Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1860299493 386 RQLLLEGPVRVKEGREGKLDVYLFLFSDVLLVTKP-QRKADKAKVIRPPLMLEKLVCQPLRDPStSFL 452
Cdd:cd13244     1 RRLLLEGDLRLKEGKGSKVDVHCFLFTDMLLICKPvKRKKDRLKVIRPPYLVDKLVVQELKDPG-GFL 67

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 1860299493  143 ALWELLTTELIYVRKLKIMTDLLAAGLLnlQRVGLLMEVSAETLFGNVPSLIRTHRSFWDEvlgptLEETRA-SGQPLDP 221
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLK--KELKLLSPNELETLFGNIEEIYEFHRDFLDE-----LEERIEeWDDSVER 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299493  222 IGlqSGFLTFGQRFHPYVQYCLRVKQTMAYaREQQETNPLFHAFVQWCEKHKRSGRQMLCDLLIKPHQRITKYPLLLHAV 301
Cdd:smart00325  74 IG--DVFLKLEEFFKIYSEYCSNHPDALEL-LKKLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKEL 150

                          170       180
                   ....*....|....*....|....*....
gi 1860299493  302 LKRSPEA-RAQEALNAMIEAVESFLRHIN 329
Cdd:smart00325 151 LKHTPEDhEDREDLKKALKAIKELANQVN 179

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 1860299493 386 RQLLLEGPVRVKEGREGKLDVYLFLFSDVLLVTKP-QRKADKAKVIRPPLMLEKLVCQPLRDPStSFL 452
Cdd:cd13244     1 RRLLLEGDLRLKEGKGSKVDVHCFLFTDMLLICKPvKRKKDRLKVIRPPYLVDKLVVQELKDPG-GFL 67

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 1860299493  143 ALWELLTTELIYVRKLKIMTDLLAAGLLnlQRVGLLMEVSAETLFGNVPSLIRTHRSFWDEvlgptLEETRA-SGQPLDP 221
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLK--KELKLLSPNELETLFGNIEEIYEFHRDFLDE-----LEERIEeWDDSVER 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299493  222 IGlqSGFLTFGQRFHPYVQYCLRVKQTMAYaREQQETNPLFHAFVQWCEKHKRSGRQMLCDLLIKPHQRITKYPLLLHAV 301
Cdd:smart00325  74 IG--DVFLKLEEFFKIYSEYCSNHPDALEL-LKKLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKEL 150

                          170       180
                   ....*....|....*....|....*....
gi 1860299493  302 LKRSPEA-RAQEALNAMIEAVESFLRHIN 329
Cdd:smart00325 151 LKHTPEDhEDREDLKKALKAIKELANQVN 179

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 1860299493 386 RQLLLEGPVRVKEGREGKLDVYLFLFSDVLLVTKP-QRKADKAKVIRPPLMLEKLVCQPLRDPStSFL 452
Cdd:cd13244     1 RRLLLEGDLRLKEGKGSKVDVHCFLFTDMLLICKPvKRKKDRLKVIRPPYLVDKLVVQELKDPG-GFL 67

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
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1860299493 387 QLLLEGPVRVKEGreGK-LDVYLFLFSDVLLVTKPQRKADKAKVIRPPLMLEKLVCQPL 444
Cdd:cd13245     1 QLLHEGPLTLIES--GKtLDVYLFLFDDMLLITKMKKNLKKKKSSDSENSMPSLELTPL 57

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 1860299493 383 EHTRQLLLEGPVRVKEGREgkldVYLFLFSDVLLVTKPQRKADKA--KVIRPPLMLEKLVCQPLRD 446
Cdd:cd13224    15 ENSKALLCHGELRNKSGHK----LYVFLFQDILVLTRPVTRNERQsfQVYRQPIPVQELVLEDLQD 76

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal Pleckstrin Homology (PH) domain; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH 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
                  ....*....|....*....|....*....|....*....|....*.
gi 1860299493 386 RQLLLEGPVrVKEGREGKLDVYLFLFSDVLLVTKPQRKADKAKVIR 431
Cdd:cd13389    12 RKLIKEGEL-MKVSRKEMQPRYFFLFNDCLLYTTPVQSSGMLKLNN 56