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Q9UJY4 (GGA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
ADP-ribosylation factor-binding protein GGA2
Alternative name(s):
Gamma-adaptin-related protein 2
Golgi-localized, gamma ear-containing, ARF-binding protein 2
VHS domain and ear domain of gamma-adaptin
Short name=Vear
Gene names
Name:GGA2
Synonyms:KIAA1080
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length613 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Plays a role in protein sorting and trafficking between the trans-Golgi network (TGN) and endosomes. Mediates the ARF-dependent recruitment of clathrin to the TGN and binds ubiquitinated proteins and membrane cargo molecules with a cytosolic acidic cluster-dileucine (AC-LL) motif.

Subunit structure

Monomer. Interacts with NECAP1, TSG101, UBC and AFTPH/aftiphilin. Interacts with CNST By similarity. Interacts with GGA1 and GGA3. Binds to clathrin and activated ARFs. Binds RABEP1 and RABGEF1. Interacts with the type-I membrane proteins SORT1, SORL1, LRP3, M6PR/CD-MPR, IGF2R/CI-MPR and BACE1. Binds the accessory proteins CCDC91, P200, SYNRG, EPN4 and NECAP2. Ref.7 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21

Subcellular location

Golgi apparatustrans-Golgi network membrane; Peripheral membrane protein. Endosome membrane; Peripheral membrane protein Ref.22.

Tissue specificity

Ubiquitously expressed.

Domain

The VHS domain functions as a recognition module for sorting signals composed of an acidic cluster followed by two leucines (AC-LL motif).

The GAT domain is responsible for interaction with ARF-GTP, UBC and RABEP1. Required for recruitment to the TGN it prevents ARF-GTP hydrolysis.

The unstructured hinge region contains clathrin-binding but no autoinhibitory (AC-LL) motifs.

The GAE domain binds accessory proteins regulating GGAs function.

Post-translational modification

Ubiquitinated By similarity.

Sequence similarities

Belongs to the GGA protein family.

Contains 1 GAE domain.

Contains 1 GAT domain.

Contains 1 VHS domain.

Sequence caution

The sequence AAK38634.1 differs from that shown. Reason: Frameshift at position 193.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

RABEP1Q152766EBI-447646,EBI-447043

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 613613ADP-ribosylation factor-binding protein GGA2
PRO_0000212682

Regions

Domain33 – 163131VHS
Domain188 – 315128GAT
Domain484 – 605122GAE
Region316 – 483168Unstructured hinge

Natural variations

Natural variant4241A → P. Ref.1 Ref.2 Ref.6 Ref.7
Corresponds to variant rs1135045 [ dbSNP | Ensembl ].
VAR_028275

Experimental info

Mutagenesis349 – 3535LIDLE → AADAA: Partial loss of clathrin-binding. Ref.10
Sequence conflict2811R → W in AAF05708. Ref.1

Secondary structure

................. 613
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9UJY4 [UniParc].

Last modified April 3, 2007. Version 3.
Checksum: 4B627ABA474A069C

FASTA61367,150
        10         20         30         40         50         60 
MAATAVAAAV AGTESAQGPP GPAASLELWL NKATDPSMSE QDWSAIQNFC EQVNTDPNGP 

        70         80         90        100        110        120 
THAPWLLAHK IQSPQEKEAL YALTVLEMCM NHCGEKFHSE VAKFRFLNEL IKVLSPKYLG 

       130        140        150        160        170        180 
SWATGKVKGR VIEILFSWTV WFPEDIKIRD AYQMLKKQGI IKQDPKLPVD KILPPPSPWP 

       190        200        210        220        230        240 
KSSIFDADEE KSKLLTRLLK SNHPEDLQAA NRLIKNLVKE EQEKSEKVSK RVSAVEEVRS 

       250        260        270        280        290        300 
HVKVLQEMLS MYRRPGQAPP DQEALQVVYE RCEKLRPTLF RLASDTTDDD DALAEILQAN 

       310        320        330        340        350        360 
DLLTQGVLLY KQVMEGRVTF GNRVTSSLGD IPVSRVFQNP AGCMKTCPLI DLEVDNGPAQ 

       370        380        390        400        410        420 
MGTVVPSLLH QDLAALGISD APVTGMVSGQ NCCEEKRNPS SSTLPGGGVQ NPSADRNLLD 

       430        440        450        460        470        480 
LLSAQPAPCP LNYVSQKSVP KEVPPGTKSS PGWSWEAGPL APSPSSQNTP LAQVFVPLES 

       490        500        510        520        530        540 
VKPSSLPPLI VYDRNGFRIL LHFSQTGAPG HPEVQVLLLT MMSTAPQPVW DIMFQVAVPK 

       550        560        570        580        590        600 
SMRVKLQPAS SSKLPAFSPL MPPAVISQML LLDNPHKEPI RLRYKLTFNQ GGQPFSEVGE 

       610 
VKDFPDLAVL GAA 

« Hide

References

« Hide 'large scale' references
[1]"A family of ADP-ribosylation factor effectors that can alter transport through the trans-Golgi."
Boman A.L., Zhang C.-J., Zhu X., Kahn R.A.
Mol. Biol. Cell 11:1241-1255(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PRO-424.
[2]"A family of proteins with gamma-adaptin and VHS domains that facilitate trafficking between the trans-Golgi network and the vacuole/lysosome."
Hirst J., Lui W.W.Y., Bright N.A., Totty N., Seaman M.N.J., Robinson M.S.
J. Cell Biol. 149:67-80(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PRO-424.
[3]"Vear, a novel Golgi-associated protein with VHS and gamma-adaptin 'ear' domains."
Poussu A., Lohi O., Lehto V.-P.
J. Biol. Chem. 275:7176-7183(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q."
Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R., Fuhrmann J., Mason T., Crosby M.L., Barnstead M., Cronin L., Mays A.D., Cao Y., Xu R.X., Kang H.-L., Mitchell S., Eichler E.E., Harris P.C., Venter J.C., Adams M.D.
Genomics 60:295-308(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT PRO-424.
Tissue: Eye.
[7]"The sortilin cytoplasmic tail conveys Golgi-endosome transport and binds the VHS domain of the GGA2 sorting protein."
Nielsen M.S., Madsen P., Christensen E.I., Nykjaer A., Gliemann J., Kasper D., Pohlmann R., Petersen C.M.
EMBO J. 20:2180-2190(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-455, VARIANT PRO-424, INTERACTION WITH SORT1.
Tissue: Mammary gland.
[8]"Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 6:197-205(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 97-613.
Tissue: Brain.
[9]"Adaptor gamma ear homology domain conserved in gamma-adaptin and GGA proteins that interact with gamma-synergin."
Takatsu H., Yoshino K., Nakayama K.
Biochem. Biophys. Res. Commun. 271:719-725(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SYNRG.
[10]"The GGAs promote ARF-dependent recruitment of clathrin to the TGN."
Puertollano R., Randazzo P.A., Presley J.F., Hartnell L.M., Bonifacino J.S.
Cell 105:93-102(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CLATHRIN, MUTAGENESIS OF 349-LEU--GLU-353.
[11]"Golgi-localizing, gamma-adaptin ear homology domain, ADP-ribosylation factor-binding (GGA) proteins interact with acidic dileucine sequences within the cytoplasmic domains of sorting receptors through their Vps27p/Hrs/STAM (VHS) domains."
Takatsu H., Katoh Y., Shiba Y., Nakayama K.
J. Biol. Chem. 276:28541-28545(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SORT; LRP3 AND IGF2R.
[12]"Sorting of mannose 6-phosphate receptors mediated by the GGAs."
Puertollano R., Aguilar R.C., Gorshkova I., Crouch R.J., Bonifacino J.S.
Science 292:1712-1716(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IGF2R.
[13]"GGA proteins associate with Golgi membranes through interaction between their GGAH domains and ADP-ribosylation factors."
Takatsu H., Yoshino K., Toda K., Nakayama K.
Biochem. J. 365:369-378(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ARF1; ARF5 AND ARF6.
[14]"The sorLA cytoplasmic domain interacts with GGA1 and -2 and defines minimum requirements for GGA binding."
Jacobsen L., Madsen P., Nielsen M.S., Geraerts W.P.M., Gliemann J., Smit A.B., Petersen C.M.
FEBS Lett. 511:155-158(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SORL1.
[15]"Interaction of the cation-dependent mannose 6-phosphate receptor with GGA proteins."
Doray B., Bruns K., Ghosh P., Kornfeld S.
J. Biol. Chem. 277:18477-18482(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH M6PR AND IGF2R.
[16]"Clint: a novel clathrin-binding ENTH-domain protein at the Golgi."
Kalthoff C., Groos S., Kohl R., Mahrhold S., Ungewickell E.J.
Mol. Biol. Cell 13:4060-4073(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EPN4.
[17]"Biochemical and structural characterization of the interaction of memapsin 2 (beta-secretase) cytosolic domain with the VHS domain of GGA proteins."
He X., Zhu G., Koelsch G., Rodgers K.K., Zhang X.C., Tang J.
Biochemistry 42:12174-12180(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BACE1.
[18]"Divalent interaction of the GGAs with the Rabaptin-5-Rabex-5 complex."
Mattera R., Arighi C.N., Lodge R., Zerial M., Bonifacino J.S.
EMBO J. 22:78-88(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RABEP1 AND RABGEF1.
[19]"Binding partners for the COOH-terminal appendage domains of the GGAs and gamma-adaptin."
Lui W.W.Y., Collins B.M., Hirst J., Motley A., Millar C., Schu P., Owen D.J., Robinson M.S.
Mol. Biol. Cell 14:2385-2398(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CCDC91; P200 AND SYNRG.
[20]"Mammalian GGAs act together to sort mannose 6-phosphate receptors."
Ghosh P., Griffith J., Geuze H.J., Kornfeld S.
J. Cell Biol. 163:755-766(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GGA1 AND GGA3.
[21]"Definition of the consensus motif recognized by gamma-adaptin ear domains."
Mattera R., Ritter B., Sidhu S.S., McPherson P.S., Bonifacino J.S.
J. Biol. Chem. 279:8018-8028(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NECAP2.
[22]"Interactions of GGA3 with the ubiquitin sorting machinery."
Puertollano R., Bonifacino J.S.
Nat. Cell Biol. 6:244-251(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[23]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[24]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[25]"Crystal structure of GGA2 VHS domain and its implication in plasticity in the ligand binding pocket."
Zhu G., He X., Zhai P., Terzyan S., Tang J., Zhang X.C.
FEBS Lett. 537:171-176(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 25-167.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF190863 mRNA. Translation: AAF05708.1.
AF233522 mRNA. Translation: AAF35394.1.
AF165531 mRNA. Translation: AAF42806.1.
AC002400 Genomic DNA. Translation: AAC05813.1.
CH471145 Genomic DNA. Translation: EAW55827.1.
CH471145 Genomic DNA. Translation: EAW55828.1.
BC000284 mRNA. Translation: AAH00284.1.
AF323754 mRNA. Translation: AAK38634.1. Frameshift.
AB029003 mRNA. Translation: BAA83032.1.
PIRT00744.
RefSeqNP_055859.1. NM_015044.4.
UniGeneHs.460336.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1MHQX-ray2.20A/B25-172[»]
ProteinModelPortalQ9UJY4.
SMRQ9UJY4. Positions 25-167, 188-316, 471-605.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116697. 30 interactions.
DIPDIP-31601N.
IntActQ9UJY4. 16 interactions.
MINTMINT-126110.
STRING9606.ENSP00000311962.

PTM databases

PhosphoSiteQ9UJY4.

Polymorphism databases

DMDM143811397.

Proteomic databases

PaxDbQ9UJY4.
PRIDEQ9UJY4.

Protocols and materials databases

DNASU23062.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000309859; ENSP00000311962; ENSG00000103365.
GeneID23062.
KEGGhsa:23062.
UCSCuc002dlq.3. human.

Organism-specific databases

CTD23062.
GeneCardsGC16M023474.
HGNCHGNC:16064. GGA2.
HPACAB034422.
HPA043313.
MIM606005. gene.
neXtProtNX_Q9UJY4.
PharmGKBPA28658.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG321636.
HOGENOMHOG000231169.
HOVERGENHBG015945.
InParanoidQ9UJY4.
KOK12404.
OMAMKNCPLI.
OrthoDBEOG7V49Z0.
PhylomeDBQ9UJY4.
TreeFamTF318574.

Gene expression databases

ArrayExpressQ9UJY4.
BgeeQ9UJY4.
CleanExHS_GGA2.
GenevestigatorQ9UJY4.

Family and domain databases

Gene3D1.25.40.90. 1 hit.
2.60.40.1230. 1 hit.
InterProIPR008152. Clathrin_a/b/g-adaptin_app_Ig.
IPR008153. Clathrin_g-adaptin_app.
IPR013041. Coatomer/clathrin_app_Ig-like.
IPR008942. ENTH_VHS.
IPR004152. GAT.
IPR002014. VHS.
IPR018205. VHS_subgr.
[Graphical view]
PfamPF02883. Alpha_adaptinC2. 1 hit.
PF03127. GAT. 1 hit.
PF00790. VHS. 1 hit.
[Graphical view]
SMARTSM00809. Alpha_adaptinC2. 1 hit.
SM00288. VHS. 1 hit.
[Graphical view]
SUPFAMSSF48464. SSF48464. 1 hit.
SSF49348. SSF49348. 1 hit.
PROSITEPS50180. GAE. 1 hit.
PS50909. GAT. 1 hit.
PS50179. VHS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSGGA2. human.
EvolutionaryTraceQ9UJY4.
GeneWikiGGA2.
GenomeRNAi23062.
NextBio44137.
PROQ9UJY4.
SOURCESearch...

Entry information

Entry nameGGA2_HUMAN
AccessionPrimary (citable) accession number: Q9UJY4
Secondary accession number(s): D3DWF0 expand/collapse secondary AC list , O14564, Q9NYN2, Q9UPS2
Entry history
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: April 3, 2007
Last modified: April 16, 2014
This is version 139 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM