1WR6,1X79,1YD8


Conserved Protein Domain Family
GAT_GGA_meta

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cd14234: GAT_GGA_meta 
Click on image for an interactive view with Cn3D
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.
Statistics
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PSSM-Id: 410582
Aligned: 26 rows
Threshold Bit Score: 100.762
Created: 6-Sep-2012
Updated: 25-Oct-2021
Structure
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Program:
Drawing:
Aligned Rows:
 
ubiquitinRabaptin5
Conserved site includes 14 residues -Click on image for an interactive view with Cn3D
Feature 1:ubiquitin binding site [polypeptide binding site]
Evidence:
  • Structure:1WR6; Homo sapiens ADP-ribosylation factor-binding protein GGA3 binds ubiquitin through its GAT domain, contacts at 4A.
    View structure with Cn3D
  • Structure:1YD8: Human GGA3 GAT domain binds ubiquitin; contacts at 4A.
    View structure with Cn3D
  • Comment:GGAs play important roles in ubiquitin-dependent sorting of cargo proteins both in biosynthetic and endocytic pathways.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1               #  ##  #  ##  #         ## ##  ##  #                                     
1WR6_A         5 KRLHTLEEVNNNVRLLSEXLLHYsqe-dssDGDRELXKELFDQCENKRRTLFKLASETe--DNDNSLGDILQASDNLSRV 81  human
XP_002423932 215 KRISEIETIRNNVRLLSEMLETYkpd-sssSDEFDLIKELHLSCERLKPNIMRLASDVq--DNDEFLNQVLSVDDELDQV 291 human body louse
EFX90451     213 RRQLEIETVNSNIRLLEELLDNFean-gatAEEMELCKELASNCDKLRPNLSKLATETd--DKGDTLADILQTSDELSHA 289 common water flea
XP_002109730 226 QRLNDLERARNNGKLLSDMLDYYsts--ssGQEKETMEELYRSCEEIRNQLQKNAGEVe--SDEALLQNIIKVSEELSAV 301 Trichoplax adha...
ADY43993     163 KRIDDVEKAKNNCRVLNEILAYCnte-pmsERESELAAELYTILVEMRPSLFRYAGEAa-eYDDAALADILAVNDAVNKT 240 pig roundworm
CCD80854     213 QRTSEMEALRNNTILLEEMIGTYllg-estEAELELMNELVQNIRRARPLLYSFSLTHe-eQDIETLTEIGQICDKASEV 290 Schistosoma man...
XP_003745190 214 RKRLDLEEAVNNCAVFSDLLKNFsnvgtktFDELELLRQMFENCDTLRPKLFTLATEFsliEDFPSVQDVLQQNDQLTAL 293 western predato...
Q7QGJ6       190 RRLAELQKVAENTKLLAEMLDQYrag-etsDDGLAVLSEIYESCESAHPTIVRLAEETq--HSEEMLEKIFEVNDALTQA 266 Anopheles gambi...
ACZ28159     204 KRLLELNKIKDLIELLEAMLDNYcpg-ettQDELETIQDQYLACKKTPATIHRLAAETq--HSEGILDNILQTGVKIQEV 280 Simulium nigrim...
XP_027213224 211 RRVVEVETALNNVRVLDEMLSRHqes-pasQADLDLMQELHSSCSTLRSNIYRLVSEMd--DKEEGIGDLLKANDELSRV 287 Streptococcus p...
Feature 1               
1WR6_A        82 INSYKTI 88  human
XP_002423932 292 LKKYNTI 298 human body louse
EFX90451     290 LDRYEVL 296 common water flea
XP_002109730 302 MERYQNV 308 Trichoplax adhaerens
ADY43993     241 VQQYKNL 247 pig roundworm
CCD80854     291 LANYEQK 297 Schistosoma mansoni
XP_003745190 294 INDYKER 300 western predatory mite
Q7QGJ6       267 LDKYRVK 273 Anopheles gambiae str. PEST
ACZ28159     281 LQKYENL 287 Simulium nigrimanum
XP_027213224 288 MGRYKLV 294 Streptococcus pneumoniae

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