ZNT3_HUMAN
ID ZNT3_HUMAN Reviewed; 388 AA.
AC Q99726; Q8TC03;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Zinc transporter 3 {ECO:0000305|PubMed:19521526};
DE Short=ZnT-3 {ECO:0000303|PubMed:8962159};
DE AltName: Full=Solute carrier family 30 member 3 {ECO:0000312|HGNC:HGNC:11014};
GN Name=SLC30A3 {ECO:0000312|HGNC:HGNC:11014};
GN Synonyms=ZNT3 {ECO:0000303|PubMed:8962159};
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=Temporal cortex;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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].
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 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, AND 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 [6]
RP FUNCTION, TRANSPORTER ACTIVITY, SUBUNIT, DITYROSINE BOND, AND MUTAGENESIS
RP OF TYR-330; TYR-357 AND TYR-372.
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 [7]
RP VARIANT CYS-298, CHARACTERIZATION OF VARIANT CYS-298, FUNCTION, TRANSPORTER
RP ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=26647834; DOI=10.1038/srep17816;
RA Hildebrand M.S., Phillips A.M., Mullen S.A., Adlard P.A., Hardies K.,
RA Damiano J.A., Wimmer V., Bellows S.T., McMahon J.M., Burgess R.,
RA Hendrickx R., Weckhuysen S., Suls A., De Jonghe P., Scheffer I.E.,
RA Petrou S., Berkovic S.F., Reid C.A.;
RT "Loss of synaptic Zn2+ transporter function increases risk of febrile
RT seizures.";
RL Sci. Rep. 5:17816-17816(2015).
CC -!- FUNCTION: Zinc ion transporter mediating the import of zinc from
CC cytoplasm into synaptic vesicles and participating to cellular zinc ion
CC homeostasis in the brain. {ECO:0000269|PubMed:17349999,
CC ECO:0000269|PubMed:19521526, ECO:0000269|PubMed:26647834}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Zn(2+)(in) = Zn(2+)(out); Xref=Rhea:RHEA:29351,
CC ChEBI:CHEBI:29105; Evidence={ECO:0000305|PubMed:17349999,
CC ECO:0000305|PubMed:19521526, ECO:0000305|PubMed:26647834};
CC -!- SUBUNIT: Homodimer; dityrosine-linked. Homodimerization seems specific
CC of the human protein and enhances the zinc transport efficiency.
CC {ECO:0000269|PubMed:19521526}.
CC -!- INTERACTION:
CC Q99726; P25942: CD40; NbExp=3; IntAct=EBI-10294651, EBI-525714;
CC Q99726; Q99675: CGRRF1; NbExp=3; IntAct=EBI-10294651, EBI-2130213;
CC Q99726; Q9GZR5: ELOVL4; NbExp=3; IntAct=EBI-10294651, EBI-18535450;
CC Q99726; Q96P31-6: FCRL3; NbExp=3; IntAct=EBI-10294651, EBI-17443171;
CC Q99726; P48165: GJA8; NbExp=3; IntAct=EBI-10294651, EBI-17458373;
CC Q99726; Q8NBJ4: GOLM1; NbExp=3; IntAct=EBI-10294651, EBI-712073;
CC Q99726; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-10294651, EBI-13345167;
CC Q99726; O15529: GPR42; NbExp=3; IntAct=EBI-10294651, EBI-18076404;
CC Q99726; Q8TED1: GPX8; NbExp=3; IntAct=EBI-10294651, EBI-11721746;
CC Q99726; Q7Z5P4: HSD17B13; NbExp=3; IntAct=EBI-10294651, EBI-18053395;
CC Q99726; Q58DX5: NAALADL2; NbExp=3; IntAct=EBI-10294651, EBI-10178964;
CC Q99726; Q9NX40: OCIAD1; NbExp=3; IntAct=EBI-10294651, EBI-2683029;
CC Q99726; Q86VR2: RETREG3; NbExp=3; IntAct=EBI-10294651, EBI-10192441;
CC Q99726; Q6ZMZ0: RNF19B; NbExp=3; IntAct=EBI-10294651, EBI-2466594;
CC Q99726; O95197-3: RTN3; NbExp=3; IntAct=EBI-10294651, EBI-11525735;
CC Q99726; Q9NY72: SCN3B; NbExp=3; IntAct=EBI-10294651, EBI-17247926;
CC Q99726; O95470: SGPL1; NbExp=3; IntAct=EBI-10294651, EBI-1046170;
CC Q99726; Q3KNW5: SLC10A6; NbExp=3; IntAct=EBI-10294651, EBI-18159983;
CC Q99726; Q6XR72: SLC30A10; NbExp=3; IntAct=EBI-10294651, EBI-13917996;
CC Q99726; Q9BRI3: SLC30A2; NbExp=7; IntAct=EBI-10294651, EBI-8644112;
CC Q99726; O14863: SLC30A4; NbExp=8; IntAct=EBI-10294651, EBI-13918058;
CC Q99726; Q8IWU4: SLC30A8; NbExp=3; IntAct=EBI-10294651, EBI-10262251;
CC Q99726; O95436-2: SLC34A2; NbExp=5; IntAct=EBI-10294651, EBI-12811757;
CC Q99726; Q9NQQ7-3: SLC35C2; NbExp=3; IntAct=EBI-10294651, EBI-17295964;
CC Q99726; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-10294651, EBI-8638294;
CC Q99726; Q9NWH2: TMEM242; NbExp=3; IntAct=EBI-10294651, EBI-10315004;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, synaptic
CC vesicle membrane {ECO:0000305|PubMed:26647834}; Multi-pass membrane
CC protein {ECO:0000255}. Synapse, synaptosome
CC {ECO:0000250|UniProtKB:P97441}. 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}.
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; U76010; AAB39732.1; -; mRNA.
DR EMBL; AK313600; BAG36366.1; -; mRNA.
DR EMBL; AC013413; AAY24294.1; -; Genomic_DNA.
DR EMBL; BC028358; AAH28358.1; -; mRNA.
DR CCDS; CCDS1743.1; -.
DR RefSeq; NP_001305878.1; NM_001318949.1.
DR RefSeq; NP_001305879.1; NM_001318950.1.
DR RefSeq; NP_001305880.1; NM_001318951.1.
DR RefSeq; NP_003450.2; NM_003459.4.
DR AlphaFoldDB; Q99726; -.
DR SMR; Q99726; -.
DR BioGRID; 113562; 37.
DR IntAct; Q99726; 29.
DR STRING; 9606.ENSP00000233535; -.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR TCDB; 2.A.4.3.2; the cation diffusion facilitator (cdf) family.
DR iPTMnet; Q99726; -.
DR PhosphoSitePlus; Q99726; -.
DR BioMuta; SLC30A3; -.
DR DMDM; 215273923; -.
DR MassIVE; Q99726; -.
DR MaxQB; Q99726; -.
DR PaxDb; Q99726; -.
DR PeptideAtlas; Q99726; -.
DR PRIDE; Q99726; -.
DR ProteomicsDB; 78440; -.
DR Antibodypedia; 47345; 154 antibodies from 25 providers.
DR DNASU; 7781; -.
DR Ensembl; ENST00000233535.9; ENSP00000233535.4; ENSG00000115194.11.
DR GeneID; 7781; -.
DR KEGG; hsa:7781; -.
DR MANE-Select; ENST00000233535.9; ENSP00000233535.4; NM_003459.5; NP_003450.2.
DR UCSC; uc002rjk.4; human.
DR CTD; 7781; -.
DR DisGeNET; 7781; -.
DR GeneCards; SLC30A3; -.
DR HGNC; HGNC:11014; SLC30A3.
DR HPA; ENSG00000115194; Group enriched (brain, epididymis, testis).
DR MIM; 602878; gene.
DR neXtProt; NX_Q99726; -.
DR OpenTargets; ENSG00000115194; -.
DR PharmGKB; PA35884; -.
DR VEuPathDB; HostDB:ENSG00000115194; -.
DR eggNOG; KOG1482; Eukaryota.
DR GeneTree; ENSGT00940000161480; -.
DR InParanoid; Q99726; -.
DR OMA; RTWGWAR; -.
DR OrthoDB; 973492at2759; -.
DR PhylomeDB; Q99726; -.
DR TreeFam; TF313382; -.
DR PathwayCommons; Q99726; -.
DR Reactome; R-HSA-435368; Zinc efflux and compartmentalization by the SLC30 family.
DR SignaLink; Q99726; -.
DR BioGRID-ORCS; 7781; 5 hits in 1064 CRISPR screens.
DR GeneWiki; SLC30A3; -.
DR GenomeRNAi; 7781; -.
DR Pharos; Q99726; Tbio.
DR PRO; PR:Q99726; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q99726; protein.
DR Bgee; ENSG00000115194; Expressed in corpus epididymis and 140 other tissues.
DR ExpressionAtlas; Q99726; baseline and differential.
DR Genevisible; Q99726; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0097457; C:hippocampal mossy fiber; IEA:Ensembl.
DR GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; IEA:Ensembl.
DR GO; GO:0030285; C:integral component of synaptic vesicle membrane; IEA:Ensembl.
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:0043005; C:neuron projection; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0008021; C:synaptic vesicle; IDA:UniProtKB.
DR GO; GO:0005385; F:zinc ion transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0051050; P:positive regulation of transport; IEA:Ensembl.
DR GO; GO:0061088; P:regulation of sequestering of zinc ion; IDA:BHF-UCL.
DR GO; GO:0010043; P:response to zinc ion; IBA:GO_Central.
DR GO; GO:0099180; P:zinc ion import into synaptic vesicle; 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 Cytoplasmic vesicle; Endosome; Ion transport; Lysosome; Membrane;
KW Reference proteome; Synapse; Synaptosome; Transmembrane;
KW Transmembrane helix; Transport; Zinc; Zinc transport.
FT CHAIN 1..388
FT /note="Zinc transporter 3"
FT /id="PRO_0000206096"
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..264
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 265..285
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 286..388
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 1..46
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 357
FT /note="Dityrosine (Tyr-Tyr) (interchain with Y-372)"
FT /evidence="ECO:0000305|PubMed:19521526"
FT CROSSLNK 372
FT /note="Dityrosine (Tyr-Tyr) (interchain with Y-357)"
FT /evidence="ECO:0000305|PubMed:19521526"
FT VARIANT 298
FT /note="R -> C (may be associated with increased risk for
FT febrile seizures; decreased zinc transport; decreased
FT localization to synaptic vesicles; dbSNP:rs146572471)"
FT /evidence="ECO:0000269|PubMed:26647834"
FT /id="VAR_077209"
FT MUTAGEN 330
FT /note="Y->F: No effect on homodimerization."
FT /evidence="ECO:0000269|PubMed:19521526"
FT MUTAGEN 357
FT /note="Y->F: Increased homodimerization. Increased
FT localization to intracellular vesicles."
FT /evidence="ECO:0000269|PubMed:19521526"
FT MUTAGEN 372
FT /note="Y->F: Decreased homodimerization. Decreased
FT localization to intracellular vesicles. Loss of zinc
FT transporter activity."
FT /evidence="ECO:0000269|PubMed:19521526"
FT CONFLICT 223
FT /note="E -> Q (in Ref. 1; AAB39732)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 388 AA; 41945 MW; D73DE65F46860FD8 CRC64;
MEPSPAAGGL ETTRLVSPRD RGGAGGSLRL KSLFTEPSEP LPEESKPVEM PFHHCHRDPL
PPPGLTPERL HARRQLYAAC AVCFVFMAGE VVGGYLAHSL AIMTDAAHLL ADVGSMMGSL
FSLWLSTRPA TRTMTFGWHR SETLGALASV VSLWMVTGIL LYLAFVRLLH SDYHIEGGAM
LLTASIAVCA NLLMAFVLHQ AGPPHSHGSR GAEYAPLEEG PEEPLPLGNT SVRAAFVHVL
GDLLQSFGVL AASILIYFKP QYKAADPIST FLFSICALGS TAPTLRDVLR ILMEGTPRNV
GFEPVRDTLL SVPGVRATHE LHLWALTLTY HVASAHLAID STADPEAVLA EASSRLYSRF
GFSSCTLQVE QYQPEMAQCL RCQEPPQA
