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 966960842 368 KLEYLDEKQRDPRIEASKVLLCHGELRSKSGHKLYIFLFQDILVLTRPVTRNERHSYQVYRQPIPVQELVLEDLQDGDVR 447
Cdd:cd13224    1 KLEYLDDKQRDPRIENSKALLCHGELRNKSGHKLYVFLFQDILVLTRPVTRNERQSFQVYRQPIPVQELVLEDLQDGDVR 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 966960842 448 MGGSFRGAFSNSEKAKNIFRIRFHDPSPGQSHTLQANDVFHKQQWFNCIRAAIAP 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 966960842 368 KLEYLDEKQRDPRIEASKVLLCHGELRSKSGHKLYIFLFQDILVLTRPVTRNERHSYQVYRQPIPVQELVLEDLQDGDVR 447
Cdd:cd13224    1 KLEYLDDKQRDPRIENSKALLCHGELRNKSGHKLYVFLFQDILVLTRPVTRNERQSFQVYRQPIPVQELVLEDLQDGDVR 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 966960842 448 MGGSFRGAFSNSEKAKNIFRIRFHDPSPGQSHTLQANDVFHKQQWFNCIRAAIAP 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 966960842 175 RQEAIYEMSRGEQDLIEDLKLARKAYHDPMLKLSI-MSEEELTHIFGDLDSYIPLHEDLLTRIGEATK-PDGTVEQIGHI 252
Cdd:cd00160    1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLpLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEeWDKSGPRIGDV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966960842 253 LVNWLPRLNAYRGYCSNQLAAKALLDQKKqdpRVQDFLQRCLESPFS--RKLDLWSFLDIPRSRLVKYPLLLKEILKHTP 330
Cdd:cd00160   81 FLKLAPFFKIYSEYCSNHPDALELLKKLK---KFNKFFQEFLEKAESecGRLKLESLLLKPVQRLTKYPLLLKELLKHTP 157

                        170       180
                 ....*....|....*....|....
gi 966960842 331 KEHPDVQLLEDAISIIQGVLSDIN 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 966960842  155 LWSEMLDITMKESLTTREIKRQEAIYEMSRGEQDLIEDLKLARKAYHDPMLKLSIMSE----EELTHIFGDLDSYIPLHE 230
Cdd:COG5422   465 LWTLSVPKEVWESLPKQEIKRQEAIYEVIYTERDFVKDLEYLRDTWIKPLEESNIIPEnarrNFIKHVFANINEIYAVNS 544

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966960842  231 DLLTRIGEATKPDGTVEQIGHILVNWLPRLNAYRGYCSNQLAAKALLD-QKKQDPRVQDFLQRCLESPFSRKLDLWSFLD 309
Cdd:COG5422   545 KLLKALTNRQCLSPIVNGIADIFLDYVPKFEPFIKYGASQPYAKYEFErEKSVNPNFARFDHEVERLDESRKLELDGYLT 624

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966960842  310 IPRSRLVKYPLLLKEILKHTPKEHPDVQLLEDAISIIQGVLSDINLKKGESE--------CQYYIDKLEYLDEKQRDPRi 381
Cdd:COG5422   625 KPTTRLARYPLLLEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNFESGKAEnrgdlfhlNQQLLFKPEYVNLGLNDEY- 703

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966960842  382 easKVLLCHGELRSKSGHK--------LYIFLFQDILVLTRPVTRNERHSYQVYRQPIPVQELVLEDLQD 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 966960842   387 LLCHGELRSKSGHKLYIFLFQDILVLTRPVTRNERHSYqvyRQPIPVQELVLEDLQDGDvrmggsfrgafsnSEKAKNIF 466
Cdd:smart00233   7 LYKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKKSYKP---KGSIDLSGCTVREAPDPD-------------SSKKPHCF 70

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 966960842   467 RIRFHDpspGQSHTLQANDVFHKQQWFNCIRAAIA 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 966960842 368 KLEYLDEKQRDPRIEASKVLLCHGELRSKSGHKLYIFLFQDILVLTRPVTRNERHSYQVYRQPIPVQELVLEDLQDGDVR 447
Cdd:cd13224    1 KLEYLDDKQRDPRIENSKALLCHGELRNKSGHKLYVFLFQDILVLTRPVTRNERQSFQVYRQPIPVQELVLEDLQDGDVR 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 966960842 448 MGGSFRGAFSNSEKAKNIFRIRFHDPSPGQSHTLQANDVFHKQQWFNCIRAAIAP 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 966960842   178 AIYEMSRGEQDLIEDLKLARKAYHDPMLK-LSIMSEEELTHIFGDLDSYIPLHEDLLTRIGEATK-PDGTVEQIGHILVN 255
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKeLKLLSPNELETLFGNIEEIYEFHRDFLDELEERIEeWDDSVERIGDVFLK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966960842   256 WLPRLNAYRGYCSNQLAAKALLDQKKQDPRVQDFLQRCLESPFSRKLDLWSFLDIPRSRLVKYPLLLKEILKHTPKEHPD 335
Cdd:smart00325  81 LEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDHED 160

                          170
                   ....*....|....*....
gi 966960842   336 VQLLEDAISIIQGVLSDIN 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 966960842  178 AIYEMSRGEQDLIEDLKLARKAYHDPMLKLSIMSEEELTHIFGDLDSYIPLHEDLLtrIGEATKPDGTVEQIGHILVNWL 257
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQLL--LEELLKEWISIQRIGDIFLKFA 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966960842  258 PRLNAYRGYCSNQLAAKALLDQKKQ-DPRVQDFLQRCLESPFSRKLDLWSFLDIPRSRLVKYPLLLKEILKHTPKEHPDV 336
Cdd:pfam00621  79 PGFKVYSTYCSNYPKALKLLKKLLKkNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPPDHPDY 158

                         170
                  ....*....|....*...
gi 966960842  337 QLLEDAISIIQGVLSDIN 354
Cdd:pfam00621 159 EDLKKALEAIKEVAKQIN 176

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966960842  387 LLCHGELRSKSG------HKLYIFLFQDILVLTRPVTRNERHSyqvyrqpiPVQELVLEDLQDGDVRMggsfrgafSNSE 460
Cdd:pfam00169   1 VVKEGWLLKKGGgkkkswKKRYFVLFDGSLLYYKDDKSGKSKE--------PKGSISLSGCEVVEVVA--------SDSP 64

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 966960842  461 KAKNIFRIRFHDPSPGQSHTLQANDVFHKQQWFNCIRAAIA 501
Cdd:pfam00169  65 KRKFCFELRTGERTGKRTYLLQAESEEERKDWIKAIQSAIR 105

Pleckstrin homology domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 966960842  387 LLCHGEL-RSKSGHKLYIFLFQDILVLTRPV------------TRNERHSYQVYRQPIPVQELVLEDLQDGD 445
Cdd:pfam16652  24 LLHSGKLyKVKSNKELVGFLFNDFLLLTQPVkplssagtdklfSSKSNIQYKMYKTPIFLNEVMVKLPTDPS 95

Pleckstrin homology domain-containing family G member 5 and 6 pleckstrin homology (PH) domain; PLEKHG5 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG5 activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in PLEKHG5 are associated with autosomal recessive distal spinal muscular atrophy. PLEKHG6 (also called MyoGEF) has no known function to date. 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 966960842 387 LLCHGELRSKSGHK----LYIFLFQDILVLTRPVTRNeRHSYQVYRQPIPVQELVLEDLQDGD 445
Cdd:cd13244    3 LLLEGDLRLKEGKGskvdVHCFLFTDMLLICKPVKRK-KDRLKVIRPPYLVDKLVVQELKDPG 64

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966960842 378 DPRIEASKVLLCHGEL--------RSKSGHKLYIFLFQDILVLTRPVTRNERHS---YqVYRQPIPVQELVLEDLQDGDv 446
Cdd:cd13241    8 DGKITAQGKLLLQGTLlvsepsagLLQKGKERRVFLFEQIIIFSEILGKKTQFSnpgY-IYKNHIKVNKMSLEENVDGD- 85

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 966960842 447 rmggSFRgafsnsekakniFRIRFHDP-SPGQSHTLQANDVFHKQQWFNCIRA 498
Cdd:cd13241   86 ----PLR------------FALKSRDPnNPSETFILQAASPEVRQEWVDTINQ 122

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966960842  395 SKSGHKLYIFLFQDILVLTRPVTRNERHSYQVYRQPIPVQELVLEDLQDGDVRMGGSFRGAFSNSEKAKN 464
Cdd:pfam15405  14 SSDSADIQVYLFDHALLLVKIKTVNKREQYKVYRRPIPLELLFISEMEDVPPRGGTVKRPSSSLIPKKPT 83