ZNT8_MOUSE
ID ZNT8_MOUSE Reviewed; 367 AA.
AC Q8BGG0;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 133.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Pancreas;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=16984975; DOI=10.1242/jcs.03164;
RA Chimienti F., Devergnas S., Pattou F., Schuit F., Garcia-Cuenca R.,
RA Vandewalle B., Kerr-Conte J., Van Lommel L., Grunwald D., Favier A.,
RA Seve M.;
RT "In vivo expression and functional characterization of the zinc transporter
RT ZnT8 in glucose-induced insulin secretion.";
RL J. Cell Sci. 119:4199-4206(2006).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=18250168; DOI=10.1074/jbc.m707005200;
RA Gyulkhandanyan A.V., Lu H., Lee S.C., Bhattacharjee A., Wijesekara N.,
RA Fox J.E., MacDonald P.E., Chimienti F., Dai F.F., Wheeler M.B.;
RT "Investigation of transport mechanisms and regulation of intracellular Zn2+
RT in pancreatic alpha-cells.";
RL J. Biol. Chem. 283:10184-10197(2008).
RN [5]
RP HOMODIMERIZATION, 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).
CC -!- FUNCTION: Facilitates the accumulation of zinc from the cytoplasm into
CC intracellular vesicles, being a zinc-efflux transporter. May be a major
CC component for providing zinc to insulin maturation and/or storage
CC processes in insulin-secreting pancreatic beta-cells (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane
CC protein {ECO:0000250}. Cytoplasmic vesicle, secretory vesicle membrane
CC {ECO:0000250}; Multi-pass membrane protein {ECO:0000250}.
CC Note=Associated with the insulin and glucagon secretory granules.
CC {ECO:0000269|PubMed:19095428}.
CC -!- TISSUE SPECIFICITY: Expressed in endocrine pancreatic islet alpha and
CC beta cells. Not detected in the brain. {ECO:0000269|PubMed:16984975,
CC ECO:0000269|PubMed:18250168, ECO:0000269|PubMed:19095428}.
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}.
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DR EMBL; AK050482; BAC34281.1; -; mRNA.
DR EMBL; AK050494; BAC34289.1; -; mRNA.
DR EMBL; BC117544; AAI17545.1; -; mRNA.
DR EMBL; BC118521; AAI18522.1; -; mRNA.
DR CCDS; CCDS27464.1; -.
DR RefSeq; NP_766404.1; NM_172816.3.
DR AlphaFoldDB; Q8BGG0; -.
DR SMR; Q8BGG0; -.
DR STRING; 10090.ENSMUSP00000035257; -.
DR iPTMnet; Q8BGG0; -.
DR PhosphoSitePlus; Q8BGG0; -.
DR PaxDb; Q8BGG0; -.
DR PRIDE; Q8BGG0; -.
DR Antibodypedia; 42965; 220 antibodies from 33 providers.
DR DNASU; 239436; -.
DR Ensembl; ENSMUST00000037240; ENSMUSP00000035257; ENSMUSG00000022315.
DR GeneID; 239436; -.
DR KEGG; mmu:239436; -.
DR UCSC; uc007vrf.1; mouse.
DR CTD; 169026; -.
DR MGI; MGI:2442682; Slc30a8.
DR VEuPathDB; HostDB:ENSMUSG00000022315; -.
DR eggNOG; KOG1482; Eukaryota.
DR GeneTree; ENSGT00940000160706; -.
DR HOGENOM; CLU_013430_0_1_1; -.
DR InParanoid; Q8BGG0; -.
DR OMA; RATKMYA; -.
DR OrthoDB; 820567at2759; -.
DR PhylomeDB; Q8BGG0; -.
DR TreeFam; TF313382; -.
DR Reactome; R-MMU-264876; Insulin processing.
DR Reactome; R-MMU-435368; Zinc efflux and compartmentalization by the SLC30 family.
DR BioGRID-ORCS; 239436; 2 hits in 72 CRISPR screens.
DR PRO; PR:Q8BGG0; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q8BGG0; protein.
DR Bgee; ENSMUSG00000022315; Expressed in islet of Langerhans and 3 other tissues.
DR Genevisible; Q8BGG0; MM.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:BHF-UCL.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0030141; C:secretory granule; ISO:MGI.
DR GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL.
DR GO; GO:0005385; F:zinc ion transmembrane transporter activity; ISO:MGI.
DR GO; GO:0006882; P:cellular zinc ion homeostasis; IMP:BHF-UCL.
DR GO; GO:0030073; P:insulin secretion; IMP:BHF-UCL.
DR GO; GO:0032024; P:positive regulation of insulin secretion; ISO:MGI.
DR GO; GO:0061088; P:regulation of sequestering of zinc ion; ISO:MGI.
DR GO; GO:0060627; P:regulation of vesicle-mediated transport; ISO:MGI.
DR GO; GO:0009749; P:response to glucose; IMP:BHF-UCL.
DR GO; GO:0034341; P:response to interferon-gamma; IEA:Ensembl.
DR GO; GO:0070555; P:response to interleukin-1; IEA:Ensembl.
DR GO; GO:0010043; P:response to zinc ion; IBA:GO_Central.
DR GO; GO:0032119; P:sequestering of zinc ion; ISO:MGI.
DR GO; GO:0071577; P:zinc ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006829; P:zinc ion transport; ISO:MGI.
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 2: Evidence at transcript level;
KW Cell membrane; Cytoplasmic vesicle; Ion transport; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport; Zinc;
KW Zinc transport.
FT CHAIN 1..367
FT /note="Zinc transporter 8"
FT /id="PRO_0000281741"
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..244
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 245..265
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 266..367
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOTIF 196..204
FT /note="HXXXXX[HY]NH"
FT /evidence="ECO:0000250"
SQ SEQUENCE 367 AA; 40223 MW; 9C9484A561DE58E4 CRC64;
MEFLERTYLV NDQATKMYAF PLDRELRQKP VNKDQCPGDR PEHPEAGGIY HCHNSAKATG
NRSSKQAHAK WRLCAASAIC FIFMVAEVVG GHVAGSLAIL TDAAHLLIDL TSFLLSLFSL
WLSSRPPSKR LTFGWYRAEI LGALLSVLCI WVVTGVLLYL ACERLLYPDY QIQAGIMITV
SGCAVAANIV LTMILHQRNF GYNHKDVQAN ASVRAAFVHA LGDVFQSISV LISALIIYFK
PDYKIADPVC TFIFSILVLA STVMILKDFS ILLMEGVPKG LSYNSVKEII LAVDGVISVH
SLHIWSLTVN QVILSVHVAT AASQDSQSVR TGIAQALSSF DLHSLTIQIE SAADQDPSCL
LCEDPQD
