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 19923327    124 AIYEMSRGEQDLIEDLKLARKAYHDPMLK-LSIMSEEELTHIFGDLDSYIPLHEDLLTRIGEATK-PDGTVEQIGHILVS 201
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKeLKLLSPNELETLFGNIEEIYEFHRDFLDELEERIEeWDDSVERIGDVFLK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923327    202 WLPRLNAYRGYCSNQLAAKALLDQKKQDPRVQDFLQRCLESPFSRKLDLWSFLDIPRSRLVKYPLLLKEILKHTPKEHPD 281
Cdd:smart00325  81 LEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDHED 160

                          170
                   ....*....|....*....
gi 19923327    282 VQLLEDAILIIQGVLSDIN 300
Cdd:smart00325 161 REDLKKALKAIKELANQVN 179

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 19923327    124 AIYEMSRGEQDLIEDLKLARKAYHDPMLK-LSIMSEEELTHIFGDLDSYIPLHEDLLTRIGEATK-PDGTVEQIGHILVS 201
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKeLKLLSPNELETLFGNIEEIYEFHRDFLDELEERIEeWDDSVERIGDVFLK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923327    202 WLPRLNAYRGYCSNQLAAKALLDQKKQDPRVQDFLQRCLESPFSRKLDLWSFLDIPRSRLVKYPLLLKEILKHTPKEHPD 281
Cdd:smart00325  81 LEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDHED 160

                          170
                   ....*....|....*....
gi 19923327    282 VQLLEDAILIIQGVLSDIN 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 19923327   124 AIYEMSRGEQDLIEDLKLARKAYHDPMLKLSIMSEEELTHIFGDLDSYIPLHEDLLtrIGEATKPDGTVEQIGHILVSWL 203
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQLL--LEELLKEWISIQRIGDIFLKFA 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923327   204 PRLNAYRGYCSNQLAAKALLDQKKQ-DPRVQDFLQRCLESPFSRKLDLWSFLDIPRSRLVKYPLLLKEILKHTPKEHPDV 282
Cdd:pfam00621  79 PGFKVYSTYCSNYPKALKLLKKLLKkNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPPDHPDY 158

                         170
                  ....*....|....*...
gi 19923327   283 QLLEDAILIIQGVLSDIN 300
Cdd:pfam00621 159 EDLKKALEAIKEVAKQIN 176

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923327   333 LLCHGELRSKSG------HKLYIFLFQDILVLTRPVTRNERHSyqvyrqpiPVQELVLEDLQDGDVRMggsfrgafSNSE 406
Cdd:pfam00169   1 VVKEGWLLKKGGgkkkswKKRYFVLFDGSLLYYKDDKSGKSKE--------PKGSISLSGCEVVEVVA--------SDSP 64

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 19923327   407 KAKNIFRIRFHDPSPAQSHTLQANDVFHKQQWFNCIRAAIA 447
Cdd:pfam00169  65 KRKFCFELRTGERTGKRTYLLQAESEEERKDWIKAIQSAIR 105

Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain; RhoGEF3/XPLN, a Rho family GEF, preferentially stimulates guanine nucleotide exchange on RhoA and RhoB, but not RhoC, RhoG, Rac1, or Cdc42 in vitro. It also possesses transforming activity. RhoGEF3/XPLN contains a tandem Dbl homology and PH domain, but lacks homology with other known functional domains or motifs. It is expressed in the brain, skeletal muscle, heart, kidney, platelets, and macrophage and neuronal cell lines. 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 19923327 314 KLEYLDEKQRDPRIEASKVLLCHGELRSKSGHKLYIFLFQDILVLTRPVTRNERHSYQVYRQPIPVQELVLEDLQDGDVR 393
Cdd:cd10572   1 RLEYLDEKQRDPLIDSSRLLLCHGELKNNRGTKLHVFLFEEVLVLTRPVTRNEQLCYQVYRQPIPVADLVLEDLPDGEVR 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
gi 19923327 394 MGGSFRGAFSNSEKAKNIFRIRFHDPSPAQSHTLQANDVFHKQQWFNCIRAAI 446
Cdd:cd10572  81 LGGSFRGAFSNNERAKNFFRVSFTDRSLGQSHTLQANDEFDKQQWLNCIRQAV 133

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 19923327 121 RQEAIYEMSRGEQDLIEDLKLARKAYHDPMLKLSI-MSEEELTHIFGDLDSYIPLHEDLLTRIGEATK-PDGTVEQIGHI 198
Cdd:cd00160   1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLpLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEeWDKSGPRIGDV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923327 199 LVSWLPRLNAYRGYCSNQLAAKALLDQKKqdpRVQDFLQRCLESPFS--RKLDLWSFLDIPRSRLVKYPLLLKEILKHTP 276
Cdd:cd00160  81 FLKLAPFFKIYSEYCSNHPDALELLKKLK---KFNKFFQEFLEKAESecGRLKLESLLLKPVQRLTKYPLLLKELLKHTP 157

                       170       180
                ....*....|....*....|....
gi 19923327 277 KEHPDVQLLEDAILIIQGVLSDIN 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 19923327  101 LWSEMLDITMKESLTTREIRRQEAIYEMSRGEQDLIEDLKLARKAYHDPMLKLSIMSE----EELTHIFGDLDSYIPLHE 176
Cdd:COG5422  465 LWTLSVPKEVWESLPKQEIKRQEAIYEVIYTERDFVKDLEYLRDTWIKPLEESNIIPEnarrNFIKHVFANINEIYAVNS 544

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923327  177 DLLTRIGEATKPDGTVEQIGHILVSWLPRLNAYRGYCSNQLAAKALLD-QKKQDPRVQDFLQRCLESPFSRKLDLWSFLD 255
Cdd:COG5422  545 KLLKALTNRQCLSPIVNGIADIFLDYVPKFEPFIKYGASQPYAKYEFErEKSVNPNFARFDHEVERLDESRKLELDGYLT 624

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923327  256 IPRSRLVKYPLLLKEILKHTPKEHPDVQLLEDAILIIQGVLSDINLKKGESE--------CQYYIDKLEYLDEKQRDPRi 327
Cdd:COG5422  625 KPTTRLARYPLLLEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNFESGKAEnrgdlfhlNQQLLFKPEYVNLGLNDEY- 703

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923327  328 easKVLLCHGELRSKSGHK--------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 19923327    333 LLCHGELRSKSGHKLYIFLFQDILVLTRPVTRNERHSYqvyRQPIPVQELVLEDLQDGDvrmggsfrgafsnSEKAKNIF 412
Cdd:smart00233   7 LYKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKKSYKP---KGSIDLSGCTVREAPDPD-------------SSKKPHCF 70

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 19923327    413 RIRFHDPspaQSHTLQANDVFHKQQWFNCIRAAIA 447
Cdd:smart00233  71 EIKTSDR---KTLLLQAESEEEREKWVEALRKAIA 102

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923327 333 LLCHGEL-RSKSGHKLYIFLFQDILVLTRPV-----------TRNERH-SYQVYRQPIPVQELVLEDLQDGdvrmggsfr 399
Cdd:cd13264  16 FLHSGKLyKAKSNKELYGFLFNDFLLLTQPIkplgssgndfvFDNKANiQYKMYKTPIFLNEVLVKLPTDP--------- 86

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 19923327 400 gafsnsEKAKNIFRIRFHDpspaQSHTLQANDVFHKQQWFNCIRAA 445
Cdd:cd13264  87 ------SGDEPIFHISHID----RVYTLRAESINERTAWVQKIKAA 122

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 19923327 333 LLCHGELRSKSGHK----LYIFLFQDILVLTRPVTRNeRHSYQVYRQPIPVQELVLEDLQDGD 391
Cdd:cd13244   3 LLLEGDLRLKEGKGskvdVHCFLFTDMLLICKPVKRK-KDRLKVIRPPYLVDKLVVQELKDPG 64

Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; Phafin2 is differentially expressed in the liver cancer cell and regulates the structure and function of the endosomes through Rab5-dependent processes. Phafin2 modulates the cell's response to extracellular stimulation by modulating the receptor density on the cell surface. Phafin2 contains a PH domain and a FYVE 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 19923327 348 YIFLFQDILVLTRPVTRNERHSYQvyrQPIPVQELVLEDLQDgdvrmggsfrgafsnSEKAKNIFRIRfhdpSPAQSHTL 427
Cdd:cd01218  48 QFFLFNDILVYGSIVINKKKYNKQ---RIIPLEDVKIEDLED---------------TGELKNGWQII----SPKKSFVV 105

                        90
                ....*....|....*
gi 19923327 428 QANDVFHKQQWFNCI 442
Cdd:cd01218 106 YAATATEKSEWMDHI 120

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 19923327 348 YIFLFQDILVLTR----------------------PVTRNERHSYQVYRQPIPVQELVLEDLQDGDVrmggsfrgafsNS 405
Cdd:cd13245  20 YLFLFDDMLLITKmkknlkkkkssdsensmpslelTPLIKEGGSYTVYKQPIPLDRLCLHDVDPNEA-----------TA 88

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 19923327 406 EKAKNIFRI----RFHDPSPAqsHTLQANDVFHKQQW 438
Cdd:cd13245  89 NGLKHAFVLvhlnRYQQVIGV--YTLQASSENTKQTW 123