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Conserved domains on  [gi|289577111|ref|NP_001166175|]
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ADP-ribosylation factor-binding protein GGA3 isoform 2 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
GAT_GGA3 cd14240
canonical GAT domain found in ADP-ribosylation factor-binding protein GGA3; GGA3, also called ...
91-177 2.64e-57

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: 186.98  E-value: 2.64e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289577111  91 KRLHTLEEVNNNVRLLSEMLLHYSQEDSSDGDRELMKELFDQCENKRRTLFKLASETEDNDNSLGDILQASDNLSRVINS 170
Cdd:cd14240    1 KRLHTLEEVNNNVRLLNEMLAHYSKEDSSDGDKELMKELYDRCEKKRRTLFKLASETEDNDNSLGDILQASDDLSRVINS 80

                 ....*..
gi 289577111 171 YKTIIEG 177
Cdd:cd14240   81 YKKIVEG 87
Alpha_adaptinC2 smart00809
Adaptin C-terminal domain; Adaptins are components of the adaptor complexes which link ...
479-568 2.86e-21

Adaptin C-terminal domain; Adaptins are components of the adaptor complexes which link clathrin to receptors in coated vesicles. Clathrin-associated protein complexes are believed to interact with the cytoplasmic tails of membrane proteins, leading to their selection and concentration. Gamma-adaptin is a subunit of the golgi adaptor. Alpha adaptin is a heterotetramer that regulates clathrin-bud formation. The carboxyl-terminal appendage of the alpha subunit regulates translocation of endocytic accessory proteins to the bud site. This Ig-fold domain is found in alpha, beta and gamma adaptins and consists of a beta-sandwich containing 7 strands in 2 beta-sheets in a greek-key topology.. The adaptor appendage contains an additional N-terminal strand.


:

Pssm-ID: 197886 [Multi-domain]  Cd Length: 104  Bit Score: 88.84  E-value: 2.86e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289577111   479 AYDKNGFRILFHFAKecppgRPDVLVVVVSMLNTAPLPVKSIVLQAAVPKSMKVKLQPPSGTELSPFSPIQppaaitQVM 558
Cdd:smart00809   1 AYEKNGLQIGFKFER-----RPGLIRITLTFTNKSPSPITNFSFQAAVPKSLKLQLQPPSSPTLPPGGQIT------QVL 69
                           90
                   ....*....|
gi 289577111   559 LLANPLKKQV 568
Cdd:smart00809  70 KVENPGKFPL 79
GGA_N-GAT pfam18308
N-terminal extension of GAT domain; This region is found in the N-terminal region of the GGA ...
47-85 6.89e-10

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: 54.23  E-value: 6.89e-10
                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 289577111   47 FDDEEKSKLLAKLLKSKNPDDLQEANKLIKSMVKEDEAR 85
Cdd:pfam18308   1 FDDEEKSKLLARLLKSKNPEDLQAANRLIKSMVKEDDER 39
VHS_ENTH_ANTH super family cl02544
VHS, ENTH and ANTH domain superfamily; This superfamily is composed of proteins containing a ...
1-24 1.81e-08

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.


The actual alignment was detected with superfamily member cd17008:

Pssm-ID: 470608 [Multi-domain]  Cd Length: 141  Bit Score: 53.50  E-value: 1.81e-08
                         10        20
                 ....*....|....*....|....
gi 289577111   1 MALPEEAKIKDAYHMLKRQGIVQS 24
Cdd:cd17008  118 VALPEEAKIKDAYHMLKRQGIVQS 141
 
Name Accession Description Interval E-value
GAT_GGA3 cd14240
canonical GAT domain found in ADP-ribosylation factor-binding protein GGA3; GGA3, also called ...
91-177 2.64e-57

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: 186.98  E-value: 2.64e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289577111  91 KRLHTLEEVNNNVRLLSEMLLHYSQEDSSDGDRELMKELFDQCENKRRTLFKLASETEDNDNSLGDILQASDNLSRVINS 170
Cdd:cd14240    1 KRLHTLEEVNNNVRLLNEMLAHYSKEDSSDGDKELMKELYDRCEKKRRTLFKLASETEDNDNSLGDILQASDDLSRVINS 80

                 ....*..
gi 289577111 171 YKTIIEG 177
Cdd:cd14240   81 YKKIVEG 87
GAT pfam03127
GAT domain; The GAT domain is responsible for binding of GGA proteins to several members of ...
100-177 3.19e-22

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: 90.68  E-value: 3.19e-22
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 289577111  100 NNNVRLLSEMLLHYSQEDSSDGdrELMKELFDQCENKRRTLFKLASETEDNDNSLGDILQASDNLSRVINSYKTIIEG 177
Cdd:pfam03127   1 RNNAKLLNEMLSSTDPDEELDN--ELIKELYERCKSAQPKIQKLIEETSDEDDLLAELLQLNDDLNNVLERYERLKKG 76
Alpha_adaptinC2 smart00809
Adaptin C-terminal domain; Adaptins are components of the adaptor complexes which link ...
479-568 2.86e-21

Adaptin C-terminal domain; Adaptins are components of the adaptor complexes which link clathrin to receptors in coated vesicles. Clathrin-associated protein complexes are believed to interact with the cytoplasmic tails of membrane proteins, leading to their selection and concentration. Gamma-adaptin is a subunit of the golgi adaptor. Alpha adaptin is a heterotetramer that regulates clathrin-bud formation. The carboxyl-terminal appendage of the alpha subunit regulates translocation of endocytic accessory proteins to the bud site. This Ig-fold domain is found in alpha, beta and gamma adaptins and consists of a beta-sandwich containing 7 strands in 2 beta-sheets in a greek-key topology.. The adaptor appendage contains an additional N-terminal strand.


Pssm-ID: 197886 [Multi-domain]  Cd Length: 104  Bit Score: 88.84  E-value: 2.86e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289577111   479 AYDKNGFRILFHFAKecppgRPDVLVVVVSMLNTAPLPVKSIVLQAAVPKSMKVKLQPPSGTELSPFSPIQppaaitQVM 558
Cdd:smart00809   1 AYEKNGLQIGFKFER-----RPGLIRITLTFTNKSPSPITNFSFQAAVPKSLKLQLQPPSSPTLPPGGQIT------QVL 69
                           90
                   ....*....|
gi 289577111   559 LLANPLKKQV 568
Cdd:smart00809  70 KVENPGKFPL 79
Alpha_adaptinC2 pfam02883
Adaptin C-terminal domain; Alpha adaptin is a heterotetramer which regulates clathrin-bud ...
476-569 8.88e-21

Adaptin C-terminal domain; Alpha adaptin is a heterotetramer which regulates clathrin-bud formation. The carboxyl-terminal appendage of the alpha subunit regulates translocation of endocytic accessory proteins to the bud site. This ig-fold domain is found in alpha, beta and gamma adaptins.


Pssm-ID: 460735  Cd Length: 111  Bit Score: 87.76  E-value: 8.88e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289577111  476 PVTAYDKNGFRILFHFAKecpPGRPDVLVVVVSMLNTAPLPVKSIVLQAAVPKSMKVKLQPPSGTELSPFspiqPPAAIT 555
Cdd:pfam02883   2 PVVLYESDGLQIGFSFER---SRRPGQIRITLTFTNKSSSPISNFSFQAAVPKSLKLQLQPPSSNVLPPN----PGGQIT 74
                          90
                  ....*....|....
gi 289577111  556 QVMLLANPLKKQVL 569
Cdd:pfam02883  75 QVLLIENPGKKPLR 88
GGA_N-GAT pfam18308
N-terminal extension of GAT domain; This region is found in the N-terminal region of the GGA ...
47-85 6.89e-10

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: 54.23  E-value: 6.89e-10
                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 289577111   47 FDDEEKSKLLAKLLKSKNPDDLQEANKLIKSMVKEDEAR 85
Cdd:pfam18308   1 FDDEEKSKLLARLLKSKNPEDLQAANRLIKSMVKEDDER 39
VHS_GGA3 cd17008
VHS (Vps27/Hrs/STAM) domain of ADP-ribosylation factor-binding protein GGA3; ADP-ribosylation ...
1-24 1.81e-08

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.


Pssm-ID: 340805 [Multi-domain]  Cd Length: 141  Bit Score: 53.50  E-value: 1.81e-08
                         10        20
                 ....*....|....*....|....
gi 289577111   1 MALPEEAKIKDAYHMLKRQGIVQS 24
Cdd:cd17008  118 VALPEEAKIKDAYHMLKRQGIVQS 141
 
Name Accession Description Interval E-value
GAT_GGA3 cd14240
canonical GAT domain found in ADP-ribosylation factor-binding protein GGA3; GGA3, also called ...
91-177 2.64e-57

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: 186.98  E-value: 2.64e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289577111  91 KRLHTLEEVNNNVRLLSEMLLHYSQEDSSDGDRELMKELFDQCENKRRTLFKLASETEDNDNSLGDILQASDNLSRVINS 170
Cdd:cd14240    1 KRLHTLEEVNNNVRLLNEMLAHYSKEDSSDGDKELMKELYDRCEKKRRTLFKLASETEDNDNSLGDILQASDDLSRVINS 80

                 ....*..
gi 289577111 171 YKTIIEG 177
Cdd:cd14240   81 YKKIVEG 87
GAT_GGA_meta cd14234
canonical GAT domain found in metazoan ADP-ribosylation factor (Arf)-binding proteins (GGAs); ...
91-174 5.77e-41

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: 143.13  E-value: 5.77e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289577111  91 KRLHTLEEVNNNVRLLSEMLLHYSQEDSSDGDRELMKELFDQCENKRRTLFKLASETEDNDNSLGDILQASDNLSRVINS 170
Cdd:cd14234    1 KRLLELEEVNNNVKLLNEMLDHYSPGESSQDELELMKELYESCEKMRPTLFRLASETDDDDEGLADILQANDELTRVMQR 80

                 ....
gi 289577111 171 YKTI 174
Cdd:cd14234   81 YKNL 84
GAT_GGA1_GGA2 cd14239
canonical GAT domain found in ADP-ribosylation factor (Arf)-binding proteins GGA1 and GGA2; ...
88-175 4.89e-39

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: 137.88  E-value: 4.89e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289577111  88 KVTKRLHTLEEVNNNVRLLSEMLLHYSQEDSSDGDRELMKELFDQCENKRRTLFKLASETEDNDNSLGDILQASDNLSRV 167
Cdd:cd14239    1 KVSKRVNAIEEVNNNVKLLTEMLMSYSRGELSESSEELMKELYQRCEKMRPTLFRLASDTEDNDEALAEILQANDNLTQV 80

                 ....*...
gi 289577111 168 INSYKTII 175
Cdd:cd14239   81 INLYKQLV 88
GAT_GGA cd14230
canonical GAT domain found in metazoan and fungal ADP-ribosylation factor (Arf)-binding ...
95-174 1.57e-37

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: 133.44  E-value: 1.57e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289577111  95 TLEEVNNNVRLLSEMLLHYSQEDSSDGDRELMKELFDQCENKRRTLFKLASETEDNDNSLGDILQASDNLSRVINSYKTI 174
Cdd:cd14230    1 TLEEAKNNVDLLDEMLLSYSQEDSSDGDNELMKELYDQLENMRPTLFKLASETEENDNSLGDVLQASDNVNRVINKYKDI 80
GAT_SF cd12930
GAT domain found in eukaryotic GGAs, metazoan Tom1-like proteins, metazoan STAMs, fungal Vps27, ...
97-174 3.53e-30

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: 113.10  E-value: 3.53e-30
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 289577111  97 EEVNNNVRLLSEMLLHYSQEDSSDGDRELMKELFDQCENKRRTLFKLASETEdNDNSLGDILQASDNLSRVINSYKTI 174
Cdd:cd12930    1 EEVKDNVR*FSELLEK*KSRPLEILDDELLQELAQRCFASKARLNYLLNDKA-DDQKYNTLLE*NDNLSEV*NIYDRL 77
GAT pfam03127
GAT domain; The GAT domain is responsible for binding of GGA proteins to several members of ...
100-177 3.19e-22

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: 90.68  E-value: 3.19e-22
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 289577111  100 NNNVRLLSEMLLHYSQEDSSDGdrELMKELFDQCENKRRTLFKLASETEDNDNSLGDILQASDNLSRVINSYKTIIEG 177
Cdd:pfam03127   1 RNNAKLLNEMLSSTDPDEELDN--ELIKELYERCKSAQPKIQKLIEETSDEDDLLAELLQLNDDLNNVLERYERLKKG 76
Alpha_adaptinC2 smart00809
Adaptin C-terminal domain; Adaptins are components of the adaptor complexes which link ...
479-568 2.86e-21

Adaptin C-terminal domain; Adaptins are components of the adaptor complexes which link clathrin to receptors in coated vesicles. Clathrin-associated protein complexes are believed to interact with the cytoplasmic tails of membrane proteins, leading to their selection and concentration. Gamma-adaptin is a subunit of the golgi adaptor. Alpha adaptin is a heterotetramer that regulates clathrin-bud formation. The carboxyl-terminal appendage of the alpha subunit regulates translocation of endocytic accessory proteins to the bud site. This Ig-fold domain is found in alpha, beta and gamma adaptins and consists of a beta-sandwich containing 7 strands in 2 beta-sheets in a greek-key topology.. The adaptor appendage contains an additional N-terminal strand.


Pssm-ID: 197886 [Multi-domain]  Cd Length: 104  Bit Score: 88.84  E-value: 2.86e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289577111   479 AYDKNGFRILFHFAKecppgRPDVLVVVVSMLNTAPLPVKSIVLQAAVPKSMKVKLQPPSGTELSPFSPIQppaaitQVM 558
Cdd:smart00809   1 AYEKNGLQIGFKFER-----RPGLIRITLTFTNKSPSPITNFSFQAAVPKSLKLQLQPPSSPTLPPGGQIT------QVL 69
                           90
                   ....*....|
gi 289577111   559 LLANPLKKQV 568
Cdd:smart00809  70 KVENPGKFPL 79
Alpha_adaptinC2 pfam02883
Adaptin C-terminal domain; Alpha adaptin is a heterotetramer which regulates clathrin-bud ...
476-569 8.88e-21

Adaptin C-terminal domain; Alpha adaptin is a heterotetramer which regulates clathrin-bud formation. The carboxyl-terminal appendage of the alpha subunit regulates translocation of endocytic accessory proteins to the bud site. This ig-fold domain is found in alpha, beta and gamma adaptins.


Pssm-ID: 460735  Cd Length: 111  Bit Score: 87.76  E-value: 8.88e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289577111  476 PVTAYDKNGFRILFHFAKecpPGRPDVLVVVVSMLNTAPLPVKSIVLQAAVPKSMKVKLQPPSGTELSPFspiqPPAAIT 555
Cdd:pfam02883   2 PVVLYESDGLQIGFSFER---SRRPGQIRITLTFTNKSSSPISNFSFQAAVPKSLKLQLQPPSSNVLPPN----PGGQIT 74
                          90
                  ....*....|....
gi 289577111  556 QVMLLANPLKKQVL 569
Cdd:pfam02883  75 QVLLIENPGKKPLR 88
GAT_GGA_Tom1-like cd21383
canonical GAT domain found in eukaryotic ADP-ribosylation factor (Arf)-binding proteins (GGAs), ...
96-174 1.39e-14

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: 68.83  E-value: 1.39e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289577111  96 LEEVNNNVRLLSEMLLHYSQEDssDGDRELMKELFDQCENKRRTLFKLASETED--NDNSLGDILQASDNLSRVINSYKT 173
Cdd:cd21383    2 LEEVKENASLLNEMLSAASPEE--LLDNELLQELVEFCRACQPRIVELIEATTDglDEDTLEELLELNDELNEALQRYDD 79

                 .
gi 289577111 174 I 174
Cdd:cd21383   80 L 80
GGA_N-GAT pfam18308
N-terminal extension of GAT domain; This region is found in the N-terminal region of the GGA ...
47-85 6.89e-10

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: 54.23  E-value: 6.89e-10
                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 289577111   47 FDDEEKSKLLAKLLKSKNPDDLQEANKLIKSMVKEDEAR 85
Cdd:pfam18308   1 FDDEEKSKLLARLLKSKNPEDLQAANRLIKSMVKEDDER 39
VHS_GGA3 cd17008
VHS (Vps27/Hrs/STAM) domain of ADP-ribosylation factor-binding protein GGA3; ADP-ribosylation ...
1-24 1.81e-08

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.


Pssm-ID: 340805 [Multi-domain]  Cd Length: 141  Bit Score: 53.50  E-value: 1.81e-08
                         10        20
                 ....*....|....*....|....
gi 289577111   1 MALPEEAKIKDAYHMLKRQGIVQS 24
Cdd:cd17008  118 VALPEEAKIKDAYHMLKRQGIVQS 141
GAT_TOM1_like cd14233
canonical GAT domain found in target of myb protein 1 (Tom1) protein family; Tom1 and its ...
90-171 7.81e-06

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.


Pssm-ID: 410581  Cd Length: 87  Bit Score: 44.49  E-value: 7.81e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289577111  90 TKRLHTLEEVNNNVRLLSEMLLHYSQEDSSDGDRELMKELFDQCENKRRTLFKLASETeDNDNSLGDILQASDNLSRVIN 169
Cdd:cd14233    2 AKLRSELDVVEGNLKVMSEMLTELVPGQENPDDLELLQELNSTCRAMQQRVVELISQV-SNEEVTEELLRVNDDLNNVFL 80

                 ..
gi 289577111 170 SY 171
Cdd:cd14233   81 RY 82
VHS_GGA_metazoan cd03567
VHS (Vps27/Hrs/STAM) domain of metazoan GGA (Golgi-localized, Gamma-ear-containing, ...
1-22 1.79e-05

VHS (Vps27/Hrs/STAM) domain of metazoan 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. Jawed vertebrates contain as many as three GGA proteins: GGA1, GGA2, and GGA3. 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.


Pssm-ID: 340769  Cd Length: 139  Bit Score: 44.89  E-value: 1.79e-05
                         10        20
                 ....*....|....*....|..
gi 289577111   1 MALPEEAKIKDAYHMLKRQGIV 22
Cdd:cd03567  116 RSLPHEPKIKEAYDMLKKQGII 137
GAT_TOM1 cd14236
canonical GAT domain found in target of Myb protein 1 (Tom1); Tom1 was originally identified ...
91-167 4.41e-05

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.


Pssm-ID: 260094  Cd Length: 95  Bit Score: 42.72  E-value: 4.41e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 289577111  91 KRLHT-LEEVNNNVRLLSEMLLHYSQEDSSDGDRELMKELFDQCENKRRTLFKLASETEdNDNSLGDILQASDNLSRV 167
Cdd:cd14236    5 GKLRSeLEMVSGNVRVMSEMLTELVPTQAEPADLELLQELNRTCRAMQQRVLELIPQIA-NEQLTEELLIVNDNLNNV 81
GAT_TM1L2 cd14238
canonical GAT domain found in target of Myb-like protein 2 (Tom1L2); Tom1L2, together with Myb ...
87-172 1.76e-04

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: 40.79  E-value: 1.76e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289577111  87 QKVTKRLHTLEEVNNNVRLLSEMLLHY--SQEDSSdgDRELMKELFDQCENKRRTLFKLASETEdNDNSLGDILQASDNL 164
Cdd:cd14238    2 EQIARLRSELDIVRGNTKVMSEMLTEMvpGQEDPS--DLELLQELNRTCRAMQQRIVELISRVS-NEEVTEELLHVNDDL 78

                 ....*...
gi 289577111 165 SRVINSYK 172
Cdd:cd14238   79 NNVFLRYE 86
VHS_GGA2 cd17010
VHS (Vps27/Hrs/STAM) domain of ADP-ribosylation factor-binding protein GGA2; ADP-ribosylation ...
3-23 3.45e-04

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.


Pssm-ID: 340807  Cd Length: 139  Bit Score: 41.03  E-value: 3.45e-04
                         10        20
                 ....*....|....*....|.
gi 289577111   3 LPEEAKIKDAYHMLKRQGIVQ 23
Cdd:cd17010  118 LPEEVKIRDAYQMLKKQGIIK 138
VHS_GGA1 cd17009
VHS (Vps27/Hrs/STAM) domain of ADP-ribosylation factor-binding protein GGA1; ADP-ribosylation ...
1-24 3.87e-04

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.


Pssm-ID: 340806 [Multi-domain]  Cd Length: 139  Bit Score: 41.12  E-value: 3.87e-04
                         10        20
                 ....*....|....*....|....
gi 289577111   1 MALPEEAKIKDAYHMLKRQGIVQS 24
Cdd:cd17009  116 VGLPEEVKIAEAYQMLKKQGIVKS 139
GAT_GGA_fungi cd14235
canonical GAT domain found in fungal ADP-ribosylation factor (Arf)-binding proteins (GGAs); ...
96-177 6.98e-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: 39.13  E-value: 6.98e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289577111  96 LEEVNNNVRLLSEMLL-HYSQEDSSDGDreLMKELFDQCENKRRTLFKLASETEDNDNSLGDILQASDNLSRVINSYKTI 174
Cdd:cd14235   10 LEKLKRKAILLNEMLNnATPGEIDVEGD--TYDELASSLKSAQPKIQKIIEEESEDEESVQKLLELNDLINSLLERYDLL 87

                 ...
gi 289577111 175 IEG 177
Cdd:cd14235   88 KKG 90
GAT_GGA-like_plant cd14231
canonical GAT domain found in uncharacterized Golgi-localized gamma ear-containing Arf-binding ...
101-174 2.56e-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: 36.86  E-value: 2.56e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 289577111 101 NNVRLLSEMLLHYSQEDSSDGDRELMKELFDQCENKRRTLFKLASETEDNDnSLGDILQASDNLSRVINSYKTI 174
Cdd:cd14231    7 NSLELLSDMLNAVDPRDPEALKDELTVDLVEQCRQSQPRVMQLVESTGDEG-LLFQALELNDELQRVLSKHDAI 79
VHS_GGA cd16977
VHS (Vps27/Hrs/STAM) domain of GGA (Golgi-localized, Gamma-ear-containing, Arf-binding) ...
1-19 2.68e-03

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.


Pssm-ID: 340774  Cd Length: 133  Bit Score: 38.32  E-value: 2.68e-03
                         10
                 ....*....|....*....
gi 289577111   1 MALPEEAKIKDAYHMLKRQ 19
Cdd:cd16977  115 VTLPEEGKIRDAYQMLKKQ 133
GAT_TM1L1 cd14237
canonical GAT domain found in target of Myb-like protein 1 (Tom1L1); Tom1L1, also called ...
87-172 3.15e-03

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.


Pssm-ID: 410584  Cd Length: 92  Bit Score: 37.16  E-value: 3.15e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289577111  87 QKVTKRLHTLEEVNNNVRLLSEMLLHYSQEDSSDGDRELMKELFDQCENKRRTLFKLAsETEDNDNSLGDILQASDNLSR 166
Cdd:cd14237    2 EQIGKLYSELDIVKMNVRVMSAILLENTPGAENPEDMELLEKLYKTCREMQERIMKLL-ETVENEDVIIELIQVNDDLNN 80

                 ....*.
gi 289577111 167 VINSYK 172
Cdd:cd14237   81 VFLRHE 86
 
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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