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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299455 407 RQLLLEGPVRVKEGREGKLDVYLFLFSDVLLVTKP-QRKADKAKVIRPPLMLEKLVCQPLRDPNSFLLIHLTEFQCVSSA 485
Cdd:cd13244     1 RRLLLEGDLRLKEGKGSKVDVHCFLFTDMLLICKPvKRKKDRLKVIRPPYLVDKLVVQELKDPGGFLLVYLNEFHTAVAA 80

                          90       100
                  ....*....|....*....|
gi 1860299455 486 LLVHCPSPTDRAQWLEKTQQ 505
Cdd:cd13244    81 YTFQTSSQEDTRRWLDAIRK 100

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299455 407 RQLLLEGPVRVKEGREGKLDVYLFLFSDVLLVTKP-QRKADKAKVIRPPLMLEKLVCQPLRDPNSFLLIHLTEFQCVSSA 485
Cdd:cd13244     1 RRLLLEGDLRLKEGKGSKVDVHCFLFTDMLLICKPvKRKKDRLKVIRPPYLVDKLVVQELKDPGGFLLVYLNEFHTAVAA 80

                          90       100
                  ....*....|....*....|
gi 1860299455 486 LLVHCPSPTDRAQWLEKTQQ 505
Cdd:cd13244    81 YTFQTSSQEDTRRWLDAIRK 100

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 1860299455  164 ALWELLTTELIYVRKLKIMTDLLAAGLLnlQRVGLLMEVSAETLFGNVPSLIRTHRSFWDEvlgptLEETRA-SGQPLDP 242
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLK--KELKLLSPNELETLFGNIEEIYEFHRDFLDE-----LEERIEeWDDSVER 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299455  243 IGlqSGFLTFGQRFHPYVQYCLRVKQTMAYaREQQETNPLFHAFVQWCEKHKRSGRQMLCDLLIKPHQRITKYPLLLHAV 322
Cdd:smart00325  74 IG--DVFLKLEEFFKIYSEYCSNHPDALEL-LKKLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKEL 150

                          170       180
                   ....*....|....*....|....*....
gi 1860299455  323 LKRSPEA-RAQEALNAMIEAVESFLRHIN 350
Cdd:smart00325 151 LKHTPEDhEDREDLKKALKAIKELANQVN 179

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299455  120 RLPPEDRRHWEIG---EGGDSGLTIE-----KSWRELVPgHKMSQELCHQ----QEALWELLTTELIYVRKLKIMTDLLa 187
Cdd:COG5422    433 RLEQQARLHLKLMgglKRNSSLALDKfdeekNLWTLSVP-KEVWESLPKQeikrQEAIYEVIYTERDFVKDLEYLRDTW- 510

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299455  188 agllnlqrVGLLMEVSAetlfgnVPS-----LIRTHRSFWDEVLGPT--LEETRASGQPLDPI--GLQSGFLTFGQRFHP 258
Cdd:COG5422    511 --------IKPLEESNI------IPEnarrnFIKHVFANINEIYAVNskLLKALTNRQCLSPIvnGIADIFLDYVPKFEP 576

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299455  259 YVQYclrVKQTMAYARE---QQETNPLFHAFVQWCEKHKRSGRQMLCDLLIKPHQRITKYPLLLHAVLKRS-PEARAQEA 334
Cdd:COG5422    577 FIKY---GASQPYAKYEferEKSVNPNFARFDHEVERLDESRKLELDGYLTKPTTRLARYPLLLEEVLKFTdPDNPDTED 653

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299455  335 LNAMIEAVESFLRHINgqvrqgeeQESLAAAAQrigpYEVLEPPSDEVEKNLRPFSTLdltspmlgvaSEHTRQLLLEGP 414
Cdd:COG5422    654 IPKVIDMLREFLSRLN--------FESGKAENR----GDLFHLNQQLLFKPEYVNLGL----------NDEYRKIIFKGV 711

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299455  415 VRVKEGR----EGKLDVYLFLFSDVLLVTKP--QRKADKAKVIRPPLMLEKLVCQP----------LRDPNSFLLI---- 474
Cdd:COG5422    712 LKRKAKSktdgSLRGDIQFFLLDNMLLFCKAkaVNKWRQHKVFQRPIPLELLFISPdedspdraeyLKPAPSADVLdpay 791

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....*...
gi 1860299455  475 --------HLTEFQCVSSALLV--HCPSPTDRAQWLEKTQQAQAALQK 512
Cdd:COG5422    792 ntkppknaYGFELYGNGQRYQItlYAETHAGRDTWLEHIKNQQDILRT 839

PH domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299455 384 KNLRPFSTLDLTspmlgvasehTRQLLLEGPVRVKEGREGKLDVYLFLFSD--VLLVTKPQRKA----------DKAKVI 451
Cdd:pfam17838   2 PLGEEFKKLDLT----------TRKLIHEGPLTWRNSKGKLVEVHALLLEDilVLLQEKDQKLVlaclstgsenVDQKTQ 71

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1860299455 452 RPPLMLEKL-VCQPLRDPNSFLLIHLTEFQcvSSALLVHCPSPTDRAQWLEKTQQA 506
Cdd:pfam17838  72 SPIISLKKLiVREVATDKKAFFLISTSPSD--PQMYELHASTKSERNTWTKLIQDA 125

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299455 407 RQLLLEGPVRVKEGREGKLDVYLFLFSDVLLVTKP-QRKADKAKVIRPPLMLEKLVCQPLRDPNSFLLIHLTEFQCVSSA 485
Cdd:cd13244     1 RRLLLEGDLRLKEGKGSKVDVHCFLFTDMLLICKPvKRKKDRLKVIRPPYLVDKLVVQELKDPGGFLLVYLNEFHTAVAA 80

                          90       100
                  ....*....|....*....|
gi 1860299455 486 LLVHCPSPTDRAQWLEKTQQ 505
Cdd:cd13244    81 YTFQTSSQEDTRRWLDAIRK 100

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 1860299455  164 ALWELLTTELIYVRKLKIMTDLLAAGLLnlQRVGLLMEVSAETLFGNVPSLIRTHRSFWDEvlgptLEETRA-SGQPLDP 242
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLK--KELKLLSPNELETLFGNIEEIYEFHRDFLDE-----LEERIEeWDDSVER 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299455  243 IGlqSGFLTFGQRFHPYVQYCLRVKQTMAYaREQQETNPLFHAFVQWCEKHKRSGRQMLCDLLIKPHQRITKYPLLLHAV 322
Cdd:smart00325  74 IG--DVFLKLEEFFKIYSEYCSNHPDALEL-LKKLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKEL 150

                          170       180
                   ....*....|....*....|....*....
gi 1860299455  323 LKRSPEA-RAQEALNAMIEAVESFLRHIN 350
Cdd:smart00325 151 LKHTPEDhEDREDLKKALKAIKELANQVN 179

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 1860299455 408 QLLLEGPVRVKEGreGK-LDVYLFLFSDVLLVTKPQRKADKAK------------------------VIRPPLMLEKLV- 461
Cdd:cd13245     1 QLLHEGPLTLIES--GKtLDVYLFLFDDMLLITKMKKNLKKKKssdsensmpsleltplikeggsytVYKQPIPLDRLCl 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1860299455 462 -------CQPLRDPNSFLLIHLTEFQCVSSALLVHCPSPTDRAQWLEKTQ 504
Cdd:cd13245    79 hdvdpneATANGLKHAFVLVHLNRYQQVIGVYTLQASSENTKQTWMSKLR 128

Ephexin Pleckstrin homology (PH) domain; Ephexin-1 (also called NGEF/ neuronal guanine nucleotide exchange factor) plays a role in the homeostatic modulation of presynaptic neurotransmitter release. Specific functions are still unknown for Ephexin-2 (also called RhoGEF19) and Ephexin-3 (also called Rho guanine nucleotide exchange factor 5/RhoGEF5, Transforming immortalized mammary oncogene/p60 TIM, and NGEF/neuronalGEF). Ephexin-4 (also called RhoGEF16) acts downstream of EphA2 to promote ligand-independent breast cancer cell migration and invasion toward epidermal growth factor through activation of RhoG. This in turn results in the activation of RhoG which recruits ELMO2 and Dock4 to form a complex with EphA2 at the tips of cortactin-rich protrusions in migrating breast cancer cells. Ephexin-5 is the specific GEF for RhoA activation and the regulation of vascular smooth muscle contractility. It interacts with EPHA4 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. The members of the Ephexin family contains a RhoGEF (DH) followed by a PH domain and an SH3 domain. The ephexin PH domain is believed to act with the DH domain in mediating protein-protein interactions. 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 1860299455 405 HTRQLLLEGPVRVKEGREGKL---------DVYLFLFSDVLLVTKP------------QRKADKAKVIRPPLMLEKLVCq 463
Cdd:cd01221    10 SSRWLVKRGELTELVEDGGSLtfrkkfsktPVYLFLFNDLLLITKKkseerylvldyaPRNLVQVEEVEDPLQLPQPLG- 88

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1860299455 464 plrdPNSFLLIHLTEFQCVSSALLVHCPSPTDRAQWLE 501
Cdd:cd01221    89 ----KNLFLLTLLENHEGKTVELLLSAESESDRERWLS 122

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 1860299455  409 LLLEGPVRVKE--GREGKLDVYLFLFSDVLLVTKpQRKADKAKVIRPPLMLEKLVCQPLRD------PNSFLLIHLTEFQ 480
Cdd:smart00233   1 VIKEGWLYKKSggGKKSWKKRYFVLFNSTLLYYK-SKKDKKSYKPKGSIDLSGCTVREAPDpdsskkPHCFEIKTSDRKT 79

                           90       100
                   ....*....|....*....|....*...
gi 1860299455  481 cvssaLLVHCPSPTDRAQWLEKTQQAQA 508
Cdd:smart00233  80 -----LLLQAESEEEREKWVEALRKAIA 102

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 1860299455 411 LEGPVRVKEGREGKL--DVYLFLFSDVLLVTKPQRKADKA--KVIRPPLMLEKLVCQPLRDPNSFLLIHLTEfqcvsSAL 486
Cdd:cd00821     1 KEGYLLKRGGGGLKSwkKRWFVLFEGVLLYYKSKKDSSYKpkGSIPLSGILEVEEVSPKERPHCFELVTPDG-----RTY 75

                          90
                  ....*....|....*
gi 1860299455 487 LVHCPSPTDRAQWLE 501
Cdd:cd00821    76 YLQADSEEERQEWLK 90

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1860299455 404 EHTRQLLLEGPVRVKEGREgkldVYLFLFSDVLLVTKPQRKADKA--KVIRPPLMLEKLVCQPLRD 467
Cdd:cd13224    15 ENSKALLCHGELRNKSGHK----LYVFLFQDILVLTRPVTRNERQsfQVYRQPIPVQELVLEDLQD 76

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299455 409 LLLEGPVRVKEGREGKL--DVYLFLFSDVLLVTKPqRKADKAKVIRPPLMLEKLVCQPLRD------PNSFLLIHLTefQ 480
Cdd:pfam00169   1 VVKEGWLLKKGGGKKKSwkKRYFVLFDGSLLYYKD-DKSGKSKEPKGSISLSGCEVVEVVAsdspkrKFCFELRTGE--R 77

                          90       100
                  ....*....|....*....|....*.
gi 1860299455 481 CVSSALLVHCPSPTDRAQWLEKTQQA 506
Cdd:pfam00169  78 TGKRTYLLQAESEEERKDWIKAIQSA 103