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zinc transporter 8; solute carrier family 30 member 8; ZnT-8 (SLC30A8, ZNT8)
Function:
1) facilitates accumulation of zinc from cytolplasm into intracellular vesicles
2) may be a major component providing zinc to insulin maturation &/or storage processes in pancreatic beta-cells
Structure:
- homodimer
- belongs to the cation diffusion facilitator (CDF) transporter (TC 2.A.4) family. SLC30A subfamily
- contains a histidine-rich region which is a ligand for zinc
Compartment:
- cell membrane
- cytoplasmic vesicle, secretory vesicle membrane
- associated with insulin secretory granules & glucagon secretory granules (putative)
Alternative splicing: named isoforms=2
Expression:
- expressed in beta-cells of pancreatic islets
- expressed at relatively high levels in subcutaneous fat from lean persons
- much lower levels in visceral fat, whether from lean or obese individuals, & in subcutaneous fat tissue from obese persons
- expressed in peripheral blood mononuclear cells, including T-cells & B-cells, with great variation among individuals
Pathology:
- antibodies to ZNT8 are found in 65% of patients with diabetes melltus type-1 [3]
Laboratory:
- ZnT8 autoantibody
Polymorphism:
- variant Trp-325 is a risk factor that confers susceptibility to diabetes mellitus type-2
- SLC30A8 loss of function diminishes risk of type 2 diabetes [2]
General
glycoprotein
solute carrier family 30 (SLC30, SLC30A)
transmembrane 6e protein
Properties
SIZE: MW = 41 kD
entity length = 369 aa
COMPARTMENT: cytoplasm
MOTIF: exoplasmic domain {1-79}
transmembrane domain {80-100}
cytoplasmic loop {101-103}
transmembrane domain {104-124}
exoplasmic loop {125-140}
transmembrane domain {141-161}
cytoplasmic loop {162-175}
transmembrane domain {176-196}
exoplasmic loop {197-217}
MOTIF: histidine-rich region {197-205}
MOTIF: histidine residue (SEVERAL)
N-glycosylation site {N211}
transmembrane domain {218-238}
cytoplasmic loop {239-245}
transmembrane domain {246-266}
exoplasmic domain {267-369}
MOTIF: N-glycosylation site {N283}
Database Correlations
OMIM 125853
UniProt Q8IWU4
Pfam PF01545
References
- UniProt :accession Q8IWU4
- Flannick J et al
Loss-of-function mutations in SLC30A8 protect against type 2
diabetes.
Nature Genetics. March 2, 2014
PMID: 24584071
http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.2915.html
- Kelley KJ and Sofair A
New Type 1 Diabetes Test Approved.
Physician's First Watch, Aug 22, 2014
David G. Fairchild, MD, MPH, Editor-in-Chief
Massachusetts Medical Society
http://www.jwatch.org
- FDA News Release. August 20, 2104
FDA allows marketing of first ZnT8Ab autoantibody test to help
diagnose type 1 diabetes.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm410830.htm