ID ZNT1_HUMAN Reviewed; 507 AA. AC Q9Y6M5; Q0VAK9; Q9BZF6; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 07-JUL-2009, sequence version 3. DT 27-MAR-2024, entry version 184. DE RecName: Full=Proton-coupled zinc antiporter SLC30A1 {ECO:0000305|PubMed:31471319}; DE AltName: Full=Solute carrier family 30 member 1 {ECO:0000312|HGNC:HGNC:11012}; DE AltName: Full=Zinc transporter 1 {ECO:0000303|PubMed:31471319}; GN Name=SLC30A1 {ECO:0000312|HGNC:HGNC:11012}; GN Synonyms=ZNT1 {ECO:0000303|Ref.1}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Nanji M.S., Coronado V.A., Cox D.W.; RT "Cloning and characterization of human zinc transporter 1 (ZNT1)."; RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B., RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., RA Nomura N.; RT "Human Protein Factory: an infrastructure to convert the human RT transcriptome into the in vitro-expressed human proteome of versatile RT utility."; RL Submitted (JUL-2008) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 411-507. RA Inoue H., Oka Y.; RT "Assignment of the human zinc transporter gene 1 (ZnT1) to chromosomes 1."; RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases. RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-506, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [10] RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION BY ZINC, GLYCOSYLATION AT RP ASN-299, TOPOLOGY, AND MUTAGENESIS OF ASN-299. RX PubMed=31471319; DOI=10.1074/jbc.ra119.010227; RA Nishito Y., Kambe T.; RT "Zinc transporter 1 (ZNT1) expression on the cell surface is elaborately RT controlled by cellular zinc levels."; RL J. Biol. Chem. 294:15686-15697(2019). RN [11] RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION BY LPS. RX PubMed=32441444; DOI=10.1002/jlb.2hi0420-160r; RA Stocks C.J., von Pein J.B., Curson J.E.B., Rae J., Phan M.D., Foo D., RA Bokil N.J., Kambe T., Peters K.M., Parton R.G., Schembri M.A., RA Kapetanovic R., Sweet M.J.; RT "Frontline Science: LPS-inducible SLC30A1 drives human macrophage-mediated RT zinc toxicity against intracellular Escherichia coli."; RL J. Leukoc. Biol. 109:287-297(2021). RN [12] RP INTERACTION WITH TMEM163. RX PubMed=36204728; DOI=10.1016/j.bbrep.2022.101362; RA Escobar A., Styrpejko D.J., Ali S., Cuajungco M.P.; RT "Transmembrane 163 (TMEM163) protein interacts with specific mammalian RT SLC30 zinc efflux transporter family members."; RL Biochem. Biophys. Rep. 32:101362-101362(2022). CC -!- FUNCTION: Zinc ion:proton antiporter that could function at the plasma CC membrane mediating zinc efflux from cells against its electrochemical CC gradient protecting them from intracellular zinc accumulation and CC toxicity (PubMed:31471319). Alternatively, could prevent the transport CC to the plasma membrane of CACNB2, the L-type calcium channels CC regulatory subunit, through a yet to be defined mechanism. By CC modulating the expression of these channels at the plasma membrane, CC could prevent calcium and zinc influx into cells. By the same CC mechanism, could also prevent L-type calcium channels-mediated heavy CC metal influx into cells (By similarity). In some cells, could also CC function as a zinc ion:proton antiporter mediating zinc entry into the CC lumen of cytoplasmic vesicles. In macrophages, can increase zinc ions CC concentration into the lumen of cytoplasmic vesicles containing CC engulfed bacteria and could help inactivate them (PubMed:32441444). CC {ECO:0000250|UniProtKB:Q62720, ECO:0000269|PubMed:31471319, CC ECO:0000269|PubMed:32441444}. 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:Q62720}; CC -!- SUBUNIT: Homodimer. Interacts with TMEM163 (PubMed:36204728). CC {ECO:0000250|UniProtKB:Q62720, ECO:0000269|PubMed:36204728}. CC -!- INTERACTION: CC Q9Y6M5; Q9BRI3: SLC30A2; NbExp=4; IntAct=EBI-10982148, EBI-8644112; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:31471319, CC ECO:0000269|PubMed:32441444}; Multi-pass membrane protein CC {ECO:0000255}. Basolateral cell membrane {ECO:0000269|PubMed:31471319}; CC Multi-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle membrane CC {ECO:0000269|PubMed:32441444}; Multi-pass membrane protein CC {ECO:0000255}. Note=Localization to the plasma membrane is regulated by CC cellular zinc status. Recruitment to the plasma membrane from an CC internal pool is stimulated by zinc while in absence of zinc the plasma CC membrane pool is endocytosed and degraded (PubMed:31471319). Localizes CC to the basolateral surface of enterocytes (By similarity). Localizes to CC zinc-containing intracellular vesicles in macrophages CC (PubMed:32441444). {ECO:0000250|UniProtKB:Q62720, CC ECO:0000269|PubMed:31471319, ECO:0000269|PubMed:32441444}. CC -!- INDUCTION: Up-regulated by zinc (at protein level) (PubMed:31471319). CC Up-regulated in macrophages by LPS (at protein level) CC (PubMed:32441444). {ECO:0000269|PubMed:31471319, CC ECO:0000269|PubMed:32441444}. CC -!- PTM: N-glycosylated at Asn-299. N-glycosylation promotes endocytosis CC and degradation through the proteasomal or lysosomal pathways. CC {ECO:0000269|PubMed:31471319}. 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; AF323590; AAG53405.1; -; Genomic_DNA. DR EMBL; AB451467; BAG70281.1; -; mRNA. DR EMBL; CH471100; EAW93412.1; -; Genomic_DNA. DR EMBL; BC121015; AAI21016.1; -; mRNA. DR EMBL; BC121016; AAI21017.1; -; mRNA. DR EMBL; AF048701; AAD29840.1; -; Genomic_DNA. DR CCDS; CCDS1499.1; -. DR RefSeq; NP_067017.2; NM_021194.2. DR AlphaFoldDB; Q9Y6M5; -. DR SASBDB; Q9Y6M5; -. DR SMR; Q9Y6M5; -. DR BioGRID; 113560; 128. DR IntAct; Q9Y6M5; 41. DR MINT; Q9Y6M5; -. DR STRING; 9606.ENSP00000355968; -. DR DrugBank; DB14533; Zinc chloride. DR DrugBank; DB14548; Zinc sulfate, unspecified form. DR TCDB; 2.A.4.2.6; the cation diffusion facilitator (cdf) family. DR GlyCosmos; Q9Y6M5; 1 site, No reported glycans. DR GlyGen; Q9Y6M5; 2 sites, 2 O-linked glycans (1 site). DR iPTMnet; Q9Y6M5; -. DR PhosphoSitePlus; Q9Y6M5; -. DR SwissPalm; Q9Y6M5; -. DR BioMuta; SLC30A1; -. DR DMDM; 251757423; -. DR EPD; Q9Y6M5; -. DR jPOST; Q9Y6M5; -. DR MassIVE; Q9Y6M5; -. DR MaxQB; Q9Y6M5; -. DR PaxDb; 9606-ENSP00000355968; -. DR PeptideAtlas; Q9Y6M5; -. DR ProteomicsDB; 86733; -. DR Pumba; Q9Y6M5; -. DR Antibodypedia; 20709; 273 antibodies from 26 providers. DR DNASU; 7779; -. DR Ensembl; ENST00000367001.5; ENSP00000355968.4; ENSG00000170385.10. DR GeneID; 7779; -. DR KEGG; hsa:7779; -. DR MANE-Select; ENST00000367001.5; ENSP00000355968.4; NM_021194.3; NP_067017.2. DR UCSC; uc001hio.2; human. DR AGR; HGNC:11012; -. DR CTD; 7779; -. DR DisGeNET; 7779; -. DR GeneCards; SLC30A1; -. DR HGNC; HGNC:11012; SLC30A1. DR HPA; ENSG00000170385; Tissue enhanced (liver). DR MIM; 609521; gene. DR neXtProt; NX_Q9Y6M5; -. DR OpenTargets; ENSG00000170385; -. DR PharmGKB; PA35882; -. DR VEuPathDB; HostDB:ENSG00000170385; -. DR eggNOG; KOG1483; Eukaryota. DR GeneTree; ENSGT00940000156484; -. DR HOGENOM; CLU_013430_4_3_1; -. DR InParanoid; Q9Y6M5; -. DR OMA; TYTYGWQ; -. DR OrthoDB; 5482779at2759; -. DR PhylomeDB; Q9Y6M5; -. DR TreeFam; TF313924; -. DR PathwayCommons; Q9Y6M5; -. DR Reactome; R-HSA-435368; Zinc efflux and compartmentalization by the SLC30 family. DR SignaLink; Q9Y6M5; -. DR BioGRID-ORCS; 7779; 39 hits in 1158 CRISPR screens. DR GeneWiki; SLC30A1; -. DR GenomeRNAi; 7779; -. DR Pharos; Q9Y6M5; Tbio. DR PRO; PR:Q9Y6M5; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q9Y6M5; Protein. DR Bgee; ENSG00000170385; Expressed in jejunal mucosa and 206 other cell types or tissues. DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IDA:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0031965; C:nuclear membrane; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0098839; C:postsynaptic density membrane; IEA:Ensembl. DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IEA:Ensembl. DR GO; GO:0030315; C:T-tubule; ISS:BHF-UCL. DR GO; GO:0019855; F:calcium channel inhibitor activity; ISS:BHF-UCL. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0005385; F:zinc ion transmembrane transporter activity; IBA:GO_Central. DR GO; GO:0140826; F:zinc:proton antiporter activity; ISS:UniProtKB. DR GO; GO:0070574; P:cadmium ion transmembrane transport; ISS:BHF-UCL. DR GO; GO:0070509; P:calcium ion import; IEA:Ensembl. DR GO; GO:0042742; P:defense response to bacterium; IDA:UniProtKB. DR GO; GO:0071585; P:detoxification of cadmium ion; IEA:Ensembl. DR GO; GO:0010312; P:detoxification of zinc ion; IBA:GO_Central. DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; ISS:BHF-UCL. DR GO; GO:0006882; P:intracellular zinc ion homeostasis; ISS:BHF-UCL. DR GO; GO:0090281; P:negative regulation of calcium ion import; ISS:BHF-UCL. DR GO; GO:0046929; P:negative regulation of neurotransmitter secretion; ISS:BHF-UCL. DR GO; GO:0071584; P:negative regulation of zinc ion transmembrane import; ISS:BHF-UCL. DR GO; GO:0140882; P:zinc export across plasma membrane; ISS:UniProtKB. DR GO; GO:0062111; P:zinc ion import into organelle; IDA:UniProtKB. DR GO; GO:0071577; P:zinc ion transmembrane transport; IBA:GO_Central. DR GO; GO:0006829; P:zinc ion transport; ISS:BHF-UCL. 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; PTHR45820; FI23527P1; 1. DR PANTHER; PTHR45820:SF1; ZINC TRANSPORTER 1; 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; Q9Y6M5; HS. PE 1: Evidence at protein level; KW Antiport; Cell membrane; Cytoplasmic vesicle; Glycoprotein; Ion transport; KW Membrane; Metal-binding; Phosphoprotein; Reference proteome; Repeat; KW Transmembrane; Transmembrane helix; Transport; Zinc; Zinc transport. FT CHAIN 1..507 FT /note="Proton-coupled zinc antiporter SLC30A1" FT /id="PRO_0000206090" FT TOPO_DOM 1..10 FT /note="Cytoplasmic" FT /evidence="ECO:0000305|PubMed:31471319" FT TRANSMEM 11..31 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 32..35 FT /note="Extracellular" FT /evidence="ECO:0000305|PubMed:31471319" FT TRANSMEM 36..56 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 57..78 FT /note="Cytoplasmic" FT /evidence="ECO:0000305|PubMed:31471319" FT TRANSMEM 79..99 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 100..113 FT /note="Extracellular" FT /evidence="ECO:0000305|PubMed:31471319" FT TRANSMEM 114..134 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 135..248 FT /note="Cytoplasmic" FT /evidence="ECO:0000305|PubMed:31471319" FT TRANSMEM 249..269 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 270..308 FT /note="Extracellular" FT /evidence="ECO:0000305|PubMed:31471319" FT TRANSMEM 309..329 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 330..507 FT /note="Cytoplasmic" FT /evidence="ECO:0000305|PubMed:31471319" FT REGION 142..217 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 146..158 FT /note="6 X 2 AA approximate repeats of H-G" FT COMPBIAS 183..204 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 43 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="transported zinc" FT /evidence="ECO:0000250|UniProtKB:Q62720" FT BINDING 47 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="transported zinc" FT /evidence="ECO:0000250|UniProtKB:P69380" FT BINDING 251 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="transported zinc" FT /evidence="ECO:0000250|UniProtKB:P69380" FT BINDING 255 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="transported zinc" FT /evidence="ECO:0000250|UniProtKB:Q62720" FT MOD_RES 506 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT CARBOHYD 299 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:31471319" FT MUTAGEN 299 FT /note="N->A: Loss of N-glycosylation. No effect on FT localization to the plasma membrane. Increased stability at FT the plasma membrane. No effect on resistance to FT zinc-induced cytotoxicity." FT /evidence="ECO:0000269|PubMed:31471319" FT CONFLICT 386 FT /note="A -> V (in Ref. 1; AAG53405)" FT /evidence="ECO:0000305" SQ SEQUENCE 507 AA; 55300 MW; 2FC5B67F033AE457 CRC64; MGCWGRNRGR LLCMLALTFM FMVLEVVVSR VTSSLAMLSD SFHMLSDVLA LVVALVAERF ARRTHATQKN TFGWIRAEVM GALVNAIFLT GLCFAILLEA IERFIEPHEM QQPLVVLGVG VAGLLVNVLG LCLFHHHSGF SQDSGHGHSH GGHGHGHGLP KGPRVKSTRP GSSDINVAPG EQGPDQEETN TLVANTSNSN GLKLDPADPE NPRSGDTVEV QVNGNLVREP DHMELEEDRA GQLNMRGVFL HVLGDALGSV IVVVNALVFY FSWKGCSEGD FCVNPCFPDP CKAFVEIINS THASVYEAGP CWVLYLDPTL CVVMVCILLY TTYPLLKESA LILLQTVPKQ IDIRNLIKEL RNVEGVEEVH ELHVWQLAGS RIIATAHIKC EDPTSYMEVA KTIKDVFHNH GIHATTIQPE FASVGSKSSV VPCELACRTQ CALKQCCGTL PQAPSGKDAE KTPAVSISCL ELSNNLEKKP RRTKAENIPA VVIEIKNMPN KQPESSL //