S39A8_MOUSE
ID S39A8_MOUSE Reviewed; 462 AA.
AC Q91W10; Q8BTQ3; Q8BUD6; Q9D426; Q9D5V4;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=Metal cation symporter ZIP8 {ECO:0000305|PubMed:16638970};
DE AltName: Full=Solute carrier family 39 member 8 {ECO:0000312|MGI:MGI:1914797};
DE AltName: Full=Zrt- and Irt-like protein 8 {ECO:0000303|PubMed:15722412};
DE Short=ZIP-8 {ECO:0000303|PubMed:15722412};
DE Flags: Precursor;
GN Name=Slc39a8 {ECO:0000312|MGI:MGI:1914797};
GN Synonyms=Zip8 {ECO:0000303|PubMed:29337306};
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] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Mammary gland, Testis, and Thymus;
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] (ISOFORM 1).
RC STRAIN=129; TISSUE=Mammary tumor;
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 FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND MISCELLANEOUS.
RX PubMed=15722412; DOI=10.1073/pnas.0406085102;
RA Dalton T.P., He L., Wang B., Miller M.L., Jin L., Stringer K.F., Chang X.,
RA Baxter C.S., Nebert D.W.;
RT "Identification of mouse SLC39A8 as the transporter responsible for
RT cadmium-induced toxicity in the testis.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:3401-3406(2005).
RN [4]
RP FUNCTION, TRANSPORTER ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RX PubMed=16638970; DOI=10.1124/mol.106.024521;
RA He L., Girijashanker K., Dalton T.P., Reed J., Li H., Soleimani M.,
RA Nebert D.W.;
RT "ZIP8, member of the solute-carrier-39 (SLC39) metal-transporter family:
RT characterization of transporter properties.";
RL Mol. Pharmacol. 70:171-180(2006).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND MISCELLANEOUS.
RX PubMed=17108009; DOI=10.1152/ajpcell.00409.2006;
RA Wang B., Schneider S.N., Dragin N., Girijashanker K., Dalton T.P., He L.,
RA Miller M.L., Stringer K.F., Soleimani M., Richardson D.D., Nebert D.W.;
RT "Enhanced cadmium-induced testicular necrosis and renal proximal tubule
RT damage caused by gene-dose increase in a Slc39a8-transgenic mouse line.";
RL Am. J. Physiol. 292:C1523-C1535(2007).
RN [6]
RP FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE
RP SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=18037372; DOI=10.1016/j.bbrc.2007.11.067;
RA Liu Z., Li H., Soleimani M., Girijashanker K., Reed J.M., He L.,
RA Dalton T.P., Nebert D.W.;
RT "Cd2+ versus Zn2+ uptake by the ZIP8 HCO3--dependent symporter: kinetics,
RT electrogenicity and trafficking.";
RL Biochem. Biophys. Res. Commun. 365:814-820(2008).
RN [7]
RP FUNCTION, AND TRANSPORTER ACTIVITY.
RX PubMed=22898811; DOI=10.1074/jbc.m112.367284;
RA Wang C.Y., Jenkitkasemwong S., Duarte S., Sparkman B.K., Shawki A.,
RA Mackenzie B., Knutson M.D.;
RT "ZIP8 is an iron and zinc transporter whose cell-surface expression is up-
RT regulated by cellular iron loading.";
RL J. Biol. Chem. 287:34032-34043(2012).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22563477; DOI=10.1371/journal.pone.0036055;
RA Galvez-Peralta M., He L., Jorge-Nebert L.F., Wang B., Miller M.L.,
RA Eppert B.L., Afton S., Nebert D.W.;
RT "ZIP8 zinc transporter: indispensable role for both multiple-organ
RT organogenesis and hematopoiesis in utero.";
RL PLoS ONE 7:E36055-E36055(2012).
RN [9]
RP FUNCTION.
RX PubMed=23403290; DOI=10.1016/j.celrep.2013.01.009;
RA Liu M.J., Bao S., Galvez-Peralta M., Pyle C.J., Rudawsky A.C.,
RA Pavlovicz R.E., Killilea D.W., Li C., Nebert D.W., Wewers M.D.,
RA Knoell D.L.;
RT "ZIP8 regulates host defense through zinc-mediated inhibition of NF-
RT kappaB.";
RL Cell Rep. 3:386-400(2013).
RN [10]
RP FUNCTION, AND INDUCTION BY IL1B.
RX PubMed=24529376; DOI=10.1016/j.cell.2014.01.007;
RA Kim J.H., Jeon J., Shin M., Won Y., Lee M., Kwak J.S., Lee G., Rhee J.,
RA Ryu J.H., Chun C.H., Chun J.S.;
RT "Regulation of the catabolic cascade in osteoarthritis by the zinc-ZIP8-
RT MTF1 axis.";
RL Cell 156:730-743(2014).
RN [11]
RP FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP SUBCELLULAR LOCATION.
RX PubMed=27166256; DOI=10.18632/oncotarget.9205;
RA McDermott J.R., Geng X., Jiang L., Galvez-Peralta M., Chen F., Nebert D.W.,
RA Liu Z.;
RT "Zinc- and bicarbonate-dependent ZIP8 transporter mediates selenite
RT uptake.";
RL Oncotarget 7:35327-35340(2016).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=28481222; DOI=10.1172/jci90896;
RA Lin W., Vann D.R., Doulias P.T., Wang T., Landesberg G., Li X.,
RA Ricciotti E., Scalia R., He M., Hand N.J., Rader D.J.;
RT "Hepatic metal ion transporter ZIP8 regulates manganese homeostasis and
RT manganese-dependent enzyme activity.";
RL J. Clin. Invest. 127:2407-2417(2017).
RN [13]
RP FUNCTION, AND INDUCTION.
RX PubMed=30015240; DOI=10.1016/j.intimp.2018.06.018;
RA Cheng G., Chang F.J., You P.H., Lin J., Huang X.Y., Wu H.Y., Yan L.,
RA Deng J.Z., You H.J., Sun C.F.;
RT "ZIP8 induces monocyte adhesion to the aortas ex-vivo by regulating zinc
RT influx.";
RL Int. Immunopharmacol. 62:203-211(2018).
RN [14]
RP FUNCTION, TRANSPORTER ACTIVITY, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE,
RP AND MISCELLANEOUS.
RX PubMed=29337306; DOI=10.1172/jci96993;
RA Lin W., Li D., Cheng L., Li L., Liu F., Hand N.J., Epstein J.A.,
RA Rader D.J.;
RT "Zinc transporter Slc39a8 is essential for cardiac ventricular
RT compaction.";
RL J. Clin. Invest. 128:826-833(2018).
RN [15]
RP FUNCTION.
RX PubMed=29927450; DOI=10.1039/c8mt00079d;
RA Geng X., Liu L., Banes-Berceli A., Yang Z., Kang P., Shen J., Tsai K.J.,
RA Liu Z.;
RT "Role of ZIP8 in regulating cell morphology and NF-kappaB/Snail2
RT signaling.";
RL Metallomics 10:953-964(2018).
CC -!- FUNCTION: Electroneutral transporter of the plasma membrane mediating
CC the cellular uptake of zinc and manganese, two divalent metal cations
CC important for development, tissue homeostasis or immunity
CC (PubMed:16638970, PubMed:18037372, PubMed:22563477, PubMed:24529376,
CC PubMed:29337306). Functions as an energy-dependent symporter,
CC transporting through the membranes an electroneutral complex composed
CC of a divalent metal cation, a bicarbonate and a selenite anion or yet a
CC metal cation and two bicarbonate anions (PubMed:16638970,
CC PubMed:18037372, PubMed:22563477, PubMed:27166256). May also transport
CC iron, mercury and cobalt through membranes (PubMed:16638970,
CC PubMed:22898811, PubMed:24529376). Beside these endogenous cellular
CC substrates, also imports cadmium a non-essential metal which is
CC cytotoxic and carcinogenic (PubMed:15722412, PubMed:16638970,
CC PubMed:17108009, PubMed:18037372, PubMed:24529376). Through zinc
CC import, indirectly regulates the metal-dependent transcription factor
CC MTF1 and the expression of some metalloproteases involved in cartilage
CC catabolism and also probably heart development (PubMed:24529376,
CC PubMed:29337306). Also indirectly regulates the expression of proteins
CC involved in cell morphology and cytoskeleton organization
CC (PubMed:29927450). Indirectly controls innate immune function and
CC inflammatory response by regulating zinc cellular uptake which in turn
CC modulates the expression of genes specific of these processes
CC (PubMed:23403290). Protects, for instance, cells from injury and death
CC at the onset of inflammation (By similarity). By regulating zinc influx
CC into monocytes also directly modulates their adhesion to endothelial
CC cells and arteries (PubMed:30015240). At the apical membrane of
CC hepatocytes, reclaims manganese from the bile and regulates, through
CC the systemic levels of the nutrient, the activity of manganese-
CC dependent enzymes (PubMed:28481222). Also participates in manganese
CC reabsorption in the proximal tubule of the kidney (By similarity). By
CC mediating the extracellular uptake of manganese by cells of the blood-
CC brain barrier, may also play a role in the transport of the
CC micronutrient to the brain. Through manganese cellular uptake also
CC participates in mitochondrial proper function (By similarity). Finally,
CC also probably functions intracellularly, translocating zinc from
CC lysosome to cytosol to indirectly enhance the expression of specific
CC genes during TCR-mediated T cell activation (By similarity).
CC {ECO:0000250|UniProtKB:Q9C0K1, ECO:0000269|PubMed:15722412,
CC ECO:0000269|PubMed:16638970, ECO:0000269|PubMed:17108009,
CC ECO:0000269|PubMed:18037372, ECO:0000269|PubMed:22563477,
CC ECO:0000269|PubMed:22898811, ECO:0000269|PubMed:23403290,
CC ECO:0000269|PubMed:24529376, ECO:0000269|PubMed:27166256,
CC ECO:0000269|PubMed:28481222, ECO:0000269|PubMed:29337306,
CC ECO:0000269|PubMed:29927450, ECO:0000269|PubMed:30015240}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hydrogencarbonate(out) + selenite(out) + Zn(2+)(out) =
CC hydrogencarbonate(in) + selenite(in) + Zn(2+)(in);
CC Xref=Rhea:RHEA:62264, ChEBI:CHEBI:17544, ChEBI:CHEBI:18212,
CC ChEBI:CHEBI:29105; Evidence={ECO:0000269|PubMed:27166256};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62265;
CC Evidence={ECO:0000269|PubMed:27166256};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 hydrogencarbonate(out) + Zn(2+)(out) = 2
CC hydrogencarbonate(in) + Zn(2+)(in); Xref=Rhea:RHEA:62252,
CC ChEBI:CHEBI:17544, ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:18037372};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62253;
CC Evidence={ECO:0000269|PubMed:18037372, ECO:0000269|PubMed:29337306};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 hydrogencarbonate(out) + Mn(2+)(out) = 2
CC hydrogencarbonate(in) + Mn(2+)(in); Xref=Rhea:RHEA:62260,
CC ChEBI:CHEBI:17544, ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:16638970};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62261;
CC Evidence={ECO:0000269|PubMed:16638970};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cd(2+)(out) + 2 hydrogencarbonate(out) = Cd(2+)(in) + 2
CC hydrogencarbonate(in); Xref=Rhea:RHEA:62256, ChEBI:CHEBI:17544,
CC ChEBI:CHEBI:48775; Evidence={ECO:0000269|PubMed:16638970,
CC ECO:0000269|PubMed:18037372};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62257;
CC Evidence={ECO:0000269|PubMed:15722412, ECO:0000269|PubMed:16638970,
CC ECO:0000269|PubMed:18037372};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Fe(2+)(in) = Fe(2+)(out); Xref=Rhea:RHEA:28486,
CC ChEBI:CHEBI:29033; Evidence={ECO:0000269|PubMed:22898811};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:28488;
CC Evidence={ECO:0000269|PubMed:22898811};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hg(2+)(in) = Hg(2+)(out); Xref=Rhea:RHEA:32815,
CC ChEBI:CHEBI:16793; Evidence={ECO:0000269|PubMed:16638970};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:32817;
CC Evidence={ECO:0000269|PubMed:16638970};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Co(2+)(in) = Co(2+)(out); Xref=Rhea:RHEA:28578,
CC ChEBI:CHEBI:48828; Evidence={ECO:0000250|UniProtKB:Q5FVQ0};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:28580;
CC Evidence={ECO:0000250|UniProtKB:Q5FVQ0};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.84 uM for Cd(2+) {ECO:0000269|PubMed:15722412};
CC KM=0.62 uM for Cd(2+) {ECO:0000269|PubMed:16638970};
CC KM=0.48 uM for Cd(2+) (measured in xenopus oocytes)
CC {ECO:0000269|PubMed:18037372};
CC KM=0.26 uM for Zn(2+) (measured in xenopus oocytes)
CC {ECO:0000269|PubMed:18037372};
CC KM=2.2 uM for Mn(2+) {ECO:0000269|PubMed:16638970};
CC KM=5.9 uM for selenite/HSeO3(-) {ECO:0000269|PubMed:27166256};
CC Vmax=204 pmol/min/mg enzyme for the uptake of Cd(2+)
CC {ECO:0000269|PubMed:15722412};
CC Vmax=92 pmol/min/mg enzyme for the uptake of Cd(2+)
CC {ECO:0000269|PubMed:16638970};
CC Vmax=73.8 pmol/min/mg enzyme for the uptake of Mn(2+)
CC {ECO:0000269|PubMed:16638970};
CC pH dependence:
CC Optimum pH is 7.5. {ECO:0000269|PubMed:16638970};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q5FVQ0}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15722412,
CC ECO:0000269|PubMed:18037372, ECO:0000269|PubMed:27166256}; Multi-pass
CC membrane protein {ECO:0000255}. Apical cell membrane
CC {ECO:0000269|PubMed:16638970, ECO:0000269|PubMed:17108009,
CC ECO:0000269|PubMed:28481222}; Multi-pass membrane protein
CC {ECO:0000255}. Basolateral cell membrane
CC {ECO:0000250|UniProtKB:Q9C0K1}; Multi-pass membrane protein
CC {ECO:0000255}. Lysosome membrane {ECO:0000250|UniProtKB:Q9C0K1}; Multi-
CC pass membrane protein {ECO:0000255}. Note=Localizes to the lysosome of
CC activated T-cells. A large fraction of the protein is found
CC intracellularly in microvascular capillary endothelial cells that
CC constitute the blood-brain barrier. Localized and functional at both
CC apical and basolateral membranes of microvascular capillary endothelial
CC cells that constitute the blood-brain barrier.
CC {ECO:0000250|UniProtKB:Q9C0K1}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q91W10-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q91W10-2; Sequence=VSP_029886, VSP_029887;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:15722412}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the developing heart by cardiac
CC endothelial cells with a peak of expression at 12.5 dpc and a decline
CC to low levels in adult heart. {ECO:0000269|PubMed:29337306}.
CC -!- INDUCTION: Up-regulated in monocytes upon adhesion and recruitment to
CC arteries (PubMed:30015240). Up-regulated by the pro-inflammatory
CC cytokine interleukin-1 beta/IL1B (PubMed:24529376).
CC {ECO:0000269|PubMed:24529376, ECO:0000269|PubMed:30015240}.
CC -!- PTM: N-glycosylated (PubMed:16638970). N-glycosylation is not required
CC for proper iron and zinc transport (By similarity).
CC {ECO:0000250|UniProtKB:Q5FVQ0, ECO:0000269|PubMed:16638970}.
CC -!- DISRUPTION PHENOTYPE: The homozygous knockout of Slc39a8 is embryonic
CC lethal by 16.5 dpc. Hearts exhibit hypertrabeculation and non-
CC compaction phenotypes including excessive trabeculae and thin compact
CC myocardium. These phenotypes are evident at 12.5 dpc and prominent at
CC 14.5 dpc, and embryos that survive until 16.5 dpc display an even
CC stronger phenotype. Ventricular septal defects are also observed. Some
CC 14.5 dpc embryos exhibit body edema, suggesting that cardiac muscle
CC function is compromised. Hearts display increased cardiomyocyte
CC proliferation (PubMed:29337306). This is associated with decreased
CC expression of metalloproteases and impaired degradation of the
CC extracellular matrix leading to its aberrant accumulation in heart
CC (PubMed:29337306). In mice homozygous for an hypomorphic allele of the
CC gene, resulting in significant decreased expression of the protein,
CC hematopoiesis and the development of multiple organs are affected from
CC very early embryogenesis (PubMed:22563477). Conditional knockout of the
CC gene at the level of the whole organism decreases manganese levels in
CC tissues but has no effect on zinc and iron (PubMed:28481222).
CC Conditional liver-specific knockout of the gene results in decreased
CC systemic tissue manganese levels coupled to increased manganese in bile
CC but has no effect on zinc or iron levels (PubMed:28481222).
CC {ECO:0000269|PubMed:22563477, ECO:0000269|PubMed:28481222,
CC ECO:0000269|PubMed:29337306}.
CC -!- MISCELLANEOUS: The decreased expression of the channel in testis
CC vascular endothelial cells confers the resistance to cadmium-induced
CC testicular damage trait to some mice strains.
CC {ECO:0000269|PubMed:15722412, ECO:0000269|PubMed:17108009}.
CC -!- SIMILARITY: Belongs to the ZIP transporter (TC 2.A.5) family.
CC {ECO:0000305}.
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DR EMBL; AK014895; BAB29610.1; -; mRNA.
DR EMBL; AK016853; BAB30465.1; -; mRNA.
DR EMBL; AK085740; BAC39526.1; -; mRNA.
DR EMBL; AK089060; BAC40727.1; -; mRNA.
DR EMBL; BC006731; AAH06731.1; -; mRNA.
DR CCDS; CCDS17859.1; -. [Q91W10-1]
DR RefSeq; NP_001128621.1; NM_001135149.1. [Q91W10-1]
DR RefSeq; NP_001128622.1; NM_001135150.1. [Q91W10-1]
DR RefSeq; NP_080504.3; NM_026228.5. [Q91W10-1]
DR RefSeq; XP_006501997.1; XM_006501934.2. [Q91W10-1]
DR AlphaFoldDB; Q91W10; -.
DR SMR; Q91W10; -.
DR STRING; 10090.ENSMUSP00000080640; -.
DR TCDB; 2.A.5.4.8; the zinc (zn(2+))-iron (fe(2+)) permease (zip) family.
DR GlyGen; Q91W10; 3 sites.
DR PhosphoSitePlus; Q91W10; -.
DR EPD; Q91W10; -.
DR MaxQB; Q91W10; -.
DR PaxDb; Q91W10; -.
DR PeptideAtlas; Q91W10; -.
DR PRIDE; Q91W10; -.
DR ProteomicsDB; 256685; -. [Q91W10-1]
DR ProteomicsDB; 256686; -. [Q91W10-2]
DR Antibodypedia; 45037; 177 antibodies from 29 providers.
DR DNASU; 67547; -.
DR Ensembl; ENSMUST00000029810; ENSMUSP00000029810; ENSMUSG00000053897. [Q91W10-1]
DR Ensembl; ENSMUST00000081978; ENSMUSP00000080640; ENSMUSG00000053897. [Q91W10-1]
DR Ensembl; ENSMUST00000167390; ENSMUSP00000128245; ENSMUSG00000053897. [Q91W10-1]
DR Ensembl; ENSMUST00000180196; ENSMUSP00000136634; ENSMUSG00000053897. [Q91W10-1]
DR GeneID; 67547; -.
DR KEGG; mmu:67547; -.
DR UCSC; uc008rlz.3; mouse. [Q91W10-1]
DR UCSC; uc008rma.2; mouse. [Q91W10-2]
DR CTD; 64116; -.
DR MGI; MGI:1914797; Slc39a8.
DR VEuPathDB; HostDB:ENSMUSG00000053897; -.
DR eggNOG; KOG2693; Eukaryota.
DR GeneTree; ENSGT00940000158926; -.
DR HOGENOM; CLU_015114_13_0_1; -.
DR InParanoid; Q91W10; -.
DR OMA; WLRGQRI; -.
DR OrthoDB; 657777at2759; -.
DR PhylomeDB; Q91W10; -.
DR TreeFam; TF318470; -.
DR Reactome; R-MMU-442380; Zinc influx into cells by the SLC39 gene family.
DR BioGRID-ORCS; 67547; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Slc39a8; mouse.
DR PRO; PR:Q91W10; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q91W10; protein.
DR Bgee; ENSMUSG00000053897; Expressed in molar tooth and 248 other tissues.
DR Genevisible; Q91W10; MM.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0031090; C:organelle membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0015296; F:anion:cation symporter activity; IDA:UniProtKB.
DR GO; GO:0015106; F:bicarbonate transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015086; F:cadmium ion transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015087; F:cobalt ion transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0005381; F:iron ion transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0005384; F:manganese ion transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0097079; F:selenite:proton symporter activity; ISO:MGI.
DR GO; GO:0005385; F:zinc ion transmembrane transporter activity; IMP:UniProtKB.
DR GO; GO:0140412; F:zinc:bicarbonate symporter activity; IDA:UniProtKB.
DR GO; GO:0006525; P:arginine metabolic process; IMP:UniProtKB.
DR GO; GO:0015701; P:bicarbonate transport; IDA:UniProtKB.
DR GO; GO:0070574; P:cadmium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:1990079; P:cartilage homeostasis; IMP:UniProtKB.
DR GO; GO:0006876; P:cellular cadmium ion homeostasis; ISS:UniProtKB.
DR GO; GO:0030026; P:cellular manganese ion homeostasis; IMP:UniProtKB.
DR GO; GO:0006882; P:cellular zinc ion homeostasis; IDA:UniProtKB.
DR GO; GO:0006824; P:cobalt ion transport; ISS:UniProtKB.
DR GO; GO:0030198; P:extracellular matrix organization; IMP:UniProtKB.
DR GO; GO:0098711; P:iron ion import across plasma membrane; IMP:UniProtKB.
DR GO; GO:0061757; P:leukocyte adhesion to arterial endothelial cell; IMP:UniProtKB.
DR GO; GO:0071421; P:manganese ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:1990540; P:mitochondrial manganese ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0097080; P:plasma membrane selenite transport; IDA:UniProtKB.
DR GO; GO:0006487; P:protein N-linked glycosylation; IMP:UniProtKB.
DR GO; GO:0042391; P:regulation of membrane potential; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0071578; P:zinc ion import across plasma membrane; IDA:UniProtKB.
DR GO; GO:0071577; P:zinc ion transmembrane transport; IMP:UniProtKB.
DR GO; GO:0006829; P:zinc ion transport; ISS:UniProtKB.
DR InterPro; IPR003689; ZIP.
DR Pfam; PF02535; Zip; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Glycoprotein; Ion transport; Lysosome;
KW Membrane; Reference proteome; Signal; Transmembrane; Transmembrane helix;
KW Transport; Zinc; Zinc transport.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..462
FT /note="Metal cation symporter ZIP8"
FT /evidence="ECO:0000255"
FT /id="PRO_0000312708"
FT TOPO_DOM 20..132
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q5FVQ0"
FT TRANSMEM 133..153
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 154..160
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q5FVQ0"
FT TRANSMEM 161..181
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 182..191
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q5FVQ0"
FT TRANSMEM 192..212
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 213..367
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q5FVQ0"
FT TRANSMEM 368..388
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 389..390
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q5FVQ0"
FT TRANSMEM 391..411
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 412..431
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q5FVQ0"
FT TRANSMEM 432..452
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 453..462
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q5FVQ0"
FT MOTIF 345..350
FT /note="XEXPHE-motif"
FT /evidence="ECO:0000250|UniProtKB:Q9C0K1"
FT CARBOHYD 40
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 88
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 96
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 283..341
FT /note="DGKTEPSSCTCLKGPKLSEIGTIAWMITLCDALHNFIDGLAIGASCTLSLLQ
FT GLSTSIA -> VCPADCTFLLIFCVIFTIKVAGNAGSQYFKCSHVKPAHLHRRSHFTFF
FT LLSLWMLRPTK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_029886"
FT VAR_SEQ 342..462
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_029887"
FT CONFLICT 94
FT /note="S -> R (in Ref. 1; BAC40727)"
FT /evidence="ECO:0000305"
FT CONFLICT 98
FT /note="S -> C (in Ref. 1; BAC40727)"
FT /evidence="ECO:0000305"
FT CONFLICT 104
FT /note="I -> M (in Ref. 1; BAC40727)"
FT /evidence="ECO:0000305"
FT CONFLICT 108
FT /note="L -> V (in Ref. 1; BAC40727)"
FT /evidence="ECO:0000305"
FT CONFLICT 113
FT /note="C -> W (in Ref. 1; BAC40727)"
FT /evidence="ECO:0000305"
FT CONFLICT 116
FT /note="L -> V (in Ref. 1; BAC40727)"
FT /evidence="ECO:0000305"
FT CONFLICT 316
FT /note="H -> Y (in Ref. 1; BAB30465)"
FT /evidence="ECO:0000305"
FT CONFLICT 371
FT /note="N -> S (in Ref. 1; BAB29610)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 462 AA; 50082 MW; 52EBA157C295411C CRC64;
MAPGRAVAGL LLLAATSLGH PSEGPELAFS EDVLSVFGAN RSLSAAQLGR LLERLGAASQ
QGALDLGQLH FNQCLSAEDI FSLHGFSNVT QITSSNFSAI CPAILQQLNF HPCEDLRKHN
AKPSLSEVWG YGFLSVTIIN LASLLGLILT PLIKKSYFPK ILTYFVGLAI GTLFSNAIFQ
LIPEAFGFNP KIDNYVEKAV AVFGGFYMLF FVERTLKMLL KTYGQNDHTH FRNDDFGSKE
KTHQPKTLPL PAVNGVTCYA NPAVTEPNGH IHFDTVSVVS LQDGKTEPSS CTCLKGPKLS
EIGTIAWMIT LCDALHNFID GLAIGASCTL SLLQGLSTSI AILCEEFPHE LGDFVILLNA
GMSTRQALLF NFLSACSCYV GLAFGILVGN NFAPNIIFAL AGGMFLYISL ADMFPEMNDM
LREKVTGRQT DFTFFMIQNA GMLTGFTAIL LITLYAGDIE LQ
