ID S39A4_MOUSE Reviewed; 660 AA. AC Q78IQ7; Q8CHL4; DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 1. DT 02-SEP-2026, entry version 160. DE RecName: Full=Zinc transporter ZIP4; DE AltName: Full=Activated in W/Wv mouse stomach 2; DE Short=mAWMS2; DE AltName: Full=Solute carrier family 39 member 4; DE AltName: Full=Zrt- and Irt-like protein 4; DE Short=ZIP-4; DE Flags: Precursor; GN Name=Slc39a4; Synonyms=Zip4; 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 [MRNA] (ISOFORMS 1 AND 2), FUNCTION, TRANSPORTER RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, INDUCTION, AND RP SUBCELLULAR LOCATION. RX PubMed=12801924; DOI=10.1074/jbc.m305000200; RA Dufner-Beattie J., Wang F., Kuo Y.-M., Gitschier J., Eide D., Andrews G.K.; RT "The acrodermatitis enteropathica gene ZIP4 encodes a tissue-specific, RT zinc-regulated zinc transporter in mice."; RL J. Biol. Chem. 278:33474-33481(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC STRAIN=C57BL/6J; TISSUE=Stomach; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC STRAIN=FVB/N-3; 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 [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 431-660. RA Daigo Y., Takayama I., Fujino M.A.; RT "Isolation and characterization of novel human and mouse genes, which are RT expressed in the digestive tract."; RL Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases. RN [5] RP SUBCELLULAR LOCATION, FUNCTION, AND TRANSPORTER ACTIVITY. RX PubMed=14612438; DOI=10.1074/jbc.m310799200; RA Kim B.-E., Wang F., Dufner-Beattie J., Andrews G.K., Eide D.J., RA Petris M.J.; RT "Zn2+-stimulated endocytosis of the mZIP4 zinc transporter regulates its RT location at the plasma membrane."; RL J. Biol. Chem. 279:4523-4530(2004). RN [6] RP FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR RP LOCATION, GLYCOSYLATION, AND MUTAGENESIS OF PRO-200; GLY-340; LEU-382; RP GLY-384; GLY-539 AND GLY-643. RX PubMed=14709598; DOI=10.1093/hmg/ddh049; RA Wang F., Kim B.E., Dufner-Beattie J., Petris M.J., Andrews G., Eide D.J.; RT "Acrodermatitis enteropathica mutations affect transport activity, RT localization and zinc-responsive trafficking of the mouse ZIP4 zinc RT transporter."; RL Hum. Mol. Genet. 13:563-571(2004). RN [7] RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY. RX PubMed=17483098; DOI=10.1093/hmg/ddm088; RA Dufner-Beattie J., Weaver B.P., Geiser J., Bilgen M., Larson M., Xu W., RA Andrews G.K.; RT "The mouse acrodermatitis enteropathica gene Slc39a4 (Zip4) is essential RT for early development and heterozygosity causes hypersensitivity to zinc RT deficiency."; RL Hum. Mol. Genet. 16:1391-1399(2007). RN [8] RP SUBCELLULAR LOCATION. RX PubMed=18020946; DOI=10.1515/bc.2007.149; RA Weaver B.P., Dufner-Beattie J., Kambe T., Andrews G.K.; RT "Novel zinc-responsive post-transcriptional mechanisms reciprocally RT regulate expression of the mouse Slc39a4 and Slc39a5 zinc transporters RT (Zip4 and Zip5)."; RL Biol. Chem. 388:1301-1312(2007). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=17242355; DOI=10.1073/pnas.0609836104; RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; RT "Large-scale phosphorylation analysis of mouse liver."; RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). RN [10] RP SUBCELLULAR LOCATION, AND PROTEOLYTIC CLEAVAGE. RX PubMed=18936158; DOI=10.1128/mcb.00963-08; RA Kambe T., Andrews G.K.; RT "Novel proteolytic processing of the ectodomain of the zinc transporter RT ZIP4 (SLC39A4) during zinc deficiency is inhibited by acrodermatitis RT enteropathica mutations."; RL Mol. Cell. Biol. 29:129-139(2009). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Lung; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [12] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=22737083; DOI=10.1371/journal.pgen.1002766; RA Geiser J., Venken K.J., De Lisle R.C., Andrews G.K.; RT "A mouse model of acrodermatitis enteropathica: loss of intestine zinc RT transporter ZIP4 (Slc39a4) disrupts the stem cell niche and intestine RT integrity."; RL PLoS Genet. 8:e1002766-e1002766(2012). RN [13] RP SUBUNIT, AND SUBCELLULAR LOCATION. RX PubMed=30593504; DOI=10.1074/jbc.ra118.005203; RA Chun H., Korolnek T., Lee C.J., Coyne H.J. III, Winge D.R., Kim B.E., RA Petris M.J.; RT "An extracellular histidine-containing motif in the zinc transporter ZIP4 RT plays a role in zinc sensing and zinc-induced endocytosis in mammalian RT cells."; RL J. Biol. Chem. 294:2815-2826(2019). CC -!- FUNCTION: Selective transporter that mediates the uptake of Zn(2+) CC (PubMed:12801924, PubMed:14612438, PubMed:14709598). Plays an essential CC role for dietary zinc uptake from small intestine (PubMed:12801924). CC The Zn(2+) uniporter activity is regulated by zinc availability (By CC similarity). Also exhibits polyspecific binding and transport of CC Cu(2+), Cd(2+) and possibly Ni(2+) but at higher concentrations CC (PubMed:12801924). {ECO:0000250|UniProtKB:Q6P5W5, CC ECO:0000269|PubMed:12801924, ECO:0000269|PubMed:14612438, CC ECO:0000269|PubMed:14709598}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Zn(2+)(in) = Zn(2+)(out); Xref=Rhea:RHEA:29351, CC ChEBI:CHEBI:29105; Evidence={ECO:0000269|PubMed:12801924, CC ECO:0000269|PubMed:14612438, ECO:0000269|PubMed:14709598}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=1.7 uM for Zn(2+) {ECO:0000269|PubMed:14709598}; CC KM=1.6 uM for Zn(2+) {ECO:0000269|PubMed:12801924}; CC Vmax=8.9 pmol/min/mg enzyme with Zn(2+) as substrate CC {ECO:0000269|PubMed:14709598}; CC Vmax=13.1 pmol/min/mg enzyme with Zn(2+) as substrate CC {ECO:0000269|PubMed:12801924}; CC -!- SUBUNIT: Homodimer (PubMed:30593504). Homodimerization is mediated by CC the transmembrane domain (By similarity). CC {ECO:0000250|UniProtKB:Q6P5W5, ECO:0000269|PubMed:30593504}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14612438, CC ECO:0000269|PubMed:14709598, ECO:0000269|PubMed:18020946, CC ECO:0000269|PubMed:30593504}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:A0A0H3LM39}. Recycling endosome membrane CC {ECO:0000269|PubMed:14612438}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:A0A0H3LM39}. Apical cell membrane CC {ECO:0000269|PubMed:12801924, ECO:0000269|PubMed:18020946, CC ECO:0000269|PubMed:18936158}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:A0A0H3LM39}. Note=Colocalized with TFRC in the CC recycling endosomes. Cycles between endosomal compartments and the CC plasma membrane in response to Zn(2+) availability. Zn(2+) deficiency CC promotes accumulation of SLC39A4 on the surface membrane, whereas high CC extracellular Zn(2+) levels induce internalization of SLC39A4, but also CC trigger drastic removal of cellular SLC39A4 via proteasomal and CC lysosomal degradation pathways (PubMed:14612438, PubMed:18020946, CC PubMed:30593504). Translocates to the apical membrane during zinc CC deficiency (PubMed:12801924, PubMed:18020946). Expressed on the apical CC surface of the intestinal wall (PubMed:18936158). CC {ECO:0000269|PubMed:12801924, ECO:0000269|PubMed:14612438, CC ECO:0000269|PubMed:18020946, ECO:0000269|PubMed:18936158, CC ECO:0000269|PubMed:30593504}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=Long; CC IsoId=Q78IQ7-1; Sequence=Displayed; CC Name=2; Synonyms=Short; CC IsoId=Q78IQ7-2; Sequence=VSP_015913, VSP_015914; CC -!- TISSUE SPECIFICITY: Highly expressed in the small intestine and CC embryonic visceral yolk sac. Weakly expressed in the stomach and liver. CC {ECO:0000269|PubMed:12801924, ECO:0000269|PubMed:17483098}. CC -!- INDUCTION: Up-regulated under conditions of dietary zinc deficiency. CC Down-regulated under conditions of dietary zinc excess. CC {ECO:0000269|PubMed:12801924}. CC -!- DOMAIN: The two metal binding sites M1 and M2 that are halfway through CC the membrane form a binuclear metal center. M1 is essential to Zn(2+) CC transport, while the other, M2 appears to have an auxiliary role CC presumably by acting as an additional transport site that can modulate CC the properties of the primary transport site. The binuclear metal CC center plays a key role in Zn(2+) sensing. CC {ECO:0000250|UniProtKB:Q6P5W5}. CC -!- PTM: The extracellular N-terminal ectodomain is cleaved when cells are CC Zn(2+) deficient, N-terminally cleaved SLC39A4 is then internalized CC faster. {ECO:0000269|PubMed:18936158, ECO:0000269|PubMed:30593504}. CC -!- PTM: Under excess Zn(2+) conditions, SLC39A4 on the cell surface is CC rapidly endocytosed, ubiquitinated, and degraded. CC {ECO:0000305|PubMed:18020946}. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:14709598}. CC -!- DISRUPTION PHENOTYPE: Knockout mice die in utero during early CC development. Mice heterozygous for a null allele exhibit developmental CC defects similar to the teratology of zinc deficiency (PubMed:17483098). CC Slc39a4-intestine knockout mice reveal that total zinc is dramatically CC and rapidly decreased in these organs whereas iron, manganese, and CC copper slowly accumulated to high levels in the liver as the disease CC progressed. Defect in zinc uptake are followed by a switch from CC anabolic to catabolic metabolism in the mouse leading to dramatic CC weight loss, dyshomeostasis of several essential metals and ultimately CC lethality in the absence of excess dietary zinc (PubMed:22737083). CC {ECO:0000269|PubMed:17483098, ECO:0000269|PubMed:22737083}. CC -!- SIMILARITY: Belongs to the ZIP transporter (TC 2.A.5) family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK146977; BAE27581.1; -; mRNA. DR EMBL; AK147107; BAE27679.1; -; mRNA. DR EMBL; BC023498; AAH23498.1; -; mRNA. DR EMBL; AB052762; BAC53795.1; -; mRNA. DR CCDS; CCDS27578.1; -. [Q78IQ7-1] DR RefSeq; NP_082340.1; NM_028064.3. [Q78IQ7-1] DR AlphaFoldDB; Q78IQ7; -. DR SMR; Q78IQ7; -. DR FunCoup; Q78IQ7; 71. DR STRING; 10090.ENSMUSP00000155442; -. DR GlyCosmos; Q78IQ7; 4 sites, No reported glycans. DR GlyGen; Q78IQ7; 4 sites, 1 N-linked glycan (1 site). DR iPTMnet; Q78IQ7; -. DR PhosphoSitePlus; Q78IQ7; -. DR SwissPalm; Q78IQ7; -. DR jPOST; Q78IQ7; -. DR PaxDb; 10090-ENSMUSP00000155442; -. DR ProteomicsDB; 260784; -. [Q78IQ7-1] DR ProteomicsDB; 260785; -. [Q78IQ7-2] DR Antibodypedia; 28508; 223 antibodies from 35 providers. DR DNASU; 72027; -. DR Ensembl; ENSMUST00000230977.2; ENSMUSP00000155442.2; ENSMUSG00000063354.8. [Q78IQ7-1] DR GeneID; 72027; -. DR KEGG; mmu:72027; -. DR UCSC; uc007wlb.1; mouse. [Q78IQ7-1] DR AGR; MGI:1919277; -. DR CTD; 55630; -. DR MGI; MGI:1919277; Slc39a4. DR VEuPathDB; HostDB:ENSMUSG00000063354; -. DR eggNOG; KOG2693; Eukaryota. DR GeneTree; ENSGT00940000160042; -. DR HOGENOM; CLU_015114_12_0_1; -. DR InParanoid; Q78IQ7; -. DR OMA; PPKQPHE; -. DR OrthoDB; 200954at2759; -. DR PhylomeDB; Q78IQ7; -. DR Reactome; R-MMU-442380; Zinc influx into cells by the SLC39 gene family. DR BioGRID-ORCS; 72027; 2 hits in 78 CRISPR screens. DR PRO; PR:Q78IQ7; -. DR Proteomes; UP000000589; Chromosome 15. DR RNAct; Q78IQ7; protein. DR Bgee; ENSMUSG00000063354; Expressed in small intestine Peyer's patch and 95 other cell types or tissues. DR ExpressionAtlas; Q78IQ7; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; IDA:MGI. DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:MGI. DR GO; GO:0005768; C:endosome; IDA:MGI. DR GO; GO:0005886; C:plasma membrane; IDA:MGI. DR GO; GO:0055038; C:recycling endosome membrane; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; ISO:GO_Central. DR GO; GO:0140410; F:monoatomic cation:bicarbonate symporter activity; IBA:GO_Central. DR GO; GO:0008270; F:zinc ion binding; ISO:GO_Central. DR GO; GO:0106219; F:zinc ion sensor activity; ISS:UniProtKB. DR GO; GO:0140486; F:zinc ion sequestering activity; ISO:GO_Central. DR GO; GO:0005385; F:zinc ion transmembrane transporter activity; IDA:MGI. DR GO; GO:0034224; P:cellular response to zinc ion starvation; IDA:MGI. DR GO; GO:0030003; P:intracellular monoatomic cation homeostasis; IBA:GO_Central. DR GO; GO:0006882; P:intracellular zinc ion homeostasis; IDA:MGI. DR GO; GO:0071578; P:zinc ion import across plasma membrane; IBA:GO_Central. DR GO; GO:0071577; P:zinc ion transmembrane transport; ISO:GO_Central. DR GO; GO:0006829; P:zinc ion transport; IDA:MGI. DR InterPro; IPR003689; ZIP. DR InterPro; IPR049406; ZIP4_12_EF-hand. DR InterPro; IPR041137; ZIP4_N. DR InterPro; IPR050799; ZIP_Transporter. DR PANTHER; PTHR12191; SOLUTE CARRIER FAMILY 39; 1. DR PANTHER; PTHR12191:SF21; ZINC TRANSPORTER ZIP4; 1. DR Pfam; PF21116; EF-hand_Zip; 1. DR Pfam; PF02535; Zip; 1. DR Pfam; PF18292; ZIP4_domain; 1. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Disulfide bond; Endosome; KW Glycoprotein; Ion transport; Membrane; Metal-binding; Reference proteome; KW Signal; Transmembrane; Transmembrane helix; Transport; Ubl conjugation; KW Zinc; Zinc transport. FT SIGNAL 1..22 FT /evidence="ECO:0000255" FT CHAIN 23..660 FT /note="Zinc transporter ZIP4" FT /id="PRO_0000042621" FT TOPO_DOM 23..337 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 338..358 FT /note="Helical; Name=1" FT /evidence="ECO:0000250|UniProtKB:A0A0H3LM39" FT TOPO_DOM 359..376 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 377..397 FT /note="Helical; Name=2" FT /evidence="ECO:0000250|UniProtKB:A0A0H3LM39" FT TOPO_DOM 398..420 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 421..441 FT /note="Helical; Name=3" FT /evidence="ECO:0000250|UniProtKB:A0A0H3LM39" FT TOPO_DOM 442..511 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 512..531 FT /note="Helical; Name=4" FT /evidence="ECO:0000250|UniProtKB:A0A0H3LM39" FT TOPO_DOM 532..539 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 540..566 FT /note="Helical; Name=5" FT /evidence="ECO:0000250|UniProtKB:A0A0H3LM39" FT TOPO_DOM 567..571 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 572..592 FT /note="Helical; Name=6" FT /evidence="ECO:0000250|UniProtKB:A0A0H3LM39" FT TOPO_DOM 593..599 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 600..620 FT /note="Helical; Name=7" FT /evidence="ECO:0000250|UniProtKB:A0A0H3LM39" FT TOPO_DOM 621..630 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 631..651 FT /note="Helical; Name=8" FT /evidence="ECO:0000250|UniProtKB:A0A0H3LM39" FT TOPO_DOM 652..660 FT /note="Extracellular" FT /evidence="ECO:0000255" FT REGION 233..273 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 465..467 FT /note="Essential for SLC39A4 endocytosis" FT /evidence="ECO:0000250|UniProtKB:Q6P5W5" FT COMPBIAS 236..267 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 520 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /note="M1 metal binding site" FT /evidence="ECO:0000250|UniProtKB:A0A0H3LM39" FT BINDING 521 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /note="M2 metal binding site" FT /evidence="ECO:0000250|UniProtKB:A0A0H3LM39" FT BINDING 524 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /note="M1 metal binding site" FT /evidence="ECO:0000250|UniProtKB:A0A0H3LM39" FT BINDING 524 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /note="M2 metal binding site" FT /evidence="ECO:0000250|UniProtKB:A0A0H3LM39" FT BINDING 549 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /note="M1 metal binding site" FT /evidence="ECO:0000250|UniProtKB:A0A0H3LM39" FT BINDING 550 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /note="M2 metal binding site" FT /evidence="ECO:0000250|UniProtKB:A0A0H3LM39" FT BINDING 553 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /note="M1 metal binding site" FT /evidence="ECO:0000250|UniProtKB:A0A0H3LM39" FT SITE 524 FT /note="Essential role in Zn(2+) sensing" FT /evidence="ECO:0000250|UniProtKB:Q6P5W5" FT CARBOHYD 192 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 219 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 272 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000250|UniProtKB:Q6P5W5" FT CARBOHYD 657 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 56..61 FT /evidence="ECO:0000250|UniProtKB:L5KLU7" FT DISULFID 64..110 FT /evidence="ECO:0000250|UniProtKB:L5KLU7" FT DISULFID 160..195 FT /evidence="ECO:0000250|UniProtKB:L5KLU7" FT DISULFID 280..319 FT /evidence="ECO:0000250|UniProtKB:L5KLU7" FT VAR_SEQ 1..47 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12801924" FT /id="VSP_015913" FT VAR_SEQ 48..63 FT /note="NTLVARVHCTDGPCEK -> MPGRLSLAQILSVCPQ (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12801924" FT /id="VSP_015914" FT MUTAGEN 200 FT /note="P->L: Reduces zinc uptake activity. Does not affect FT KM. Accumulated to high levels in the plasma membrane. No FT longer zinc responsive." FT /evidence="ECO:0000269|PubMed:14709598" FT MUTAGEN 340 FT /note="G->D: Reduces zinc uptake activity. Reduces plasma FT membrane localization." FT /evidence="ECO:0000269|PubMed:14709598" FT MUTAGEN 382 FT /note="L->P: Reduces zinc uptake activity. Reduces plasma FT membrane localization." FT /evidence="ECO:0000269|PubMed:14709598" FT MUTAGEN 384 FT /note="G->R: Reduces zinc uptake activity. Reduces plasma FT membrane localization." FT /evidence="ECO:0000269|PubMed:14709598" FT MUTAGEN 539 FT /note="G->R: Reduces zinc uptake activity. Accumulated to FT high levels in the plasma membrane. Does not affect KM. No FT longer zinc responsive." FT /evidence="ECO:0000269|PubMed:14709598" FT MUTAGEN 643 FT /note="G->R: Loss of zinc uptake activity. Abolishes plasma FT membrane localization." FT /evidence="ECO:0000269|PubMed:14709598" FT CONFLICT 431..435 FT /note="FFLFE -> RPRVR (in Ref. 4)" FT /evidence="ECO:0000305" SQ SEQUENCE 660 AA; 71063 MW; CA7236080C81B7BE CRC64; MLPKSVTQGL VLALLVGTVA VARPRNLLSL LALGQGALDR LELDGLLNTL VARVHCTDGP CEKCLSVENV LALGKPDKPQ PAPESVLESR HIIYLSAAAA LYLNNPEKTC KDIQAGLLAS HVDDYLATLE SPEAMTLGLS QLLQKIEAHA ASQPTGEKTC VDLPQLLEEA EAAGVSKSAG LVLTALLDHV INGSCFQGLP SPQYFVDFVF RLHSSDPPNI TLHELENLMH HLGVGGEDHS DHDDHGDHAD HSHPDRKASH QDSELHTPHN SNSSVWDTLC LSAKDIMAVY GLSEEAGVSP QAWAQLTPAL VQQQLSGACS PYPTIRIQDQ LSQTERYLYG SLATLLICLC AVFGLLLLTC AKCSTATHYI MQTFLSLAVG ALTGDALLHL IPKVLGLHTH GGEGHTHEEE VGVGGQATWR LLAVLGGFYI FFLFESFFNL LLPRDQDSEK DGPCSHGGHS HGISLQLAPS NLRQSKQTHE SSRSDLVAEE TPELLNPETR RLRAELRLLP YLITLGDAVH NFADGLAVGA AFSSSWKTGL ATSLAVFCHE LPHELGDFAA LLHAGLSVKR ALLLNLASAL TAFAGLYVAL AVGVGEEGEA WILAVATGLF LYVALCDMLP AMMNVRDQRP WLLFLLHNVG LLGGWTVLLL LSLYEDNITF //