ZNT6_HUMAN
ID ZNT6_HUMAN Reviewed; 461 AA.
AC Q6NXT4; A5YM45; B7Z901; Q8N5C9; Q96NC3;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 04-DEC-2007, sequence version 2.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Zinc transporter 6;
DE Short=ZnT-6;
DE AltName: Full=Solute carrier family 30 member 6;
GN Name=SLC30A6; Synonyms=ZNT6;
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 4).
RC TISSUE=Trachea;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Seminoma, and Uterus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain, and Eye;
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 [6]
RP TISSUE SPECIFICITY.
RX PubMed=15154973; DOI=10.1186/1471-2164-5-32;
RA Seve M., Chimienti F., Devergnas S., Favier A.;
RT "In silico identification and expression of SLC30 family genes: an
RT expressed sequence tag data mining strategy for the characterization of
RT zinc transporters' tissue expression.";
RL BMC Genomics 5:32-32(2004).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=16580781; DOI=10.1016/j.neuroscience.2006.02.049;
RA Smith J.L., Xiong S., Markesbery W.R., Lovell M.A.;
RT "Altered expression of zinc transporters-4 and -6 in mild cognitive
RT impairment, early and late Alzheimer's disease brain.";
RL Neuroscience 140:879-888(2006).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [9]
RP IDENTIFICATION BY 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 [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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).
CC -!- FUNCTION: Zinc-efflux transporter which allocates the cytoplasmic zinc
CC to the trans-Golgi network (TGN) as well as the vesicular compartment.
CC {ECO:0000250}.
CC -!- SUBUNIT: Heterooligomer. Interacts with ZNT5 (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC Q6NXT4-4; Q6PKX4: DOK6; NbExp=3; IntAct=EBI-13046630, EBI-2880244;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane;
CC Multi-pass membrane protein. Note=Found in vesicles. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q6NXT4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6NXT4-2; Sequence=VSP_029861;
CC Name=4;
CC IsoId=Q6NXT4-4; Sequence=VSP_045198;
CC Name=3;
CC IsoId=Q6NXT4-3; Sequence=VSP_029862;
CC -!- TISSUE SPECIFICITY: Expressed in brain; especially in cerebellum,
CC hippocampus, parahippocampal gyrus, superior and middle temporal gyrus.
CC Also expressed in B-cells, colon, eye, and lung. Lower expression was
CC present in bone, brain, cervix, ear, heart, kidney, muscle, nerve,
CC pancreas, prostate, skin, stomach, and testis.
CC {ECO:0000269|PubMed:15154973, ECO:0000269|PubMed:16580781}.
CC -!- MISCELLANEOUS: Seems to have lost most of the histidine residues in the
CC loop between the fourth and fifth transmembrane regions and appears to
CC exert transport function by forming complexes with ZNT5. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the cation diffusion facilitator (CDF)
CC transporter (TC 2.A.4) family. SLC30A subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH32525.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK055663; BAB70980.1; -; mRNA.
DR EMBL; AK304225; BAH14137.1; -; mRNA.
DR EMBL; EF560719; ABQ59029.1; -; mRNA.
DR EMBL; EF560726; ABQ59036.1; -; mRNA.
DR EMBL; AL121653; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL121658; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471053; EAX00456.1; -; Genomic_DNA.
DR EMBL; BC032525; AAH32525.1; ALT_INIT; mRNA.
DR EMBL; BC066903; AAH66903.1; -; mRNA.
DR CCDS; CCDS1780.1; -. [Q6NXT4-1]
DR CCDS; CCDS54341.1; -. [Q6NXT4-2]
DR CCDS; CCDS54342.1; -. [Q6NXT4-3]
DR CCDS; CCDS54343.1; -. [Q6NXT4-4]
DR RefSeq; NP_001180442.1; NM_001193513.2. [Q6NXT4-2]
DR RefSeq; NP_001180443.1; NM_001193514.2. [Q6NXT4-3]
DR RefSeq; NP_001180444.1; NM_001193515.2. [Q6NXT4-4]
DR RefSeq; NP_060434.2; NM_017964.4. [Q6NXT4-1]
DR AlphaFoldDB; Q6NXT4; -.
DR SMR; Q6NXT4; -.
DR BioGRID; 120806; 105.
DR IntAct; Q6NXT4; 28.
DR MINT; Q6NXT4; -.
DR STRING; 9606.ENSP00000368648; -.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR TCDB; 2.A.4.4.4; the cation diffusion facilitator (cdf) family.
DR GlyGen; Q6NXT4; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q6NXT4; -.
DR PhosphoSitePlus; Q6NXT4; -.
DR SwissPalm; Q6NXT4; -.
DR BioMuta; SLC30A6; -.
DR DMDM; 162416263; -.
DR EPD; Q6NXT4; -.
DR jPOST; Q6NXT4; -.
DR MassIVE; Q6NXT4; -.
DR MaxQB; Q6NXT4; -.
DR PeptideAtlas; Q6NXT4; -.
DR PRIDE; Q6NXT4; -.
DR ProteomicsDB; 66772; -. [Q6NXT4-1]
DR ProteomicsDB; 66773; -. [Q6NXT4-2]
DR ProteomicsDB; 66774; -. [Q6NXT4-3]
DR ProteomicsDB; 6994; -.
DR Antibodypedia; 29149; 167 antibodies from 24 providers.
DR DNASU; 55676; -.
DR Ensembl; ENST00000282587.9; ENSP00000282587.5; ENSG00000152683.14. [Q6NXT4-1]
DR Ensembl; ENST00000357055.7; ENSP00000349563.4; ENSG00000152683.14. [Q6NXT4-4]
DR Ensembl; ENST00000379343.6; ENSP00000368648.2; ENSG00000152683.14. [Q6NXT4-2]
DR Ensembl; ENST00000435660.5; ENSP00000399005.1; ENSG00000152683.14. [Q6NXT4-3]
DR GeneID; 55676; -.
DR KEGG; hsa:55676; -.
DR MANE-Select; ENST00000282587.9; ENSP00000282587.5; NM_017964.5; NP_060434.2.
DR UCSC; uc002roe.3; human. [Q6NXT4-1]
DR CTD; 55676; -.
DR DisGeNET; 55676; -.
DR GeneCards; SLC30A6; -.
DR HGNC; HGNC:19305; SLC30A6.
DR HPA; ENSG00000152683; Low tissue specificity.
DR MIM; 611148; gene.
DR neXtProt; NX_Q6NXT4; -.
DR OpenTargets; ENSG00000152683; -.
DR PharmGKB; PA134923067; -.
DR VEuPathDB; HostDB:ENSG00000152683; -.
DR eggNOG; KOG1484; Eukaryota.
DR GeneTree; ENSGT00940000159934; -.
DR HOGENOM; CLU_034201_0_0_1; -.
DR InParanoid; Q6NXT4; -.
DR OMA; EINNYYA; -.
DR OrthoDB; 969431at2759; -.
DR PhylomeDB; Q6NXT4; -.
DR TreeFam; TF313167; -.
DR PathwayCommons; Q6NXT4; -.
DR Reactome; R-HSA-264876; Insulin processing.
DR Reactome; R-HSA-435368; Zinc efflux and compartmentalization by the SLC30 family.
DR SignaLink; Q6NXT4; -.
DR BioGRID-ORCS; 55676; 11 hits in 1083 CRISPR screens.
DR ChiTaRS; SLC30A6; human.
DR GenomeRNAi; 55676; -.
DR Pharos; Q6NXT4; Tbio.
DR PRO; PR:Q6NXT4; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q6NXT4; protein.
DR Bgee; ENSG00000152683; Expressed in left ventricle myocardium and 182 other tissues.
DR ExpressionAtlas; Q6NXT4; baseline and differential.
DR Genevisible; Q6NXT4; HS.
DR GO; GO:0005794; C:Golgi apparatus; IDA:BHF-UCL.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005385; F:zinc ion transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0030070; P:insulin processing; TAS:Reactome.
DR GO; GO:0071577; P:zinc ion transmembrane transport; TAS:Reactome.
DR GO; GO:0006829; P:zinc ion transport; IBA:GO_Central.
DR Gene3D; 1.20.1510.10; -; 1.
DR InterPro; IPR002524; Cation_efflux.
DR InterPro; IPR027469; Cation_efflux_TMD_sf.
DR Pfam; PF01545; Cation_efflux; 1.
DR SUPFAM; SSF161111; SSF161111; 1.
DR TIGRFAMs; TIGR01297; CDF; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Golgi apparatus; Ion transport; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport; Zinc;
KW Zinc transport.
FT CHAIN 1..461
FT /note="Zinc transporter 6"
FT /id="PRO_0000312573"
FT TOPO_DOM 1..33
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 34..54
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 55..64
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 65..85
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 86..98
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 99..119
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 120..134
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 135..155
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 156..200
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 201..221
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 222..223
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 224..244
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 245..461
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 371..392
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..30
FT /note="MGTIHLFRKPQRSFFGKLLREFRLVAADRR -> M (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045198"
FT VAR_SEQ 72
FT /note="F -> FRDGVSPFWLGWSQTPDLKWSTHLGLPKCWDNRRELPCLSN (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_029861"
FT VAR_SEQ 273..295
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_029862"
FT CONFLICT 198..199
FT /note="MN -> TR (in Ref. 5; AAH32525)"
FT /evidence="ECO:0000305"
FT CONFLICT 454
FT /note="N -> S (in Ref. 5; AAH66903)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 461 AA; 51116 MW; 7926F6888EF1F1F9 CRC64;
MGTIHLFRKP QRSFFGKLLR EFRLVAADRR SWKILLFGVI NLICTGFLLM WCSSTNSIAL
TAYTYLTIFD LFSLMTCLIS YWVTLRKPSP VYSFGFERLE VLAVFASTVL AQLGALFILK
ESAERFLEQP EIHTGRLLVG TFVALCFNLF TMLSIRNKPF AYVSEAASTS WLQEHVADLS
RSLCGIIPGL SSIFLPRMNP FVLIDLAGAF ALCITYMLIE INNYFAVDTA SAIAIALMTF
GTMYPMSVYS GKVLLQTTPP HVIGQLDKLI REVSTLDGVL EVRNEHFWTL GFGSLAGSVH
VRIRRDANEQ MVLAHVTNRL YTLVSTLTVQ IFKDDWIRPA LLSGPVAANV LNFSDHHVIP
MPLLKGTDDL NPVTSTPAKP SSPPPEFSFN TPGKNVNPVI LLNTQTRPYG FGLNHGHTPY
SSMLNQGLGV PGIGATQGLR TGFTNIPSRY GTNNRIGQPR P
