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 24-JAN-2024, entry version 179. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 Genevisible; P97441; MM. 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; IEA:Ensembl. 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. 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 //