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Q8IWU4 (ZNT8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 91. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Zinc transporter 8

Short name=ZnT-8
Alternative name(s):
Solute carrier family 30 member 8
Gene names
Name:SLC30A8
Synonyms:ZNT8
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length369 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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. Ref.8

Subunit structure

Homodimer By similarity.

Subcellular location

Cell membrane; Multi-pass membrane protein Probable. Cytoplasmic vesiclesecretory vesicle membrane; Multi-pass membrane protein Probable. Note: Associated with insulin and glucagon secretory granules By similarity. Ref.1 Ref.8

Tissue specificity

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. Ref.1 Ref.7 Ref.8 Ref.9 Ref.10

Domain

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

Polymorphism

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

Sequence similarities

Belongs to the cation diffusion facilitator (CDF) transporter (TC 2.A.4) family. SLC30A subfamily. [View classification]

Ontologies

Keywords
   Biological processIon transport
Transport
Zinc transport
   Cellular componentCell membrane
Cytoplasmic vesicle
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDiabetes mellitus
   DomainTransmembrane
Transmembrane helix
   LigandZinc
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular zinc ion homeostasis

Inferred from sequence or structural similarity. Source: BHF-UCL

insulin secretion

Inferred from mutant phenotype Ref.8. Source: BHF-UCL

positive regulation of insulin secretion

Inferred from sequence or structural similarity. Source: BHF-UCL

regulation of sequestering of zinc ion

Inferred from sequence or structural similarity. Source: BHF-UCL

regulation of vesicle-mediated transport

Inferred from sequence or structural similarity. Source: BHF-UCL

response to glucose

Inferred from mutant phenotype Ref.8. Source: BHF-UCL

response to interferon-gamma

Inferred from electronic annotation. Source: Ensembl

response to interleukin-1

Inferred from electronic annotation. Source: Ensembl

sequestering of zinc ion

Inferred from direct assay Ref.1. Source: BHF-UCL

transmembrane transport

Traceable author statement. Source: Reactome

zinc ion transmembrane transport

Inferred from direct assay Ref.1. Source: GOC

zinc ion transport

Inferred from direct assay Ref.1. Source: BHF-UCL

   Cellular_componentcytoplasmic membrane-bounded vesicle

Inferred from sequence or structural similarity. Source: BHF-UCL

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from direct assay Ref.1. Source: BHF-UCL

secretory granule

Inferred from direct assay Ref.1. Source: BHF-UCL

secretory granule membrane

Traceable author statement. Source: Reactome

transport vesicle membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionprotein homodimerization activity

Inferred from sequence or structural similarity. Source: BHF-UCL

zinc ion binding

Inferred by curator Ref.1. Source: BHF-UCL

zinc ion transmembrane transporter activity

Inferred from direct assay Ref.1. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8IWU4-1)

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.
Isoform 2 (identifier: Q8IWU4-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 369369Zinc transporter 8
PRO_0000281740

Regions

Topological domain1 – 7979Cytoplasmic Potential
Transmembrane80 – 10021Helical; Potential
Topological domain101 – 1033Extracellular Potential
Transmembrane104 – 12421Helical; Potential
Topological domain125 – 14016Cytoplasmic Potential
Transmembrane141 – 16121Helical; Potential
Topological domain162 – 17514Extracellular Potential
Transmembrane176 – 19621Helical; Potential
Topological domain197 – 21721Cytoplasmic Potential
Transmembrane218 – 23821Helical; Potential
Topological domain239 – 2457Extracellular Potential
Transmembrane246 – 26621Helical; Potential
Topological domain267 – 369103Cytoplasmic Potential
Motif197 – 2059HXXXXX[HY]NH-motif

Natural variations

Alternative sequence1 – 4949Missing in isoform 2.
VSP_024025
Natural variant3251R → Q.
Corresponds to variant rs16889462 [ dbSNP | Ensembl ].
VAR_031258
Natural variant3251R → W. Ref.11
Corresponds to variant rs13266634 [ dbSNP | Ensembl ].
VAR_031259

Experimental info

Sequence conflict181Y → H in AAM80562. Ref.1
Sequence conflict1231L → S in ABQ59023. Ref.3
Sequence conflict2221L → P in CAD28545. Ref.3
Sequence conflict3021S → C in CAD28545. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 10, 2008. Version 2.
Checksum: 45926FADCEE18FF3

FASTA36940,755
        10         20         30         40         50         60 
MEFLERTYLV NDKAAKMYAF TLESVELQQK PVNKDQCPRE RPEELESGGM YHCHSGSKPT 

        70         80         90        100        110        120 
EKGANEYAYA KWKLCSASAI CFIFMIAEVV GGHIAGSLAV VTDAAHLLID LTSFLLSLFS 

       130        140        150        160        170        180 
LWLSSKPPSK RLTFGWHRAE ILGALLSILC IWVVTGVLVY LACERLLYPD YQIQATVMII 

       190        200        210        220        230        240 
VSSCAVAANI VLTVVLHQRC LGHNHKEVQA NASVRAAFVH ALGDLFQSIS VLISALIIYF 

       250        260        270        280        290        300 
KPEYKIADPI CTFIFSILVL ASTITILKDF SILLMEGVPK SLNYSGVKEL ILAVDGVLSV 

       310        320        330        340        350        360 
HSLHIWSLTM NQVILSAHVA TAASRDSQVV RREIAKALSK SFTMHSLTIQ MESPVDQDPD 


CLFCEDPCD 

« Hide

Isoform 2 [UniParc].

Checksum: 5D6EE4250AFD9492
Show »

FASTA32035,053

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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]"A genome-wide association study identifies novel risk loci for type 2 diabetes."
Sladek R., Rocheleau G., Rung J., Dina C., Shen L., Serre D., Boutin P., Vincent D., Belisle A., Hadjadj S., Balkau B., Heude B., Charpentier G., Hudson T.J., Montpetit A., Pshezhetsky A.V., Prentki M., Posner B.I. expand/collapse author list , Balding D.J., Meyre D., Polychronakos C., Froguel P.
Nature 445:881-885(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TRP-325, INVOLVEMENT IN NONINSULIN-DEPENDENT DIABETES MELLITUS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001166282.1. NM_001172811.1.
NP_001166284.1. NM_001172813.1.
NP_001166285.1. NM_001172814.1.
NP_001166286.1. NM_001172815.1.
NP_776250.2. NM_173851.2.
UniGeneHs.532270.

3D structure databases

ProteinModelPortalQ8IWU4.
SMRQ8IWU4. Positions 73-170.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

MINTMINT-4722284.
STRING9606.ENSP00000297345.

Protein family/group databases

TCDB2.A.4.3.5. the cation diffusion facilitator (cdf) family.

PTM databases

PhosphoSiteQ8IWU4.

Polymorphism databases

DMDM190358866.

Proteomic databases

PaxDbQ8IWU4.
PRIDEQ8IWU4.

Protocols and materials databases

DNASU169026.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000427715; ENSP00000407505; ENSG00000164756. [Q8IWU4-2]
ENST00000456015; ENSP00000415011; ENSG00000164756. [Q8IWU4-1]
ENST00000519688; ENSP00000431069; ENSG00000164756. [Q8IWU4-2]
ENST00000521243; ENSP00000428545; ENSG00000164756. [Q8IWU4-2]
GeneID169026.
KEGGhsa:169026.
UCSCuc003yog.3. human. [Q8IWU4-1]

Organism-specific databases

CTD169026.
GeneCardsGC08P117963.
HGNCHGNC:20303. SLC30A8.
MIM125853. phenotype.
611145. gene.
neXtProtNX_Q8IWU4.
PharmGKBPA134915546.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1230.
HOGENOMHOG000079023.
HOVERGENHBG003345.
InParanoidQ8IWU4.
KOK14695.
OMALLYPDYQ.
OrthoDBEOG7S4X68.
PhylomeDBQ8IWU4.
TreeFamTF313382.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressQ8IWU4.
BgeeQ8IWU4.
CleanExHS_SLC30A8.
GenevestigatorQ8IWU4.

Family and domain databases

Gene3D1.20.1510.10. 1 hit.
InterProIPR002524. Cation_efflux.
IPR027469. Cation_efflux_TMD.
[Graphical view]
PANTHERPTHR11562. PTHR11562. 1 hit.
PfamPF01545. Cation_efflux. 1 hit.
[Graphical view]
TIGRFAMsTIGR01297. CDF. 1 hit.
ProtoNetSearch...

Other

GeneWikiSLC30A8.
GenomeRNAi169026.
NextBio88780.
PROQ8IWU4.
SOURCESearch...

Entry information

Entry nameZNT8_HUMAN
AccessionPrimary (citable) accession number: Q8IWU4
Secondary accession number(s): A0AVP9 expand/collapse secondary AC list , A5YM39, B4DPE0, Q8TCL3
Entry history
Integrated into UniProtKB/Swiss-Prot: March 20, 2007
Last sequence update: June 10, 2008
Last modified: April 16, 2014
This is version 91 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM