Q8IWU4 (ZNT8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Zinc transporter 8
Short name=ZnT-8

Alternative name(s):
Solute carrier family 30 member 8

Gene names

Name:	SLC30A8
Synonyms:	ZNT8

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	369 AA.
Sequence status	Complete.
Protein existence	Evidence 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 vesicle › secretory 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 process	Ion transport Transport Zinc transport
Cellular component	Cell membrane Cytoplasmic vesicle Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Diabetes mellitus
Domain	Transmembrane Transmembrane helix
Ligand	Zinc
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	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 stimulus Inferred from mutant phenotype Ref.8. Source: BHF-UCL response to interferon-gamma Inferred from electronic annotation. Source: Compara response to interleukin-1 Inferred from electronic annotation. Source: Compara sequestering of zinc ion Inferred from direct assay Ref.1. Source: BHF-UCL
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane 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_function	protein 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 369	369	Zinc transporter 8		PRO_0000281740
Regions
	Topological domain	1 – 79	79	Cytoplasmic Potential
	Transmembrane	80 – 100	21	Helical; Potential
	Topological domain	101 – 103	3	Extracellular Potential
	Transmembrane	104 – 124	21	Helical; Potential
	Topological domain	125 – 140	16	Cytoplasmic Potential
	Transmembrane	141 – 161	21	Helical; Potential
	Topological domain	162 – 175	14	Extracellular Potential
	Transmembrane	176 – 196	21	Helical; Potential
	Topological domain	197 – 217	21	Cytoplasmic Potential
	Transmembrane	218 – 238	21	Helical; Potential
	Topological domain	239 – 245	7	Extracellular Potential
	Transmembrane	246 – 266	21	Helical; Potential
	Topological domain	267 – 369	103	Cytoplasmic Potential
	Motif	197 – 205	9	HXXXXX[HY]NH-motif
Natural variations
	Alternative sequence	1 – 49	49	Missing in isoform 2.		VSP_024025
	Natural variant	325	1	R → Q. Corresponds to variant rs16889462 [ dbSNP | Ensembl ].		VAR_031258
	Natural variant	325	1	R → W. Ref.11 Corresponds to variant rs13266634 [ dbSNP | Ensembl ].		VAR_031259
Experimental info
	Sequence conflict	18	1	Y → H in AAM80562. Ref.1
	Sequence conflict	123	1	L → S in ABQ59023. Ref.3
	Sequence conflict	222	1	L → P in CAD28545. Ref.3
	Sequence conflict	302	1	S → C in CAD28545. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 10, 2008. Version 2. Checksum: 45926FADCEE18FF3	FASTA	369	40,755
	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
	Isoform 2 [UniParc]. Checksum: 5D6EE4250AFD9492	FASTA	320	35,053
	10 20 30 40 50 60 MYHCHSGSKP TEKGANEYAY AKWKLCSASA ICFIFMIAEV VGGHIAGSLA VVTDAAHLLI 70 80 90 100 110 120 DLTSFLLSLF SLWLSSKPPS KRLTFGWHRA EILGALLSIL CIWVVTGVLV YLACERLLYP 130 140 150 160 170 180 DYQIQATVMI IVSSCAVAAN IVLTVVLHQR CLGHNHKEVQ ANASVRAAFV HALGDLFQSI 190 200 210 220 230 240 SVLISALIIY FKPEYKIADP ICTFIFSILV LASTITILKD FSILLMEGVP KSLNYSGVKE 250 260 270 280 290 300 LILAVDGVLS VHSLHIWSLT MNQVILSAHV ATAASRDSQV VRREIAKALS KSFTMHSLTI 310 320 QMESPVDQDP DCLFCEDPCD

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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. , 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.
IPI	IPI00217394. IPI00829922.
RefSeq	NP_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.
UniGene	Hs.532270.
3D structure databases
ProteinModelPortal	Q8IWU4.
SMR	Q8IWU4. Positions 73-169.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000297345.
PTM databases
PhosphoSite	Q8IWU4.
Polymorphism databases
DMDM	190358866.
Proteomic databases
PaxDb	Q8IWU4.
PRIDE	Q8IWU4.
Protocols and materials databases
DNASU	169026.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000427715; ENSP00000407505; ENSG00000164756. ENST00000456015; ENSP00000415011; ENSG00000164756. ENST00000519688; ENSP00000431069; ENSG00000164756. ENST00000521243; ENSP00000428545; ENSG00000164756.
GeneID	169026.
KEGG	hsa:169026.
UCSC	uc003yog.3. human.
Organism-specific databases
CTD	169026.
GeneCards	GC08P117963.
HGNC	HGNC:20303. SLC30A8.
MIM	125853. phenotype. 611145. gene.
neXtProt	NX_Q8IWU4.
PharmGKB	PA134915546.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1230.
HOGENOM	HOG000079023.
HOVERGEN	HBG003345.
InParanoid	Q8IWU4.
KO	K14695.
OMA	IQMESPV.
OrthoDB	EOG4Z36FG.
PhylomeDB	Q8IWU4.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	Q8IWU4.
Bgee	Q8IWU4.
CleanEx	HS_SLC30A8.
Genevestigator	Q8IWU4.
Family and domain databases
InterPro	IPR002524. Cation_efflux. [Graphical view]
PANTHER	PTHR11562. PTHR11562. 1 hit.
Pfam	PF01545. Cation_efflux. 1 hit. [Graphical view]
TIGRFAMs	TIGR01297. CDF. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	169026.
NextBio	88780.
SOURCE	Search...

Entry information

Entry name

ZNT8_HUMAN

Accession

Primary (citable) accession number: Q8IWU4
Secondary accession number(s): A0AVP9 , A5YM39, B4DPE0, Q8TCL3

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 20, 2007
Last sequence update:	June 10, 2008
Last modified:	May 1, 2013
This is version 82 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.