ID   ZNT3_MOUSE              Reviewed;         388 AA.
AC   P97441; P97511;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1997, sequence version 1.
DT   27-MAR-2024, entry version 180.
DE   RecName: Full=Probable proton-coupled zinc antiporter SLC30A3 {ECO:0000305|PubMed:9990090};
DE   AltName: Full=Solute carrier family 30 member 3 {ECO:0000312|MGI:MGI:1345280};
DE   AltName: Full=Zinc transporter 3 {ECO:0000305|PubMed:9990090};
DE            Short=ZnT-3 {ECO:0000303|PubMed:8962159};
GN   Name=Slc30a3 {ECO:0000312|MGI:MGI:1345280}; Synonyms=Znt3;
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 [GENOMIC DNA / MRNA], AND TISSUE SPECIFICITY.
RC   STRAIN=129; TISSUE=Brain;
RX   PubMed=8962159; DOI=10.1073/pnas.93.25.14934;
RA   Palmiter R.D., Cole T.B., Quaife C.J., Findley S.D.;
RT   "ZnT-3, a putative transporter of zinc into synaptic vesicles.";
RL   Proc. Natl. Acad. Sci. U.S.A. 93:14934-14939(1996).
RN   [2]
RP   SUBCELLULAR LOCATION.
RX   PubMed=9356509; DOI=10.1073/pnas.94.23.12676;
RA   Wenzel H.J., Cole T.B., Born D.E., Schwartzkroin P.A., Palmiter R.D.;
RT   "Ultrastructural localization of zinc transporter-3 (ZnT-3) to synaptic
RT   vesicle membranes within mossy fiber boutons in the hippocampus of mouse
RT   and monkey.";
RL   Proc. Natl. Acad. Sci. U.S.A. 94:12676-12681(1997).
RN   [3]
RP   FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP   AND DISRUPTION PHENOTYPE.
RX   PubMed=9990090; DOI=10.1073/pnas.96.4.1716;
RA   Cole T.B., Wenzel H.J., Kafer K.E., Schwartzkroin P.A., Palmiter R.D.;
RT   "Elimination of zinc from synaptic vesicles in the intact mouse brain by
RT   disruption of the ZnT3 gene.";
RL   Proc. Natl. Acad. Sci. U.S.A. 96:1716-1721(1999).
RN   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain cortex;
RX   PubMed=17114649; DOI=10.1074/mcp.m600046-mcp200;
RA   Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F.,
RA   Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B.,
RA   Panse C., Schlapbach R., Mansuy I.M.;
RT   "Qualitative and quantitative analyses of protein phosphorylation in naive
RT   and stimulated mouse synaptosomal preparations.";
RL   Mol. Cell. Proteomics 6:283-293(2007).
RN   [5]
RP   SUBUNIT.
RX   PubMed=19521526; DOI=10.1371/journal.pone.0005896;
RA   Salazar G., Falcon-Perez J.M., Harrison R., Faundez V.;
RT   "SLC30A3 (ZnT3) oligomerization by dityrosine bonds regulates its
RT   subcellular localization and metal transport capacity.";
RL   PLoS ONE 4:e5896-e5896(2009).
RN   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain;
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).
RN   [7]
RP   SUBCELLULAR LOCATION.
RX   PubMed=21998198; DOI=10.1091/mbc.e11-07-0592;
RA   Larimore J., Tornieri K., Ryder P.V., Gokhale A., Zlatic S.A., Craige B.,
RA   Lee J.D., Talbot K., Pare J.F., Smith Y., Faundez V.;
RT   "The schizophrenia susceptibility factor dysbindin and its associated
RT   complex sort cargoes from cell bodies to the synapse.";
RL   Mol. Biol. Cell 22:4854-4867(2011).
CC   -!- FUNCTION: Probable proton-coupled zinc ion antiporter mediating the
CC       import of zinc from cytoplasm into synaptic vesicles and participating
CC       to cellular zinc ion homeostasis in the brain.
CC       {ECO:0000269|PubMed:9990090}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 H(+)(out) + Zn(2+)(in) = 2 H(+)(in) + Zn(2+)(out);
CC         Xref=Rhea:RHEA:72627, ChEBI:CHEBI:15378, ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000250|UniProtKB:Q99726};
CC   -!- SUBUNIT: Homodimer. Homodimerization is negligible compared to the
CC       human protein. It could explain the lower efficiency of zinc transport.
CC       Interacts with TMEM163 (By similarity). {ECO:0000250|UniProtKB:Q99726,
CC       ECO:0000269|PubMed:19521526}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, synaptic
CC       vesicle membrane {ECO:0000269|PubMed:9356509,
CC       ECO:0000305|PubMed:21998198, ECO:0000305|PubMed:9990090}; Multi-pass
CC       membrane protein {ECO:0000305|PubMed:21998198}. Synapse, synaptosome
CC       {ECO:0000269|PubMed:21998198}. Late endosome membrane
CC       {ECO:0000250|UniProtKB:Q99726}; Multi-pass membrane protein
CC       {ECO:0000255}. Lysosome membrane {ECO:0000250|UniProtKB:Q99726}; Multi-
CC       pass membrane protein {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: Expression is restricted to brain (at protein
CC       level). In the brain, most abundant in hippocampus and cerebral cortex.
CC       The mRNA is also detected in testis, expression being restricted to
CC       germ cells and highest in pachytene spermatocytes and round spermatids.
CC       {ECO:0000269|PubMed:8962159, ECO:0000269|PubMed:9990090}.
CC   -!- DEVELOPMENTAL STAGE: In brain expression is negligible at birth, then
CC       increases linearly, reaching a maximum at about 3 weeks postpartum.
CC       {ECO:0000269|PubMed:9990090}.
CC   -!- DISRUPTION PHENOTYPE: Homozygous knockout mice lacking Slc30a3 do not
CC       display overt phenotype with morphology, body weight, lifespan,
CC       fertility, litter size being normal (PubMed:9990090). Zinc ions are
CC       eliminated from synaptic vesicles in brain of the knockout mice and the
CC       overall levels of zinc in brain is decreased (PubMed:9990090).
CC       {ECO:0000269|PubMed:9990090}.
CC   -!- SIMILARITY: Belongs to the cation diffusion facilitator (CDF)
CC       transporter (TC 2.A.4) family. SLC30A subfamily. {ECO:0000305}.
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DR   EMBL; U76007; AAB39731.1; -; mRNA.
DR   EMBL; U76009; AAB39733.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; U76008; AAB39733.1; JOINED; Genomic_DNA.
DR   CCDS; CCDS51455.1; -.
DR   RefSeq; NP_035903.2; NM_011773.3.
DR   AlphaFoldDB; P97441; -.
DR   SMR; P97441; -.
DR   BioGRID; 204705; 4.
DR   IntAct; P97441; 2.
DR   MINT; P97441; -.
DR   STRING; 10090.ENSMUSP00000031037; -.
DR   GlyGen; P97441; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P97441; -.
DR   PhosphoSitePlus; P97441; -.
DR   SwissPalm; P97441; -.
DR   PaxDb; 10090-ENSMUSP00000031037; -.
DR   PeptideAtlas; P97441; -.
DR   ProteomicsDB; 302147; -.
DR   Antibodypedia; 47345; 171 antibodies from 25 providers.
DR   DNASU; 22784; -.
DR   Ensembl; ENSMUST00000031037.14; ENSMUSP00000031037.8; ENSMUSG00000029151.15.
DR   GeneID; 22784; -.
DR   KEGG; mmu:22784; -.
DR   UCSC; uc008wxa.2; mouse.
DR   AGR; MGI:1345280; -.
DR   CTD; 7781; -.
DR   MGI; MGI:1345280; Slc30a3.
DR   VEuPathDB; HostDB:ENSMUSG00000029151; -.
DR   eggNOG; KOG1482; Eukaryota.
DR   GeneTree; ENSGT00940000161480; -.
DR   InParanoid; P97441; -.
DR   OMA; RTWGWAR; -.
DR   OrthoDB; 1331349at2759; -.
DR   PhylomeDB; P97441; -.
DR   TreeFam; TF313382; -.
DR   BioGRID-ORCS; 22784; 3 hits in 78 CRISPR screens.
DR   ChiTaRS; Slc30a3; mouse.
DR   PRO; PR:P97441; -.
DR   Proteomes; UP000000589; Chromosome 5.
DR   RNAct; P97441; Protein.
DR   Bgee; ENSMUSG00000029151; Expressed in entorhinal cortex and 145 other cell types or tissues.
DR   ExpressionAtlas; P97441; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR   GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR   GO; GO:0097457; C:hippocampal mossy fiber; IDA:MGI.
DR   GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; IDA:SynGO.
DR   GO; GO:0005770; C:late endosome; ISO:MGI.
DR   GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0043005; C:neuron projection; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0008021; C:synaptic vesicle; ISO:MGI.
DR   GO; GO:0030672; C:synaptic vesicle membrane; IDA:UniProtKB.
DR   GO; GO:0015297; F:antiporter activity; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0005385; F:zinc ion transmembrane transporter activity; IDA:UniProtKB.
DR   GO; GO:0010312; P:detoxification of zinc ion; TAS:BHF-UCL.
DR   GO; GO:0051050; P:positive regulation of transport; IGI:MGI.
DR   GO; GO:0010043; P:response to zinc ion; IBA:GO_Central.
DR   GO; GO:0032119; P:sequestering of zinc ion; TAS:BHF-UCL.
DR   GO; GO:0140916; P:zinc ion import into lysosome; ISO:MGI.
DR   GO; GO:0099180; P:zinc ion import into synaptic vesicle; IDA:SynGO.
DR   GO; GO:0071577; P:zinc ion transmembrane transport; ISS:UniProtKB.
DR   Gene3D; 1.20.1510.10; Cation efflux protein transmembrane domain; 1.
DR   InterPro; IPR002524; Cation_efflux.
DR   InterPro; IPR036837; Cation_efflux_CTD_sf.
DR   InterPro; IPR027469; Cation_efflux_TMD_sf.
DR   NCBIfam; TIGR01297; CDF; 1.
DR   PANTHER; PTHR11562; CATION EFFLUX PROTEIN/ ZINC TRANSPORTER; 1.
DR   PANTHER; PTHR11562:SF30; ZINC TRANSPORTER 3; 1.
DR   Pfam; PF01545; Cation_efflux; 1.
DR   SUPFAM; SSF160240; Cation efflux protein cytoplasmic domain-like; 1.
DR   SUPFAM; SSF161111; Cation efflux protein transmembrane domain-like; 1.
DR   Genevisible; P97441; MM.
PE   1: Evidence at protein level;
KW   Antiport; Cytoplasmic vesicle; Endosome; Ion transport; Lysosome; Membrane;
KW   Metal-binding; Phosphoprotein; Reference proteome; Synapse; Synaptosome;
KW   Transmembrane; Transmembrane helix; Transport; Zinc; Zinc transport.
FT   CHAIN           1..388
FT                   /note="Probable proton-coupled zinc antiporter SLC30A3"
FT                   /id="PRO_0000206097"
FT   TOPO_DOM        1..75
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        76..96
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        97..105
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        106..126
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        127..145
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        146..166
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        167..177
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        178..198
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        199..235
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        236..256
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        257..263
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        264..284
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        285..388
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   REGION          1..41
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1..19
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         108
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="transported zinc"
FT                   /evidence="ECO:0000250|UniProtKB:Q8IWU4"
FT   BINDING         112
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="transported zinc"
FT                   /evidence="ECO:0000250|UniProtKB:Q8IWU4"
FT   BINDING         238
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="transported zinc"
FT                   /evidence="ECO:0000250|UniProtKB:Q8IWU4"
FT   BINDING         242
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="transported zinc"
FT                   /evidence="ECO:0000250|UniProtKB:Q8IWU4"
FT   MOD_RES         63
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q6QIX3"
FT   MOD_RES         66
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q6QIX3"
SQ   SEQUENCE   388 AA;  41824 MW;  3CCDD0A37074EF41 CRC64;
     MEPSLATGGS ETTRLVSARD RSSAGGGLRL KSLFTEPSEP LPEEPKLEGM AFHHCHKDPV
     PQSGLSPERV QARRQLYAAC AVCFIFMAGE VVGGYLAHSL AIMTDAAHLL ADIGSMLASL
     FSLWLSTRPA TRTMTFGWHR SETLGALASV VSLWIVTGIL LYLAFLRLLH SDYHIEAGAM
     LLTASIAVCA NLLMAFVLHQ TGAPHSHGST GAEYAPLEEG HGYPMSLGNT SVRAAFVHVL
     GDLLQSFGVL AASILIYFKP QYKVADPIST FLFSICALGS TAPTLRDVLL VLMEGAPRSV
     EFEPVRDTLL SVPGVRATHD LHLWALTLTY HVASAHLAID STADPEAVLA EASSRLYSRF
     GFSSCTLQVE QYQPEMAQCL RCQEPSQA
//