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 1845971905  523 RTLIYRGDLRMQEGKkGSKADVHCIIFTDMFLICRKVQGKKDRLKILKPPIHMGKMMFHYFADQNGFYLVHLTDFHTAQA 602
Cdd:cd13244      1 RRLLLEGDLRLKEGK-GSKVDVHCFLFTDMLLICKPVKRKKDRLKVIRPPYLVDKLVVQELKDPGGFLLVYLNEFHTAVA 79

                           90       100
                   ....*....|....*....|.
gi 1845971905  603 LYSMHTSGPEDTLRWTDMLKM 623
Cdd:cd13244     80 AYTFQTSSQEDTRRWLDAIRK 100

Ras-binding domain (RBD) found in pleckstrin homology (PH) and RhoGEF domain containing G5 (PLEKHG5) and similar proteins; PLEKHG5, is also termed PH domain-containing family G member 5, or guanine nucleotide exchange factor 720 (GEF720), Syx, or Tech, is a novel Dbl-like protein related to p115Rho-GEF. It functions as a Rho guanine nucleotide exchange factor directly activating RhoA in vivo and potentially involved in the control of neuronal cell differentiation. It also regulates the balance of the RhoA downstream effector Dia and ROCK activities to promote polarized-cancer-cell migration. Moreover, PLEKHG5 activates the nuclear factor kappaB (NFkappaB) signaling pathway. Mutations in the PLEKHG5 gene are relevant with autosomal recessive intermediate Charcot-Marie-Tooth disease (CMT) and lower motor neuron disease (LMND).

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1845971905   44 NYFIAVFKDLDDreKDSVEHIRFDCNQLIYEVFEPFLRIRGLTINDVEFFLEKSSTPIPENSGARFLAGQRIFVRGR 120
Cdd:cd17068      1 KECFTVKFDDDD--DDDVEIVPAVKGKTLRDVLEPLLERRGLDLDRVNVFLDSSNTPLPLEFDTYFLGGHTLRVKAK 75

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 1845971905  523 RTLIYRGDLRMQEGKkGSKADVHCIIFTDMFLICRKVQGKKDRLKILKPPIHMGKMMFHYFADQNGFYLVHLTDFHTAQA 602
Cdd:cd13244      1 RRLLLEGDLRLKEGK-GSKVDVHCFLFTDMLLICKPVKRKKDRLKVIRPPYLVDKLVVQELKDPGGFLLVYLNEFHTAVA 79

                           90       100
                   ....*....|....*....|.
gi 1845971905  603 LYSMHTSGPEDTLRWTDMLKM 623
Cdd:cd13244     80 AYTFQTSSQEDTRRWLDAIRK 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 1845971905   280 AIWEIVTTEFRYIKLLRYLSNLsfYLTDLQNCG-FLKDIENRLVFFNFVTLFNVNydSLWLQSIEPILAKSRETGEpldv 358
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEV--FLKPLKKELkLLSPNELETLFGNIEEIYEFH--RDFLDELEERIEEWDDSVE---- 72

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1845971905   359 nYLQNGFRDIENWSRCYTNFHLAHSDSLKHIqKKLKESENFRDFVTWAEAQENLDRQKLIDTFSVPMQRLTRYNLLLKAV 438
Cdd:smart00325   73 -RIGDVFLKLEEFFKIYSEYCSNHPDALELL-KKLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKEL 150

                           170       180       190
                    ....*....|....*....|....*....|
gi 1845971905   439 LKVTTDE-NEREMISNLVDCAESATAQLNK 467
Cdd:smart00325  151 LKHTPEDhEDREDLKKALKAIKELANQVNE 180

Ras-binding domain (RBD) found in pleckstrin homology (PH) and RhoGEF domain containing G5 (PLEKHG5) and similar proteins; PLEKHG5, is also termed PH domain-containing family G member 5, or guanine nucleotide exchange factor 720 (GEF720), Syx, or Tech, is a novel Dbl-like protein related to p115Rho-GEF. It functions as a Rho guanine nucleotide exchange factor directly activating RhoA in vivo and potentially involved in the control of neuronal cell differentiation. It also regulates the balance of the RhoA downstream effector Dia and ROCK activities to promote polarized-cancer-cell migration. Moreover, PLEKHG5 activates the nuclear factor kappaB (NFkappaB) signaling pathway. Mutations in the PLEKHG5 gene are relevant with autosomal recessive intermediate Charcot-Marie-Tooth disease (CMT) and lower motor neuron disease (LMND).

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1845971905   44 NYFIAVFKDLDDreKDSVEHIRFDCNQLIYEVFEPFLRIRGLTINDVEFFLEKSSTPIPENSGARFLAGQRIFVRGR 120
Cdd:cd17068      1 KECFTVKFDDDD--DDDVEIVPAVKGKTLRDVLEPLLERRGLDLDRVNVFLDSSNTPLPLEFDTYFLGGHTLRVKAK 75

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 1845971905  523 RTLIYRGDLRMQEGKkGSKADVHCIIFTDMFLICRKVQGKKDRLKILKPPIHMGKMMFHYFADQNGFYLVHLTDFHTAQA 602
Cdd:cd13244      1 RRLLLEGDLRLKEGK-GSKVDVHCFLFTDMLLICKPVKRKKDRLKVIRPPYLVDKLVVQELKDPGGFLLVYLNEFHTAVA 79

                           90       100
                   ....*....|....*....|.
gi 1845971905  603 LYSMHTSGPEDTLRWTDMLKM 623
Cdd:cd13244     80 AYTFQTSSQEDTRRWLDAIRK 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 1845971905   280 AIWEIVTTEFRYIKLLRYLSNLsfYLTDLQNCG-FLKDIENRLVFFNFVTLFNVNydSLWLQSIEPILAKSRETGEpldv 358
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEV--FLKPLKKELkLLSPNELETLFGNIEEIYEFH--RDFLDELEERIEEWDDSVE---- 72

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1845971905   359 nYLQNGFRDIENWSRCYTNFHLAHSDSLKHIqKKLKESENFRDFVTWAEAQENLDRQKLIDTFSVPMQRLTRYNLLLKAV 438
Cdd:smart00325   73 -RIGDVFLKLEEFFKIYSEYCSNHPDALELL-KKLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKEL 150

                           170       180       190
                    ....*....|....*....|....*....|
gi 1845971905   439 LKVTTDE-NEREMISNLVDCAESATAQLNK 467
Cdd:smart00325  151 LKHTPEDhEDREDLKKALKAIKELANQVNE 180

Ras-binding domain (RBD) found in pleckstrin homology (PH) and RhoGEF domain containing G5 (PLEKHG5) and similar proteins; PLEKHG5, is also termed PH domain-containing family G member 5, or guanine nucleotide exchange factor 720 (GEF720), Syx, or Tech, is a novel Dbl-like protein related to p115Rho-GEF. It functions as a Rho guanine nucleotide exchange factor directly activating RhoA in vivo and potentially involved in the control of neuronal cell differentiation. It also regulates the balance of the RhoA downstream effector Dia and ROCK activities to promote polarized-cancer-cell migration. Moreover, PLEKHG5 activates the nuclear factor kappaB (NFkappaB) signaling pathway. Mutations in the PLEKHG5 gene are relevant with autosomal recessive intermediate Charcot-Marie-Tooth disease (CMT) and lower motor neuron disease (LMND).

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1845971905   44 NYFIAVFKDLDDreKDSVEHIRFDCNQLIYEVFEPFLRIRGLTINDVEFFLEKSSTPIPENSGARFLAGQRIFVRGR 120
Cdd:cd17068      1 KECFTVKFDDDD--DDDVEIVPAVKGKTLRDVLEPLLERRGLDLDRVNVFLDSSNTPLPLEFDTYFLGGHTLRVKAK 75

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
                   ....*....|....*....|....*....|....*....|....*....|
gi 1845971905  522 HRTLIYRGDLR--------MQEGKKGSKADVHCIIFTDMFLICRKVQGKK 563
Cdd:cd01221     11 SRWLVKRGELTelvedggsLTFRKKFSKTPVYLFLFNDLLLITKKKSEER 60

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 1845971905  524 TLIYRGDLRMQEGKKGSkaDVHCIIFTDMFLICRKVQGKKDRLKI-----------------------LKPPIHMGKMMF 580
Cdd:cd13245      1 QLLHEGPLTLIESGKTL--DVYLFLFDDMLLITKMKKNLKKKKSSdsensmpsleltplikeggsytvYKQPIPLDRLCL 78

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1845971905  581 H--------YFADQNGFYLVHLTDFHTAQALYSMHTSGPEDTLRWTDMLK 622
Cdd:cd13245     79 HdvdpneatANGLKHAFVLVHLNRYQQVIGVYTLQASSENTKQTWMSKLR 128