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 84781678 314 KLEYLDEKQKDPRIEASKVLLCHGELKNKSGHKLYIFLFQDILVLTRPVTRNERHSYQVYRQPIPVQELVLEDLQDGDVR 393
Cdd:cd13224   1 KLEYLDDKQRDPRIENSKALLCHGELRNKSGHKLYVFLFQDILVLTRPVTRNERQSFQVYRQPIPVQELVLEDLQDGDVR 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 84781678 394 MGGSFRGAFGNSDKAKNIFRVRFQDPSPGQSHTLQANDVFHKQQWFNCIRSAIAP 448
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 84781678 314 KLEYLDEKQKDPRIEASKVLLCHGELKNKSGHKLYIFLFQDILVLTRPVTRNERHSYQVYRQPIPVQELVLEDLQDGDVR 393
Cdd:cd13224   1 KLEYLDDKQRDPRIENSKALLCHGELRNKSGHKLYVFLFQDILVLTRPVTRNERQSFQVYRQPIPVQELVLEDLQDGDVR 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 84781678 394 MGGSFRGAFGNSDKAKNIFRVRFQDPSPGQSHTLQANDVFHKQQWFNCIRSAIAP 448
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 84781678 121 RQEAIYELSRGEQDLIEDLKLARKAYHDPMLKLSI-MSEEELTHIFGDLDAYIPLHEDLLARIGEATK-PDGTVEQIGHI 198
Cdd:cd00160   1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLpLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEeWDKSGPRIGDV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 84781678 199 LVNWLPGLNAYRGYCSNQLAAKALLDQKKqdpRVQDFLQRCLESPFS--RKLDLWSFLDIPRSRLVKYPLLLKEILRHTP 276
Cdd:cd00160  81 FLKLAPFFKIYSEYCSNHPDALELLKKLK---KFNKFFQEFLEKAESecGRLKLESLLLKPVQRLTKYPLLLKELLKHTP 157

                       170       180
                ....*....|....*....|....
gi 84781678 277 KDHLDVQLLEKAILIIQEVLSDIN 300
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 84781678  101 LWSEMLDISMKESLTTREIKRQEAIYELSRGEQDLIEDLKLARKAYHDPMLKLSIMSE----EELTHIFGDLDAYIPLHE 176
Cdd:COG5422  465 LWTLSVPKEVWESLPKQEIKRQEAIYEVIYTERDFVKDLEYLRDTWIKPLEESNIIPEnarrNFIKHVFANINEIYAVNS 544

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 84781678  177 DLLARIGEATKPDGTVEQIGHILVNWLPGLNAYRGYCSNQLAAKALLD-QKKQDPRVQDFLQRCLESPFSRKLDLWSFLD 255
Cdd:COG5422  545 KLLKALTNRQCLSPIVNGIADIFLDYVPKFEPFIKYGASQPYAKYEFErEKSVNPNFARFDHEVERLDESRKLELDGYLT 624

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 84781678  256 IPRSRLVKYPLLLKEILRHTPKDHLDVQLLEKAILIIQEVLSDINLKKGESE--------CQYYIDKLEYLDEKQKDPRi 327
Cdd:COG5422  625 KPTTRLARYPLLLEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNFESGKAEnrgdlfhlNQQLLFKPEYVNLGLNDEY- 703

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 84781678  328 easKVLLCHGELKNKSGHK--------LYIFLFQDILVLTRPVTRNERHSYQVYRQPIPVQELVLEDLQD 389
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 84781678    333 LLCHGELKNKSGHKLYIFLFQDILVLTRPVTRNERHSYqvyRQPIPVQELVLEDLQDGDvrmggsfrgafgnSDKAKNIF 412
Cdd:smart00233   7 LYKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKKSYKP---KGSIDLSGCTVREAPDPD-------------SSKKPHCF 70

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 84781678    413 RVRFQDpspGQSHTLQANDVFHKQQWFNCIRSAIA 447
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 84781678 314 KLEYLDEKQKDPRIEASKVLLCHGELKNKSGHKLYIFLFQDILVLTRPVTRNERHSYQVYRQPIPVQELVLEDLQDGDVR 393
Cdd:cd13224   1 KLEYLDDKQRDPRIENSKALLCHGELRNKSGHKLYVFLFQDILVLTRPVTRNERQSFQVYRQPIPVQELVLEDLQDGDVR 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 84781678 394 MGGSFRGAFGNSDKAKNIFRVRFQDPSPGQSHTLQANDVFHKQQWFNCIRSAIAP 448
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 84781678    124 AIYELSRGEQDLIEDLKLARKAYHDPMLK-LSIMSEEELTHIFGDLDAYIPLHEDLLARIGEATK-PDGTVEQIGHILVN 201
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKeLKLLSPNELETLFGNIEEIYEFHRDFLDELEERIEeWDDSVERIGDVFLK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 84781678    202 WLPGLNAYRGYCSNQLAAKALLDQKKQDPRVQDFLQRCLESPFSRKLDLWSFLDIPRSRLVKYPLLLKEILRHTPKDHLD 281
Cdd:smart00325  81 LEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDHED 160

                          170
                   ....*....|....*....
gi 84781678    282 VQLLEKAILIIQEVLSDIN 300
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 84781678   124 AIYELSRGEQDLIEDLKLARKAYHDPMLKLSIMSEEELTHIFGDLDAYIPLHEDLLARigEATKPDGTVEQIGHILVNWL 203
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQLLLE--ELLKEWISIQRIGDIFLKFA 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 84781678   204 PGLNAYRGYCSNQLAAKALLDQKKQ-DPRVQDFLQRCLESPFSRKLDLWSFLDIPRSRLVKYPLLLKEILRHTPKDHLDV 282
Cdd:pfam00621  79 PGFKVYSTYCSNYPKALKLLKKLLKkNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPPDHPDY 158

                         170
                  ....*....|....*...
gi 84781678   283 QLLEKAILIIQEVLSDIN 300
Cdd:pfam00621 159 EDLKKALEAIKEVAKQIN 176

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 84781678   333 LLCHGELKNKSG------HKLYIFLFQDILVLTRPVTRNERHSyqvyrqpiPVQELVLEDLQDGDVRMGgsfrgafgNSD 406
Cdd:pfam00169   1 VVKEGWLLKKGGgkkkswKKRYFVLFDGSLLYYKDDKSGKSKE--------PKGSISLSGCEVVEVVAS--------DSP 64

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 84781678   407 KAKNIFRVRFQDPSPGQSHTLQANDVFHKQQWFNCIRSAIA 447
Cdd:pfam00169  65 KRKFCFELRTGERTGKRTYLLQAESEEERKDWIKAIQSAIR 105

Pleckstrin homology domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 84781678   333 LLCHGEL-KNKSGHKLYIFLFQDILVLTRPV------------TRNERHSYQVYRQPIPVQELVLEDLQDGD 391
Cdd:pfam16652  24 LLHSGKLyKVKSNKELVGFLFNDFLLLTQPVkplssagtdklfSSKSNIQYKMYKTPIFLNEVMVKLPTDPS 95

Intersectin Pleckstrin homology (PH) domain; ITSNs, an adaptor protein family, play a role in endo- and exocytosis, actin cytoskeleton rearrangement and signal transduction. There are two human ITSN genes: ITSN1 and ITSN2. They share significant sequence identity and a similar domain structure having both short and long isoforms produced by alternative splicing. The short isoform (ITSN-S) consists of two Eps15 homology domains (EH1 and EH2), a coiled-coil region (CCR) and five Src homology 3 domains (SH3A-E). The EH domains bind to Asn-Pro-Phe motifs and are implicated in endocytosis and vesicle transport. The SH3 domains bind to proline-rich sequences and are commonly found in proteins implicated in cell signalling pathways, cytoskeletal organization and membrane traffic. The long isoform (ITSN-L) contains three additional C-terminal domains, a Dbl homology domain (DH), a Pleckstrin homology domain (PH) and a C2 domain. The tandem DH-PH domains are present in all Dbl family of GEFs. ITSN acts specifically on Cdc42 through its DH domain with no portion of the PH domain making contact with Cdc42. This is in contrast to Dbs which requires the PH domain for full catalytic activity. The ITSN PH domain binds phosphoinositides. C2 domains are usually involved in Ca2+-dependent and Ca2+-independent phospholipid binding. There are more than 30 proteins that interact with ITSNs. ITSN-S is present in mammals, frogs, flies and nematodes, while ITSN-L is present only in vertebrates. 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 84781678 333 LLCHGEL-KNKSGHKLYIFLFQDILVLTRPV-----------TRNERH-SYQVYRQPIPVQELVLEDLQDG 390
Cdd:cd13264  16 FLHSGKLyKAKSNKELYGFLFNDFLLLTQPIkplgssgndfvFDNKANiQYKMYKTPIFLNEVLVKLPTDP 86

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 84781678 324 DPRIEASKVLLCHGEL--------KNKSGHKLYIFLFQDILVLTRPVTRNERHS---YqVYRQPIPVQELVLEDLQDGDv 392
Cdd:cd13241   8 DGKITAQGKLLLQGTLlvsepsagLLQKGKERRVFLFEQIIIFSEILGKKTQFSnpgY-IYKNHIKVNKMSLEENVDGD- 85

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 84781678 393 rmggSFRgafgnsdkakniFRVRFQDP-SPGQSHTLQANDVFHKQQWFNCIR 443
Cdd:cd13241  86 ----PLR------------FALKSRDPnNPSETFILQAASPEVRQEWVDTIN 121

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 84781678 348 YIFLFQDILVLTR----------------------PVTRNERHSYQVYRQPIPVQELVLEDLQDGDVrmggsfrGAFGns 405
Cdd:cd13245  20 YLFLFDDMLLITKmkknlkkkkssdsensmpslelTPLIKEGGSYTVYKQPIPLDRLCLHDVDPNEA-------TANG-- 90

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 84781678 406 dkAKNIFRV----RFQdpspgQ---SHTLQANDVFHKQQW 438
Cdd:cd13245  91 --LKHAFVLvhlnRYQ-----QvigVYTLQASSENTKQTW 123