GGA3_RAT
ID GGA3_RAT Reviewed; 727 AA.
AC A0A0G2JV04;
DT 05-DEC-2018, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2015, sequence version 1.
DT 03-AUG-2022, entry version 48.
DE RecName: Full=ADP-ribosylation factor-binding protein GGA3 {ECO:0000305};
DE AltName: Full=Golgi-localized, gamma ear-containing, ARF-binding protein 3;
GN Name=Gga3 {ECO:0000312|RGD:1309553};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [3]
RP FUNCTION, INTERACTION WITH NTRK1, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP ASN-194.
RX PubMed=26446845; DOI=10.1091/mbc.e15-02-0087;
RA Li X., Lavigne P., Lavoie C.;
RT "GGA3 mediates TrkA endocytic recycling to promote sustained Akt
RT phosphorylation and cell survival.";
RL Mol. Biol. Cell 26:4412-4426(2015).
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 (PubMed:26446845).
CC {ECO:0000250|UniProtKB:Q9NZ52, ECO:0000269|PubMed:26446845}.
CC -!- SUBUNIT: Monomer. Interacts with GGA1 and GGA2. Binds to clathrin and
CC activated ARFs, such as ARF1, ARF5 and ARF6. Binds RABEP1 and RABGEF1.
CC Interacts with the membrane proteins M6PR/CD-MPR and IGF2R/CI-MPR and
CC the accessory proteins SYNRG, EPN4, NECAP1, NECAP2 and
CC AFTPH/aftiphilin. Interacts with TSG101 and UBC. Interacts with ADRA2B
CC (By similarity). Interacts with NTRK1; the interaction is independent
CC of NTRK1 activation and ubiquitination (PubMed:26446845). Interacts
CC (via VHS domain) with BACE1 (via DXXLL motif) (By similarity).
CC {ECO:0000250|UniProtKB:Q9NZ52, ECO:0000269|PubMed:26446845}.
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:0000269|PubMed:26446845}; Peripheral membrane protein
CC {ECO:0000305}. Recycling endosome membrane
CC {ECO:0000269|PubMed:26446845}; 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|UniProtKB:Q9NZ52}.
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. {ECO:0000250|UniProtKB:Q9NZ52}.
CC -!- DOMAIN: The unstructured hinge region contains clathrin-binding and an
CC autoinhibitory (DXXLL) motifs. {ECO:0000250|UniProtKB:Q9NZ52}.
CC -!- DOMAIN: The GAE domain binds accessory proteins regulating GGAs
CC function. {ECO:0000250|UniProtKB:Q9NZ52}.
CC -!- PTM: Phosphorylated by CK2 and dephosphorylated by PP2A (By
CC similarity). Phosphorylation of GGA3 allows the internal DXXLL motif to
CC bind the VHS domain and to inhibit the recognition of cargo signals.
CC {ECO:0000250}.
CC -!- PTM: Ubiquitinated. {ECO:0000250|UniProtKB:Q9NZ52}.
CC -!- PTM: Proteolytically cleaved during apoptosis by CASP3.
CC {ECO:0000250|UniProtKB:Q9NZ52}.
CC -!- SIMILARITY: Belongs to the GGA protein family. {ECO:0000305}.
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DR EMBL; AABR07030782; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_006247781.1; XM_006247719.3.
DR AlphaFoldDB; A0A0G2JV04; -.
DR SMR; A0A0G2JV04; -.
DR STRING; 10116.ENSRNOP00000060463; -.
DR jPOST; A0A0G2JV04; -.
DR Ensembl; ENSRNOT00000114183; ENSRNOP00000090243; ENSRNOG00000027057.
DR GeneID; 360658; -.
DR CTD; 23163; -.
DR RGD; 1309553; Gga3.
DR GeneTree; ENSGT00940000157333; -.
DR OMA; MQLLNQM; -.
DR OrthoDB; 594067at2759; -.
DR PhylomeDB; A0A0G2JV04; -.
DR Reactome; R-RNO-8875656; MET receptor recycling.
DR PRO; PR:A0A0G2JV04; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000027057; Expressed in spleen and 20 other tissues.
DR ExpressionAtlas; A0A0G2JV04; baseline and differential.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005802; C:trans-Golgi network; ISO:RGD.
DR GO; GO:0035091; F:phosphatidylinositol binding; IEA:InterPro.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:RGD.
DR GO; GO:0031267; F:small GTPase binding; ISO:RGD.
DR GO; GO:0043130; F:ubiquitin binding; ISO:RGD.
DR GO; GO:0032456; P:endocytic recycling; IDA:UniProtKB.
DR GO; GO:0043001; P:Golgi to plasma membrane protein transport; ISO:RGD.
DR GO; GO:0006893; P:Golgi to plasma membrane transport; IBA:GO_Central.
DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; ISO:RGD.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; ISO:RGD.
DR GO; GO:0030163; P:protein catabolic process; IEA:Ensembl.
DR GO; GO:0031648; P:protein destabilization; ISO:RGD.
DR GO; GO:0034394; P:protein localization to cell surface; ISO:RGD.
DR GO; GO:0061462; P:protein localization to lysosome; ISO:RGD.
DR GO; GO:0006622; P:protein targeting to lysosome; ISO:RGD.
DR GO; GO:0031647; P:regulation of protein stability; ISO:RGD.
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..727
FT /note="ADP-ribosylation factor-binding protein GGA3"
FT /id="PRO_0000445935"
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 598..719
FT /note="GAE"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00093"
FT REGION 299..597
FT /note="Unstructured hinge"
FT /evidence="ECO:0000250|UniProtKB:Q8BMI3"
FT REGION 334..385
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 400..419
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 391..395
FT /note="DXXLL"
FT COMPBIAS 341..365
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 366..385
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 MUTAGEN 194
FT /note="N->A: Disrupts recycling of NTRK1 to the plasma
FT membrane."
FT /evidence="ECO:0000269|PubMed:26446845"
SQ SEQUENCE 727 AA; 78759 MW; 50BCDCC829676A18 CRC64;
MAEAEGESLE SWLNKATNPS NRQEDWEYII GFCDQINKEL EGPQIAVRLL AHKIQSPQEW
EAVQALTVLE ACMKNCGRRL HNEVGKFRFL NELIKVVSPK YLGDRVSEKV KAKVIELLFS
WTLALPEEAK IKDAYHMLKR QGIVQSDPPI PMDRTLIPSP PPRPKNPVFD DEEKSKLLAK
LLRSKNPDDL QEANQLIKSM VKEDEARIQK VTKRLHTLEE VNNNVKLLHE MLLHYSQEFS
SEADKELMKE LFDRCENKRR TLFKLASETE DNDNSLGDIL QASDNLSRVI NSYKTIIEGQ
IINGEVTTST VPDSEGNSHC GNQGALIDLA ELDTPSSSSP VLAPAPAPPT SGIPILPPPP
QTSGPPRSRS SSQAEAPSGP DSTNNALSLL DEELLCLGLS DPAPTAPKES AGNSPWHLFQ
NEPSSDLDFF SPRLVSAASC PSEGSLLPPP VSTSSLSQAP LPAAFPAPVV PASAVTHSTG
SFTFSSGPAP ALVPKAEPEG PEYPSSSISH RLDALDQLLE EAKVTSGLVK PVSCFSPGPT
ASPLLPASTP ARPLLPFSTG PGSPLFQSPA FQSQGSPQKG PELSLASVHV PLESIKPSSA
LPVTAYDKNG FRILFHFAKE CPPGRPDVLV VVVSMLNTAP LPVKSIVLQA AVPKSMKVKL
QPPSGTELSP FSPIQPPAAI TQVMLLANPM KEKVRLRYKL TFALGEQLST ELGEVDQFPP
VEQWGNL
