKVKLLIQLADSFVEKGHIHATEIR 547
Cdd:cd00176      1 KLQQFLRDADELEAWLSEKEELLSSTDYGDDLESVEA--LLKKHEALEAELAAHEERVEALNELGEQLIEEGHPDAEEIQ 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1924565257  548 KWVTTVDKHYRDFSLRMGKYRYSLEKALGVNTEDNKDLELD 588
Cdd:cd00176     79 ERLEELNQRWEELRELAEERRQRLEEALDLQQFFRDADDLE 119
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 436-575 9.70e-03

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 38.58  E-value: 9.70e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1924565257  436 QQVKAILSELLQRENRVLHFWTLKKRRLDQCQQYVVFERSAKQALDWIQETGEFYLSthTSTGETTEETQELLKEYGEFR 515
Cdd:cd00176     75 EEIQERLEELNQRWEELRELAEERRQRLEEALDLQQFFRDADDLEQWLEEKEAALAS--EDLGKDLESVEELLKKHKELE 152

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1924565257  516 VPAKQTKEKVKLLIQLADSFVEKGHIHAT-EIRKWVTTVDKHYRDFSLRMGKYRYSLEKAL 575
Cdd:cd00176    153 EELEAHEPRLKSLNELAEELLEEGHPDADeEIEEKLEELNERWEELLELAEERQKKLEEAL 213
 
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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