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 45553561 132 GNLEGKTFLNEGALIELDSNDYRPIQRVFFFLFNDVLIVCKVKHDKR----LDFLTEYDPKKIAVINIKDLDGVKNAINI 207
Cdd:cd01226   1 VEVPGRYLLHEGDLLELDPDDYKPIQKVHLFLLNDVLLIASWLPNRRgpvrYKFQALYPLEDLAVVNVKDLGPVKNAFKL 80

                        90       100       110
                ....*....|....*....|....*....|....*
gi 45553561 208 ITPDGSKIYQSITAAGKTEWIEKLEEAFRFDQQKK 242
Cdd:cd01226  81 LTFPETRVFQCENAKIKKEWLEKFEQAKRAKLAKE 115

Vps51/Vps67; This family includes a presumed domain found in a number of components of vesicular transport. The VFT tethering complex (also known as GARP complex, Golgi associated retrograde protein complex, Vps53 tethering complex) is a conserved eukaryotic docking complex which is involved recycling of proteins from endosomes to the late Golgi. Vps51 (also known as Vps67) is a subunit of VFT and interacts with the SNARE Tlg1. Cog1_N is the N-terminus of the Cog1 subunit of the eight-unit Conserved Oligomeric Golgi (COG) complex that participates in retrograde vesicular transport and is required to maintain normal Golgi structure and function. The subunits are located in two lobes and Cog1 serves to bind the two lobes together probably via the highly conserved N-terminal domain of approximately 85 residues.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45553561     4 FDDFNFSVEKYTKDLTRECvGGSDLQQRKKEIEAYNETTAATLKQTCKKNYMEFIQTAKEISrNLESEMYQLSHILIEQR 83
Cdd:pfam08700   1 LDSPSFDADRYVSELLSKA-TLEELLQFESSLRSEIERLDSELKQLVYDNYRDLIKAADTIS-KMKSEMEQLSQKLSELK 78

                  ....*..
gi 45553561    84 NILATMT 90
Cdd:pfam08700  79 QALSKIA 85

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 45553561 132 GNLEGKTFLNEGALIELDSNDYRPIQRVFFFLFNDVLIVCKVKHDKR----LDFLTEYDPKKIAVINIKDLDGVKNAINI 207
Cdd:cd01226   1 VEVPGRYLLHEGDLLELDPDDYKPIQKVHLFLLNDVLLIASWLPNRRgpvrYKFQALYPLEDLAVVNVKDLGPVKNAFKL 80

                        90       100       110
                ....*....|....*....|....*....|....*
gi 45553561 208 ITPDGSKIYQSITAAGKTEWIEKLEEAFRFDQQKK 242
Cdd:cd01226  81 LTFPETRVFQCENAKIKKEWLEKFEQAKRAKLAKE 115

Vps51/Vps67; This family includes a presumed domain found in a number of components of vesicular transport. The VFT tethering complex (also known as GARP complex, Golgi associated retrograde protein complex, Vps53 tethering complex) is a conserved eukaryotic docking complex which is involved recycling of proteins from endosomes to the late Golgi. Vps51 (also known as Vps67) is a subunit of VFT and interacts with the SNARE Tlg1. Cog1_N is the N-terminus of the Cog1 subunit of the eight-unit Conserved Oligomeric Golgi (COG) complex that participates in retrograde vesicular transport and is required to maintain normal Golgi structure and function. The subunits are located in two lobes and Cog1 serves to bind the two lobes together probably via the highly conserved N-terminal domain of approximately 85 residues.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45553561     4 FDDFNFSVEKYTKDLTRECvGGSDLQQRKKEIEAYNETTAATLKQTCKKNYMEFIQTAKEISrNLESEMYQLSHILIEQR 83
Cdd:pfam08700   1 LDSPSFDADRYVSELLSKA-TLEELLQFESSLRSEIERLDSELKQLVYDNYRDLIKAADTIS-KMKSEMEQLSQKLSELK 78

                  ....*..
gi 45553561    84 NILATMT 90
Cdd:pfam08700  79 QALSKIA 85

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 45553561 132 GNLEGKTFLNEGALIELDSNDYRPIQRVFFFLFNDVLIVCKVKHDKR----LDFLTEYDPKKIAVINIKDLDGVKNAINI 207
Cdd:cd01226   1 VEVPGRYLLHEGDLLELDPDDYKPIQKVHLFLLNDVLLIASWLPNRRgpvrYKFQALYPLEDLAVVNVKDLGPVKNAFKL 80

                        90       100       110
                ....*....|....*....|....*....|....*
gi 45553561 208 ITPDGSKIYQSITAAGKTEWIEKLEEAFRFDQQKK 242
Cdd:cd01226  81 LTFPETRVFQCENAKIKKEWLEKFEQAKRAKLAKE 115

Vps51/Vps67; This family includes a presumed domain found in a number of components of vesicular transport. The VFT tethering complex (also known as GARP complex, Golgi associated retrograde protein complex, Vps53 tethering complex) is a conserved eukaryotic docking complex which is involved recycling of proteins from endosomes to the late Golgi. Vps51 (also known as Vps67) is a subunit of VFT and interacts with the SNARE Tlg1. Cog1_N is the N-terminus of the Cog1 subunit of the eight-unit Conserved Oligomeric Golgi (COG) complex that participates in retrograde vesicular transport and is required to maintain normal Golgi structure and function. The subunits are located in two lobes and Cog1 serves to bind the two lobes together probably via the highly conserved N-terminal domain of approximately 85 residues.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45553561     4 FDDFNFSVEKYTKDLTRECvGGSDLQQRKKEIEAYNETTAATLKQTCKKNYMEFIQTAKEISrNLESEMYQLSHILIEQR 83
Cdd:pfam08700   1 LDSPSFDADRYVSELLSKA-TLEELLQFESSLRSEIERLDSELKQLVYDNYRDLIKAADTIS-KMKSEMEQLSQKLSELK 78

                  ....*..
gi 45553561    84 NILATMT 90
Cdd:pfam08700  79 QALSKIA 85

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 45553561    142 EGALIELDSNDYRPIQRVFFFLFNDVLIVCKVKHDKRldfltEYDPKKiaVINIKDL----------DGVKNAINIITPD 211
Cdd:smart00233   4 EGWLYKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKK-----SYKPKG--SIDLSGCtvreapdpdsSKKPHCFEIKTSD 76

                           90       100
                   ....*....|....*....|....
gi 45553561    212 GSKIY-QSITAAGKTEWIEKLEEA 234
Cdd:smart00233  77 RKTLLlQAESEEEREKWVEALRKA 100

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 45553561 135 EGKTFLNEGALIELDSNDYRPIQrvfFFLFNDVLIVCKVK-HDKRLDFLTEYDPKKIAVINIKDLDGVKNAINIITPDGS 213
Cdd:cd01218  26 PGRVLVGEGVLTKVCRKKPKPRQ---FFLFNDILVYGSIViNKKKYNKQRIIPLEDVKIEDLEDTGELKNGWQIISPKKS 102

                        90       100
                ....*....|....*....|.
gi 45553561 214 KIYQSITAAGKTEWIEKLEEA 234
Cdd:cd01218 103 FVVYAATATEKSEWMDHINKC 123

Alsin Pleckstrin homology (PH) domain; The ALS2 gene encodes alsin, a GEF, that has dual specificity for Rac1 and Rab5 GTPases. Alsin mutations in the form of truncated proteins are responsible for motor function disorders including juvenile-onset amyotrophic lateral sclerosis, familial juvenile primary lateral sclerosis, and infantile-onset ascending hereditary spastic paralysis. The alsin protein is widely expressed in the developing CNS including neurons of the cerebral cortex, brain stem, spinal cord, and cerebellum. Alsin contains a regulator of chromosome condensation 1 (RCC1) domain, a Rho guanine nucleotide exchanging factor (RhoGEF) domain, a PH domain, a Membrane Occupation and Recognition Nexus (MORN), a vacuolar protein sorting 9 (Vps9) domain, and a Dbl homology (DH) domain. Alsin interacts with Rab5 through its Vps9 domain and through this interaction modulates early endosome fusion and trafficking. The GEF activity of alsin towards Rab5 is regulated by Rac1 function. The GEF activity of alsin for Rac1 occurs via its DH domain and this interaction plays a role in promoting spinal motor neuron survival via multiple Rac-dependent signaling pathways. 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 45553561 161 FFLFNDVLIvckvkhdkRLDFLTE--YDPKKIAVINIKDLDGVKNAINIITPDGSKIYQSITAAGKTEWIEKLEEAFR 236
Cdd:cd13269  32 FILFNDALV--------HAQFSTHhiFPLATLWVEPIPDEDSGQNALKITTPEESFTLVASTPQEKAEWLRAINQAID 101