ZNT4_HUMAN
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 03-AUG-2022, entry version 175.
DE RecName: Full=Zinc transporter 4 {ECO:0000305|PubMed:19521526};
DE Short=ZnT-4;
DE AltName: Full=Solute carrier family 30 member 4 {ECO:0000312|HGNC:HGNC:11015};
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).
CC -!- FUNCTION: Zinc ion transporter mediating zinc import from cytoplasm
CC potentially into the endocytic compartment (PubMed:19521526). Controls
CC zinc deposition in milk (By similarity). {ECO:0000250|UniProtKB:O35149,
CC ECO:0000305|PubMed:19521526}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Zn(2+)(in) = Zn(2+)(out); Xref=Rhea:RHEA:29351,
CC ChEBI:CHEBI:29105; 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. {ECO:0000269|PubMed:19521526}.
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}.
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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 BioMuta; SLC30A4; -.
DR MassIVE; O14863; -.
DR MaxQB; O14863; -.
DR PaxDb; O14863; -.
DR PeptideAtlas; O14863; -.
DR PRIDE; O14863; -.
DR ProteomicsDB; 48276; -.
DR Antibodypedia; 11839; 71 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 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; HDLHIWE; -.
DR OrthoDB; 820567at2759; -.
DR PhylomeDB; O14863; -.
DR TreeFam; TF313382; -.
DR PathwayCommons; O14863; -.
DR SignaLink; O14863; -.
DR BioGRID-ORCS; 7782; 7 hits in 1072 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 182 other tissues.
DR Genevisible; O14863; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0010008; C:endosome membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0005385; F:zinc ion transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0061088; P:regulation of sequestering of zinc ion; IDA:BHF-UCL.
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:0055069; P:zinc ion homeostasis; IEA:Ensembl.
DR GO; GO:0071577; P:zinc ion transmembrane transport; IDA:UniProtKB.
DR Gene3D; 1.20.1510.10; -; 1.
DR InterPro; IPR002524; Cation_efflux.
DR InterPro; IPR036837; Cation_efflux_CTD_sf.
DR InterPro; IPR027469; Cation_efflux_TMD_sf.
DR Pfam; PF01545; Cation_efflux; 1.
DR SUPFAM; SSF160240; SSF160240; 1.
DR SUPFAM; SSF161111; SSF161111; 1.
DR TIGRFAMs; TIGR01297; CDF; 1.
PE 1: Evidence at protein level;
KW Endosome; Ion transport; Lysosome; Membrane; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport; Zinc; Zinc transport.
FT CHAIN 1..429
FT /note="Zinc transporter 4"
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 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
