ZNT8_RAT
ID ZNT8_RAT Reviewed; 368 AA.
AC P0CE46;
DT 23-MAR-2010, integrated into UniProtKB/Swiss-Prot.
DT 23-MAR-2010, sequence version 1.
DT 03-AUG-2022, entry version 74.
DE RecName: Full=Zinc transporter 8;
DE Short=ZnT-8;
DE AltName: Full=Solute carrier family 30 member 8;
GN Name=Slc30a8; Synonyms=Znt8;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=19095428; DOI=10.1016/j.numecd.2008.09.004;
RA Murgia C., Devirgiliis C., Mancini E., Donadel G., Zalewski P., Perozzi G.;
RT "Diabetes-linked zinc transporter ZnT8 is a homodimeric protein expressed
RT by distinct rodent endocrine cell types in the pancreas and other glands.";
RL Nutr. Metab. Cardiovasc. Dis. 19:431-439(2009).
RN [3]
RP FUNCTION.
RX PubMed=19479076; DOI=10.1371/journal.pone.0005679;
RA Fu Y., Tian W., Pratt E.B., Dirling L.B., Shyng S.L., Meshul C.K.,
RA Cohen D.M.;
RT "Down-regulation of ZnT8 expression in INS-1 rat pancreatic beta cells
RT reduces insulin content and glucose-inducible insulin secretion.";
RL PLoS ONE 4:E5679-E5679(2009).
RN [4]
RP INDUCTION BY IL1B AND IFNG.
RX PubMed=19243577; DOI=10.1186/1472-6823-9-7;
RA Egefjord L., Jensen J.L., Bang-Berthelsen C.H., Petersen A.B., Smidt K.,
RA Schmitz O., Karlsen A.E., Pociot F., Chimienti F., Rungby J.,
RA Magnusson N.E.;
RT "Zinc transporter gene expression is regulated by pro-inflammatory
RT cytokines: a potential role for zinc transporters in beta-cell apoptosis?";
RL BMC Endocr. Disord. 9:7-7(2009).
CC -!- FUNCTION: Facilitates the accumulation of zinc from the cytoplasm into
CC intracellular vesicles, being a zinc-efflux transporter (By
CC similarity). May be a major component for providing zinc to insulin
CC maturation and/or storage processes in insulin-secreting pancreatic
CC beta-cells. {ECO:0000250, ECO:0000269|PubMed:19479076}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane
CC protein {ECO:0000250}. Cytoplasmic vesicle, secretory vesicle membrane
CC {ECO:0000269|PubMed:19095428}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:19095428}. Note=Associated with insulin and
CC glucagon secretory granules. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in endocrine pancreatic islet alpha and
CC beta cells. May be more abundant in beta cells than in alpha cells.
CC Expressed in cubical epithelium lining thyroid follicles (at protein
CC level). In the adrenal gland, detected in the cortex, but not in the
CC medulla (at protein level). {ECO:0000269|PubMed:19095428}.
CC -!- INDUCTION: Down-regulated by IL1B and IFNG.
CC {ECO:0000269|PubMed:19243577}.
CC -!- DOMAIN: Contains a histidine-rich region, HXXXXXHNH-motif, which is a
CC ligand for zinc. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the cation diffusion facilitator (CDF)
CC transporter (TC 2.A.4) family. SLC30A subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EDM16273.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; CH473950; EDM16273.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; NP_001124010.1; NM_001130538.1.
DR RefSeq; XP_006241707.1; XM_006241645.3.
DR AlphaFoldDB; P0CE46; -.
DR SMR; P0CE46; -.
DR STRING; 10116.ENSRNOP00000006410; -.
DR PaxDb; P0CE46; -.
DR PRIDE; P0CE46; -.
DR Ensembl; ENSRNOT00000006410; ENSRNOP00000006410; ENSRNOG00000004747.
DR GeneID; 299903; -.
DR KEGG; rno:299903; -.
DR UCSC; RGD:1308282; rat.
DR CTD; 169026; -.
DR RGD; 1308282; Slc30a8.
DR eggNOG; KOG1482; Eukaryota.
DR GeneTree; ENSGT00940000160706; -.
DR HOGENOM; CLU_013430_0_1_1; -.
DR InParanoid; P0CE46; -.
DR OMA; RATKMYA; -.
DR OrthoDB; 820567at2759; -.
DR PhylomeDB; P0CE46; -.
DR TreeFam; TF313382; -.
DR Reactome; R-RNO-264876; Insulin processing.
DR Reactome; R-RNO-435368; Zinc efflux and compartmentalization by the SLC30 family.
DR PRO; PR:P0CE46; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Proteomes; UP000234681; Chromosome 7.
DR Bgee; ENSRNOG00000004747; Expressed in pancreas and 5 other tissues.
DR ExpressionAtlas; P0CE46; baseline.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0030141; C:secretory granule; ISO:RGD.
DR GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0005385; F:zinc ion transmembrane transporter activity; ISO:RGD.
DR GO; GO:0006882; P:cellular zinc ion homeostasis; IMP:BHF-UCL.
DR GO; GO:0030073; P:insulin secretion; IMP:RGD.
DR GO; GO:0032024; P:positive regulation of insulin secretion; IMP:BHF-UCL.
DR GO; GO:0061088; P:regulation of sequestering of zinc ion; IMP:BHF-UCL.
DR GO; GO:0060627; P:regulation of vesicle-mediated transport; IMP:BHF-UCL.
DR GO; GO:0009749; P:response to glucose; IMP:BHF-UCL.
DR GO; GO:0034341; P:response to interferon-gamma; IEP:RGD.
DR GO; GO:0070555; P:response to interleukin-1; IEP:RGD.
DR GO; GO:0010043; P:response to zinc ion; IBA:GO_Central.
DR GO; GO:0032119; P:sequestering of zinc ion; ISO:RGD.
DR GO; GO:0071577; P:zinc ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006829; P:zinc ion transport; ISO:RGD.
DR Gene3D; 1.20.1510.10; -; 1.
DR InterPro; IPR002524; Cation_efflux.
DR InterPro; IPR036837; Cation_efflux_CTD_sf.
DR InterPro; IPR027469; Cation_efflux_TMD_sf.
DR InterPro; IPR033572; ZnT-8.
DR PANTHER; PTHR11562:SF37; PTHR11562:SF37; 1.
DR Pfam; PF01545; Cation_efflux; 1.
DR SUPFAM; SSF160240; SSF160240; 1.
DR SUPFAM; SSF161111; SSF161111; 1.
DR TIGRFAMs; TIGR01297; CDF; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cytoplasmic vesicle; Ion transport; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport; Zinc;
KW Zinc transport.
FT CHAIN 1..368
FT /note="Zinc transporter 8"
FT /id="PRO_0000392208"
FT TOPO_DOM 1..78
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 79..99
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 100..102
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 103..123
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 124..139
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 140..160
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 161..174
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 175..195
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 196..216
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 217..237
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 238..245
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 246..266
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 267..368
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOTIF 196..204
FT /note="HXXXXX[HY]NH"
SQ SEQUENCE 368 AA; 40128 MW; C1E62FDCB524AFAE CRC64;
MEFLERTYLV NDQATKMYAF TSDRERGQKP VNKDQCPGDG PERPEAGAIY HCHNSFKATG
NRSSKQVHAK WRLCAASAIC FFFMVAEVVG GHVAGSLAVL TDAAHLLIDL TSFLLSLFSL
WLSSRPPSKR LTFGWYRAEI LGALLSVLCI WVVTGVLVYL ACERLLYPDY QIQAGIMITV
SGCAVAANIV LTLILHQRHL GHNHKDAQAN ASVRAAFVHA LGDVFQSTSV LISALIIYFK
PDYKMADPVC TFISSVLALA STVMILKDFS ILLMEGVPKG LSYNSVKELL LTVDGVISVH
NLHIWSLTVN QVILSVHVAT AASQDSQSVR TGIACALSSS FDLHSLTIQI ESAADQDPSC
LLCEDPQD
