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Conserved domains on  [gi|29726571]
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Chain A, ADP-ribosylation factor binding protein GGA1

Protein Classification

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List of domain hits

Name Accession Description Interval E-value
GAT_GGA1_GGA2 cd14239
canonical GAT domain found in ADP-ribosylation factor (Arf)-binding proteins GGA1 and GGA2; ...
54-142 3.10e-50

canonical GAT domain found in ADP-ribosylation factor (Arf)-binding proteins GGA1 and GGA2; This subfamily includes GGA1 and GGA2, both of 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. GGA1, also called gamma-adaptin-related protein 1, or Golgi-localized gamma ear-containing Arf-binding protein 1, regulates the low-density lipoprotein and sorting receptor LR11/SorLA endocytic traffic and further alters amyloid-beta precursor protein (APP) intracellular distribution and amyloid-beta production. It is also critical for the effects of beta-site APP-cleaving enzyme-1 (BACE1) on amyloid-beta generation. It interacts with BACE1 and promotes its traffic from early endosomes to late endocytic compartments or the TGN. Moreover, GGA1 acts as a clathrin assembly protein with the ability to polymerize clathrin into tubules. GGA2, also called gamma-adaptin-related protein 2, Golgi-localized gamma ear-containing Arf-binding protein 2, or VHS domain and ear domain of gamma-adaptin (Vear), interacts with the acidic cluster-dileucine motif in the cytoplasmic tail of the cation-independent mannose 6-phosphate receptor (CI-MPR) and further plays a major role in the sorting of lysosomal enzymes. It also mediates a vital function that cannot be compensated for by GGA1 and/or GGA3. Both GGA1 and GGA2 have 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).


:

Pssm-ID: 410586  Cd Length: 88  Bit Score: 155.59  E-value: 3.10e-50
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29726571  54 KISKRVNAIEEVNNNVKLLTE*V*SHSQGGAAaGSSEDL*KELYQRCER*RPTLFRLASDTEDNDEALAEILQANDNLTQ 133
Cdd:cd14239   1 KVSKRVNAIEEVNNNVKLLTEMLMSYSRGELS-ESSEELMKELYQRCEKMRPTLFRLASDTEDNDEALAEILQANDNLTQ 79

                ....*....
gi 29726571 134 VINLYKQLV 142
Cdd:cd14239  80 VINLYKQLV 88
GGA_N-GAT pfam18308
N-terminal extension of GAT domain; This region is found in the N-terminal region of the GGA ...
13-51 1.22e-13

N-terminal extension of GAT domain; This region is found in the N-terminal region of the GGA and Tom1 (GAT) domain in Golgi-localizing gamma-adaptin ARF-binding protein 1 (GGA1) present in Homo sapiens. The GAT domain is the key region in GGA that interacts with ARF. ARF plays a crucial role in docking adaptor proteins to membranes. This region is referred to as N-GAT and it interacts extensively with ARF.


:

Pssm-ID: 465702  Cd Length: 39  Bit Score: 61.16  E-value: 1.22e-13
                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 29726571    13 FEDEEKSK*LARLLKSSHPEDLRAANKLIKE*VQEDQKR 51
Cdd:pfam18308   1 FDDEEKSKLLARLLKSKNPEDLQAANRLIKSMVKEDDER 39
 
Name Accession Description Interval E-value
GAT_GGA1_GGA2 cd14239
canonical GAT domain found in ADP-ribosylation factor (Arf)-binding proteins GGA1 and GGA2; ...
54-142 3.10e-50

canonical GAT domain found in ADP-ribosylation factor (Arf)-binding proteins GGA1 and GGA2; This subfamily includes GGA1 and GGA2, both of 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. GGA1, also called gamma-adaptin-related protein 1, or Golgi-localized gamma ear-containing Arf-binding protein 1, regulates the low-density lipoprotein and sorting receptor LR11/SorLA endocytic traffic and further alters amyloid-beta precursor protein (APP) intracellular distribution and amyloid-beta production. It is also critical for the effects of beta-site APP-cleaving enzyme-1 (BACE1) on amyloid-beta generation. It interacts with BACE1 and promotes its traffic from early endosomes to late endocytic compartments or the TGN. Moreover, GGA1 acts as a clathrin assembly protein with the ability to polymerize clathrin into tubules. GGA2, also called gamma-adaptin-related protein 2, Golgi-localized gamma ear-containing Arf-binding protein 2, or VHS domain and ear domain of gamma-adaptin (Vear), interacts with the acidic cluster-dileucine motif in the cytoplasmic tail of the cation-independent mannose 6-phosphate receptor (CI-MPR) and further plays a major role in the sorting of lysosomal enzymes. It also mediates a vital function that cannot be compensated for by GGA1 and/or GGA3. Both GGA1 and GGA2 have 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).


Pssm-ID: 410586  Cd Length: 88  Bit Score: 155.59  E-value: 3.10e-50
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29726571  54 KISKRVNAIEEVNNNVKLLTE*V*SHSQGGAAaGSSEDL*KELYQRCER*RPTLFRLASDTEDNDEALAEILQANDNLTQ 133
Cdd:cd14239   1 KVSKRVNAIEEVNNNVKLLTEMLMSYSRGELS-ESSEELMKELYQRCEKMRPTLFRLASDTEDNDEALAEILQANDNLTQ 79

                ....*....
gi 29726571 134 VINLYKQLV 142
Cdd:cd14239  80 VINLYKQLV 88
GAT pfam03127
GAT domain; The GAT domain is responsible for binding of GGA proteins to several members of ...
66-144 1.20e-19

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.


Pssm-ID: 460818  Cd Length: 76  Bit Score: 77.58  E-value: 1.20e-19
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 29726571    66 NNNVKLLTE*V*SHSQGGaaaGSSEDL*KELYQRCER*RPTLFRLASDTEDNDEALAEILQANDNLTQVINLYKQLVRG 144
Cdd:pfam03127   1 RNNAKLLNEMLSSTDPDE---ELDNELIKELYERCKSAQPKIQKLIEETSDEDDLLAELLQLNDDLNNVLERYERLKKG 76
GGA_N-GAT pfam18308
N-terminal extension of GAT domain; This region is found in the N-terminal region of the GGA ...
13-51 1.22e-13

N-terminal extension of GAT domain; This region is found in the N-terminal region of the GGA and Tom1 (GAT) domain in Golgi-localizing gamma-adaptin ARF-binding protein 1 (GGA1) present in Homo sapiens. The GAT domain is the key region in GGA that interacts with ARF. ARF plays a crucial role in docking adaptor proteins to membranes. This region is referred to as N-GAT and it interacts extensively with ARF.


Pssm-ID: 465702  Cd Length: 39  Bit Score: 61.16  E-value: 1.22e-13
                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 29726571    13 FEDEEKSK*LARLLKSSHPEDLRAANKLIKE*VQEDQKR 51
Cdd:pfam18308   1 FDDEEKSKLLARLLKSKNPEDLQAANRLIKSMVKEDDER 39
 
Name Accession Description Interval E-value
GAT_GGA1_GGA2 cd14239
canonical GAT domain found in ADP-ribosylation factor (Arf)-binding proteins GGA1 and GGA2; ...
54-142 3.10e-50

canonical GAT domain found in ADP-ribosylation factor (Arf)-binding proteins GGA1 and GGA2; This subfamily includes GGA1 and GGA2, both of 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. GGA1, also called gamma-adaptin-related protein 1, or Golgi-localized gamma ear-containing Arf-binding protein 1, regulates the low-density lipoprotein and sorting receptor LR11/SorLA endocytic traffic and further alters amyloid-beta precursor protein (APP) intracellular distribution and amyloid-beta production. It is also critical for the effects of beta-site APP-cleaving enzyme-1 (BACE1) on amyloid-beta generation. It interacts with BACE1 and promotes its traffic from early endosomes to late endocytic compartments or the TGN. Moreover, GGA1 acts as a clathrin assembly protein with the ability to polymerize clathrin into tubules. GGA2, also called gamma-adaptin-related protein 2, Golgi-localized gamma ear-containing Arf-binding protein 2, or VHS domain and ear domain of gamma-adaptin (Vear), interacts with the acidic cluster-dileucine motif in the cytoplasmic tail of the cation-independent mannose 6-phosphate receptor (CI-MPR) and further plays a major role in the sorting of lysosomal enzymes. It also mediates a vital function that cannot be compensated for by GGA1 and/or GGA3. Both GGA1 and GGA2 have 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).


Pssm-ID: 410586  Cd Length: 88  Bit Score: 155.59  E-value: 3.10e-50
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29726571  54 KISKRVNAIEEVNNNVKLLTE*V*SHSQGGAAaGSSEDL*KELYQRCER*RPTLFRLASDTEDNDEALAEILQANDNLTQ 133
Cdd:cd14239   1 KVSKRVNAIEEVNNNVKLLTEMLMSYSRGELS-ESSEELMKELYQRCEKMRPTLFRLASDTEDNDEALAEILQANDNLTQ 79

                ....*....
gi 29726571 134 VINLYKQLV 142
Cdd:cd14239  80 VINLYKQLV 88
GAT_GGA_meta cd14234
canonical GAT domain found in metazoan ADP-ribosylation factor (Arf)-binding proteins (GGAs); ...
57-141 1.13e-31

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.


Pssm-ID: 410582  Cd Length: 84  Bit Score: 108.47  E-value: 1.13e-31
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29726571  57 KRVNAIEEVNNNVKLLTE*V*SHSQGGAAAGSSEdL*KELYQRCER*RPTLFRLASDTEDNDEALAEILQANDNLTQVIN 136
Cdd:cd14234   1 KRLLELEEVNNNVKLLNEMLDHYSPGESSQDELE-LMKELYESCEKMRPTLFRLASETDDDDEGLADILQANDELTRVMQ 79

                ....*
gi 29726571 137 LYKQL 141
Cdd:cd14234  80 RYKNL 84
GAT_GGA3 cd14240
canonical GAT domain found in ADP-ribosylation factor-binding protein GGA3; GGA3, also called ...
57-144 1.35e-26

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).


Pssm-ID: 410587  Cd Length: 87  Bit Score: 95.68  E-value: 1.35e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29726571  57 KRVNAIEEVNNNVKLLTE*V*SHSQGGAAAGSSEdL*KELYQRCER*RPTLFRLASDTEDNDEALAEILQANDNLTQVIN 136
Cdd:cd14240   1 KRLHTLEEVNNNVRLLNEMLAHYSKEDSSDGDKE-LMKELYDRCEKKRRTLFKLASETEDNDNSLGDILQASDDLSRVIN 79

                ....*...
gi 29726571 137 LYKQLVRG 144
Cdd:cd14240  80 SYKKIVEG 87
GAT pfam03127
GAT domain; The GAT domain is responsible for binding of GGA proteins to several members of ...
66-144 1.20e-19

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.


Pssm-ID: 460818  Cd Length: 76  Bit Score: 77.58  E-value: 1.20e-19
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 29726571    66 NNNVKLLTE*V*SHSQGGaaaGSSEDL*KELYQRCER*RPTLFRLASDTEDNDEALAEILQANDNLTQVINLYKQLVRG 144
Cdd:pfam03127   1 RNNAKLLNEMLSSTDPDE---ELDNELIKELYERCKSAQPKIQKLIEETSDEDDLLAELLQLNDDLNNVLERYERLKKG 76
GAT_GGA cd14230
canonical GAT domain found in metazoan and fungal ADP-ribosylation factor (Arf)-binding ...
62-141 2.01e-16

canonical GAT domain found in metazoan and fungal 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. GGAs also play important roles in ubiquitin-dependent sorting of cargo proteins both in biosynthetic and endocytic pathways. The family includes three GGAs (GGA1, GGA2, and GGA3) identified in mammals and two GGAs (Gga1p and Gga2p) identified in the budding yeast Saccharomyces cerevisiae. All these GGAs have a multidomain structure consisting of: an N-terminal VHS (Vps27/Hrs/Stam) domain that binds 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. In contrast to other GGAs-like proteins, members of this family contain a GAT N-terminal region, a helix-loop-helix in the complex with Arf1-GTP.


Pssm-ID: 410578  Cd Length: 80  Bit Score: 69.50  E-value: 2.01e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29726571  62 IEEVNNNVKLLTE*V*SHSQGGAAAGSSEdL*KELYQRCER*RPTLFRLASDTEDNDEALAEILQANDNLTQVINLYKQL 141
Cdd:cd14230   2 LEEAKNNVDLLDEMLLSYSQEDSSDGDNE-LMKELYDQLENMRPTLFKLASETEENDNSLGDVLQASDNVNRVINKYKDI 80
GGA_N-GAT pfam18308
N-terminal extension of GAT domain; This region is found in the N-terminal region of the GGA ...
13-51 1.22e-13

N-terminal extension of GAT domain; This region is found in the N-terminal region of the GGA and Tom1 (GAT) domain in Golgi-localizing gamma-adaptin ARF-binding protein 1 (GGA1) present in Homo sapiens. The GAT domain is the key region in GGA that interacts with ARF. ARF plays a crucial role in docking adaptor proteins to membranes. This region is referred to as N-GAT and it interacts extensively with ARF.


Pssm-ID: 465702  Cd Length: 39  Bit Score: 61.16  E-value: 1.22e-13
                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 29726571    13 FEDEEKSK*LARLLKSSHPEDLRAANKLIKE*VQEDQKR 51
Cdd:pfam18308   1 FDDEEKSKLLARLLKSKNPEDLQAANRLIKSMVKEDDER 39
GAT_SF cd12930
GAT domain found in eukaryotic GGAs, metazoan Tom1-like proteins, metazoan STAMs, fungal Vps27, ...
63-141 1.15e-09

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.


Pssm-ID: 410577  Cd Length: 77  Bit Score: 51.85  E-value: 1.15e-09
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 29726571  63 EEVNNNVKLLTE*V*SHSQGGAAAGSSEdL*KELYQRCER*RPTLFRLASDTEDnDEALAEILQANDNLTQVINLYKQL 141
Cdd:cd12930   1 EEVKDNVR*FSELLEK*KSRPLEILDDE-LLQELAQRCFASKARLNYLLNDKAD-DQKYNTLLE*NDNLSEV*NIYDRL 77
GAT_GGA_Tom1-like cd21383
canonical GAT domain found in eukaryotic ADP-ribosylation factor (Arf)-binding proteins (GGAs), ...
62-141 3.23e-08

canonical GAT domain found in eukaryotic ADP-ribosylation factor (Arf)-binding proteins (GGAs), metazoan myb protein 1 (Tom1)-like proteins, and similar proteins; This model represents the canonical GAT (GGA and Tom1) domain found in GGAs from eukaryotes, 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. In addition, Tom1 family proteins recruit clathrin onto endosomes through their C-terminal region. The C-terminal clathrin-binding region of Tom1 and Tom1L2 are similar to each other, but distinguishable from Tom1L1.


Pssm-ID: 410588  Cd Length: 80  Bit Score: 48.03  E-value: 3.23e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29726571  62 IEEVNNNVKLLTE*V*shSQGGAAAGSSEDL*KELYQRCER*RPTLFRLASDTED--NDEALAEILQANDNLTQVINLYK 139
Cdd:cd21383   2 LEEVKENASLLNEML---SAASPEELLDNELLQELVEFCRACQPRIVELIEATTDglDEDTLEELLELNDELNEALQRYD 78

                ..
gi 29726571 140 QL 141
Cdd:cd21383  79 DL 80
GAT_GGA_fungi cd14235
canonical GAT domain found in fungal ADP-ribosylation factor (Arf)-binding proteins (GGAs); ...
62-144 7.40e-04

canonical GAT domain found in fungal 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. Two GGAs (Gga1p and Gga2p) have been identified in the budding yeast Saccharomyces cerevisiae. Yeast GGAs play important roles in the carboxypeptidase Y (CPY) pathway, vacuole biogenesis, alpha-factor maturation, and interactions with clathrin. They have a multidomain structure consisting of VHS (Vps27/Hrs/ STAM), GAT (GGA and TOM), hinge, and GAE (gamma-adaptin ear) domains. Both Gga1p and Gga2p function as effectors of Arf in yeast. They interact with Arf1p and Arf2p in a GTP-dependent manner. Moreover, Gga2p mediates sequential ubiquitin-independent and ubiquitin-dependent steps in the trafficking of ARN1, a ferrichrome transporter in S. cerevisiae, from the TGN to the vacuole. It also acts as a phosphatidylinositol 4-phosphate effector at the Golgi exit, which binds directly to the TGN PtdIns(4)-kinase Pik1p and contributes to Pik1p recruitment. In addition, Gga2p is required for sorting of the yeast siderophore iron transporter1 (Sit1) to the vacuolar pathway. 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).


Pssm-ID: 410583  Cd Length: 92  Bit Score: 36.82  E-value: 7.40e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29726571  62 IEEVNNNVKLLTE*V*SHSQGgaAAGSSEDL*KELYQRCER*RPTLFRLASDTEDNDEALAEILQANDNLTQVINLYKQL 141
Cdd:cd14235  10 LEKLKRKAILLNEMLNNATPG--EIDVEGDTYDELASSLKSAQPKIQKIIEEESEDEESVQKLLELNDLINSLLERYDLL 87

                ...
gi 29726571 142 VRG 144
Cdd:cd14235  88 KKG 90
GAT_GGA-like_plant cd14231
canonical GAT domain found in uncharacterized Golgi-localized gamma ear-containing Arf-binding ...
62-141 2.27e-03

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.


Pssm-ID: 410579  Cd Length: 79  Bit Score: 35.31  E-value: 2.27e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29726571  62 IEEVNNNVKLLTE*V*SHSQGGAAAgSSEDL*KELYQRCER*RPTLFRLASDTEDnDEALAEILQANDNLTQVINLYKQL 141
Cdd:cd14231   2 LQVARNSLELLSDMLNAVDPRDPEA-LKDELTVDLVEQCRQSQPRVMQLVESTGD-EGLLFQALELNDELQRVLSKHDAI 79
GAT_TM1L2 cd14238
canonical GAT domain found in target of Myb-like protein 2 (Tom1L2); Tom1L2, together with Myb ...
53-143 6.22e-03

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.


Pssm-ID: 410585  Cd Length: 92  Bit Score: 34.25  E-value: 6.22e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29726571  53 EKISKRVNAIEEVNNNVKLLTE*V*SHSQGGAAAgSSEDL*KELYQRCER*RPTLFRLASDTEdNDEALAEILQANDNLT 132
Cdd:cd14238   2 EQIARLRSELDIVRGNTKVMSEMLTEMVPGQEDP-SDLELLQELNRTCRAMQQRIVELISRVS-NEEVTEELLHVNDDLN 79
                        90
                ....*....|.
gi 29726571 133 QVINLYKQLVR 143
Cdd:cd14238  80 NVFLRYERFER 90
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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