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Protein

Zinc transporter 8

Gene

SLC30A8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Facilitates the accumulation of zinc from the cytoplasm into intracellular vesicles, being a zinc-efflux transporter. May be a major component for providing zinc to insulin maturation and/or storage processes in insulin-secreting pancreatic beta-cells.1 Publication

GO - Molecular functioni

  • protein homodimerization activity Source: BHF-UCL
  • zinc ion binding Source: BHF-UCL
  • zinc ion transmembrane transporter activity Source: BHF-UCL

GO - Biological processi

  • cellular protein metabolic process Source: Reactome
  • cellular zinc ion homeostasis Source: BHF-UCL
  • insulin secretion Source: BHF-UCL
  • positive regulation of insulin secretion Source: BHF-UCL
  • regulation of sequestering of zinc ion Source: BHF-UCL
  • regulation of vesicle-mediated transport Source: BHF-UCL
  • response to glucose Source: BHF-UCL
  • response to interferon-gamma Source: Ensembl
  • response to interleukin-1 Source: Ensembl
  • sequestering of zinc ion Source: BHF-UCL
  • transmembrane transport Source: Reactome
  • zinc II ion transmembrane transport Source: GOC
  • zinc II ion transport Source: BHF-UCL
Complete GO annotation...

Keywords - Biological processi

Ion transport, Transport, Zinc transport

Keywords - Ligandi

Zinc

Enzyme and pathway databases

ReactomeiREACT_15550. Insulin processing.
REACT_20582. Zinc efflux and compartmentalization by the SLC30 family.

Protein family/group databases

TCDBi2.A.4.3.5. the cation diffusion facilitator (cdf) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Zinc transporter 8
Short name:
ZnT-8
Alternative name(s):
Solute carrier family 30 member 8
Gene namesi
Name:SLC30A8
Synonyms:ZNT8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:20303. SLC30A8.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 7979CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei80 – 10021HelicalSequence AnalysisAdd
BLAST
Topological domaini101 – 1033ExtracellularSequence Analysis
Transmembranei104 – 12421HelicalSequence AnalysisAdd
BLAST
Topological domaini125 – 14016CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei141 – 16121HelicalSequence AnalysisAdd
BLAST
Topological domaini162 – 17514ExtracellularSequence AnalysisAdd
BLAST
Transmembranei176 – 19621HelicalSequence AnalysisAdd
BLAST
Topological domaini197 – 21721CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei218 – 23821HelicalSequence AnalysisAdd
BLAST
Topological domaini239 – 2457ExtracellularSequence Analysis
Transmembranei246 – 26621HelicalSequence AnalysisAdd
BLAST
Topological domaini267 – 369103CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  • cytoplasmic membrane-bounded vesicle Source: BHF-UCL
  • integral component of membrane Source: UniProtKB-KW
  • plasma membrane Source: BHF-UCL
  • secretory granule Source: BHF-UCL
  • secretory granule membrane Source: Reactome
  • transport vesicle membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasmic vesicle, Membrane

Pathology & Biotechi

Keywords - Diseasei

Diabetes mellitus

Organism-specific databases

MIMi125853. phenotype.
PharmGKBiPA134915546.

Polymorphism and mutation databases

BioMutaiSLC30A8.
DMDMi190358866.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 369369Zinc transporter 8PRO_0000281740Add
BLAST

Proteomic databases

PaxDbiQ8IWU4.
PRIDEiQ8IWU4.

PTM databases

PhosphoSiteiQ8IWU4.

Expressioni

Tissue specificityi

In the endocrine pancreas, expressed in insulin-producing beta cells. Expressed at relatively high levels in subcutaneous fat tissue from lean persons; much lower levels in visceral fat, whether from lean or obese individuals, and in subcutaneous fat tissue from obese individuals. Expressed in peripheral blood mononuclear cells, including T-cells and B-cells, with great variation among individuals ranging from negative to strongly positive.5 Publications

Gene expression databases

BgeeiQ8IWU4.
CleanExiHS_SLC30A8.
ExpressionAtlasiQ8IWU4. baseline and differential.
GenevisibleiQ8IWU4. HS.

Interactioni

Subunit structurei

Homodimer.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
CREB3L1Q96BA83EBI-10262251,EBI-6942903

Protein-protein interaction databases

BioGridi127975. 1 interaction.
IntActiQ8IWU4. 1 interaction.
MINTiMINT-4722284.
STRINGi9606.ENSP00000415011.

Structurei

3D structure databases

ProteinModelPortaliQ8IWU4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi197 – 2059HXXXXX[HY]NH-motif

Domaini

Contains a histidine-rich region, HXXXXXHNH-motif, which is a ligand for zinc.By similarity

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG1230.
GeneTreeiENSGT00550000074381.
HOGENOMiHOG000079023.
HOVERGENiHBG003345.
InParanoidiQ8IWU4.
KOiK14695.
OMAiQMESPVD.
OrthoDBiEOG7S4X68.
PhylomeDBiQ8IWU4.
TreeFamiTF313382.

Family and domain databases

Gene3Di1.20.1510.10. 1 hit.
InterProiIPR002524. Cation_efflux.
IPR027469. Cation_efflux_TMD.
[Graphical view]
PANTHERiPTHR11562. PTHR11562. 1 hit.
PfamiPF01545. Cation_efflux. 1 hit.
[Graphical view]
TIGRFAMsiTIGR01297. CDF. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8IWU4-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEFLERTYLV NDKAAKMYAF TLESVELQQK PVNKDQCPRE RPEELESGGM
60 70 80 90 100
YHCHSGSKPT EKGANEYAYA KWKLCSASAI CFIFMIAEVV GGHIAGSLAV
110 120 130 140 150
VTDAAHLLID LTSFLLSLFS LWLSSKPPSK RLTFGWHRAE ILGALLSILC
160 170 180 190 200
IWVVTGVLVY LACERLLYPD YQIQATVMII VSSCAVAANI VLTVVLHQRC
210 220 230 240 250
LGHNHKEVQA NASVRAAFVH ALGDLFQSIS VLISALIIYF KPEYKIADPI
260 270 280 290 300
CTFIFSILVL ASTITILKDF SILLMEGVPK SLNYSGVKEL ILAVDGVLSV
310 320 330 340 350
HSLHIWSLTM NQVILSAHVA TAASRDSQVV RREIAKALSK SFTMHSLTIQ
360
MESPVDQDPD CLFCEDPCD
Length:369
Mass (Da):40,755
Last modified:June 10, 2008 - v2
Checksum:i45926FADCEE18FF3
GO
Isoform 2 (identifier: Q8IWU4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-49: Missing.

Show »
Length:320
Mass (Da):35,053
Checksum:i5D6EE4250AFD9492
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti18 – 181Y → H in AAM80562 (PubMed:15331542).Curated
Sequence conflicti123 – 1231L → S in ABQ59023 (PubMed:17974005).Curated
Sequence conflicti222 – 2221L → P in CAD28545 (PubMed:17974005).Curated
Sequence conflicti302 – 3021S → C in CAD28545 (PubMed:17974005).Curated

Polymorphismi

Variant Trp-325 is a risk factor that confers susceptibility to diabetes mellitus, noninsulin-dependent (NIDDM) [MIMi:125853].

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti325 – 3251R → Q.
Corresponds to variant rs16889462 [ dbSNP | Ensembl ].
VAR_031258
Natural varianti325 – 3251R → W.1 Publication
Corresponds to variant rs13266634 [ dbSNP | Ensembl ].
VAR_031259

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 4949Missing in isoform 2. 3 PublicationsVSP_024025Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY117411 mRNA. Translation: AAM80562.1.
AK298294 mRNA. Translation: BAG60552.1.
AL713790 mRNA. Translation: CAD28545.1.
EF560713 mRNA. Translation: ABQ59023.1.
AC027419 Genomic DNA. No translation available.
AC084114 Genomic DNA. No translation available.
CH471060 Genomic DNA. Translation: EAW91968.1.
BC126446 mRNA. No translation available.
CCDSiCCDS55272.1. [Q8IWU4-2]
CCDS6322.1. [Q8IWU4-1]
RefSeqiNP_001166282.1. NM_001172811.1. [Q8IWU4-2]
NP_001166284.1. NM_001172813.1. [Q8IWU4-2]
NP_001166285.1. NM_001172814.1. [Q8IWU4-2]
NP_001166286.1. NM_001172815.1. [Q8IWU4-2]
NP_776250.2. NM_173851.2. [Q8IWU4-1]
UniGeneiHs.532270.

Genome annotation databases

EnsembliENST00000427715; ENSP00000407505; ENSG00000164756. [Q8IWU4-2]
ENST00000456015; ENSP00000415011; ENSG00000164756. [Q8IWU4-1]
ENST00000519688; ENSP00000431069; ENSG00000164756. [Q8IWU4-2]
ENST00000521243; ENSP00000428545; ENSG00000164756. [Q8IWU4-2]
GeneIDi169026.
KEGGihsa:169026.
UCSCiuc003yog.3. human. [Q8IWU4-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY117411 mRNA. Translation: AAM80562.1.
AK298294 mRNA. Translation: BAG60552.1.
AL713790 mRNA. Translation: CAD28545.1.
EF560713 mRNA. Translation: ABQ59023.1.
AC027419 Genomic DNA. No translation available.
AC084114 Genomic DNA. No translation available.
CH471060 Genomic DNA. Translation: EAW91968.1.
BC126446 mRNA. No translation available.
CCDSiCCDS55272.1. [Q8IWU4-2]
CCDS6322.1. [Q8IWU4-1]
RefSeqiNP_001166282.1. NM_001172811.1. [Q8IWU4-2]
NP_001166284.1. NM_001172813.1. [Q8IWU4-2]
NP_001166285.1. NM_001172814.1. [Q8IWU4-2]
NP_001166286.1. NM_001172815.1. [Q8IWU4-2]
NP_776250.2. NM_173851.2. [Q8IWU4-1]
UniGeneiHs.532270.

3D structure databases

ProteinModelPortaliQ8IWU4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi127975. 1 interaction.
IntActiQ8IWU4. 1 interaction.
MINTiMINT-4722284.
STRINGi9606.ENSP00000415011.

Protein family/group databases

TCDBi2.A.4.3.5. the cation diffusion facilitator (cdf) family.

PTM databases

PhosphoSiteiQ8IWU4.

Polymorphism and mutation databases

BioMutaiSLC30A8.
DMDMi190358866.

Proteomic databases

PaxDbiQ8IWU4.
PRIDEiQ8IWU4.

Protocols and materials databases

DNASUi169026.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000427715; ENSP00000407505; ENSG00000164756. [Q8IWU4-2]
ENST00000456015; ENSP00000415011; ENSG00000164756. [Q8IWU4-1]
ENST00000519688; ENSP00000431069; ENSG00000164756. [Q8IWU4-2]
ENST00000521243; ENSP00000428545; ENSG00000164756. [Q8IWU4-2]
GeneIDi169026.
KEGGihsa:169026.
UCSCiuc003yog.3. human. [Q8IWU4-1]

Organism-specific databases

CTDi169026.
GeneCardsiGC08P117963.
HGNCiHGNC:20303. SLC30A8.
MIMi125853. phenotype.
611145. gene.
neXtProtiNX_Q8IWU4.
PharmGKBiPA134915546.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG1230.
GeneTreeiENSGT00550000074381.
HOGENOMiHOG000079023.
HOVERGENiHBG003345.
InParanoidiQ8IWU4.
KOiK14695.
OMAiQMESPVD.
OrthoDBiEOG7S4X68.
PhylomeDBiQ8IWU4.
TreeFamiTF313382.

Enzyme and pathway databases

ReactomeiREACT_15550. Insulin processing.
REACT_20582. Zinc efflux and compartmentalization by the SLC30 family.

Miscellaneous databases

GeneWikiiSLC30A8.
GenomeRNAii169026.
NextBioi88780.
PROiQ8IWU4.
SOURCEiSearch...

Gene expression databases

BgeeiQ8IWU4.
CleanExiHS_SLC30A8.
ExpressionAtlasiQ8IWU4. baseline and differential.
GenevisibleiQ8IWU4. HS.

Family and domain databases

Gene3Di1.20.1510.10. 1 hit.
InterProiIPR002524. Cation_efflux.
IPR027469. Cation_efflux_TMD.
[Graphical view]
PANTHERiPTHR11562. PTHR11562. 1 hit.
PfamiPF01545. Cation_efflux. 1 hit.
[Graphical view]
TIGRFAMsiTIGR01297. CDF. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Identification and cloning of a beta-cell-specific zinc transporter, ZnT-8, localized into insulin secretory granules."
    Chimienti F., Devergnas S., Favier A., Seve M.
    Diabetes 53:2330-2337(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
    Tissue: Pancreas.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Kidney.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Amygdala and Brain.
  4. "DNA sequence and analysis of human chromosome 8."
    Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T.
    , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
    Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Lung.
  7. "ZnT-8, a pancreatic beta-cell-specific zinc transporter."
    Chimienti F., Favier A., Seve M.
    BioMetals 18:313-317(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  8. "In vivo expression and functional characterization of the zinc transporter ZnT8 in glucose-induced insulin secretion."
    Chimienti F., Devergnas S., Pattou F., Schuit F., Garcia-Cuenca R., Vandewalle B., Kerr-Conte J., Van Lommel L., Grunwald D., Favier A., Seve M.
    J. Cell Sci. 119:4199-4206(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, FUNCTION.
  9. "Zinc-transporter genes in human visceral and subcutaneous adipocytes: lean versus obese."
    Smidt K., Pedersen S.B., Brock B., Schmitz O., Fisker S., Bendix J., Wogensen L., Rungby J.
    Mol. Cell. Endocrinol. 264:68-73(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  10. "Intracellular zinc homeostasis in leukocyte subsets is regulated by different expression of zinc exporters ZnT-1 to ZnT-9."
    Overbeck S., Uciechowski P., Ackland M.L., Ford D., Rink L.
    J. Leukoc. Biol. 83:368-380(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  11. Cited for: VARIANT TRP-325, INVOLVEMENT IN NONINSULIN-DEPENDENT DIABETES MELLITUS.

Entry informationi

Entry nameiZNT8_HUMAN
AccessioniPrimary (citable) accession number: Q8IWU4
Secondary accession number(s): A0AVP9
, A5YM39, B4DPE0, Q8TCL3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 20, 2007
Last sequence update: June 10, 2008
Last modified: June 24, 2015
This is version 102 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.