Exocyst complex 84-kDa subunit Ral-binding domain/Pleckstrin Homology (PH) domain; The Sec6/8 complex, also called the exocyst complex, forms an octameric protein (Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70 and Exo84) involved in the tethering of secretory vesicles to specific regions on the plasma membrane. The regulation of Sec6/8 complex differs between mammals and yeast. Mamalian Exo84 and Sec5 are effector targets for active Ral GTPases which are not present in yeast. Ral GTPases are members of the Ras superfamily, and as such cycle between an active GTP-bound state and an inactive GDP-bound state. The Exo84 Ral-binding domain adopts a PH domain fold. Mammalian Exo84 and Sec5 competitively bind to active RalA. 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 37674218 167 LETPGQYLVYNGDLVEYDADHMAQLQRVHGFLMNDCLLVATWLPQRRG--MYRYNALYPLDRLAVVNVKDNPPMKDMFKL 244
Cdd:cd01226   1 VEVPGRYLLHEGDLLELDPDDYKPIQKVHLFLLNDVLLIASWLPNRRGpvRYKFQALYPLEDLAVVNVKDLGPVKNAFKL 80

                        90       100       110
                ....*....|....*....|....*....|....*
gi 37674218 245 LMFPESRIFQAENAKIKREWLEVLEETKRALSDKR 279
Cdd:cd01226  81 LTFPETRVFQCENAKIKKEWLEKFEQAKRAKLAKE 115

Exocyst complex 84-kDa subunit Ral-binding domain/Pleckstrin Homology (PH) domain; The Sec6/8 complex, also called the exocyst complex, forms an octameric protein (Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70 and Exo84) involved in the tethering of secretory vesicles to specific regions on the plasma membrane. The regulation of Sec6/8 complex differs between mammals and yeast. Mamalian Exo84 and Sec5 are effector targets for active Ral GTPases which are not present in yeast. Ral GTPases are members of the Ras superfamily, and as such cycle between an active GTP-bound state and an inactive GDP-bound state. The Exo84 Ral-binding domain adopts a PH domain fold. Mammalian Exo84 and Sec5 competitively bind to active RalA. 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 37674218 167 LETPGQYLVYNGDLVEYDADHMAQLQRVHGFLMNDCLLVATWLPQRRG--MYRYNALYPLDRLAVVNVKDNPPMKDMFKL 244
Cdd:cd01226   1 VEVPGRYLLHEGDLLELDPDDYKPIQKVHLFLLNDVLLIASWLPNRRGpvRYKFQALYPLEDLAVVNVKDLGPVKNAFKL 80

                        90       100       110
                ....*....|....*....|....*....|....*
gi 37674218 245 LMFPESRIFQAENAKIKREWLEVLEETKRALSDKR 279
Cdd:cd01226  81 LTFPETRVFQCENAKIKKEWLEKFEQAKRAKLAKE 115

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 37674218    174 LVYNGDLVEYDADHMAQLQRVHGFLMNDCLLVATWLPQRRGmYRYNALYPLDRLAVVNVKDNPPMKD--MFKLLMF-PES 250
Cdd:smart00233   1 VIKEGWLYKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKKS-YKPKGSIDLSGCTVREAPDPDSSKKphCFEIKTSdRKT 79

                           90       100
                   ....*....|....*....|...
gi 37674218    251 RIFQAENAKIKREWLEVLEETKR 273
Cdd:smart00233  80 LLLQAESEEEREKWVEALRKAIA 102

Exocyst complex 84-kDa subunit Ral-binding domain/Pleckstrin Homology (PH) domain; The Sec6/8 complex, also called the exocyst complex, forms an octameric protein (Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70 and Exo84) involved in the tethering of secretory vesicles to specific regions on the plasma membrane. The regulation of Sec6/8 complex differs between mammals and yeast. Mamalian Exo84 and Sec5 are effector targets for active Ral GTPases which are not present in yeast. Ral GTPases are members of the Ras superfamily, and as such cycle between an active GTP-bound state and an inactive GDP-bound state. The Exo84 Ral-binding domain adopts a PH domain fold. Mammalian Exo84 and Sec5 competitively bind to active RalA. 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 37674218 167 LETPGQYLVYNGDLVEYDADHMAQLQRVHGFLMNDCLLVATWLPQRRG--MYRYNALYPLDRLAVVNVKDNPPMKDMFKL 244
Cdd:cd01226   1 VEVPGRYLLHEGDLLELDPDDYKPIQKVHLFLLNDVLLIASWLPNRRGpvRYKFQALYPLEDLAVVNVKDLGPVKNAFKL 80

                        90       100       110
                ....*....|....*....|....*....|....*
gi 37674218 245 LMFPESRIFQAENAKIKREWLEVLEETKRALSDKR 279
Cdd:cd01226  81 LTFPETRVFQCENAKIKKEWLEKFEQAKRAKLAKE 115

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 37674218 176 YNGDLVEYDADHMAQLQRVHGFLMNDCLLVATwlPQRRGMYRYNALYPLDRLAVVNVKDNPPMKDMFKLLMFPESRI-FQ 254
Cdd:cd00821   1 KEGYLLKRGGGGLKSWKKRWFVLFEGVLLYYK--SKKDSSYKPKGSIPLSGILEVEEVSPKERPHCFELVTPDGRTYyLQ 78

                        90
                ....*....|....
gi 37674218 255 AENAKIKREWLEVL 268
Cdd:cd00821  79 ADSEEERQEWLKAL 92

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        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674218 170 PGQYLVYNGDLVEYDADHMaqlQRVHGFLMNDCLLVATWLpQRRGMYRYNALYPLDRLAVvNVKDNPPMKDMFKLLMFPE 249
Cdd:cd13389  10 PGRKLIKEGELMKVSRKEM---QPRYFFLFNDCLLYTTPV-QSSGMLKLNNELPLSGMKV-KLPEDEEYSNEFQIISTKR 84

                        90       100       110
                ....*....|....*....|....*....|..
gi 37674218 250 SRIFQAENAKIKREWLEVLEETKRALSDKRRR 281
Cdd:cd13389  85 SFTLIASSEEERDEWVKALSRAIEEHTKKQRT 116