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2.A.4.3.5
Homodimeric solute carrier family 30 (zinc transporter), member 8, ZnT8.  An inherited R325W mutant gives aberant zinc transport in pancreatic beta cells (Weijers 2010). It is chiefly expressed in pancreatic islet cells, where it mediates zinc (Zn2+) uptake into secretory granules. It plays a role in gllucose tolerance (Mitchell et al. 2016). ZnT8 is one of four human vesicular zinc transporters. It supplies millimolar zinc concentrations to insulin granules in pancreatic beta-cells, affecting insulin processing, crystallisation, and secretion. ZnT8 has a transmembrane and a C-terminal cytosolic domain; the latter has important functions and purportedly mediates protein-protein interactions, senses cytosolic zinc, and channels zinc to the transport site in the transmembrane domain (Parsons et al. 2018). The variant, W325R, in the C-terminal domain (CTD) increases the risk to develop type 2 diabetes and affects autoantibody specificity in type 1 diabetes.

Accession Number:Q8IWU4
Protein Name:Zinc transporter 8
Length:369
Molecular Weight:40755.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:7
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate Zn2+

Cross database links:

Genevestigator: Q8IWU4 Q8IWU4
eggNOG: COG1230 COG1230
HEGENOM: HOG000079023 HOG000079023
Entrez Gene ID: 169026   
Pfam: PF01545   
KEGG: hsa:169026    hsa:169026   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005886 C:plasma membrane
GO:0030667 C:secretory granule membrane
GO:0030658 C:transport vesicle membrane
GO:0042803 F:protein homodimerization activity
GO:0008270 F:zinc ion binding
GO:0005385 F:zinc ion transmembrane transporter activity
GO:0030073 P:insulin secretion
GO:0032024 P:positive regulation of insulin secretion
GO:0061088 P:regulation of sequestering of zinc ion
GO:0060627 P:regulation of vesicle-mediated transport
GO:0009749 P:response to glucose stimulus
GO:0032119 P:sequestering of zinc ion
GO:0034341 P:response to interferon-gamma
GO:0070555 P:response to interleukin-1

References (20)

[1] “Identification and cloning of a beta-cell-specific zinc transporter, ZnT-8, localized into insulin secretory granules.”  Chimienti F.et.al.   15331542
[2] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[3] “The full-ORF clone resource of the German cDNA consortium.”  Bechtel S.et.al.   17974005
[4] “DNA sequence and analysis of human chromosome 8.”  Nusbaum C.et.al.   16421571
[5] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[6] “ZnT-8, a pancreatic beta-cell-specific zinc transporter.”  Chimienti F.et.al.   16158222
[7] “In vivo expression and functional characterization of the zinc transporter ZnT8 in glucose-induced insulin secretion.”  Chimienti F.et.al.   16984975
[8] “Zinc-transporter genes in human visceral and subcutaneous adipocytes: lean versus obese.”  Smidt K.et.al.   17118530
[9] “Intracellular zinc homeostasis in leukocyte subsets is regulated by different expression of zinc exporters ZnT-1 to ZnT-9.”  Overbeck S.et.al.   17971500
[10] “A genome-wide association study identifies novel risk loci for type 2 diabetes.”  Sladek R.et.al.   17293876
[11] “Identification and cloning of a beta-cell-specific zinc transporter, ZnT-8, localized into insulin secretory granules.”  Chimienti F.et.al.   15331542
[12] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[13] “The full-ORF clone resource of the German cDNA consortium.”  Bechtel S.et.al.   17974005
[14] “DNA sequence and analysis of human chromosome 8.”  Nusbaum C.et.al.   16421571
[15] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[16] “ZnT-8, a pancreatic beta-cell-specific zinc transporter.”  Chimienti F.et.al.   16158222
[17] “In vivo expression and functional characterization of the zinc transporter ZnT8 in glucose-induced insulin secretion.”  Chimienti F.et.al.   16984975
[18] “Zinc-transporter genes in human visceral and subcutaneous adipocytes: lean versus obese.”  Smidt K.et.al.   17118530
[19] “Intracellular zinc homeostasis in leukocyte subsets is regulated by different expression of zinc exporters ZnT-1 to ZnT-9.”  Overbeck S.et.al.   17971500
[20] “A genome-wide association study identifies novel risk loci for type 2 diabetes.”  Sladek R.et.al.   17293876

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FASTA formatted sequence
1:	MEFLERTYLV NDKAAKMYAF TLESVELQQK PVNKDQCPRE RPEELESGGM YHCHSGSKPT 
61:	EKGANEYAYA KWKLCSASAI CFIFMIAEVV GGHIAGSLAV VTDAAHLLID LTSFLLSLFS 
121:	LWLSSKPPSK RLTFGWHRAE ILGALLSILC IWVVTGVLVY LACERLLYPD YQIQATVMII 
181:	VSSCAVAANI VLTVVLHQRC LGHNHKEVQA NASVRAAFVH ALGDLFQSIS VLISALIIYF 
241:	KPEYKIADPI CTFIFSILVL ASTITILKDF SILLMEGVPK SLNYSGVKEL ILAVDGVLSV 
301:	HSLHIWSLTM NQVILSAHVA TAASRDSQVV RREIAKALSK SFTMHSLTIQ MESPVDQDPD 
361:	CLFCEDPCD