Neuroepithelial cell transforming 1 Pleckstrin homology (PH) domain; Net1 (also called ArhGEF8) is part of the family of Rho guanine nucleotide exchange factors. Members of this family activate Rho proteins by catalyzing the exchange of GDP for GTP. The protein encoded by this gene interacts with RhoA within the cell nucleus and may play a role in repairing DNA damage after ionizing radiation. Net1 binds to caspase activation and recruitment domain (CARD)- and membrane-associated guanylate kinase-like domain-containing (CARMA) proteins and regulates nuclear factor kB activation. Net1 contains a RhoGEF domain N-terminal to 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114145477 368 KLEYLDEKQKDPRIEASKVLLCHGELKNKSGHKLYIFLFQDILVLTRPVTRNERHLYQVYRQPIPVQELVLEDLQDGDVR 447
Cdd:cd13224    1 KLEYLDDKQRDPRIENSKALLCHGELRNKSGHKLYVFLFQDILVLTRPVTRNERQSFQVYRQPIPVQELVLEDLQDGDVR 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 114145477 448 MGGSFRGAFGNSDKAKNIFRVRFQDPSPGHSHTLQANDVFHKQQWFNCIRAAIAP 502
Cdd:cd13224   81 MGGSFRGAFSNSEKAKNIFRVRFLDPSPGQSHTLQANDVFHKQQWLNCIRTAISP 135

Neuroepithelial cell transforming 1 Pleckstrin homology (PH) domain; Net1 (also called ArhGEF8) is part of the family of Rho guanine nucleotide exchange factors. Members of this family activate Rho proteins by catalyzing the exchange of GDP for GTP. The protein encoded by this gene interacts with RhoA within the cell nucleus and may play a role in repairing DNA damage after ionizing radiation. Net1 binds to caspase activation and recruitment domain (CARD)- and membrane-associated guanylate kinase-like domain-containing (CARMA) proteins and regulates nuclear factor kB activation. Net1 contains a RhoGEF domain N-terminal to 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114145477 368 KLEYLDEKQKDPRIEASKVLLCHGELKNKSGHKLYIFLFQDILVLTRPVTRNERHLYQVYRQPIPVQELVLEDLQDGDVR 447
Cdd:cd13224    1 KLEYLDDKQRDPRIENSKALLCHGELRNKSGHKLYVFLFQDILVLTRPVTRNERQSFQVYRQPIPVQELVLEDLQDGDVR 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 114145477 448 MGGSFRGAFGNSDKAKNIFRVRFQDPSPGHSHTLQANDVFHKQQWFNCIRAAIAP 502
Cdd:cd13224   81 MGGSFRGAFSNSEKAKNIFRVRFLDPSPGQSHTLQANDVFHKQQWLNCIRTAISP 135

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114145477 175 RQEAIYELSRGEQDLIEDLKLARKAYHDPMLKLSI-MSEEELTHIFGDLDAYIPLHEDLLARIGEATK-PDGTVEQIGHI 252
Cdd:cd00160    1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLpLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEeWDKSGPRIGDV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114145477 253 LVNWLPGLNAYRGYCSNQLAAKALLDQKKqdpRVQDFLQRCLESPFS--RKLDLWSFLDIPRSRLVKYPLLLKEILRHTP 330
Cdd:cd00160   81 FLKLAPFFKIYSEYCSNHPDALELLKKLK---KFNKFFQEFLEKAESecGRLKLESLLLKPVQRLTKYPLLLKELLKHTP 157

                        170       180
                 ....*....|....*....|....
gi 114145477 331 KDHRDVQLLEEAILIIQGVLSDIN 354
Cdd:cd00160  158 DGHEDREDLKKALEAIKEVASQVN 181

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114145477  155 LWSEMLDINMKESLTTREIKRQEAIYELSRGEQDLIEDLKLARKAYHDPMLKLSIMSE----EELTHIFGDLDAYIPLHE 230
Cdd:COG5422   465 LWTLSVPKEVWESLPKQEIKRQEAIYEVIYTERDFVKDLEYLRDTWIKPLEESNIIPEnarrNFIKHVFANINEIYAVNS 544

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114145477  231 DLLARIGEATKPDGTVEQIGHILVNWLPGLNAYRGYCSNQLAAKALLD-QKKQDPRVQDFLQRCLESPFSRKLDLWSFLD 309
Cdd:COG5422   545 KLLKALTNRQCLSPIVNGIADIFLDYVPKFEPFIKYGASQPYAKYEFErEKSVNPNFARFDHEVERLDESRKLELDGYLT 624

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114145477  310 IPRSRLVKYPLLLKEILRHTPKDHRDVQLLEEAILIIQGVLSDINLKKGESE--------CQYYINKLEYLDEKQKDPRi 381
Cdd:COG5422   625 KPTTRLARYPLLLEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNFESGKAEnrgdlfhlNQQLLFKPEYVNLGLNDEY- 703

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114145477  382 easKVLLCHGELKNKSGHK--------LYIFLFQDILVLTRPVTRNERHLYQVYRQPIPVQELVLEDLQD 443
Cdd:COG5422   704 ---RKIIFKGVLKRKAKSKtdgslrgdIQFFLLDNMLLFCKAKAVNKWRQHKVFQRPIPLELLFISPDED 770

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114145477   387 LLCHGELKNKSGHKLYIFLFQDILVLTRPVTRNERHlyqVYRQPIPVQELVLEDLQDGDvrmggsfrgafgnSDKAKNIF 466
Cdd:smart00233   7 LYKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKKSY---KPKGSIDLSGCTVREAPDPD-------------SSKKPHCF 70

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 114145477   467 RVRFQDpspGHSHTLQANDVFHKQQWFNCIRAAIA 501
Cdd:smart00233  71 EIKTSD---RKTLLLQAESEEEREKWVEALRKAIA 102

Neuroepithelial cell transforming 1 Pleckstrin homology (PH) domain; Net1 (also called ArhGEF8) is part of the family of Rho guanine nucleotide exchange factors. Members of this family activate Rho proteins by catalyzing the exchange of GDP for GTP. The protein encoded by this gene interacts with RhoA within the cell nucleus and may play a role in repairing DNA damage after ionizing radiation. Net1 binds to caspase activation and recruitment domain (CARD)- and membrane-associated guanylate kinase-like domain-containing (CARMA) proteins and regulates nuclear factor kB activation. Net1 contains a RhoGEF domain N-terminal to 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114145477 368 KLEYLDEKQKDPRIEASKVLLCHGELKNKSGHKLYIFLFQDILVLTRPVTRNERHLYQVYRQPIPVQELVLEDLQDGDVR 447
Cdd:cd13224    1 KLEYLDDKQRDPRIENSKALLCHGELRNKSGHKLYVFLFQDILVLTRPVTRNERQSFQVYRQPIPVQELVLEDLQDGDVR 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 114145477 448 MGGSFRGAFGNSDKAKNIFRVRFQDPSPGHSHTLQANDVFHKQQWFNCIRAAIAP 502
Cdd:cd13224   81 MGGSFRGAFSNSEKAKNIFRVRFLDPSPGQSHTLQANDVFHKQQWLNCIRTAISP 135

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114145477   178 AIYELSRGEQDLIEDLKLARKAYHDPMLK-LSIMSEEELTHIFGDLDAYIPLHEDLLARIGEATK-PDGTVEQIGHILVN 255
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKeLKLLSPNELETLFGNIEEIYEFHRDFLDELEERIEeWDDSVERIGDVFLK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114145477   256 WLPGLNAYRGYCSNQLAAKALLDQKKQDPRVQDFLQRCLESPFSRKLDLWSFLDIPRSRLVKYPLLLKEILRHTPKDHRD 335
Cdd:smart00325  81 LEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDHED 160

                          170
                   ....*....|....*....
gi 114145477   336 VQLLEEAILIIQGVLSDIN 354
Cdd:smart00325 161 REDLKKALKAIKELANQVN 179

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114145477  178 AIYELSRGEQDLIEDLKLARKAYHDPMLKLSIMSEEELTHIFGDLDAYIPLHEDLLARigEATKPDGTVEQIGHILVNWL 257
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQLLLE--ELLKEWISIQRIGDIFLKFA 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114145477  258 PGLNAYRGYCSNQLAAKALLDQKKQ-DPRVQDFLQRCLESPFSRKLDLWSFLDIPRSRLVKYPLLLKEILRHTPKDHRDV 336
Cdd:pfam00621  79 PGFKVYSTYCSNYPKALKLLKKLLKkNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPPDHPDY 158

                         170
                  ....*....|....*...
gi 114145477  337 QLLEEAILIIQGVLSDIN 354
Cdd:pfam00621 159 EDLKKALEAIKEVAKQIN 176

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114145477  387 LLCHGELKNKSG------HKLYIFLFQDILVLTRPVTRNERHlyqvyrqpIPVQELVLEDLQDGDVRMGgsfrgafgNSD 460
Cdd:pfam00169   1 VVKEGWLLKKGGgkkkswKKRYFVLFDGSLLYYKDDKSGKSK--------EPKGSISLSGCEVVEVVAS--------DSP 64

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 114145477  461 KAKNIFRVRFQDPSPGHSHTLQANDVFHKQQWFNCIRAAIA 501
Cdd:pfam00169  65 KRKFCFELRTGERTGKRTYLLQAESEEERKDWIKAIQSAIR 105

Pleckstrin homology domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 114145477  387 LLCHGEL-KNKSGHKLYIFLFQDILVLTRPV------------TRNERHLYQVYRQPIPVQELVLEDLQDGD 445
Cdd:pfam16652  24 LLHSGKLyKVKSNKELVGFLFNDFLLLTQPVkplssagtdklfSSKSNIQYKMYKTPIFLNEVMVKLPTDPS 95

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114145477 387 LLCHGELKNKSGHKLYIFLFQDILVLTRPVTRNErhlyQVYRQPIPVQELVLEDLqdgdvrmggsfrgafGNSDKAKNIF 466
Cdd:cd00821    5 LLKRGGGGLKSWKKRWFVLFEGVLLYYKSKKDSS----YKPKGSIPLSGILEVEE---------------VSPKERPHCF 65

                         90       100       110
                 ....*....|....*....|....*....|
gi 114145477 467 RVRFqdpSPGHSHTLQANDVFHKQQWFNCI 496
Cdd:cd00821   66 ELVT---PDGRTYYLQADSEEERQEWLKAL 92

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 114145477  391 GELKNKSGHK-----LYIFLFQDILVLTRPVTRNERHLYQVYRQPIPVQELVL 438
Cdd:pfam15405   5 GTLKKKPTSSsdsadIQVYLFDHALLLVKIKTVNKREQYKVYRRPIPLELLFI 57

Pleckstrin homology domain-containing family G member 7 pleckstrin homology (PH) domain; PLEKHG7 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG7 is proposed to functions as a guanine nucleotide exchange factor (GEF) and is involved in the regulation of Rho protein signal transduction. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114145477 402 YIFLFQDILVLTR----------------------PVTRNERHLYQVYRQPIPVQELVLEDLQDGDVrmggsfrGAFGns 459
Cdd:cd13245   20 YLFLFDDMLLITKmkknlkkkkssdsensmpslelTPLIKEGGSYTVYKQPIPLDRLCLHDVDPNEA-------TANG-- 90

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 114145477 460 dkAKNIFRV----RFQDPSpgHSHTLQANDVFHKQQW 492
Cdd:cd13245   91 --LKHAFVLvhlnRYQQVI--GVYTLQASSENTKQTW 123