ID ZNT4_HUMAN Reviewed; 429 AA. AC O14863; Q8TC39; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 23-SEP-2008, sequence version 2. DT 27-MAR-2024, entry version 184. DE RecName: Full=Probable proton-coupled zinc antiporter SLC30A4 {ECO:0000305|PubMed:19521526}; DE AltName: Full=Solute carrier family 30 member 4 {ECO:0000312|HGNC:HGNC:11015}; DE AltName: Full=Zinc transporter 4 {ECO:0000305|PubMed:19521526}; DE Short=ZnT-4; GN Name=SLC30A4 {ECO:0000312|HGNC:HGNC:11015}; GN Synonyms=ZNT4 {ECO:0000303|PubMed:9354792}; 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 [MRNA]. RC TISSUE=Fetal brain; RX PubMed=9354792; DOI=10.1038/ng1197-292; RA Huang L., Gitschier J.; RT "A novel gene involved in zinc transport is deficient in the lethal milk RT mouse."; RL Nat. Genet. 17:292-297(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Mesangial cell; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Testis; 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 FUNCTION, TRANSPORTER ACTIVITY, SUBUNIT, DITYROSINE BOND, AND MUTAGENESIS RP OF TYR-355; TYR-404 AND TYR-413. 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 SUBCELLULAR LOCATION. RX PubMed=17349999; DOI=10.1016/j.yexcr.2007.02.006; RA Falcon-Perez J.M., Dell'Angelica E.C.; RT "Zinc transporter 2 (SLC30A2) can suppress the vesicular zinc defect of RT adaptor protein 3-depleted fibroblasts by promoting zinc accumulation in RT lysosomes."; RL Exp. Cell Res. 313:1473-1483(2007). RN [7] 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: Probable proton-coupled zinc ion antiporter mediating zinc CC import from cytoplasm potentially into the endocytic compartment CC (PubMed:19521526). Controls zinc deposition in milk (By similarity). CC {ECO:0000250|UniProtKB:O35149, ECO:0000305|PubMed:19521526}. 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:0000305|PubMed:19521526}; CC -!- SUBUNIT: Homodimer; dityrosine-linked. Homodimerization could be CC specific of the human protein and enhances the zinc transport CC efficiency. Interacts with TMEM163 (PubMed:36204728). CC {ECO:0000269|PubMed:19521526, ECO:0000269|PubMed:36204728}. CC -!- INTERACTION: CC O14863; Q8WVV5: BTN2A2; NbExp=3; IntAct=EBI-13918058, EBI-8648738; CC O14863; Q9NWW5: CLN6; NbExp=3; IntAct=EBI-13918058, EBI-6165897; CC O14863; Q96DZ9-2: CMTM5; NbExp=3; IntAct=EBI-13918058, EBI-11522780; CC O14863; O75084: FZD7; NbExp=3; IntAct=EBI-13918058, EBI-746917; CC O14863; Q9Y5U9: IER3IP1; NbExp=3; IntAct=EBI-13918058, EBI-725665; CC O14863; O95214: LEPROTL1; NbExp=3; IntAct=EBI-13918058, EBI-750776; CC O14863; P42857: NSG1; NbExp=3; IntAct=EBI-13918058, EBI-6380741; CC O14863; I3L0A0: PEDS1-UBE2V1; NbExp=3; IntAct=EBI-13918058, EBI-12213001; CC O14863; Q8N6R1: SERP2; NbExp=3; IntAct=EBI-13918058, EBI-749270; CC O14863; Q6XR72: SLC30A10; NbExp=2; IntAct=EBI-13918058, EBI-13917996; CC O14863; Q9BRI3: SLC30A2; NbExp=4; IntAct=EBI-13918058, EBI-8644112; CC O14863; Q99726: SLC30A3; NbExp=8; IntAct=EBI-13918058, EBI-10294651; CC O14863; Q9NV29: TMEM100; NbExp=3; IntAct=EBI-13918058, EBI-8644968; CC O14863; Q9H2L4: TMEM60; NbExp=3; IntAct=EBI-13918058, EBI-2852148; CC O14863; P01375: TNF; NbExp=3; IntAct=EBI-13918058, EBI-359977; CC O14863; O14798: TNFRSF10C; NbExp=3; IntAct=EBI-13918058, EBI-717441; CC O14863; Q96EC8: YIPF6; NbExp=3; IntAct=EBI-13918058, EBI-751210; CC O14863; Q99376: Tfrc; Xeno; NbExp=5; IntAct=EBI-13918058, EBI-2112551; CC -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000250|UniProtKB:O55174}; CC Multi-pass membrane protein {ECO:0000255}. Late endosome membrane CC {ECO:0000269|PubMed:17349999}; Multi-pass membrane protein CC {ECO:0000255}. Lysosome membrane {ECO:0000269|PubMed:17349999}; Multi- CC pass membrane protein {ECO:0000255}. Note=Enriched in vesicles within CC the basal region of epithelial cells. {ECO:0000250|UniProtKB:O55174}. CC -!- PTM: Homodimerization through dityrosine bonds is stimulated by CC oxidative stress. {ECO:0000269|PubMed:19521526}. 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; AF025409; AAB82561.1; -; mRNA. DR EMBL; AK290874; BAF83563.1; -; mRNA. DR EMBL; CH471082; EAW77316.1; -; Genomic_DNA. DR EMBL; BC026089; AAH26089.1; -; mRNA. DR CCDS; CCDS10125.1; -. DR RefSeq; NP_037441.2; NM_013309.5. DR RefSeq; XP_011520299.1; XM_011521997.2. DR RefSeq; XP_016878049.1; XM_017022560.1. DR AlphaFoldDB; O14863; -. DR SMR; O14863; -. DR BioGRID; 113563; 60. DR IntAct; O14863; 30. DR STRING; 9606.ENSP00000261867; -. DR DrugBank; DB14533; Zinc chloride. DR DrugBank; DB14548; Zinc sulfate, unspecified form. DR TCDB; 2.A.4.3.7; the cation diffusion facilitator (cdf) family. DR iPTMnet; O14863; -. DR PhosphoSitePlus; O14863; -. DR SwissPalm; O14863; -. DR BioMuta; SLC30A4; -. DR MassIVE; O14863; -. DR MaxQB; O14863; -. DR PaxDb; 9606-ENSP00000261867; -. DR PeptideAtlas; O14863; -. DR ProteomicsDB; 48276; -. DR Antibodypedia; 11839; 91 antibodies from 21 providers. DR DNASU; 7782; -. DR Ensembl; ENST00000261867.5; ENSP00000261867.3; ENSG00000104154.7. DR GeneID; 7782; -. DR KEGG; hsa:7782; -. DR MANE-Select; ENST00000261867.5; ENSP00000261867.3; NM_013309.6; NP_037441.2. DR UCSC; uc001zvj.5; human. DR AGR; HGNC:11015; -. DR CTD; 7782; -. DR DisGeNET; 7782; -. DR GeneCards; SLC30A4; -. DR HGNC; HGNC:11015; SLC30A4. DR HPA; ENSG00000104154; Tissue enriched (prostate). DR MIM; 602095; gene. DR neXtProt; NX_O14863; -. DR OpenTargets; ENSG00000104154; -. DR PharmGKB; PA35885; -. DR VEuPathDB; HostDB:ENSG00000104154; -. DR eggNOG; KOG1482; Eukaryota. DR GeneTree; ENSGT00940000157545; -. DR HOGENOM; CLU_013430_0_1_1; -. DR InParanoid; O14863; -. DR OMA; KWEDVQS; -. DR OrthoDB; 1331349at2759; -. DR PhylomeDB; O14863; -. DR TreeFam; TF313382; -. DR PathwayCommons; O14863; -. DR SignaLink; O14863; -. DR BioGRID-ORCS; 7782; 8 hits in 1150 CRISPR screens. DR ChiTaRS; SLC30A4; human. DR GeneWiki; SLC30A4; -. DR GenomeRNAi; 7782; -. DR Pharos; O14863; Tbio. DR PRO; PR:O14863; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; O14863; Protein. DR Bgee; ENSG00000104154; Expressed in jejunal mucosa and 184 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL. DR GO; GO:0010008; C:endosome membrane; ISS:UniProtKB. DR GO; GO:0005770; C:late endosome; IDA:BHF-UCL. DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. 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:0009636; P:response to toxic substance; IDA:UniProtKB. DR GO; GO:0010043; P:response to zinc ion; IBA:GO_Central. DR GO; GO:0140882; P:zinc export across plasma membrane; IEA:Ensembl. DR GO; GO:0140916; P:zinc ion import into lysosome; IDA:BHF-UCL. DR GO; GO:0071577; P:zinc ion transmembrane transport; IDA: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:SF27; ZINC TRANSPORTER 4; 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; O14863; HS. PE 1: Evidence at protein level; KW Antiport; Endosome; Ion transport; Lysosome; Membrane; Metal-binding; KW Reference proteome; Transmembrane; Transmembrane helix; Transport; Zinc; KW Zinc transport. FT CHAIN 1..429 FT /note="Probable proton-coupled zinc antiporter SLC30A4" FT /id="PRO_0000206099" FT TOPO_DOM 1..113 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 114..134 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 135..143 FT /note="Lumenal" FT /evidence="ECO:0000305" FT TRANSMEM 144..164 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 165..178 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 179..199 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 200..216 FT /note="Lumenal" FT /evidence="ECO:0000305" FT TRANSMEM 217..237 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 238..274 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 275..295 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 296..310 FT /note="Lumenal" FT /evidence="ECO:0000305" FT TRANSMEM 311..331 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 332..429 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT REGION 240..264 FT /note="Zinc binding" FT /evidence="ECO:0000250|UniProtKB:O55174" FT BINDING 146 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="transported zinc" FT /evidence="ECO:0000250|UniProtKB:Q8IWU4" FT BINDING 150 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="transported zinc" FT /evidence="ECO:0000250|UniProtKB:Q8IWU4" FT BINDING 277 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="transported zinc" FT /evidence="ECO:0000250|UniProtKB:Q8IWU4" FT BINDING 281 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="transported zinc" FT /evidence="ECO:0000250|UniProtKB:Q8IWU4" FT MUTAGEN 355 FT /note="Y->F: Decreased homodimerization." FT /evidence="ECO:0000269|PubMed:19521526" FT MUTAGEN 404 FT /note="Y->F: Decreased homodimerization." FT /evidence="ECO:0000269|PubMed:19521526" FT MUTAGEN 413 FT /note="Y->F: Decreased homodimerization." FT /evidence="ECO:0000269|PubMed:19521526" FT CONFLICT 30 FT /note="D -> E (in Ref. 1; AAB82561)" FT /evidence="ECO:0000305" SQ SEQUENCE 429 AA; 47483 MW; 97B7FCBE881C8C32 CRC64; MAGSGAWKRL KSMLRKDDAP LFLNDTSAFD FSDEAGDEGL SRFNKLRVVV ADDGSEAPER PVNGAHPTLQ ADDDSLLDQD LPLTNSQLSL KVDSCDNCSK QREILKQRKV KARLTIAAVL YLLFMIGELV GGYIANSLAI MTDALHMLTD LSAIILTLLA LWLSSKSPTK RFTFGFHRLE VLSAMISVLL VYILMGFLLY EAVQRTIHMN YEINGDIMLI TAAVGVAVNV IMGFLLNQSG HRHSHSHSLP SNSPTRGSGC ERNHGQDSLA VRAAFVHALG DLVQSVGVLI AAYIIRFKPE YKIADPICTY VFSLLVAFTT FRIIWDTVVI ILEGVPSHLN VDYIKEALMK IEDVYSVEDL NIWSLTSGKS TAIVHIQLIP GSSSKWEEVQ SKANHLLLNT FGMYRCTIQL QSYRQEVDRT CANCQSSSP //