Full text data of GGA3
GGA3
(KIAA0154)
[Confidence: low (only semi-automatic identification from reviews)]
ADP-ribosylation factor-binding protein GGA3 (Golgi-localized, gamma ear-containing, ARF-binding protein 3)
ADP-ribosylation factor-binding protein GGA3 (Golgi-localized, gamma ear-containing, ARF-binding protein 3)
UniProt
Q9NZ52
ID GGA3_HUMAN Reviewed; 723 AA.
AC Q9NZ52; B7Z7E2; B7Z7M9; J3KRN0; Q15017; Q6IS16; Q9UJY3;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-2000, sequence version 1.
DT 22-JAN-2014, entry version 147.
DE RecName: Full=ADP-ribosylation factor-binding protein GGA3;
DE AltName: Full=Golgi-localized, gamma ear-containing, ARF-binding protein 3;
GN Name=GGA3; Synonyms=KIAA0154;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT).
RC TISSUE=Heart;
RX PubMed=10747089; DOI=10.1083/jcb.149.1.81;
RA Dell'Angelica E.C., Puertollano R., Mullins C., Aguilar R.C.,
RA Vargas J.D., Hartnell L.M., Bonifacino J.S.;
RT "GGAs: a family of ADP ribosylation factor-binding proteins related to
RT adaptors and associated with the Golgi complex.";
RL J. Cell Biol. 149:81-94(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
RX PubMed=10749927; DOI=10.1091/mbc.11.4.1241;
RA Boman A.L., Zhang C.-J., Zhu X., Kahn R.A.;
RT "A family of ADP-ribosylation factor effectors that can alter
RT transport through the trans-Golgi.";
RL Mol. Biol. Cell 11:1241-1255(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT).
RC TISSUE=Bone marrow;
RX PubMed=8590280; DOI=10.1093/dnares/2.4.167;
RA Nagase T., Seki N., Tanaka A., Ishikawa K., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. IV.
RT The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by
RT analysis of cDNA clones from human cell line KG-1.";
RL DNA Res. 2:167-174(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in
RT the human lineage.";
RL Nature 440:1045-1049(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP INTERACTION WITH SYNRG.
RX PubMed=10814529; DOI=10.1006/bbrc.2000.2700;
RA Takatsu H., Yoshino K., Nakayama K.;
RT "Adaptor gamma ear homology domain conserved in gamma-adaptin and GGA
RT proteins that interact with gamma-synergin.";
RL Biochem. Biophys. Res. Commun. 271:719-725(2000).
RN [9]
RP MUTAGENESIS OF ASN-194; SER-199 AND THR-217, INTERACTION WITH ARF1 AND
RP CLATHRIN, AND FUNCTION.
RX PubMed=11301005; DOI=10.1016/S0092-8674(01)00299-9;
RA Puertollano R., Randazzo P.A., Presley J.F., Hartnell L.M.,
RA Bonifacino J.S.;
RT "The GGAs promote ARF-dependent recruitment of clathrin to the TGN.";
RL Cell 105:93-102(2001).
RN [10]
RP INTERACTION WITH M6PR AND IGF2R.
RX PubMed=11387475; DOI=10.1126/science.1060750;
RA Puertollano R., Aguilar R.C., Gorshkova I., Crouch R.J.,
RA Bonifacino J.S.;
RT "Sorting of mannose 6-phosphate receptors mediated by the GGAs.";
RL Science 292:1712-1716(2001).
RN [11]
RP INTERACTION WITH ARF1; ARF5 AND ARF6.
RX PubMed=11950392; DOI=10.1042/BJ20020428;
RA Takatsu H., Yoshino K., Toda K., Nakayama K.;
RT "GGA proteins associate with Golgi membranes through interaction
RT between their GGAH domains and ADP-ribosylation factors.";
RL Biochem. J. 365:369-378(2002).
RN [12]
RP INTERACTION WITH EPN4.
RX PubMed=12213833; DOI=10.1083/jcb.200205078;
RA Wasiak S., Legendre-Guillemin V., Puertollano R., Blondeau F.,
RA Girard M., de Heuvel E., Boismenu D., Bell A.W., Bonifacino J.S.,
RA McPherson P.S.;
RT "Enthoprotin: a novel clathrin-associated protein identified through
RT subcellular proteomics.";
RL J. Cell Biol. 158:855-862(2002).
RN [13]
RP MUTAGENESIS OF 391-ASP--LEU-395, INTERACTION WITH IGF2R, AND
RP AUTOINHIBITION.
RX PubMed=12060753; DOI=10.1073/pnas.082235699;
RA Doray B., Bruns K., Ghosh P., Kornfeld S.A.;
RT "Autoinhibition of the ligand-binding site of GGA1/3 VHS domains by an
RT internal acidic cluster-dileucine motif.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:8072-8077(2002).
RN [14]
RP INTERACTION WITH BACE1.
RX PubMed=14567678; DOI=10.1021/bi035199h;
RA He X., Zhu G., Koelsch G., Rodgers K.K., Zhang X.C., Tang J.;
RT "Biochemical and structural characterization of the interaction of
RT memapsin 2 (beta-secretase) cytosolic domain with the VHS domain of
RT GGA proteins.";
RL Biochemistry 42:12174-12180(2003).
RN [15]
RP INTERACTION WITH RABEP1 AND RABGEF1.
RX PubMed=12505986; DOI=10.1093/emboj/cdg015;
RA Mattera R., Arighi C.N., Lodge R., Zerial M., Bonifacino J.S.;
RT "Divalent interaction of the GGAs with the Rabaptin-5-Rabex-5
RT complex.";
RL EMBO J. 22:78-88(2003).
RN [16]
RP INTERACTION WITH GGA1 AND GGA2.
RX PubMed=14638859; DOI=10.1083/jcb.200308038;
RA Ghosh P., Griffith J., Geuze H.J., Kornfeld S.;
RT "Mammalian GGAs act together to sort mannose 6-phosphate receptors.";
RL J. Cell Biol. 163:755-766(2003).
RN [17]
RP MUTAGENESIS OF LEU-247; LEU-262; LEU-276; LEU-280; ASP-284 AND
RP TYR-293, INTERACTION WITH UBC, AND UBIQUITINATION.
RX PubMed=14660606; DOI=10.1074/jbc.M311702200;
RA Shiba Y., Katoh Y., Shiba T., Yoshino K., Takatsu H., Kobayashi H.,
RA Shin H.-W., Wakatsuki S., Nakayama K.;
RT "GAT (GGA and Tom1) domain responsible for ubiquitin binding and
RT ubiquitination.";
RL J. Biol. Chem. 279:7105-7111(2004).
RN [18]
RP INTERACTION WITH NECAP1; NECAP2 AND AFTPH.
RX PubMed=14665628; DOI=10.1074/jbc.M311873200;
RA Mattera R., Ritter B., Sidhu S.S., McPherson P.S., Bonifacino J.S.;
RT "Definition of the consensus motif recognized by gamma-adaptin ear
RT domains.";
RL J. Biol. Chem. 279:8018-8028(2004).
RN [19]
RP MUTAGENESIS OF LYS-258 AND SER-283, AND INTERACTION WITH RABEP1.
RX PubMed=15143060; DOI=10.1074/jbc.M402183200;
RA Mattera R., Puertollano R., Smith W.J., Bonifacino J.S.;
RT "The trihelical bundle subdomain of the GGA proteins interacts with
RT multiple partners through overlapping but distinct sites.";
RL J. Biol. Chem. 279:31409-31418(2004).
RN [20]
RP SUBCELLULAR LOCATION, MUTAGENESIS OF LEU-276, AND INTERACTION WITH UBC
RP AND TSG101.
RX PubMed=15039775; DOI=10.1038/ncb1106;
RA Puertollano R., Bonifacino J.S.;
RT "Interactions of GGA3 with the ubiquitin sorting machinery.";
RL Nat. Cell Biol. 6:244-251(2004).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-166.
RX PubMed=12032548; DOI=10.1038/nsb807;
RA Kato Y., Misra S., Puertollano R., Hurley J.H., Bonifacino J.S.;
RT "Phosphoregulation of sorting signal-VHS domain interactions by a
RT direct electrostatic mechanism.";
RL Nat. Struct. Biol. 9:532-536(2002).
RN [23]
RP VARIANT [LARGE SCALE ANALYSIS] LEU-574.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Plays a role in protein sorting and trafficking between
CC the trans-Golgi network (TGN) and endosomes. Mediates the ARF-
CC dependent recruitment of clathrin to the TGN and binds
CC ubiquitinated proteins and membrane cargo molecules with a
CC cytosolic acidic cluster-dileucine (AC-LL) motif.
CC -!- SUBUNIT: Monomer. Interacts with SORT1, SORL1, LRP3, GGA binding
CC partner (GGABP) and P200 (By similarity). Interacts with GGA1 and
CC GGA2. Binds to clathrin and activated ARFs. Binds RABEP1 and
CC RABGEF1. Interacts with the membrane proteins M6PR/CD-MPR,
CC IGF2R/CI-MPR and BACE1 and the accessory proteins SYNRG, EPN4,
CC NECAP1, NECAP2 and AFTPH/aftiphilin. Interacts with TSG101 and
CC UBC.
CC -!- INTERACTION:
CC P11717:IGF2R; NbExp=3; IntAct=EBI-447404, EBI-1048580;
CC Q6VY07:PACS1; NbExp=5; IntAct=EBI-447404, EBI-2555014;
CC Q15276:RABEP1; NbExp=4; IntAct=EBI-447404, EBI-447043;
CC P0CG47:UBB; NbExp=2; IntAct=EBI-447404, EBI-413034;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network
CC membrane; Peripheral membrane protein. Endosome membrane;
CC Peripheral membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=Long;
CC IsoId=Q9NZ52-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=Q9NZ52-2; Sequence=VSP_001745;
CC Name=3;
CC IsoId=Q9NZ52-3; Sequence=VSP_045133, VSP_045134;
CC Name=4;
CC IsoId=Q9NZ52-4; Sequence=VSP_046868;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC -!- DOMAIN: The VHS domain functions as a recognition module for
CC sorting signals composed of an acidic cluster followed by two
CC leucines (AC-LL motif).
CC -!- DOMAIN: The GAT domain is responsible for interaction with ARF-
CC GTP, UBC and RABEP1. Required for recruitment to the TGN it
CC prevents ARF-GTP hydrolysis.
CC -!- DOMAIN: The unstructured hinge region contains clathrin-binding
CC and an autoinhibitory (AC-LL) motifs.
CC -!- DOMAIN: The GAE domain binds accessory proteins regulating GGAs
CC function.
CC -!- PTM: Phosphorylated by CK2 and dephosphorylated by PP2A (By
CC similarity). Phosphorylation of GGA3 allows the internal AC-LL
CC motif to bind the VHS domain and to inhibit the recognition of
CC cargo signals.
CC -!- PTM: Ubiquitinated.
CC -!- SIMILARITY: Belongs to the GGA protein family.
CC -!- SIMILARITY: Contains 1 GAE domain.
CC -!- SIMILARITY: Contains 1 GAT domain.
CC -!- SIMILARITY: Contains 1 VHS domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA09926.1; Type=Erroneous initiation;
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DR EMBL; AF219138; AAF42848.1; -; mRNA.
DR EMBL; AF190864; AAF05709.1; -; mRNA.
DR EMBL; AF219139; AAF42849.1; -; mRNA.
DR EMBL; D63876; BAA09926.1; ALT_INIT; mRNA.
DR EMBL; AK301895; BAH13578.1; -; mRNA.
DR EMBL; AK302278; BAH13665.1; -; mRNA.
DR EMBL; AC022211; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471099; EAW89258.1; -; Genomic_DNA.
DR EMBL; BC070044; AAH70044.1; -; mRNA.
DR RefSeq; NP_001166174.1; NM_001172703.1.
DR RefSeq; NP_001166175.1; NM_001172704.1.
DR RefSeq; NP_054720.1; NM_014001.3.
DR RefSeq; NP_619525.1; NM_138619.2.
DR UniGene; Hs.87726; -.
DR PDB; 1JPL; X-ray; 2.40 A; A/B/C/D=1-166.
DR PDB; 1JUQ; X-ray; 2.20 A; A/B/C/D=1-166.
DR PDB; 1LF8; X-ray; 2.30 A; A/B/C/D=1-166.
DR PDB; 1P4U; X-ray; 2.20 A; A=571-723.
DR PDB; 1WR6; X-ray; 2.60 A; A/B/C/D=209-319.
DR PDB; 1YD8; X-ray; 2.80 A; G/H=208-301.
DR PDBsum; 1JPL; -.
DR PDBsum; 1JUQ; -.
DR PDBsum; 1LF8; -.
DR PDBsum; 1P4U; -.
DR PDBsum; 1WR6; -.
DR PDBsum; 1YD8; -.
DR ProteinModelPortal; Q9NZ52; -.
DR SMR; Q9NZ52; 1-157, 168-304, 579-723.
DR DIP; DIP-31600N; -.
DR IntAct; Q9NZ52; 14.
DR MINT; MINT-126320; -.
DR STRING; 9606.ENSP00000245541; -.
DR PhosphoSite; Q9NZ52; -.
DR DMDM; 14548064; -.
DR PaxDb; Q9NZ52; -.
DR PRIDE; Q9NZ52; -.
DR Ensembl; ENST00000245541; ENSP00000245541; ENSG00000125447.
DR Ensembl; ENST00000351904; ENSP00000326575; ENSG00000125447.
DR Ensembl; ENST00000578348; ENSP00000463288; ENSG00000125447.
DR Ensembl; ENST00000582717; ENSP00000462081; ENSG00000125447.
DR GeneID; 23163; -.
DR KEGG; hsa:23163; -.
DR UCSC; uc010wrw.2; human.
DR CTD; 23163; -.
DR GeneCards; GC17M073229; -.
DR HGNC; HGNC:17079; GGA3.
DR HPA; HPA022945; -.
DR MIM; 606006; gene.
DR neXtProt; NX_Q9NZ52; -.
DR PharmGKB; PA28659; -.
DR eggNOG; NOG321636; -.
DR HOGENOM; HOG000231169; -.
DR HOVERGEN; HBG015945; -.
DR InParanoid; Q9NZ52; -.
DR KO; K12404; -.
DR OMA; QGSPMKG; -.
DR PhylomeDB; Q9NZ52; -.
DR EvolutionaryTrace; Q9NZ52; -.
DR GeneWiki; GGA3; -.
DR GenomeRNAi; 23163; -.
DR NextBio; 35535625; -.
DR PRO; PR:Q9NZ52; -.
DR ArrayExpress; Q9NZ52; -.
DR Bgee; Q9NZ52; -.
DR CleanEx; HS_GGA3; -.
DR Genevestigator; Q9NZ52; -.
DR GO; GO:0030131; C:clathrin adaptor complex; IEA:InterPro.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005802; C:trans-Golgi network; IDA:UniProtKB.
DR GO; GO:0030306; F:ADP-ribosylation factor binding; IDA:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; NAS:UniProtKB.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IEA:Ensembl.
DR GO; GO:0016192; P:vesicle-mediated transport; IEA:InterPro.
DR Gene3D; 1.25.40.90; -; 1.
DR Gene3D; 2.60.40.1230; -; 1.
DR InterPro; IPR008152; Clathrin_a/b/g-adaptin_app_Ig.
DR InterPro; IPR008153; Clathrin_g-adaptin_app.
DR InterPro; IPR013041; Coatomer/clathrin_app_Ig-like.
DR InterPro; IPR008942; ENTH_VHS.
DR InterPro; IPR004152; GAT.
DR InterPro; IPR027422; GGA3.
DR InterPro; IPR002014; VHS.
DR InterPro; IPR018205; VHS_subgr.
DR PANTHER; PTHR13856:SF34; PTHR13856:SF34; 1.
DR Pfam; PF02883; Alpha_adaptinC2; 1.
DR Pfam; PF03127; GAT; 1.
DR Pfam; PF00790; VHS; 1.
DR SMART; SM00809; Alpha_adaptinC2; 1.
DR SMART; SM00288; VHS; 1.
DR SUPFAM; SSF48464; SSF48464; 1.
DR SUPFAM; SSF49348; SSF49348; 1.
DR PROSITE; PS50180; GAE; 1.
DR PROSITE; PS50909; GAT; 1.
DR PROSITE; PS50179; VHS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; Endosome;
KW Golgi apparatus; Membrane; Phosphoprotein; Polymorphism;
KW Protein transport; Reference proteome; Transport; Ubl conjugation.
FT CHAIN 1 723 ADP-ribosylation factor-binding protein
FT GGA3.
FT /FTId=PRO_0000212684.
FT DOMAIN 16 146 VHS.
FT DOMAIN 171 298 GAT.
FT DOMAIN 594 715 GAE.
FT REGION 1 313 Binds to ARF1 (in long isoform).
FT REGION 299 593 Unstructured hinge.
FT MOTIF 391 395 Autoinhibitory.
FT COMPBIAS 357 360 Poly-Pro.
FT COMPBIAS 453 457 Poly-Ser.
FT COMPBIAS 624 629 Poly-Val.
FT VAR_SEQ 1 122 Missing (in isoform 3).
FT /FTId=VSP_045133.
FT VAR_SEQ 1 72 Missing (in isoform 4).
FT /FTId=VSP_046868.
FT VAR_SEQ 68 100 Missing (in isoform Short).
FT /FTId=VSP_001745.
FT VAR_SEQ 688 723 EKVRLRYKLTFALGEQLSTEVGEVDQFPPVEQWGNL -> K
FT QVLSFLGKACLQPWGQAILLTTSCLA (in isoform
FT 3).
FT /FTId=VSP_045134.
FT VARIANT 574 574 P -> L (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_036524.
FT MUTAGEN 194 194 N->A: Loss of interaction with ARF1 and
FT Golgi localization.
FT MUTAGEN 199 199 S->P: Loss of interaction with ARF1 and
FT Golgi localization.
FT MUTAGEN 217 217 T->P: Loss of interaction with ARF1 and
FT Golgi localization.
FT MUTAGEN 247 247 L->P: Loss of UBC-binding and
FT ubiquitination.
FT MUTAGEN 258 258 K->M: No effect. Confers an affinity to
FT RABEP1 identical to GGA1; when associated
FT with N-283.
FT MUTAGEN 262 262 L->S: Loss of UBC-binding and
FT ubiquitination.
FT MUTAGEN 276 276 L->A: Loss of UBC-binding and
FT ubiquitination.
FT MUTAGEN 276 276 L->S: Loss of UBC-binding and
FT ubiquitination.
FT MUTAGEN 280 280 L->R: Loss of UBC-binding and
FT ubiquitination.
FT MUTAGEN 283 283 S->N: Can bind RABEP1. Confers an
FT affinity to RABEP1 identical to GGA1;
FT when associated with M-258.
FT MUTAGEN 284 284 D->G: Loss of UBC-binding and
FT ubiquitination.
FT MUTAGEN 293 293 Y->H: Loss of UBC-binding and
FT ubiquitination.
FT MUTAGEN 391 395 DEELL->AAAAA: Increased binding to IGF2R.
FT CONFLICT 448 448 Q -> K (in Ref. 7; AAH70044).
FT CONFLICT 562 562 F -> S (in Ref. 4; BAH13665).
FT HELIX 9 16
FT HELIX 26 38
FT HELIX 42 54
FT HELIX 59 75
FT HELIX 77 84
FT HELIX 87 97
FT HELIX 99 103
FT HELIX 108 124
FT HELIX 129 140
FT HELIX 218 231
FT TURN 232 234
FT TURN 237 239
FT HELIX 242 267
FT HELIX 276 290
FT HELIX 292 295
FT TURN 296 298
FT HELIX 588 590
FT STRAND 599 604
FT STRAND 607 616
FT STRAND 624 633
FT STRAND 635 637
FT STRAND 639 647
FT STRAND 652 656
FT STRAND 675 683
FT STRAND 692 700
FT STRAND 703 711
FT HELIX 717 719
SQ SEQUENCE 723 AA; 78315 MW; 4F80D6032239168C CRC64;
MAEAEGESLE SWLNKATNPS NRQEDWEYII GFCDQINKEL EGPQIAVRLL AHKIQSPQEW
EALQALTVLE ACMKNCGRRF HNEVGKFRFL NELIKVVSPK YLGDRVSEKV KTKVIELLYS
WTMALPEEAK IKDAYHMLKR QGIVQSDPPI PVDRTLIPSP PPRPKNPVFD DEEKSKLLAK
LLKSKNPDDL QEANKLIKSM VKEDEARIQK VTKRLHTLEE VNNNVRLLSE MLLHYSQEDS
SDGDRELMKE LFDQCENKRR TLFKLASETE DNDNSLGDIL QASDNLSRVI NSYKTIIEGQ
VINGEVATLT LPDSEGNSQC SNQGTLIDLA ELDTTNSLSS VLAPAPTPPS SGIPILPPPP
QASGPPRSRS SSQAEATLGP SSTSNALSWL DEELLCLGLA DPAPNVPPKE SAGNSQWHLL
QREQSDLDFF SPRPGTAACG ASDAPLLQPS APSSSSSQAP LPPPFPAPVV PASVPAPSAG
SSLFSTGVAP ALAPKVEPAV PGHHGLALGN SALHHLDALD QLLEEAKVTS GLVKPTTSPL
IPTTTPARPL LPFSTGPGSP LFQPLSFQSQ GSPPKGPELS LASIHVPLES IKPSSALPVT
AYDKNGFRIL FHFAKECPPG RPDVLVVVVS MLNTAPLPVK SIVLQAAVPK SMKVKLQPPS
GTELSPFSPI QPPAAITQVM LLANPLKEKV RLRYKLTFAL GEQLSTEVGE VDQFPPVEQW
GNL
//
ID GGA3_HUMAN Reviewed; 723 AA.
AC Q9NZ52; B7Z7E2; B7Z7M9; J3KRN0; Q15017; Q6IS16; Q9UJY3;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-2000, sequence version 1.
DT 22-JAN-2014, entry version 147.
DE RecName: Full=ADP-ribosylation factor-binding protein GGA3;
DE AltName: Full=Golgi-localized, gamma ear-containing, ARF-binding protein 3;
GN Name=GGA3; Synonyms=KIAA0154;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT).
RC TISSUE=Heart;
RX PubMed=10747089; DOI=10.1083/jcb.149.1.81;
RA Dell'Angelica E.C., Puertollano R., Mullins C., Aguilar R.C.,
RA Vargas J.D., Hartnell L.M., Bonifacino J.S.;
RT "GGAs: a family of ADP ribosylation factor-binding proteins related to
RT adaptors and associated with the Golgi complex.";
RL J. Cell Biol. 149:81-94(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
RX PubMed=10749927; DOI=10.1091/mbc.11.4.1241;
RA Boman A.L., Zhang C.-J., Zhu X., Kahn R.A.;
RT "A family of ADP-ribosylation factor effectors that can alter
RT transport through the trans-Golgi.";
RL Mol. Biol. Cell 11:1241-1255(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT).
RC TISSUE=Bone marrow;
RX PubMed=8590280; DOI=10.1093/dnares/2.4.167;
RA Nagase T., Seki N., Tanaka A., Ishikawa K., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. IV.
RT The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by
RT analysis of cDNA clones from human cell line KG-1.";
RL DNA Res. 2:167-174(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in
RT the human lineage.";
RL Nature 440:1045-1049(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP INTERACTION WITH SYNRG.
RX PubMed=10814529; DOI=10.1006/bbrc.2000.2700;
RA Takatsu H., Yoshino K., Nakayama K.;
RT "Adaptor gamma ear homology domain conserved in gamma-adaptin and GGA
RT proteins that interact with gamma-synergin.";
RL Biochem. Biophys. Res. Commun. 271:719-725(2000).
RN [9]
RP MUTAGENESIS OF ASN-194; SER-199 AND THR-217, INTERACTION WITH ARF1 AND
RP CLATHRIN, AND FUNCTION.
RX PubMed=11301005; DOI=10.1016/S0092-8674(01)00299-9;
RA Puertollano R., Randazzo P.A., Presley J.F., Hartnell L.M.,
RA Bonifacino J.S.;
RT "The GGAs promote ARF-dependent recruitment of clathrin to the TGN.";
RL Cell 105:93-102(2001).
RN [10]
RP INTERACTION WITH M6PR AND IGF2R.
RX PubMed=11387475; DOI=10.1126/science.1060750;
RA Puertollano R., Aguilar R.C., Gorshkova I., Crouch R.J.,
RA Bonifacino J.S.;
RT "Sorting of mannose 6-phosphate receptors mediated by the GGAs.";
RL Science 292:1712-1716(2001).
RN [11]
RP INTERACTION WITH ARF1; ARF5 AND ARF6.
RX PubMed=11950392; DOI=10.1042/BJ20020428;
RA Takatsu H., Yoshino K., Toda K., Nakayama K.;
RT "GGA proteins associate with Golgi membranes through interaction
RT between their GGAH domains and ADP-ribosylation factors.";
RL Biochem. J. 365:369-378(2002).
RN [12]
RP INTERACTION WITH EPN4.
RX PubMed=12213833; DOI=10.1083/jcb.200205078;
RA Wasiak S., Legendre-Guillemin V., Puertollano R., Blondeau F.,
RA Girard M., de Heuvel E., Boismenu D., Bell A.W., Bonifacino J.S.,
RA McPherson P.S.;
RT "Enthoprotin: a novel clathrin-associated protein identified through
RT subcellular proteomics.";
RL J. Cell Biol. 158:855-862(2002).
RN [13]
RP MUTAGENESIS OF 391-ASP--LEU-395, INTERACTION WITH IGF2R, AND
RP AUTOINHIBITION.
RX PubMed=12060753; DOI=10.1073/pnas.082235699;
RA Doray B., Bruns K., Ghosh P., Kornfeld S.A.;
RT "Autoinhibition of the ligand-binding site of GGA1/3 VHS domains by an
RT internal acidic cluster-dileucine motif.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:8072-8077(2002).
RN [14]
RP INTERACTION WITH BACE1.
RX PubMed=14567678; DOI=10.1021/bi035199h;
RA He X., Zhu G., Koelsch G., Rodgers K.K., Zhang X.C., Tang J.;
RT "Biochemical and structural characterization of the interaction of
RT memapsin 2 (beta-secretase) cytosolic domain with the VHS domain of
RT GGA proteins.";
RL Biochemistry 42:12174-12180(2003).
RN [15]
RP INTERACTION WITH RABEP1 AND RABGEF1.
RX PubMed=12505986; DOI=10.1093/emboj/cdg015;
RA Mattera R., Arighi C.N., Lodge R., Zerial M., Bonifacino J.S.;
RT "Divalent interaction of the GGAs with the Rabaptin-5-Rabex-5
RT complex.";
RL EMBO J. 22:78-88(2003).
RN [16]
RP INTERACTION WITH GGA1 AND GGA2.
RX PubMed=14638859; DOI=10.1083/jcb.200308038;
RA Ghosh P., Griffith J., Geuze H.J., Kornfeld S.;
RT "Mammalian GGAs act together to sort mannose 6-phosphate receptors.";
RL J. Cell Biol. 163:755-766(2003).
RN [17]
RP MUTAGENESIS OF LEU-247; LEU-262; LEU-276; LEU-280; ASP-284 AND
RP TYR-293, INTERACTION WITH UBC, AND UBIQUITINATION.
RX PubMed=14660606; DOI=10.1074/jbc.M311702200;
RA Shiba Y., Katoh Y., Shiba T., Yoshino K., Takatsu H., Kobayashi H.,
RA Shin H.-W., Wakatsuki S., Nakayama K.;
RT "GAT (GGA and Tom1) domain responsible for ubiquitin binding and
RT ubiquitination.";
RL J. Biol. Chem. 279:7105-7111(2004).
RN [18]
RP INTERACTION WITH NECAP1; NECAP2 AND AFTPH.
RX PubMed=14665628; DOI=10.1074/jbc.M311873200;
RA Mattera R., Ritter B., Sidhu S.S., McPherson P.S., Bonifacino J.S.;
RT "Definition of the consensus motif recognized by gamma-adaptin ear
RT domains.";
RL J. Biol. Chem. 279:8018-8028(2004).
RN [19]
RP MUTAGENESIS OF LYS-258 AND SER-283, AND INTERACTION WITH RABEP1.
RX PubMed=15143060; DOI=10.1074/jbc.M402183200;
RA Mattera R., Puertollano R., Smith W.J., Bonifacino J.S.;
RT "The trihelical bundle subdomain of the GGA proteins interacts with
RT multiple partners through overlapping but distinct sites.";
RL J. Biol. Chem. 279:31409-31418(2004).
RN [20]
RP SUBCELLULAR LOCATION, MUTAGENESIS OF LEU-276, AND INTERACTION WITH UBC
RP AND TSG101.
RX PubMed=15039775; DOI=10.1038/ncb1106;
RA Puertollano R., Bonifacino J.S.;
RT "Interactions of GGA3 with the ubiquitin sorting machinery.";
RL Nat. Cell Biol. 6:244-251(2004).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-166.
RX PubMed=12032548; DOI=10.1038/nsb807;
RA Kato Y., Misra S., Puertollano R., Hurley J.H., Bonifacino J.S.;
RT "Phosphoregulation of sorting signal-VHS domain interactions by a
RT direct electrostatic mechanism.";
RL Nat. Struct. Biol. 9:532-536(2002).
RN [23]
RP VARIANT [LARGE SCALE ANALYSIS] LEU-574.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Plays a role in protein sorting and trafficking between
CC the trans-Golgi network (TGN) and endosomes. Mediates the ARF-
CC dependent recruitment of clathrin to the TGN and binds
CC ubiquitinated proteins and membrane cargo molecules with a
CC cytosolic acidic cluster-dileucine (AC-LL) motif.
CC -!- SUBUNIT: Monomer. Interacts with SORT1, SORL1, LRP3, GGA binding
CC partner (GGABP) and P200 (By similarity). Interacts with GGA1 and
CC GGA2. Binds to clathrin and activated ARFs. Binds RABEP1 and
CC RABGEF1. Interacts with the membrane proteins M6PR/CD-MPR,
CC IGF2R/CI-MPR and BACE1 and the accessory proteins SYNRG, EPN4,
CC NECAP1, NECAP2 and AFTPH/aftiphilin. Interacts with TSG101 and
CC UBC.
CC -!- INTERACTION:
CC P11717:IGF2R; NbExp=3; IntAct=EBI-447404, EBI-1048580;
CC Q6VY07:PACS1; NbExp=5; IntAct=EBI-447404, EBI-2555014;
CC Q15276:RABEP1; NbExp=4; IntAct=EBI-447404, EBI-447043;
CC P0CG47:UBB; NbExp=2; IntAct=EBI-447404, EBI-413034;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network
CC membrane; Peripheral membrane protein. Endosome membrane;
CC Peripheral membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=Long;
CC IsoId=Q9NZ52-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=Q9NZ52-2; Sequence=VSP_001745;
CC Name=3;
CC IsoId=Q9NZ52-3; Sequence=VSP_045133, VSP_045134;
CC Name=4;
CC IsoId=Q9NZ52-4; Sequence=VSP_046868;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC -!- DOMAIN: The VHS domain functions as a recognition module for
CC sorting signals composed of an acidic cluster followed by two
CC leucines (AC-LL motif).
CC -!- DOMAIN: The GAT domain is responsible for interaction with ARF-
CC GTP, UBC and RABEP1. Required for recruitment to the TGN it
CC prevents ARF-GTP hydrolysis.
CC -!- DOMAIN: The unstructured hinge region contains clathrin-binding
CC and an autoinhibitory (AC-LL) motifs.
CC -!- DOMAIN: The GAE domain binds accessory proteins regulating GGAs
CC function.
CC -!- PTM: Phosphorylated by CK2 and dephosphorylated by PP2A (By
CC similarity). Phosphorylation of GGA3 allows the internal AC-LL
CC motif to bind the VHS domain and to inhibit the recognition of
CC cargo signals.
CC -!- PTM: Ubiquitinated.
CC -!- SIMILARITY: Belongs to the GGA protein family.
CC -!- SIMILARITY: Contains 1 GAE domain.
CC -!- SIMILARITY: Contains 1 GAT domain.
CC -!- SIMILARITY: Contains 1 VHS domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA09926.1; Type=Erroneous initiation;
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DR EMBL; AF219138; AAF42848.1; -; mRNA.
DR EMBL; AF190864; AAF05709.1; -; mRNA.
DR EMBL; AF219139; AAF42849.1; -; mRNA.
DR EMBL; D63876; BAA09926.1; ALT_INIT; mRNA.
DR EMBL; AK301895; BAH13578.1; -; mRNA.
DR EMBL; AK302278; BAH13665.1; -; mRNA.
DR EMBL; AC022211; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471099; EAW89258.1; -; Genomic_DNA.
DR EMBL; BC070044; AAH70044.1; -; mRNA.
DR RefSeq; NP_001166174.1; NM_001172703.1.
DR RefSeq; NP_001166175.1; NM_001172704.1.
DR RefSeq; NP_054720.1; NM_014001.3.
DR RefSeq; NP_619525.1; NM_138619.2.
DR UniGene; Hs.87726; -.
DR PDB; 1JPL; X-ray; 2.40 A; A/B/C/D=1-166.
DR PDB; 1JUQ; X-ray; 2.20 A; A/B/C/D=1-166.
DR PDB; 1LF8; X-ray; 2.30 A; A/B/C/D=1-166.
DR PDB; 1P4U; X-ray; 2.20 A; A=571-723.
DR PDB; 1WR6; X-ray; 2.60 A; A/B/C/D=209-319.
DR PDB; 1YD8; X-ray; 2.80 A; G/H=208-301.
DR PDBsum; 1JPL; -.
DR PDBsum; 1JUQ; -.
DR PDBsum; 1LF8; -.
DR PDBsum; 1P4U; -.
DR PDBsum; 1WR6; -.
DR PDBsum; 1YD8; -.
DR ProteinModelPortal; Q9NZ52; -.
DR SMR; Q9NZ52; 1-157, 168-304, 579-723.
DR DIP; DIP-31600N; -.
DR IntAct; Q9NZ52; 14.
DR MINT; MINT-126320; -.
DR STRING; 9606.ENSP00000245541; -.
DR PhosphoSite; Q9NZ52; -.
DR DMDM; 14548064; -.
DR PaxDb; Q9NZ52; -.
DR PRIDE; Q9NZ52; -.
DR Ensembl; ENST00000245541; ENSP00000245541; ENSG00000125447.
DR Ensembl; ENST00000351904; ENSP00000326575; ENSG00000125447.
DR Ensembl; ENST00000578348; ENSP00000463288; ENSG00000125447.
DR Ensembl; ENST00000582717; ENSP00000462081; ENSG00000125447.
DR GeneID; 23163; -.
DR KEGG; hsa:23163; -.
DR UCSC; uc010wrw.2; human.
DR CTD; 23163; -.
DR GeneCards; GC17M073229; -.
DR HGNC; HGNC:17079; GGA3.
DR HPA; HPA022945; -.
DR MIM; 606006; gene.
DR neXtProt; NX_Q9NZ52; -.
DR PharmGKB; PA28659; -.
DR eggNOG; NOG321636; -.
DR HOGENOM; HOG000231169; -.
DR HOVERGEN; HBG015945; -.
DR InParanoid; Q9NZ52; -.
DR KO; K12404; -.
DR OMA; QGSPMKG; -.
DR PhylomeDB; Q9NZ52; -.
DR EvolutionaryTrace; Q9NZ52; -.
DR GeneWiki; GGA3; -.
DR GenomeRNAi; 23163; -.
DR NextBio; 35535625; -.
DR PRO; PR:Q9NZ52; -.
DR ArrayExpress; Q9NZ52; -.
DR Bgee; Q9NZ52; -.
DR CleanEx; HS_GGA3; -.
DR Genevestigator; Q9NZ52; -.
DR GO; GO:0030131; C:clathrin adaptor complex; IEA:InterPro.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005802; C:trans-Golgi network; IDA:UniProtKB.
DR GO; GO:0030306; F:ADP-ribosylation factor binding; IDA:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; NAS:UniProtKB.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IEA:Ensembl.
DR GO; GO:0016192; P:vesicle-mediated transport; IEA:InterPro.
DR Gene3D; 1.25.40.90; -; 1.
DR Gene3D; 2.60.40.1230; -; 1.
DR InterPro; IPR008152; Clathrin_a/b/g-adaptin_app_Ig.
DR InterPro; IPR008153; Clathrin_g-adaptin_app.
DR InterPro; IPR013041; Coatomer/clathrin_app_Ig-like.
DR InterPro; IPR008942; ENTH_VHS.
DR InterPro; IPR004152; GAT.
DR InterPro; IPR027422; GGA3.
DR InterPro; IPR002014; VHS.
DR InterPro; IPR018205; VHS_subgr.
DR PANTHER; PTHR13856:SF34; PTHR13856:SF34; 1.
DR Pfam; PF02883; Alpha_adaptinC2; 1.
DR Pfam; PF03127; GAT; 1.
DR Pfam; PF00790; VHS; 1.
DR SMART; SM00809; Alpha_adaptinC2; 1.
DR SMART; SM00288; VHS; 1.
DR SUPFAM; SSF48464; SSF48464; 1.
DR SUPFAM; SSF49348; SSF49348; 1.
DR PROSITE; PS50180; GAE; 1.
DR PROSITE; PS50909; GAT; 1.
DR PROSITE; PS50179; VHS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; Endosome;
KW Golgi apparatus; Membrane; Phosphoprotein; Polymorphism;
KW Protein transport; Reference proteome; Transport; Ubl conjugation.
FT CHAIN 1 723 ADP-ribosylation factor-binding protein
FT GGA3.
FT /FTId=PRO_0000212684.
FT DOMAIN 16 146 VHS.
FT DOMAIN 171 298 GAT.
FT DOMAIN 594 715 GAE.
FT REGION 1 313 Binds to ARF1 (in long isoform).
FT REGION 299 593 Unstructured hinge.
FT MOTIF 391 395 Autoinhibitory.
FT COMPBIAS 357 360 Poly-Pro.
FT COMPBIAS 453 457 Poly-Ser.
FT COMPBIAS 624 629 Poly-Val.
FT VAR_SEQ 1 122 Missing (in isoform 3).
FT /FTId=VSP_045133.
FT VAR_SEQ 1 72 Missing (in isoform 4).
FT /FTId=VSP_046868.
FT VAR_SEQ 68 100 Missing (in isoform Short).
FT /FTId=VSP_001745.
FT VAR_SEQ 688 723 EKVRLRYKLTFALGEQLSTEVGEVDQFPPVEQWGNL -> K
FT QVLSFLGKACLQPWGQAILLTTSCLA (in isoform
FT 3).
FT /FTId=VSP_045134.
FT VARIANT 574 574 P -> L (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_036524.
FT MUTAGEN 194 194 N->A: Loss of interaction with ARF1 and
FT Golgi localization.
FT MUTAGEN 199 199 S->P: Loss of interaction with ARF1 and
FT Golgi localization.
FT MUTAGEN 217 217 T->P: Loss of interaction with ARF1 and
FT Golgi localization.
FT MUTAGEN 247 247 L->P: Loss of UBC-binding and
FT ubiquitination.
FT MUTAGEN 258 258 K->M: No effect. Confers an affinity to
FT RABEP1 identical to GGA1; when associated
FT with N-283.
FT MUTAGEN 262 262 L->S: Loss of UBC-binding and
FT ubiquitination.
FT MUTAGEN 276 276 L->A: Loss of UBC-binding and
FT ubiquitination.
FT MUTAGEN 276 276 L->S: Loss of UBC-binding and
FT ubiquitination.
FT MUTAGEN 280 280 L->R: Loss of UBC-binding and
FT ubiquitination.
FT MUTAGEN 283 283 S->N: Can bind RABEP1. Confers an
FT affinity to RABEP1 identical to GGA1;
FT when associated with M-258.
FT MUTAGEN 284 284 D->G: Loss of UBC-binding and
FT ubiquitination.
FT MUTAGEN 293 293 Y->H: Loss of UBC-binding and
FT ubiquitination.
FT MUTAGEN 391 395 DEELL->AAAAA: Increased binding to IGF2R.
FT CONFLICT 448 448 Q -> K (in Ref. 7; AAH70044).
FT CONFLICT 562 562 F -> S (in Ref. 4; BAH13665).
FT HELIX 9 16
FT HELIX 26 38
FT HELIX 42 54
FT HELIX 59 75
FT HELIX 77 84
FT HELIX 87 97
FT HELIX 99 103
FT HELIX 108 124
FT HELIX 129 140
FT HELIX 218 231
FT TURN 232 234
FT TURN 237 239
FT HELIX 242 267
FT HELIX 276 290
FT HELIX 292 295
FT TURN 296 298
FT HELIX 588 590
FT STRAND 599 604
FT STRAND 607 616
FT STRAND 624 633
FT STRAND 635 637
FT STRAND 639 647
FT STRAND 652 656
FT STRAND 675 683
FT STRAND 692 700
FT STRAND 703 711
FT HELIX 717 719
SQ SEQUENCE 723 AA; 78315 MW; 4F80D6032239168C CRC64;
MAEAEGESLE SWLNKATNPS NRQEDWEYII GFCDQINKEL EGPQIAVRLL AHKIQSPQEW
EALQALTVLE ACMKNCGRRF HNEVGKFRFL NELIKVVSPK YLGDRVSEKV KTKVIELLYS
WTMALPEEAK IKDAYHMLKR QGIVQSDPPI PVDRTLIPSP PPRPKNPVFD DEEKSKLLAK
LLKSKNPDDL QEANKLIKSM VKEDEARIQK VTKRLHTLEE VNNNVRLLSE MLLHYSQEDS
SDGDRELMKE LFDQCENKRR TLFKLASETE DNDNSLGDIL QASDNLSRVI NSYKTIIEGQ
VINGEVATLT LPDSEGNSQC SNQGTLIDLA ELDTTNSLSS VLAPAPTPPS SGIPILPPPP
QASGPPRSRS SSQAEATLGP SSTSNALSWL DEELLCLGLA DPAPNVPPKE SAGNSQWHLL
QREQSDLDFF SPRPGTAACG ASDAPLLQPS APSSSSSQAP LPPPFPAPVV PASVPAPSAG
SSLFSTGVAP ALAPKVEPAV PGHHGLALGN SALHHLDALD QLLEEAKVTS GLVKPTTSPL
IPTTTPARPL LPFSTGPGSP LFQPLSFQSQ GSPPKGPELS LASIHVPLES IKPSSALPVT
AYDKNGFRIL FHFAKECPPG RPDVLVVVVS MLNTAPLPVK SIVLQAAVPK SMKVKLQPPS
GTELSPFSPI QPPAAITQVM LLANPLKEKV RLRYKLTFAL GEQLSTEVGE VDQFPPVEQW
GNL
//
MIM
606006
*RECORD*
*FIELD* NO
606006
*FIELD* TI
*606006 GOLGI-ASSOCIATED, GAMMA-ADAPTIN EAR-CONTAINING, ARF-BINDING PROTEIN
3; GGA3
read more;;ADP-RIBOSYLATION FACTOR-BINDING PROTEIN 3;;
ARF-BINDING PROTEIN 3;;
KIAA0154
*FIELD* TX
For general information on cloning and function of the GGA family, see
GGA1 (606004).
CLONING
By sequencing clones obtained from a size-fractionated immature myeloid
cell line cDNA library, Nagase et al. (1995) cloned GGA3, which they
designated KIAA0154. The deduced protein shares significant identity
with mouse gamma-adaptin (AP1G1; 603533). Northern blot analysis
detected GGA3 expression in all tissues and cell lines examined.
Hirst et al. (2000), Takatsu et al. (2000), and Dell'Angelica et al.
(2000) independently cloned GGA1, GGA2 (606005), and GGA3. The GGA3 gene
encodes a protein of 723 amino acids (Dell'Angelica et al., 2000). GGA3
shares 46% amino acid sequence identity with GGA1 and 38% with GGA2
(Takatsu et al., 2000).
GENE FUNCTION
Doray et al. (2002) demonstrated that GGA1 and GGA3 and the coat protein
adaptor protein-1 (AP-1) complex (see AP1G2, 603534) colocalize in
clathrin-coated buds of the trans-Golgi networks of mouse L cells and
human HeLa cells. Binding studies revealed a direct interaction between
the hinge domains of the GGAs and the gamma-ear domain of AP-1. Further,
AP-1 contained bound casein kinase-2 (see CSNK2A1, 115440) that
phosphorylated GGA1 and GGA3, thereby causing autoinhibition. Doray et
al. (2002) demonstrated that this autoinhibition could induce the
directed transfer of mannose 6-phosphate receptors (see 154540) from the
GGAs to AP-1. Mannose 6-phosphate receptors that were defective in
binding to GGAs were poorly incorporated into adaptor protein complex
containing clathrin coated vesicles. Thus, Doray et al. (2002) concluded
that GGAs and the AP-1 complex interact to package mannose 6-phosphate
receptors into AP-1-containing coated vesicles.
BACE (604252) is required for beta-secretase activity and production of
the Alzheimer disease (AD; 104300)-associated A-beta protein from APP
(104760). Tesco et al. (2007) identified GGA3 as a BACE trafficking
molecule and found that it was cleaved by caspase-3 (CASP3; 600636)
during apoptosis in a human neuroglioma cell line and in a rat model of
cerebral ischemia. As GGA3 was removed by caspase cleavage, BACE was
stabilized, leading to elevated beta-secretase cleavage of APP.
Silencing of GGA3 by RNA interference led to increased levels of BACE
and the APP cleavage products C99 and A-beta. GGA3 protein levels were
significantly decreased and were inversely correlated with BACE levels
in AD brains, but not in nondemented control brains. Tesco et al. (2007)
concluded that depletion of GGA3 is responsible for enhanced BACE levels
and beta-secretase activity during ischemia and in AD brain.
MAPPING
By radiation hybrid analysis, Nagase et al. (1995) mapped the GGA3 gene
(KIAA0154) to chromosome 17.
*FIELD* RF
1. Dell'Angelica, E. C.; Puertollano, R.; Mullins, C.; Aguilar, R.
C.; Vargas, J. D.; Hartnell, L. M.; Bonifacino, J. S.: GGAs: a family
of ADP ribosylation factor-binding proteins related to adaptors and
associated with the Golgi complex. J. Cell Biol. 149: 81-93, 2000.
2. Doray, B.; Ghosh, P.; Griffith, J.; Geuze, H. J.; Kornfeld, S.
: Cooperation of GGAs and AP-1 in packaging MPRs at the trans-Golgi
network. Science 297: 1700-1703, 2002.
3. Hirst, J.; Lui, W. W. Y.; Bright, N. A.; Totty, N.; Seaman, M.
N. J.; Robinson, M. S.: A family of proteins with gamma-adaptin and
VHS domains that facilitate trafficking between the trans-Golgi network
and the vacuole/lysosome. J. Cell Biol. 149: 67-69, 2000.
4. Nagase, T.; Seki, N.; Tanaka, A.; Ishikawa, K.; Nomura, N.: Prediction
of the coding sequences of unidentified human genes. IV. The coding
sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis
of cDNA clones from human cell line KG-1. DNA Res. 2: 167-174, 1995.
5. Takatsu, H.; Yoshino, K.; Nakayama, K.: Adaptor gamma-ear homology
domain conserved in gamma-adaptin and GGA proteins that interact with
gamma-synergin. Biochem. Biophys. Res. Commun. 271: 719-725, 2000.
6. Tesco, G.; Koh, Y. H.; Kang, E. L.; Cameron, A. N.; Das, S.; Sena-Esteves,
M.; Hiltunen, M.; Yang, S.-H.; Zhong, Z.; Shen, Y.; Simpkins, J. W.;
Tanzi, R. E.: Depletion of GGA3 stabilizes BACE and enhances beta-secretase
activity. Neuron 54: 721-737, 2007.
*FIELD* CN
Patricia A. Hartz - updated: 8/1/2007
Ada Hamosh - updated: 10/23/2002
Anne M. Stumpf - updated: 10/23/2002
Joanna S. Amberger - updated: 12/19/2001
*FIELD* CD
Ada Hamosh: 6/13/2001
*FIELD* ED
mgross: 08/06/2007
terry: 8/1/2007
alopez: 10/23/2002
joanna: 12/19/2001
alopez: 6/14/2001
*RECORD*
*FIELD* NO
606006
*FIELD* TI
*606006 GOLGI-ASSOCIATED, GAMMA-ADAPTIN EAR-CONTAINING, ARF-BINDING PROTEIN
3; GGA3
read more;;ADP-RIBOSYLATION FACTOR-BINDING PROTEIN 3;;
ARF-BINDING PROTEIN 3;;
KIAA0154
*FIELD* TX
For general information on cloning and function of the GGA family, see
GGA1 (606004).
CLONING
By sequencing clones obtained from a size-fractionated immature myeloid
cell line cDNA library, Nagase et al. (1995) cloned GGA3, which they
designated KIAA0154. The deduced protein shares significant identity
with mouse gamma-adaptin (AP1G1; 603533). Northern blot analysis
detected GGA3 expression in all tissues and cell lines examined.
Hirst et al. (2000), Takatsu et al. (2000), and Dell'Angelica et al.
(2000) independently cloned GGA1, GGA2 (606005), and GGA3. The GGA3 gene
encodes a protein of 723 amino acids (Dell'Angelica et al., 2000). GGA3
shares 46% amino acid sequence identity with GGA1 and 38% with GGA2
(Takatsu et al., 2000).
GENE FUNCTION
Doray et al. (2002) demonstrated that GGA1 and GGA3 and the coat protein
adaptor protein-1 (AP-1) complex (see AP1G2, 603534) colocalize in
clathrin-coated buds of the trans-Golgi networks of mouse L cells and
human HeLa cells. Binding studies revealed a direct interaction between
the hinge domains of the GGAs and the gamma-ear domain of AP-1. Further,
AP-1 contained bound casein kinase-2 (see CSNK2A1, 115440) that
phosphorylated GGA1 and GGA3, thereby causing autoinhibition. Doray et
al. (2002) demonstrated that this autoinhibition could induce the
directed transfer of mannose 6-phosphate receptors (see 154540) from the
GGAs to AP-1. Mannose 6-phosphate receptors that were defective in
binding to GGAs were poorly incorporated into adaptor protein complex
containing clathrin coated vesicles. Thus, Doray et al. (2002) concluded
that GGAs and the AP-1 complex interact to package mannose 6-phosphate
receptors into AP-1-containing coated vesicles.
BACE (604252) is required for beta-secretase activity and production of
the Alzheimer disease (AD; 104300)-associated A-beta protein from APP
(104760). Tesco et al. (2007) identified GGA3 as a BACE trafficking
molecule and found that it was cleaved by caspase-3 (CASP3; 600636)
during apoptosis in a human neuroglioma cell line and in a rat model of
cerebral ischemia. As GGA3 was removed by caspase cleavage, BACE was
stabilized, leading to elevated beta-secretase cleavage of APP.
Silencing of GGA3 by RNA interference led to increased levels of BACE
and the APP cleavage products C99 and A-beta. GGA3 protein levels were
significantly decreased and were inversely correlated with BACE levels
in AD brains, but not in nondemented control brains. Tesco et al. (2007)
concluded that depletion of GGA3 is responsible for enhanced BACE levels
and beta-secretase activity during ischemia and in AD brain.
MAPPING
By radiation hybrid analysis, Nagase et al. (1995) mapped the GGA3 gene
(KIAA0154) to chromosome 17.
*FIELD* RF
1. Dell'Angelica, E. C.; Puertollano, R.; Mullins, C.; Aguilar, R.
C.; Vargas, J. D.; Hartnell, L. M.; Bonifacino, J. S.: GGAs: a family
of ADP ribosylation factor-binding proteins related to adaptors and
associated with the Golgi complex. J. Cell Biol. 149: 81-93, 2000.
2. Doray, B.; Ghosh, P.; Griffith, J.; Geuze, H. J.; Kornfeld, S.
: Cooperation of GGAs and AP-1 in packaging MPRs at the trans-Golgi
network. Science 297: 1700-1703, 2002.
3. Hirst, J.; Lui, W. W. Y.; Bright, N. A.; Totty, N.; Seaman, M.
N. J.; Robinson, M. S.: A family of proteins with gamma-adaptin and
VHS domains that facilitate trafficking between the trans-Golgi network
and the vacuole/lysosome. J. Cell Biol. 149: 67-69, 2000.
4. Nagase, T.; Seki, N.; Tanaka, A.; Ishikawa, K.; Nomura, N.: Prediction
of the coding sequences of unidentified human genes. IV. The coding
sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis
of cDNA clones from human cell line KG-1. DNA Res. 2: 167-174, 1995.
5. Takatsu, H.; Yoshino, K.; Nakayama, K.: Adaptor gamma-ear homology
domain conserved in gamma-adaptin and GGA proteins that interact with
gamma-synergin. Biochem. Biophys. Res. Commun. 271: 719-725, 2000.
6. Tesco, G.; Koh, Y. H.; Kang, E. L.; Cameron, A. N.; Das, S.; Sena-Esteves,
M.; Hiltunen, M.; Yang, S.-H.; Zhong, Z.; Shen, Y.; Simpkins, J. W.;
Tanzi, R. E.: Depletion of GGA3 stabilizes BACE and enhances beta-secretase
activity. Neuron 54: 721-737, 2007.
*FIELD* CN
Patricia A. Hartz - updated: 8/1/2007
Ada Hamosh - updated: 10/23/2002
Anne M. Stumpf - updated: 10/23/2002
Joanna S. Amberger - updated: 12/19/2001
*FIELD* CD
Ada Hamosh: 6/13/2001
*FIELD* ED
mgross: 08/06/2007
terry: 8/1/2007
alopez: 10/23/2002
joanna: 12/19/2001
alopez: 6/14/2001