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 768023106  62 PEQIGKLRSELEMVSGNVRVMSEMLTELVPTQAEPADLELLQELNRTCRAMQQRVLELIPQIANEQLTEELLIVNDNLNN 141
Cdd:cd14236    1 PEQIGKLRSELEMVSGNVRVMSEMLTELVPTQAEPADLELLQELNRTCRAMQQRVLELIPQIANEQLTEELLIVNDNLNN 80

                         90
                 ....*....|....*
gi 768023106 142 VFLRHERFERFRTGQ 156
Cdd:cd14236   81 VFLRHERFERFRTGQ 95

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 768023106  62 PEQIGKLRSELEMVSGNVRVMSEMLTELVPTQAEPADLELLQELNRTCRAMQQRVLELIPQIANEQLTEELLIVNDNLNN 141
Cdd:cd14236    1 PEQIGKLRSELEMVSGNVRVMSEMLTELVPTQAEPADLELLQELNRTCRAMQQRVLELIPQIANEQLTEELLIVNDNLNN 80

                         90
                 ....*....|....*
gi 768023106 142 VFLRHERFERFRTGQ 156
Cdd:cd14236   81 VFLRHERFERFRTGQ 95

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 768023106  62 PEQIGKLRSELEMVSGNVRVMSEMLTELVPTQAEPADLELLQELNRTCRAMQQRVLELIPQIANEQLTEELLIVNDNLNN 141
Cdd:cd14236    1 PEQIGKLRSELEMVSGNVRVMSEMLTELVPTQAEPADLELLQELNRTCRAMQQRVLELIPQIANEQLTEELLIVNDNLNN 80

                         90
                 ....*....|....*
gi 768023106 142 VFLRHERFERFRTGQ 156
Cdd:cd14236   81 VFLRHERFERFRTGQ 95

canonical GAT domain found in target of Myb-like protein 2 (Tom1L2); Tom1L2, together with Myb protein 1 (Tom1) and target of Myb-like protein 1 (Tom1L1), constitute the Tom1 family. Tom1L2 can interact with Toll-interacting protein (Tollip), clathrin, and ubiquitin. It may play a potential role in endosomal sorting, as well as in the regulation of membrane trafficking that is linked to immunity and cell proliferation. Tom1L2 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 768023106  62 PEQIGKLRSELEMVSGNVRVMSEMLTELVPTQAEPADLELLQELNRTCRAMQQRVLELIPQIANEQLTEELLIVNDNLNN 141
Cdd:cd14238    1 SEQIARLRSELDIVRGNTKVMSEMLTEMVPGQEDPSDLELLQELNRTCRAMQQRIVELISRVSNEEVTEELLHVNDDLNN 80

                         90
                 ....*....|..
gi 768023106 142 VFLRHERFERFR 153
Cdd:cd14238   81 VFLRYERFERYR 92

GAT domain found in eukaryotic GGAs, metazoan Tom1-like proteins, metazoan STAMs, fungal Vps27, and similar proteins; The GAT (GGA and Tom1) domain superfamily includes the canonical GAT domain found in ADP-ribosylation factor (Arf)-binding proteins (GGAs) from eukaryotes, myb protein 1 (Tom1)-like proteins from metazoa, and LAS seventeen-binding protein 5 (Lsb5p)-like proteins from fungi. The canonical GAT domain is a monomeric three-helix bundle that binds ubiquitin. GGAs, also called Golgi-localized gamma-ear-containing Arf-binding proteins, 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. GGAs play important roles in ubiquitin-dependent sorting of cargo proteins both in biosynthetic and endocytic pathways. Tom1 and its related proteins, Tom1L1 and Tom1L2, form a protein family sharing an N-terminal VHS-domain followed by a GAT domain. Tom1 family proteins bind to ubiquitin, ubiquitinated proteins, and Toll-interacting protein (Tollip) through its GAT domain. They do not associate with either Arf GTPases through its GAT domain nor with acidic cluster-dileucine sequences through its VHS domain. The GAT domain superfamily also includes the non-canonical GAT domain found in several components of the ESCRT-0 complex, including signal transducing adapter molecules (STAMs) and hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) from metazoa, as well as vacuolar protein sorting-associated protein 27 (Vps27) and class E vacuolar protein-sorting machinery protein Hse1 from fungi. Hrs, together with STAM, forms a Hrs/STAM core complex. Vps27, together with Hse1, forms a Vps27/Hse1 core complex. Those complexes consist of two intertwined GAT domains, each consisting of two helices from one subunit, and one from the other subunit. The intertwined GAT heterodimer acts as a scaffold for binding of ubiquitinated cargo proteins and coordinating ubiquitination and deubiquitination reactions that regulate sorting.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 768023106  73 EMVSGNVRVMSEMLTELVPTQAEPADLELLQELNRTCRAMQQRVLELIPQIANEQLTEELLIVNDNLNNVFLRHERF 149
Cdd:cd12930    1 EEVKDNVR*FSELLEK*KSRPLEILDDELLQELAQRCFASKARLNYLLNDKADDQKYNTLLE*NDNLSEV*NIYDRL 77

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 768023106   76 SGNVRVMSEMLTELvpTQAEPADLELLQELNRTCRAMQQRVLELIPQIANEQ-LTEELLIVNDNLNNVFLRHERFER 151
Cdd:pfam03127   1 RNNAKLLNEMLSST--DPDEELDNELIKELYERCKSAQPKIQKLIEETSDEDdLLAELLQLNDDLNNVLERYERLKK 75

canonical GAT domain found in metazoan ADP-ribosylation factor (Arf)-binding proteins (GGAs); GGAs, also called Golgi-localized gamma-ear-containing Arf-binding proteins, 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. Moreover, GGAs play important roles in ubiquitin-dependent sorting of cargo proteins both in biosynthetic and endocytic pathways. Three GGAs (GGA1, GGA2, and GGA3) have been identified in mammals. They may appear to behave similarly, since all of them have a multidomain structure consisting of: an N-terminal VHS (Vps27/Hrs/Stam) domain that binds the acidic-cluster dileucine (DxxLL)-type sorting signals (where x is any amino acid) found in the cytoplasmic tail of TGN sorting receptors; a GAT (GGA and TOM) domain that interacts with class I GTP-bound form of Arf proteins, Rabaptin-5, ubiquitin, and the tumor susceptibility gene 101 product (TSG101); a largely unstructured hinge region that contains clathrin-binding motifs; and a C-terminal GAE (gamma-adaptin ear homology) domain that binds accessory proteins. However, the three GGAs have some differences, which suggest they may possess their own distinct roles. For instance, both GGA1 and GGA3, but not GGA2, contains an internal DxxLL motif that binds to it own VHS domain. Only a portion of the VHS domain of GGA2 possesses distant structural homology to that of GGA1 or GGA3. Moreover, the binding affinity of GGA2 to ubiquitin is quite lower than that of GGA1 or GGA3. In addition, GGA3 has a short splicing variant that is predominantly expressed in human cell lines and tissues except the brain. It does have a VHS domain, but it is unable to bind to the DxxLL motif. GGA2 and GGA3 undergo epidermal growth factor (EGF)-induced phosphorylation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768023106  67 KLRSELEMVSGNVRVMSEMLTELVPTQAEPADLELLQELNRTCRAMQ---QRVLELIPQiaNEQLTEELLIVNDNLNNVF 143
Cdd:cd14234    1 KRLLELEEVNNNVKLLNEMLDHYSPGESSQDELELMKELYESCEKMRptlFRLASETDD--DDEGLADILQANDELTRVM 78

                 ....*
gi 768023106 144 LRHER 148
Cdd:cd14234   79 QRYKN 83

canonical GAT domain found in ADP-ribosylation factor-binding protein GGA3; GGA3, also called Golgi-localized gamma ear-containing Arf-binding protein 3, belongs 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. GGA3 interacts selectively with the Met/Hepatocyte Growth Factor receptor tyrosine kinase (RTK) when stimulated. It functions as a specific cargo adaptor to target the Met RTK into recycling tubules, and further coordinates the recycling, signaling and degradative fates of the Met RTK. Moreover, GGA3, together with PACS-1 and the protein kinase CK2, forms a complex that regulates cation-independent mannose-6-phosphate receptor (CI-MPR) trafficking. Furthermore, GGA3 has been identified as an interacting protein of the beta-site APP-cleaving enzyme-1 (BACE1), a stress-related protease that is involved in Alzheimer's disease (AD) pathology. GGA3 has a multidomain structure consisting of an N-terminal VHS (Vps27/Hrs/Stam) domain, a GAT (GGA and TOM) domain, a largely unstructured hinge region that contains clathrin-binding motifs, and a C-terminal GAE (gamma-adaptin ear homology) domain. The GAT domain of GGAs interacts with class I GTP-bound form of Arf proteins, Rabaptin-5, ubiquitin, and/or the tumor susceptibility gene 101 product (TSG101).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 768023106  72 LEMVSGNVRVMSEMLTELVPTQAEPADLELLQELNRTCRAMQQRVLELIPQIA-NEQLTEELLIVNDNLNNV 142
Cdd:cd14240    6 LEEVNNNVRLLNEMLAHYSKEDSSDGDKELMKELYDRCEKKRRTLFKLASETEdNDNSLGDILQASDDLSRV 77