VHS (Vps27/Hrs/STAM) domain of Tom1 subfamily; This subfamily is composed of Tom1 (Target of myb1 - retroviral oncogene) protein, Tom1L1 (Tom1-like1), Tom1L2 (Tom1-like2), and similar proteins. Proteins belonging to this subfamily are characterized by the presence of a VHS (Vps27p/Hrs/Stam) domain in the N-terminal portion followed by a GAT (GGA and Tom) domain. They are novel regulators for post-Golgi trafficking and signaling. Yeast do not contain homologous proteins of the Tom1 subfamily, suggesting these proteins have evolved to accommodate more complex cellular processes. Tom1 is essential for the negative regulation of Interleukin-1 and Tumor Necrosis Factor-induced signaling pathways. The VHS domain has a superhelical structure similar to the structure of the ARM repeats and is present at the very N-termini of proteins. It is a right-handed superhelix of eight alpha helices. The VHS domain has been found in a number of proteins, some of which have been implicated in intracellular trafficking and sorting.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17550228  38 PVGRKIELATDANLlATENWGLNMEICDFINGTEDGPRDAVRALKKRLHNAMSKNNAVVMYTLTVLETAVKNCNHHFHVL 117
Cdd:cd03565   1 PVGQLIERATDSGL-SSEDWALNMEICDMINETDDGPKDAIKAIKKRLSTNAGKNHTVVMYTLTLLETCVKNCGHRFHVL 79

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 17550228 118 VCNKDFVQDLIKLIGPKFDAPQIIQERVLSLIQAWADAFRGDPTLAGVVQSYDDLKSKG 176
Cdd:cd03565  80 VANKDFLQELVKLIGPKNDPPTIVQEKVLSLIQSWADAFRGQPDLQEVVKVYQELKAKG 138

VHS (Vps27/Hrs/STAM) domain of Tom1 subfamily; This subfamily is composed of Tom1 (Target of myb1 - retroviral oncogene) protein, Tom1L1 (Tom1-like1), Tom1L2 (Tom1-like2), and similar proteins. Proteins belonging to this subfamily are characterized by the presence of a VHS (Vps27p/Hrs/Stam) domain in the N-terminal portion followed by a GAT (GGA and Tom) domain. They are novel regulators for post-Golgi trafficking and signaling. Yeast do not contain homologous proteins of the Tom1 subfamily, suggesting these proteins have evolved to accommodate more complex cellular processes. Tom1 is essential for the negative regulation of Interleukin-1 and Tumor Necrosis Factor-induced signaling pathways. The VHS domain has a superhelical structure similar to the structure of the ARM repeats and is present at the very N-termini of proteins. It is a right-handed superhelix of eight alpha helices. The VHS domain has been found in a number of proteins, some of which have been implicated in intracellular trafficking and sorting.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17550228  38 PVGRKIELATDANLlATENWGLNMEICDFINGTEDGPRDAVRALKKRLHNAMSKNNAVVMYTLTVLETAVKNCNHHFHVL 117
Cdd:cd03565   1 PVGQLIERATDSGL-SSEDWALNMEICDMINETDDGPKDAIKAIKKRLSTNAGKNHTVVMYTLTLLETCVKNCGHRFHVL 79

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 17550228 118 VCNKDFVQDLIKLIGPKFDAPQIIQERVLSLIQAWADAFRGDPTLAGVVQSYDDLKSKG 176
Cdd:cd03565  80 VANKDFLQELVKLIGPKNDPPTIVQEKVLSLIQSWADAFRGQPDLQEVVKVYQELKAKG 138

VHS domain; Domain present in VPS-27, Hrs and STAM.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17550228    38 PVGRKIELATDANLLAtENWGLNMEICDFINGTEDGPRDAVRALKKRLHNamsKNNAVVMYTLTVLETAVKNCNHHFHVL 117
Cdd:pfam00790   1 PLERWIDKATDPSLRE-EDWSLILDICDLINETETGPKEAVRLIKKRINS---PNPHVALLALTLLDACVKNCGSKFHLE 76

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 17550228   118 VCNKDFVQDLIKLIGPK-FDAPQIIQERVLSLIQAWADAFRGDPTLAGVVQSYDDLKSKG 176
Cdd:pfam00790  77 IASKEFLNELVKLIPNKpYGKPAKVKKKILELIQEWADAFKNDPDLKYIRDMYKLLKRKG 136

GAT domain; The GAT domain is responsible for binding of GGA proteins to several members of the ARF family including ARF1 and ARF3. The GAT domain stabilizes membrane bound ARF1 in its GTP bound state, by interfering with GAP proteins.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 17550228   262 NQNIKVFRETLTDVVPRKETADELqlLSDLNDTCRHMQQRVLDLI-RYVSNDEVTYELLMVNDSLNSVFEKYDRFVSN 338
Cdd:pfam03127   1 RNNAKLLNEMLSSTDPDEELDNEL--IKELYERCKSAQPKIQKLIeETSDEDDLLAELLQLNDDLNNVLERYERLKKG 76

VHS (Vps27/Hrs/STAM) domain of Tom1 subfamily; This subfamily is composed of Tom1 (Target of myb1 - retroviral oncogene) protein, Tom1L1 (Tom1-like1), Tom1L2 (Tom1-like2), and similar proteins. Proteins belonging to this subfamily are characterized by the presence of a VHS (Vps27p/Hrs/Stam) domain in the N-terminal portion followed by a GAT (GGA and Tom) domain. They are novel regulators for post-Golgi trafficking and signaling. Yeast do not contain homologous proteins of the Tom1 subfamily, suggesting these proteins have evolved to accommodate more complex cellular processes. Tom1 is essential for the negative regulation of Interleukin-1 and Tumor Necrosis Factor-induced signaling pathways. The VHS domain has a superhelical structure similar to the structure of the ARM repeats and is present at the very N-termini of proteins. It is a right-handed superhelix of eight alpha helices. The VHS domain has been found in a number of proteins, some of which have been implicated in intracellular trafficking and sorting.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17550228  38 PVGRKIELATDANLlATENWGLNMEICDFINGTEDGPRDAVRALKKRLHNAMSKNNAVVMYTLTVLETAVKNCNHHFHVL 117
Cdd:cd03565   1 PVGQLIERATDSGL-SSEDWALNMEICDMINETDDGPKDAIKAIKKRLSTNAGKNHTVVMYTLTLLETCVKNCGHRFHVL 79

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 17550228 118 VCNKDFVQDLIKLIGPKFDAPQIIQERVLSLIQAWADAFRGDPTLAGVVQSYDDLKSKG 176
Cdd:cd03565  80 VANKDFLQELVKLIGPKNDPPTIVQEKVLSLIQSWADAFRGQPDLQEVVKVYQELKAKG 138

VHS (Vps27/Hrs/STAM) domain of TOM1-like protein 2; TOM1-like protein 2 (Tom1L2) is a member of the Tom1 (Target of myb1) subfamily, characterized by the presence of a VHS (Vps27p/Hrs/Stam) domain in the N-terminal portion followed by a GAT (GGA and Tom) domain. They are novel regulators for post-Golgi trafficking and signaling. Studies in Tom1L2 hypomorphic mice suggest that Tom1L2 may play roles in immune responses and tumor suppression. The VHS domain has a superhelical structure similar to the structure of the ARM repeats and is present at the very N-termini of proteins. It is a right-handed superhelix of eight alpha helices. The VHS domain has been found in a number of proteins, some of which have been implicated in intracellular trafficking and sorting.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17550228  38 PVGRKIELATDANLlATENWGLNMEICDFINGTEDGPRDAVRALKKRLHNamSKNNAVVMYTLTVLETAVKNCNHHFHVL 117
Cdd:cd16996   1 PVGQCIEKATDGSL-QSEDWTLNMEICDIINETEEGPKDAIRALKKRLNG--NKNYREVMLALTVLETCVKNCGHRFHVL 77

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 17550228 118 VCNKDFVQD-LIKLIGPKFDAPQIIQERVLSLIQAWADAFRGDPTLAGVVQSYDDLKSKG 176
Cdd:cd16996  78 VASRDFIDGvLVKIISPKNNPPTIVQDKVLALIQAWADAFRSSPDLTGVVHIYEELKRKG 137

VHS (Vps27/Hrs/STAM) domain family; The VHS domain is present in Vps27 (Vacuolar Protein Sorting), Hrs (Hepatocyte growth factor-regulated tyrosine kinase substrate) and STAM (Signal Transducing Adaptor Molecule). It has a superhelical structure similar to that of the ARM (Armadillo) repeats and is present at the N-termini of proteins involved in intracellular membrane trafficking. There are four general groups of VHS domain containing proteins based on their association with other domains. The first group consists of proteins of the STAM/EAST/Hbp family, which has the domain composition of VHS-SH3-ITAM. The second consists of proteins with a FYVE domain C-terminal to VHS. The third consists of GGA proteins with a domain composition of VHS-GAT (GGA and TOM)-GAE (Gamma-Adaptin Ear) domain. The fourth consists of proteins with a VHS domain alone or with domains other than those mentioned above. In GGA proteins, VHS domains are involved in cargo recognition in trans-Golgi, thereby having a general membrane targeting/cargo recognition role in vesicular trafficking.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17550228  39 VGRKIELATdANLLATENWGLNMEICDFINGTEDGPRDAVRALKKRLhnaMSKNNAVVMYTLTVLETAVKNCNHHFHVLV 118
Cdd:cd03561   1 VEELVEKAT-SESLTEPDWALNLEICDLVNSDPAQAKDAVRALRKRL---QSKNPKVQLLALTLLETLVKNCGAPFHSEV 76

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 17550228 119 CNKDFVQDLIKLIGPKFDAPQiIQERVLSLIQAWADAFRGDPTLAGVVQSYDDLKS 174
Cdd:cd03561  77 ASRDFLQELVKLVKKKKTSPE-VREKALALIQEWAEAFQGDGRLPLFYDTYQQLRR 131

canonical GAT domain found in target of myb protein 1 (Tom1) protein family; Tom1 and its related proteins, Tom1L1 and Tom1L2, form a protein family sharing an N-terminal VHS (Vps27p/Hrs/STAM)-domain followed by a GAT (GGA and TOM1) domain, both of which are also conserved in Golgi-localized gamma ear-containing Arf-binding proteins (GGAs). In contrast to GGAs, the Tom1 family proteins bind to ubiquitin, ubiquitinated proteins, and Toll-interacting protein (Tollip) through its GAT domain, but do not associate with Arf GTPases through its GAT domain nor with acidic cluster-dileucine sequences through its VHS domain. In addition, the Tom1 family proteins recruit clathrin onto endosomes through their C-terminal region. In their C-terminal clathrin-binding regions, Tom1 and Tom1L2 are similar to each other, but distinguishable from Tom1L1. The yeast S. cerevisiae does not contain homologous proteins of the Tom1 family. The canonical GAT domain is a monomeric three-helix bundle that binds ubiquitin.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17550228 251 LTKLRADLDVVNQNIKVFRETLTDVVPRKETADELQLLSDLNDTCRHMQQRVLDLIRYVSNDEVTYELLMVNDSLNSVFE 330
Cdd:cd14233   1 IAKLRSELDVVEGNLKVMSEMLTELVPGQENPDDLELLQELNSTCRAMQQRVVELISQVSNEEVTEELLRVNDDLNNVFL 80

                ....*
gi 17550228 331 KYDRF 335
Cdd:cd14233  81 RYERF 85

VHS (Vps27/Hrs/STAM) domain of TOM1-like protein 1; TOM1-like protein 1 (Tom1L1) is also called Src-activating and signaling molecule protein (Srcasm). It is a member of the Tom1 (Target of myb1) subfamily, characterized by the presence of a VHS (Vps27p/Hrs/Stam) domain in the N-terminal portion followed by a GAT (GGA and Tom) domain. They are novel regulators for post-Golgi trafficking and signaling. Tom1L1 has been implicated in multivesicular body (MVB) formation, viral egress from the cell, and cytokinesis. Its amplification enhances the metastatic progression of ERBB2-positive breast cancers. The VHS domain has a superhelical structure similar to the structure of the ARM repeats and is present at the very N-termini of proteins. It is a right-handed superhelix of eight alpha helices. The VHS domain has been found in a number of proteins, some of which have been implicated in intracellular trafficking and sorting.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17550228  38 PVGRKIELATDANLlATENWGLNMEICDFINGTEDGPRDAVRALKKRLhnAMSKNNAVVMYTLTVLETAVKNCNHHFHVL 117
Cdd:cd16997   1 SVGHLIEKATFGTV-QTEDWGQFMHICDIINTTEDGPKDAVKALKKRI--SKNYNHKEIRLTLSLLDMCMQNCGPSFQSL 77

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 17550228 118 VCNKDFVQD-LIKLIGPKFDAPQIIQERVLSLIQAWADAFRGDPTLAGVVQSYDDLKSKG 176
Cdd:cd16997  78 VVKKEFVKDvLVKLLNPRYNLPVDLQNKILNFIMTWAQGFQGGVDVSEVKEVYLDLVKKG 137

VHS (Vps27/Hrs/STAM) domain of Class E vacuolar protein-sorting machinery protein HSE1; Class E vacuolar protein-sorting machinery protein HSE1, together with Vps27, comprise the ESCRT-0 complex, the sorting receptor for ubiquitinated cargo proteins at the multivesicular body (MVB). The complex directly binds to ubiquitinated transmembrane proteins and recruits both ubiquitin ligases and deubiquitinating enzymes. It is also required the efficient recycling of late Golgi proteins including the carboxypeptidase Y (CPY) sorting receptor, Vps10. Similar to metazoan STAMs, HSE1 contain: an N-terminal VHS domain, which is involved in cytokine-mediated intracellular signal transduction and has a superhelical structure similar to the structure of ARM (Armadillo) repeats; a Ubiquitin-Interacting Motif (UIM); a SH3 (Src Homology 3) domain, a well-established protein-protein interaction domain; and a GAT (GGA and TOM) domain, which is essential for the normal sorting function of HSE1.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17550228  42 KIELATDANLlATENWGLNMEICDFINGT-EDGPRDAVRALKKRLhnamSKNNA-VVMYTLTVLETAVKNCNHHFHVLVC 119
Cdd:cd16978   4 LIIKATDETL-TSENWQYILDVCDKVNSDpEDGAREAIAAIQKRL----QHRNAnVQLRSLSLADALAKNCGSRLHQEIS 78

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 17550228 120 NKDFVQDLIKLIGPKfDAPQIIQERVLSLIQAWADAFRGDPTLAGVVQSYDDLKSKG 176
Cdd:cd16978  79 SRSFTQTLLRLINDR-TTHATVKKRILELIKQLSDSFKSDPSLGLMSDTYDQLKSKY 134

canonical GAT domain found in target of Myb protein 1 (Tom1); Tom1 was originally identified by its induced expression by the v-Myb oncogene. It is predominantly present in the cytosol and can interact with clathrin, endofin, Toll-interacting protein (Tollip), and ubiquitinated proteins. It acts as a linker protein to regulate the ability of endofin to recruit clathrin onto the sorting endosome. Moreover, Tom1 functions as a negative regulator of IL-1beta and tumor necrosis factor (TNF)-alpha-induced signaling pathways. It also plays a role in the TLR2/4 signaling pathways. Tom1 contains an N-terminal VHS (Vps27p/Hrs/STAM)-domain, a GAT (GGA and TOM1) domain and a C-terminal clathrin-binding region, both of which are conserved in Golgi-localized gamma ear-containing Arf-binding proteins (GGAs). In contrast to GGAs, Tom1 binds to ubiquitin, ubiquitinated proteins, and Tollip through its GAT domain, but does not associate with Arf GTPases through its GAT domain nor with acidic cluster-dileucine sequences through its VHS domain. The canonical GAT domain is a monomeric three-helix bundle that binds ubiquitin.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17550228 248 PAQLTKLRADLDVVNQNIKVFRETLTDVVPRKETADELQLLSDLNDTCRHMQQRVLDLIRYVSNDEVTYELLMVNDSLNS 327
Cdd:cd14236   1 PEQIGKLRSELEMVSGNVRVMSEMLTELVPTQAEPADLELLQELNRTCRAMQQRVLELIPQIANEQLTEELLIVNDNLNN 80

                        90
                ....*....|....*
gi 17550228 328 VFEKYDRFVSNRDGE 342
Cdd:cd14236  81 VFLRHERFERFRTGQ 95

VHS, ENTH and ANTH domain superfamily; This superfamily is composed of proteins containing a VHS, CID, ENTH, or ANTH domain. The VHS domain is present in Vps27 (Vacuolar Protein Sorting), Hrs (Hepatocyte growth factor-regulated tyrosine kinase substrate) and STAM (Signal Transducing Adaptor Molecule). It is located at the N-termini of proteins involved in intracellular membrane trafficking. The CTD-Interacting Domain (CID) is present in several RNA-processing factors and binds tightly to the carboxy-terminal domain (CTD) of RNA polymerase II (RNAP II or Pol II). The epsin N-terminal homology (ENTH) domain is an evolutionarily conserved protein module found primarily in proteins that participate in clathrin-mediated endocytosis. A set of proteins previously designated as harboring an ENTH domain in fact contains a highly similar, yet unique module referred to as an AP180 N-Terminal Homology (ANTH) domain. VHS, ENTH, and ANTH domains are structurally similar and are composed of a superhelix of eight alpha helices. ENTH and ANTH (E/ANTH) domains bind both inositol phospholipids and proteins and contribute to the nucleation and formation of clathrin coats on membranes. ENTH domains also function in the development of membrane curvature through lipid remodeling during the formation of clathrin-coated vesicles. E/ANTH domain-bearing proteins have recently been shown to function with adaptor protein-1 and GGA adaptors at the Trans-Golgi Network, which suggests that E/ANTH domains are universal components of the machinery for clathrin-mediated membrane budding.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17550228  39 VGRKIELATDaNLLATENWGLNMEICDFINGTEDGPRDAVRALKKRLHNamsKNNAVVMYTLTVLETAVKNCNHHFHVLV 118
Cdd:cd00197   1 FEKTVEKATS-NENMGPDWPLIMEICDLINETNVGPKEAVDAIKKRINN---KNPHVVLKALTLLEYCVKNCGERFHQEV 76

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 17550228 119 CNKDFVQDLIKLIGPKF---DAPQIIQERVLSLIQAWAD 154
Cdd:cd00197  77 ASNDFAVELLKFDKSGLlgdDVSTNVREKAIELVQLWAS 115

canonical GAT domain found in target of Myb-like protein 1 (Tom1L1); Tom1L1, also called Src-activating and signaling molecule protein (Srcasm), was identified as a substrate of the Src family of protein kinases. It is tyrosine-phosphorylated by Src family kinases and modulates growth factor and Src-mediated signaling pathways. It also plays a potential role in endosomal sorting and ligand-stimulated endocytosis of EGF receptors (EGFR). Tom1L1 is predominantly present in the cytosol and can interact with Toll-interacting protein (Tollip), Hrs or TSG101, clathrin, and ubiquitinated proteins. It contains an N-terminal VHS (Vps27p/Hrs/STAM)-domain, a GAT (GGA and TOM1) domain, and a C-terminal clathrin-binding region, both of which are conserved in Golgi-localized gamma ear-containing Arf-binding proteins (GGAs). It interacts with Tollip through their GAT domain and recuits clathrin onto endosomes through their C-terminal region. However, in the C-terminal clathrin-binding region, Tom1 and Tom1L2 are similar to each other, but distinguishable from Tom1L1. The canonical GAT domain is a monomeric three-helix bundle that binds ubiquitin.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17550228 248 PAQLTKLRADLDVVNQNIKVFRETLTDVVPRKETADELQLLSDLNDTCRHMQQRVLDLIRYVSNDEVTYELLMVNDSLNS 327
Cdd:cd14237   1 PEQIGKLYSELDIVKMNVRVMSAILLENTPGAENPEDMELLEKLYKTCREMQERIMKLLETVENEDVIIELIQVNDDLNN 80

                        90
                ....*....|..
gi 17550228 328 VFEKYDRFVSNR 339
Cdd:cd14237  81 VFLRHERFSRNR 92

VHS (Vps27/Hrs/STAM) domain of GGA (Golgi-localized, Gamma-ear-containing, Arf-binding) subfamily; GGA (Golgi-localized, Gamma-ear-containing, Arf-binding) comprises a subfamily of ubiquitously expressed, monomeric, motif-binding cargo/clathrin adaptor proteins involved in membrane trafficking between the Trans-Golgi Network (TGN) and endosomes. The VHS domain has a superhelical structure similar to the structure of the ARM (Armadillo) repeats and is present at the N-termini of proteins. GGA proteins have a multidomain structure consisting of an N-terminal VHS domain linked by a short proline-rich linker to a GAT (GGA and TOM) domain, which is followed by a long flexible linker to the C-terminal appendage, GAE (Gamma-Adaptin Ear) domain. The VHS domain of GGA proteins binds to the acidic-cluster dileucine (DxxLL) motif found on the cytoplasmic tails of cargo proteins trafficked between the Trans-Golgi Network and the endosomal system.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17550228  41 RKIELATDAnLLATENWGLNMEICDFINGTEDGPRDAVRALKKRLHNAMSKnnaVVMYTLTVLETAVKNCNHHFHVLVCN 120
Cdd:cd16977   3 RWINRATNP-SNAEPDWALILGFCDQINEDGEGPRDAARLLAHKIQSPQEW---EAIQALTVLEVCMKNCGYRFHLEVGK 78

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 17550228 121 KDFVQDLIKLIGPKF---DAPQIIQERVLSLIQAWADAFrgdPTLAGVVQSYDDLKSK 175
Cdd:cd16977  79 FRFLNELIKVVSPKYlgsRRSEKVKRKILELLYSWTVTL---PEEGKIRDAYQMLKKQ 133

VHS (Vps27/Hrs/STAM) domain of fungal GGA (Golgi-localized, Gamma-ear-containing, Arf-binding) proteins; GGA (Golgi-localized, Gamma-ear-containing, Arf-binding) comprises a subfamily of ubiquitously expressed, monomeric, motif-binding cargo/clathrin adaptor proteins involved in membrane trafficking between the Trans-Golgi Network (TGN) and endosomes. Yeast GGAs facilitate the specific and direct delivery of vacuolar sorting receptor Vps10p and the processing protease Kex2p from the TGN to the late endosome/prevacuolar compartment (PVC). The VHS domain has a superhelical structure similar to the structure of the ARM (Armadillo) repeats and is present at the N-termini of proteins. GGA proteins have a multidomain structure consisting of an N-terminal VHS domain linked by a short proline-rich linker to a GAT (GGA and TOM) domain, which is followed by a long flexible linker to the C-terminal appendage, GAE (Gamma-Adaptin Ear) domain. The VHS domain of GGA proteins binds to the acidic-cluster dileucine (DxxLL) motif found on the cytoplasmic tails of cargo proteins trafficked between the Trans-Golgi Network and the endosomal system.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17550228  41 RKIELATDaNLLATENWGLNMEICDFINGTE-DGPRDAVRALKKRLHNamsKNNAVVMYTLTVLETAVKNCNHHFHVLVC 119
Cdd:cd16998   3 RYIERACD-PSLEEPNLALNLEIADLINEKQgNTPREAAFAIVRLVNS---RNPTVALLALHLLDVCVKNCGYPFHLQIA 78

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 17550228 120 NKDFVQDLIKligpKFDA-----PQIIQERVLSLIQAW 152
Cdd:cd16998  79 SKEFLNELVR----RFPErppsrLNPVQHKILELIEEW 112

VHS (Vps27/Hrs/STAM) domain of ADP-ribosylation factor-binding protein GGA3; ADP-ribosylation factor-binding protein GGA3 (Golgi-localized, Gamma-ear-containing, Arf-binding 3) regulates the trafficking and is required for the lysosomal degradation of BACE (beta-site APP-cleaving enzyme), the protease that initiates the production of beta-amyloid, which causes Alzheimer's disease. It also plays a key role in GABA (+) transmission, which is important in the regulation of anxiety-like behaviors. GGA3 is a member of the GGA subfamily, which is comprised of ubiquitously expressed, monomeric, motif-binding cargo/clathrin adaptor proteins involved in membrane trafficking between the Trans-Golgi Network (TGN) and endosomes. The VHS domain has a superhelical structure similar to the structure of the ARM (Armadillo) repeats and is present at the N-termini of proteins. GGA proteins have a multidomain structure consisting of an N-terminal VHS domain linked by a short proline-rich linker to a GAT (GGA and TOM) domain, which is followed by a long flexible linker to the C-terminal appendage, GAE (Gamma-Adaptin Ear) domain. The VHS domain of GGA proteins binds to the acidic-cluster dileucine (DxxLL) motif found on the cytoplasmic tails of cargo proteins trafficked between the Trans-Golgi Network and the endosomal system.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17550228  55 ENWGLNMEICDFINGTEDGPRDAVRALKkrlHNAMSKNNAVVMYTLTVLETAVKNCNHHFHVLVCNKDFVQDLIKLIGPK 134
Cdd:cd17008  19 EDWEYIIGFCDQINKELEGPQIAVRLLA---HKIQSPQEWEALQALTVLEACMKNCGRRFHNEVGKFRFLNELIKVVSPK 95

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 17550228 135 FDAPQI---IQERVLSLIQAWADAFrgdPTLAGVVQSYDDLKSKGV 177
Cdd:cd17008  96 YLGDRVsekVKTKVIELLYSWTVAL---PEEAKIKDAYHMLKRQGI 138

VHS (Vps27/Hrs/STAM) domain of ADP-ribosylation factor-binding protein GGA1; ADP-ribosylation factor-binding protein GGA1 (Golgi-localized, Gamma-ear-containing, Arf-binding 1) is also called Gamma-adaptin-related protein 1. It is expressed in human brain and affects the generation of amyloid beta-peptide, and may be involved in the pathogenesis of Alzheimer disease. It is a member of the GGA subfamily, which is comprised of ubiquitously expressed, monomeric, motif-binding cargo/clathrin adaptor proteins involved in membrane trafficking between the Trans-Golgi Network (TGN) and endosomes. The VHS domain has a superhelical structure similar to the structure of the ARM (Armadillo) repeats and is present at the N-termini of proteins. GGA proteins have a multidomain structure consisting of an N-terminal VHS domain linked by a short proline-rich linker to a GAT (GGA and TOM) domain, which is followed by a long flexible linker to the C-terminal appendage, GAE (Gamma-Adaptin Ear) domain. The VHS domain of GGA proteins binds to the acidic-cluster dileucine (DxxLL) motif found on the cytoplasmic tails of cargo proteins trafficked between the Trans-Golgi Network and the endosomal system.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17550228  56 NWGLNMEICDFINGTEDGPRDAVRALKkrlHNAMSKNNAVVMYTLTVLETAVKNCNHHFHVLVCNKDFVQDLIKLIGPKF 135
Cdd:cd17009  18 DWASINGFCEQLNEEFEGPPLATRLLA---HKIQSPQEWEAIQALTVLETCMKSCGKRFHDEVGKFRFLNELIKVVSPKY 94

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 17550228 136 ---DAPQIIQERVLSLIQAWAdafRGDPTLAGVVQSYDDLKSKGV 177
Cdd:cd17009  95 lgsRTPEKVKNKILELLYSWT---VGLPEEVKIAEAYQMLKKQGI 136

VHS (Vps27/Hrs/STAM) domain of ADP-ribosylation factor-binding protein GGA2; ADP-ribosylation factor-binding protein GGA2 (Golgi-localized, Gamma-ear-containing, Arf-binding 2) is also called Gamma-adaptin-related protein 2 and VHS domain and ear domain of gamma-adaptin (Vear). It is a member of the GGA subfamily, which is comprised of ubiquitously expressed, monomeric, motif-binding cargo/clathrin adaptor proteins involved in membrane trafficking between the Trans-Golgi Network (TGN) and endosomes. The VHS domain has a superhelical structure similar to the structure of the ARM (Armadillo) repeats and is present at the N-termini of proteins. GGA proteins have a multidomain structure consisting of an N-terminal VHS domain linked by a short proline-rich linker to a GAT (GGA and TOM) domain, which is followed by a long flexible linker to the C-terminal appendage, GAE (Gamma-Adaptin Ear) domain. The VHS domain of GGA proteins binds to the acidic-cluster dileucine (DxxLL) motif found on the cytoplasmic tails of cargo proteins trafficked between the Trans-Golgi Network and the endosomal system.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17550228  46 ATDANLlATENWGLNMEICDFINGTEDGPRDAVRALKkrlHNAMSKNNAVVMYTLTVLETAVKNCNHHFHVLVCNKDFVQ 125
Cdd:cd17010   9 ATDPSN-SEEDWECIQGFCEQVNKEPEGPQIATRLLA---HKIQSPQEREALHALTVLEMCMNNCGERFHSEVAKFRFLN 84

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 17550228 126 DLIKLIGPKFD---APQIIQERVLSLIQAWADAFRGDPTlagVVQSYDDLKSKGV 177
Cdd:cd17010  85 ELIKVLSPKYLgtwSSEKVKSRVIEVLFSWTVWLPEEVK---IRDAYQMLKKQGI 136

canonical GAT domain found in uncharacterized Golgi-localized gamma ear-containing Arf-binding protein (GGA)-like proteins mainly found in plants; The family includes a group of uncharacterized plant proteins containing an N-terminal VHS (Vps27p/Hrs/STAM)-domain and a GAT (GGA and TOM1) domain. Both domains are also present in Golgi-localized gamma ear-containing Arf-binding proteins (GGAs), which belong to a family of ubiquitously expressed, monomeric, motif-binding cargo/clathrin adaptor proteins that regulate clathrin-mediated trafficking of cargo proteins from the trans-Golgi network (TGN) to endosomes. In contrast to GGA proteins, members in this family do not have either a GAE (gamma-adaptin ear homology) domain or a clathrin-binding motif. The canonical GAT domain is a monomeric three-helix bundle that binds ubiquitin.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 17550228 257 DLDVVNQNIKVFRETLTDVVPRKETADELQLLSDLNDTCRHMQQRVLDLIRYVSNDEVTYELLMVNDSLNSVFEKYD 333
Cdd:cd14231   1 DLQVARNSLELLSDMLNAVDPRDPEALKDELTVDLVEQCRQSQPRVMQLVESTGDEGLLFQALELNDELQRVLSKHD 77