GGA3_MOUSE
ID GGA3_MOUSE Reviewed; 718 AA.
AC Q8BMI3; Q3V1Y0; Q80U71;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, 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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Fetal brain;
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
RN [2]
RP SEQUENCE REVISION.
RA Okazaki N., Kikuno R., Nagase T., Ohara O., Koga H.;
RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Forelimb, and Head;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
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 between
RT their GGAH domains and ADP-ribosylation factors.";
RL Biochem. J. 365:369-378(2002).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Lung, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Plays a role in protein sorting and trafficking between the
CC trans-Golgi network (TGN) and endosomes. Mediates the ARF-dependent
CC recruitment of clathrin to the TGN and binds ubiquitinated proteins and
CC membrane cargo molecules with a cytosolic acidic cluster-dileucine
CC (DXXLL) motif (By similarity). {ECO:0000250}.
CC -!- FUNCTION: Plays a role in protein sorting and trafficking between the
CC trans-Golgi network (TGN) and endosomes. Mediates the ARF-dependent
CC recruitment of clathrin to the TGN and binds ubiquitinated proteins and
CC membrane cargo molecules with a cytosolic acidic cluster-dileucine
CC (DXXLL) motif. Mediates export of the GPCR receptor ADRA2B to the cell
CC surface. Involved in BACE1 transport and sorting as well as regulation
CC of BACE1 protein levels. Regulates retrograde transport of BACE1 from
CC endosomes to the trans-Golgi network via interaction through the VHS
CC motif and dependent of BACE1 phosphorylation. Modulates BACE1 protein
CC levels independently of the interaction between VHS domain and DXXLL
CC motif through recognition of ubiquitination (By similarity). Key player
CC in a novel DXXLL-mediated endosomal sorting machinery to the recycling
CC pathway that targets NTRK1 to the plasma membrane (By similarity).
CC {ECO:0000250|UniProtKB:A0A0G2JV04, ECO:0000250|UniProtKB:Q9NZ52}.
CC -!- SUBUNIT: Monomer. Interacts with GGA1 and GGA2 (By similarity). Binds
CC to clathrin and activated ARFs, such as ARF1, ARF5 and ARF6
CC (PubMed:11950392). Binds RABEP1 and RABGEF1. Interacts with the
CC membrane proteins M6PR/CD-MPR and IGF2R/CI-MPR and the accessory
CC proteins SYNRG, EPN4, NECAP1, NECAP2 and AFTPH/aftiphilin. Interacts
CC with TSG101 and UBC. Interacts with ADRA2B. Interacts with NTRK1; the
CC interaction is independent of NTRK1 activation and ubiquitination.
CC Interacts (via VHS domain) with BACE1 (via DXXLL motif) (By
CC similarity). {ECO:0000250|UniProtKB:A0A0G2JV04,
CC ECO:0000250|UniProtKB:Q9NZ52, ECO:0000269|PubMed:11950392}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane
CC {ECO:0000250|UniProtKB:Q9NZ52}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q9NZ52}. Endosome membrane
CC {ECO:0000250|UniProtKB:Q9NZ52}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q9NZ52}. Early endosome membrane
CC {ECO:0000250|UniProtKB:A0A0G2JV04}; Peripheral membrane protein
CC {ECO:0000305}. Recycling endosome membrane
CC {ECO:0000250|UniProtKB:A0A0G2JV04}; Peripheral membrane protein
CC {ECO:0000305}.
CC -!- DOMAIN: The VHS domain functions as a recognition module for sorting
CC signals composed of an acidic cluster followed by two leucines (DXXLL
CC motif). {ECO:0000250}.
CC -!- DOMAIN: The GAT domain is responsible for interaction with ARF-GTP, UBC
CC and RABEP1. Required for recruitment to the TGN it prevents ARF-GTP
CC hydrolysis (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The unstructured hinge region contains clathrin-binding and an
CC autoinhibitory (DXXLL) motifs. {ECO:0000250}.
CC -!- DOMAIN: The GAE domain binds accessory proteins regulating GGAs
CC function. {ECO:0000250}.
CC -!- PTM: Phosphorylated by CK2 and dephosphorylated by PP2A.
CC Phosphorylation of GGA3 allows the internal DXXLL motif to bind the VHS
CC domain and to inhibit the recognition of cargo signals (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Ubiquitinated. {ECO:0000250}.
CC -!- PTM: Proteolytically cleaved during apoptosis by CASP3.
CC {ECO:0000250|UniProtKB:Q9NZ52}.
CC -!- SIMILARITY: Belongs to the GGA protein family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC65494.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK122212; BAC65494.2; ALT_INIT; mRNA.
DR EMBL; AK031086; BAC27246.1; -; mRNA.
DR EMBL; AK132183; BAE21019.1; -; mRNA.
DR EMBL; AL645470; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS25641.1; -.
DR RefSeq; NP_766636.2; NM_173048.3.
DR AlphaFoldDB; Q8BMI3; -.
DR SMR; Q8BMI3; -.
DR BioGRID; 234429; 12.
DR ELM; Q8BMI3; -.
DR STRING; 10090.ENSMUSP00000019135; -.
DR iPTMnet; Q8BMI3; -.
DR PhosphoSitePlus; Q8BMI3; -.
DR EPD; Q8BMI3; -.
DR jPOST; Q8BMI3; -.
DR MaxQB; Q8BMI3; -.
DR PaxDb; Q8BMI3; -.
DR PRIDE; Q8BMI3; -.
DR ProteomicsDB; 266797; -.
DR Antibodypedia; 19520; 198 antibodies from 32 providers.
DR DNASU; 260302; -.
DR Ensembl; ENSMUST00000019135; ENSMUSP00000019135; ENSMUSG00000020740.
DR GeneID; 260302; -.
DR KEGG; mmu:260302; -.
DR UCSC; uc007mhy.2; mouse.
DR CTD; 23163; -.
DR MGI; MGI:2384159; Gga3.
DR VEuPathDB; HostDB:ENSMUSG00000020740; -.
DR eggNOG; KOG1087; Eukaryota.
DR GeneTree; ENSGT00940000157333; -.
DR InParanoid; Q8BMI3; -.
DR OMA; MQLLNQM; -.
DR OrthoDB; 594067at2759; -.
DR PhylomeDB; Q8BMI3; -.
DR TreeFam; TF318574; -.
DR Reactome; R-MMU-8875656; MET receptor recycling.
DR BioGRID-ORCS; 260302; 4 hits in 74 CRISPR screens.
DR ChiTaRS; Gga3; mouse.
DR PRO; PR:Q8BMI3; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q8BMI3; protein.
DR Bgee; ENSMUSG00000020740; Expressed in animal zygote and 227 other tissues.
DR ExpressionAtlas; Q8BMI3; baseline and differential.
DR Genevisible; Q8BMI3; MM.
DR GO; GO:0005769; C:early endosome; ISO:MGI.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0005764; C:lysosome; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0055037; C:recycling endosome; ISO:MGI.
DR GO; GO:0055038; C:recycling endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005802; C:trans-Golgi network; ISO:MGI.
DR GO; GO:0035091; F:phosphatidylinositol binding; IEA:InterPro.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0031267; F:small GTPase binding; ISO:MGI.
DR GO; GO:0043130; F:ubiquitin binding; ISS:UniProtKB.
DR GO; GO:0032456; P:endocytic recycling; ISO:MGI.
DR GO; GO:0043001; P:Golgi to plasma membrane protein transport; ISS:UniProtKB.
DR GO; GO:0006893; P:Golgi to plasma membrane transport; IBA:GO_Central.
DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; ISS:UniProtKB.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IGI:MGI.
DR GO; GO:0030163; P:protein catabolic process; IGI:MGI.
DR GO; GO:0031648; P:protein destabilization; ISS:UniProtKB.
DR GO; GO:0034394; P:protein localization to cell surface; ISS:UniProtKB.
DR GO; GO:0061462; P:protein localization to lysosome; IMP:MGI.
DR GO; GO:0006622; P:protein targeting to lysosome; ISO:MGI.
DR GO; GO:0031647; P:regulation of protein stability; ISS:UniProtKB.
DR CDD; cd14240; GAT_GGA3; 1.
DR Gene3D; 1.20.58.160; -; 1.
DR Gene3D; 1.25.40.90; -; 1.
DR InterPro; IPR008152; Clathrin_a/b/g-adaptin_app_Ig.
DR InterPro; IPR013041; Clathrin_app_Ig-like_sf.
DR InterPro; IPR008942; ENTH_VHS.
DR InterPro; IPR008153; GAE_dom.
DR InterPro; IPR004152; GAT_dom.
DR InterPro; IPR044111; GAT_GGA3.
DR InterPro; IPR038425; GAT_sf.
DR InterPro; IPR027422; GGA3.
DR InterPro; IPR041198; GGA_N-GAT.
DR InterPro; IPR002014; VHS_dom.
DR PANTHER; PTHR45905:SF3; PTHR45905:SF3; 1.
DR Pfam; PF02883; Alpha_adaptinC2; 1.
DR Pfam; PF03127; GAT; 1.
DR Pfam; PF18308; GGA_N-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 Endosome; Golgi apparatus; Membrane; Phosphoprotein; Protein transport;
KW Reference proteome; Transport; Ubl conjugation.
FT CHAIN 1..718
FT /note="ADP-ribosylation factor-binding protein GGA3"
FT /id="PRO_0000212685"
FT DOMAIN 16..146
FT /note="VHS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00218"
FT DOMAIN 171..298
FT /note="GAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00373"
FT DOMAIN 589..710
FT /note="GAE"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00093"
FT REGION 299..588
FT /note="Unstructured hinge"
FT REGION 334..381
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 395..455
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 477..506
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 387..391
FT /note="Autoinhibitory"
FT /evidence="ECO:0000250"
FT COMPBIAS 346..361
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 362..381
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 403..417
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 159
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZ52"
FT MOD_RES 275
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZ52"
FT CONFLICT 151
FT /note="P -> T (in Ref. 1; BAC27246)"
FT /evidence="ECO:0000305"
FT CONFLICT 433
FT /note="A -> V (in Ref. 1; BAC65494)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 718 AA; 77973 MW; 265A4993609D89B9 CRC64;
MAEAEGESLE SWLNKATNPS NRQEDWEYII GFCDQINKEL EGPQIAVRLL AHKIQSPQEW
EAVQALTVLE ACMKNCGRRL HNEVGKFRFL NELIKVVSPK YLGDRVSEKV KTKVIELLFS
WTLALPEEAK IKDAYHMLKR QGIVQSDPPI PMDRTLIPSP PPRPKNPVFD DEEKSKLLAR
LLKSKNPDDL QEANRLIKSM VKEDEARIQK VTKRLHTLEE VNNNVKLLHE MLLHYSQEYS
SDADKELMKE LFDRCENKRR TLFKLASETE DNDNSLGDIL QASDNLSRVI NSYKTIIEGQ
IVNGEVTTST MPDSEGNSHC GNQGALIDLA ELDAPSNSSP ALAPPTSGIP ILPPPPQTSG
PPRSRSSSQA EAPPGSDSTN NALSLLDEEL LCLGLTDPAP TAPKESPGSS QWHLFQNEPP
SDLDFFSPRP VPAASCPSDG PQLPPPVSTS SMSQAPLPAA FPAPVVPASA PTHSTGSFMF
SSGPAPALAP KAEPKGPEYP SSSTSHRLDA LDQLLEEAKV TSGLVKPVSC FSPGPTASPL
LPASAPARPL LPFSTGPGSP LFQSQGSPQK GPELSLASVH VPLESIKPSS ALPVTAYDKN
GFRILFHFAK ECPPGRPDVL VVVVSMLNTA PLPVKSIVLQ AAVPKSMKVK LQPPSGTELS
PFSPIQPPAA ITQVMLLANP MKEKVRLRYK LTFALGEQLS TELGEVDQFP PVEQWGNL
