ID COPT1_MOUSE Reviewed; 196 AA. AC Q8K211; Q3UAJ9; Q8BXJ1; DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2002, sequence version 1. DT 27-MAR-2024, entry version 142. DE RecName: Full=High affinity copper uptake protein 1 {ECO:0000305}; DE AltName: Full=Copper transporter 1 {ECO:0000303|PubMed:20699218}; DE Short=CTR1 {ECO:0000303|PubMed:20699218}; DE AltName: Full=Solute carrier family 31 member 1; DE Contains: DE RecName: Full=Truncated CTR1 form {ECO:0000305|PubMed:24167251}; GN Name=Slc31a1 {ECO:0000312|MGI:MGI:1333843}; GN Synonyms=Ctr1 {ECO:0000250|UniProtKB:O15431}; 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=Bone marrow, and Medulla oblongata; 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 GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=FVB/N; TISSUE=Mammary tumor, and Olfactory epithelium; 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 DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=11391004; DOI=10.1073/pnas.111057298; RA Kuo Y.M., Zhou B., Cosco D., Gitschier J.; RT "The copper transporter CTR1 provides an essential function in mammalian RT embryonic development."; RL Proc. Natl. Acad. Sci. U.S.A. 98:6836-6841(2001). RN [5] RP FUNCTION, TRANSPORTER ACTIVITY, AND DISRUPTION PHENOTYPE. RX PubMed=11391005; DOI=10.1073/pnas.111058698; RA Lee J., Prohaska J.R., Thiele D.J.; RT "Essential role for mammalian copper transporter Ctr1 in copper homeostasis RT and embryonic development."; RL Proc. Natl. Acad. Sci. U.S.A. 98:6842-6847(2001). RN [6] RP FUNCTION, AND TRANSPORTER ACTIVITY. RX PubMed=12177073; DOI=10.1074/jbc.m208002200; RA Lee J., Petris M.J., Thiele D.J.; RT "Characterization of mouse embryonic cells deficient in the ctr1 high RT affinity copper transporter. Identification of a Ctr1-independent copper RT transport system."; RL J. Biol. Chem. 277:40253-40259(2002). RN [7] RP FUNCTION. RX PubMed=12370430; DOI=10.1073/pnas.162491399; RA Ishida S., Lee J., Thiele D.J., Herskowitz I.; RT "Uptake of the anticancer drug cisplatin mediated by the copper transporter RT Ctr1 in yeast and mammals."; RL Proc. Natl. Acad. Sci. U.S.A. 99:14298-14302(2002). RN [8] RP FUNCTION, DISRUPTION PHENOTYPE, AND SUBCELLULAR LOCATION. RX PubMed=16950140; DOI=10.1016/j.cmet.2006.08.009; RA Nose Y., Kim B.E., Thiele D.J.; RT "Ctr1 drives intestinal copper absorption and is essential for growth, iron RT metabolism, and neonatal cardiac function."; RL Cell Metab. 4:235-244(2006). RN [9] RP FUNCTION, AND TRANSPORTER ACTIVITY. RX PubMed=16847145; DOI=10.1124/mol.106.022624; RA Holzer A.K., Manorek G.H., Howell S.B.; RT "Contribution of the major copper influx transporter CTR1 to the cellular RT accumulation of cisplatin, carboplatin, and oxaliplatin."; RL Mol. Pharmacol. 70:1390-1394(2006). RN [10] RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=19144690; DOI=10.1152/ajprenal.90545.2008; RA Pabla N., Murphy R.F., Liu K., Dong Z.; RT "The copper transporter Ctr1 contributes to cisplatin uptake by renal RT tubular cells during cisplatin nephrotoxicity."; RL Am. J. Physiol. 296:F505-F511(2009). RN [11] RP SUBCELLULAR LOCATION. RX PubMed=20699218; DOI=10.1074/jbc.m110.143826; RA Nose Y., Wood L.K., Kim B.E., Prohaska J.R., Fry R.S., Spears J.W., RA Thiele D.J.; RT "Ctr1 is an apical copper transporter in mammalian intestinal epithelial RT cells in vivo that is controlled at the level of protein stability."; RL J. Biol. Chem. 285:32385-32392(2010). RN [12] RP FUNCTION, AND TRANSPORTER ACTIVITY. RX PubMed=20569931; DOI=10.1016/j.jtemb.2010.01.009; RA Bertinato J., Cheung L., Hoque R., Plouffe L.J.; RT "Ctr1 transports silver into mammalian cells."; RL J. Trace Elem. Med. Biol. 24:178-184(2010). RN [13] RP FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH RP SLC31A2, PROTEOLYTIC CLEAVAGE, AND SITES. RX PubMed=24167251; DOI=10.1073/pnas.1311749110; RA Oehrvik H., Nose Y., Wood L.K., Kim B.E., Gleber S.C., Ralle M., RA Thiele D.J.; RT "Ctr2 regulates biogenesis of a cleaved form of mammalian Ctr1 metal RT transporter lacking the copper- and cisplatin-binding ecto-domain."; RL Proc. Natl. Acad. Sci. U.S.A. 110:E4279-E4288(2013). RN [14] RP PROTEOLYTIC CLEAVAGE. RX PubMed=27143361; DOI=10.1074/jbc.m116.731281; RA Oehrvik H., Logeman B., Turk B., Reinheckel T., Thiele D.J.; RT "Cathepsin Protease Controls Copper and Cisplatin Accumulation via Cleavage RT of the Ctr1 Metal-binding Ectodomain."; RL J. Biol. Chem. 291:13905-13916(2016). RN [15] RP FUNCTION, AND MUTAGENESIS OF CYS-195. RX PubMed=35027734; DOI=10.1038/s41556-021-00822-7; RA Das A., Ash D., Fouda A.Y., Sudhahar V., Kim Y.M., Hou Y., Hudson F.Z., RA Stansfield B.K., Caldwell R.B., McMenamin M., Littlejohn R., Su H., RA Regan M.R., Merrill B.J., Poole L.B., Kaplan J.H., Fukai T., RA Ushio-Fukai M.; RT "Cysteine oxidation of copper transporter CTR1 drives VEGFR2 signalling and RT angiogenesis."; RL Nat. Cell Biol. 24:35-50(2022). RN [16] RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE. RX PubMed=31002737; DOI=10.1371/journal.pone.0215522; RA Ghaffari R., Di Bona K.R., Riley C.L., Richburg J.H.; RT "Copper transporter 1 (CTR1) expression by mouse testicular germ cells, but RT not Sertoli cells, is essential for functional spermatogenesis."; RL PLoS ONE 14:e0215522-e0215522(2019). CC -!- FUNCTION: [High affinity copper uptake protein 1]: Uniporter that CC mediates the transport of copper(1+) from the extracellular space to CC the cytoplasm, across the plasma membrane (PubMed:11391005, CC PubMed:12177073, PubMed:16847145, PubMed:24167251). Then, delivers CC directly copper(1+) to specific chaperone such as ATOX1, via a CC copper(1+)- mediated transient interaction between the C-terminal CC domain and a copper(1+) chaperone, thus controlling intracellular CC copper(1+) levels (By similarity). May function in copper(1+) import CC from the apical membrane thus may drive intestinal copper absorption CC (PubMed:16950140). The copper(1+) transport mechanism is sodium- CC independent, saturable and of high-affinity (By similarity). Also CC mediates the uptake of silver(1+) (PubMed:20569931). May function in CC the influx of the platinum-containing chemotherapeutic agents CC (PubMed:16847145, PubMed:19144690, PubMed:12370430). The platinum- CC containing chemotherapeutic agents uptake is saturable (By similarity). CC Also participates in the first step of copper(2+) acquisition by cells CC through a direct transfer of copper(2+) from copper(2+) carriers in CC blood, such as ALB to the N-terminal domain of SLC31A1, leading to CC copper(2+) reduction and probably followed by copper(1+) stabilization CC (By similarity). In addition, functions as a redox sensor to promote CC angiogenesis in endothelial cells, in a copper(1+) transport CC independent manner, by transmitting the VEGF-induced ROS signal through CC a sulfenylation at Cys-195 leading to a subsequent disulfide bond CC formation between SLC31A1 and KDR (PubMed:35027734). The SLC31A1-KDR CC complex is then co-internalized to early endosomes, driving a sustained CC VEGFR2 signaling (By similarity). {ECO:0000250|UniProtKB:O15431, CC ECO:0000250|UniProtKB:Q9JK41, ECO:0000269|PubMed:11391005, CC ECO:0000269|PubMed:12177073, ECO:0000269|PubMed:12370430, CC ECO:0000269|PubMed:16847145, ECO:0000269|PubMed:16950140, CC ECO:0000269|PubMed:19144690, ECO:0000269|PubMed:20569931, CC ECO:0000269|PubMed:24167251, ECO:0000269|PubMed:35027734}. CC -!- FUNCTION: [Truncated CTR1 form]: Mobilizes copper(1+) out of the CC endosomal compartment, making copper(1+) available for export out of CC the cells. {ECO:0000269|PubMed:24167251}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Cu(+)(out) = Cu(+)(in); Xref=Rhea:RHEA:75211, CC ChEBI:CHEBI:49552; Evidence={ECO:0000269|PubMed:11391005, CC ECO:0000269|PubMed:12177073, ECO:0000269|PubMed:16847145, CC ECO:0000269|PubMed:24167251}; CC -!- CATALYTIC ACTIVITY: CC Reaction=Ag(+)(out) = Ag(+)(in); Xref=Rhea:RHEA:75207, CC ChEBI:CHEBI:49468; Evidence={ECO:0000269|PubMed:20569931}; CC -!- SUBUNIT: Homotrimer; is stabilized by cisplatin via interactions CC between cisplatin and the Met motif, and could be crucial for the CC copper(2+) reduction process and copper(1+) stabilization. Heterotrimer CC between SLC31A1, CCS and SOD1; this heterotrimer is copper(1+)-mediated CC and its maintenance is regulated through SOD1 activation. Interacts CC with KDR; this interaction is induced upon VEGFA stimulation leading to CC SLC31A1 and KDR subsequent co-internalization to early endosomes, CC thereby activating KDR downstream signaling in endothelial cells. CC Interacts (via C-terminal domain) with ATOX1 (via dimer form); this CC interaction improves ATOX1 stability and controls intracellular CC copper(1+) levels (By similarity). Interacts with SLC31A2; this CC interaction stabilizes SLC31A2 and protects its from ubiquitination and CC degradation (PubMed:24167251). Interacts (via C-terminal domain) with CC CCS; this interaction is copper(1+)-mediated (By similarity). CC {ECO:0000250|UniProtKB:O15431, ECO:0000269|PubMed:24167251}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:31002737}; CC Multi-pass membrane protein {ECO:0000255}. Early endosome membrane CC {ECO:0000250|UniProtKB:O15431}; Multi-pass membrane protein CC {ECO:0000255}. Recycling endosome membrane CC {ECO:0000269|PubMed:24167251}; Multi-pass membrane protein CC {ECO:0000255}. Apical cell membrane {ECO:0000269|PubMed:16950140, CC ECO:0000269|PubMed:20699218, ECO:0000269|PubMed:31002737}; Multi-pass CC membrane protein {ECO:0000255}. Late endosome membrane CC {ECO:0000269|PubMed:24167251}; Multi-pass membrane protein CC {ECO:0000255}. Basolateral cell membrane {ECO:0000269|PubMed:19144690}; CC Multi-pass membrane protein {ECO:0000255}. Note=The localization is CC controlled by the intra and extra-cellular copper concentration. Under CC conditions of elevated extracellular copper concentrations, it is CC rapidly internalized by endocytosis from the plasma membrane by a CC clathrin- and dynamin-mediated process and degradated in order to CC prevent intracellular copper accumulation and to reduce the transport CC of the copper across the membrane. The internalized SLC31A1 is then CC localized in early endosomes, and, upon a low extracellular copper CC concentrations, it is transported back to the plasma membrane in a CC RAB11A-dependent recycling pathway (By similarity). Localizes to the CC apical membrane in intestinal epithelial cells (PubMed:20699218, CC PubMed:16950140). Mainly localized on the basolateral side of renal CC tubular cells (PubMed:19144690). Localizes to the neuronal cell body CC plasma membranes (By similarity). {ECO:0000250|UniProtKB:O15431, CC ECO:0000250|UniProtKB:Q9JK41, ECO:0000269|PubMed:16950140, CC ECO:0000269|PubMed:19144690, ECO:0000269|PubMed:20699218}. CC -!- TISSUE SPECIFICITY: Expressed in the tubules in the inner cortex and CC inner medulla of the kidney, the villi of the small intestine, the CC choroid plexus of the brain, the stroma of the ovary, the seminiferous CC tubules of the testes, and the sclera of the eye (PubMed:11391004). CC Expressed in intestinal epithelial cells, with an increase expression CC from the crypt to the tip of the villus (PubMed:16950140). Mainly CC expressed in both proximal and distal tubular cells in kidneys CC (PubMed:19144690). {ECO:0000269|PubMed:11391004, CC ECO:0000269|PubMed:16950140, ECO:0000269|PubMed:19144690}. CC -!- DEVELOPMENTAL STAGE: At E14.5, expressed in the forebrain, liver, nasal CC regions, and somites (PubMed:11391004). By E16.5, expression is CC ubiquitous, with high expression in the liver, intestine, somites, and CC choroid plexus (PubMed:11391004). By E18.5 expression is more CC restricted to the choroid plexus, kidney, intestine, and tooth buds CC (PubMed:11391004). Expressed principally by Sertoli cells (SCs) and the CC spermatocytes with the highest expression in the primary pachytene CC spermatocytes within seminiferous tubule stages II-VI CC (PubMed:31002737). {ECO:0000269|PubMed:11391004, CC ECO:0000269|PubMed:31002737}. CC -!- DOMAIN: The C-terminal domain mediates copper(1+) binding and is CC involved in the copper(1+)-dependent-ATOX1 interaction. The C-terminal CC domain appears to act to limit transport through the pore by regulating CC the rate of exit of copper ions at the intracellular side. The N- CC terminal domain can collect copper(2+) from copper(2+) carriers in CC blood. The N-terminal domain, in the trimeric arrangement, tunes its CC reactivity with copper, promoting copper(2+) reduction and copper(1+) CC stabilization. The bis-His motif directly coordinate to copper(2+). CC {ECO:0000250|UniProtKB:O15431}. CC -!- PTM: O-Glycosylation at Thr-34 protects from proteolytic cleavage in CC the N-terminal extracellular domain. {ECO:0000250|UniProtKB:O15431}. CC -!- PTM: Proteolytic cleavage, leading to a truncated form, is facilitated CC by SLC31A2 (PubMed:24167251) and initiated preferentially by CTSL and CC to a minor extend by CTSB in endolysosomal compartments CC (PubMed:27143361, PubMed:24167251). A post-CTSL/cathepsin L processing CC occurs to yield to the fully truncated form (PubMed:27143361). CC {ECO:0000269|PubMed:24167251, ECO:0000269|PubMed:27143361}. CC -!- PTM: Sulfenylated at Cys-195 after stimulation with VEGFA, which CC induces SLC31A1-KDR disulfide bond formation and their co- CC internalization to early endosomes, driving to a sustained VEGFR2 CC signaling. {ECO:0000250|UniProtKB:O15431}. CC -!- DISRUPTION PHENOTYPE: Homozygous mice lacking Slc31a1 exhibit profound CC growth and developmental defects and die in utero in mid-gestation CC (PubMed:11391005, PubMed:11391004). Homozygous embryos exhibit a CC dramatic reduction in size at E7.5, which is exacerbated during the CC progression of in utero development through day E10.5 CC (PubMed:11391005). Although the fundamental mouse embryonic structures CC are conserved at E7.5, homozygous embryos show that many structures CC including the neural ectoderm and mesoderm cell layers are poorly CC developed (PubMed:11391005). Conditional knockout mice lacking Slc31a1 CC in intestinal epithelial cells, are born at the expected frequency and CC exhibit normal growth rate and mass for the first 6-8 days postpartum, CC poor growth and lethality occurred beginning approximately 10 days CC after birth (PubMed:16950140). Conditional knockout mice lacking CC Slc31a1 in germ cells (GCs) seem normal in appearance CC (PubMed:31002737). Conditional knockout mice lacking Slc31a1 in Sertoli CC cells (SCs) exhibit normal fertility and display similar appearance as CC their wild-type littermates; no obvious behavioral deficit are noted CC (PubMed:31002737). {ECO:0000269|PubMed:11391004, CC ECO:0000269|PubMed:11391005, ECO:0000269|PubMed:16950140, CC ECO:0000269|PubMed:31002737}. CC -!- SIMILARITY: Belongs to the copper transporter (Ctr) (TC 1.A.56) family. CC SLC31A subfamily. {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; AK046835; BAC32891.1; -; mRNA. DR EMBL; AK151337; BAE30315.1; -; mRNA. DR EMBL; AL732548; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC034674; AAH34674.1; -; mRNA. DR EMBL; BC058227; AAH58227.1; -; mRNA. DR CCDS; CCDS18237.1; -. DR RefSeq; NP_780299.2; NM_175090.4. DR RefSeq; XP_006537774.1; XM_006537711.2. DR AlphaFoldDB; Q8K211; -. DR BMRB; Q8K211; -. DR SMR; Q8K211; -. DR BioGRID; 203308; 2. DR STRING; 10090.ENSMUSP00000081574; -. DR GlyCosmos; Q8K211; 2 sites, No reported glycans. DR GlyGen; Q8K211; 2 sites. DR PhosphoSitePlus; Q8K211; -. DR jPOST; Q8K211; -. DR MaxQB; Q8K211; -. DR PaxDb; 10090-ENSMUSP00000081574; -. DR ProteomicsDB; 283352; -. DR Pumba; Q8K211; -. DR Antibodypedia; 3008; 291 antibodies from 31 providers. DR DNASU; 20529; -. DR Ensembl; ENSMUST00000084526.12; ENSMUSP00000081574.6; ENSMUSG00000066150.13. DR GeneID; 20529; -. DR KEGG; mmu:20529; -. DR UCSC; uc008ten.2; mouse. DR AGR; MGI:1333843; -. DR CTD; 1317; -. DR MGI; MGI:1333843; Slc31a1. DR VEuPathDB; HostDB:ENSMUSG00000066150; -. DR eggNOG; KOG3386; Eukaryota. DR GeneTree; ENSGT00940000155147; -. DR HOGENOM; CLU_079690_2_0_1; -. DR InParanoid; Q8K211; -. DR OMA; AKTVACH; -. DR OrthoDB; 3399710at2759; -. DR PhylomeDB; Q8K211; -. DR TreeFam; TF315142; -. DR Reactome; R-MMU-425410; Metal ion SLC transporters. DR BioGRID-ORCS; 20529; 11 hits in 77 CRISPR screens. DR ChiTaRS; Slc31a1; mouse. DR PRO; PR:Q8K211; -. DR Proteomes; UP000000589; Chromosome 4. DR RNAct; Q8K211; Protein. DR Bgee; ENSMUSG00000066150; Expressed in ileal epithelium and 274 other cell types or tissues. DR ExpressionAtlas; Q8K211; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB. DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB. DR GO; GO:0031901; C:early endosome membrane; ISS:UniProtKB. DR GO; GO:0014704; C:intercalated disc; IDA:MGI. DR GO; GO:0005770; C:late endosome; IDA:MGI. DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0043025; C:neuronal cell body; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0055037; C:recycling endosome; IDA:MGI. DR GO; GO:0055038; C:recycling endosome membrane; ISS:UniProtKB. DR GO; GO:0005507; F:copper ion binding; ISS:UniProtKB. DR GO; GO:0005375; F:copper ion transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0015080; F:silver ion transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0042910; F:xenobiotic transmembrane transporter activity; IMP:UniProtKB. DR GO; GO:0001525; P:angiogenesis; IMP:UniProtKB. DR GO; GO:0072719; P:cellular response to cisplatin; ISO:MGI. DR GO; GO:0015677; P:copper ion import; IDA:UniProtKB. DR GO; GO:0098705; P:copper ion import across plasma membrane; ISO:MGI. DR GO; GO:0006825; P:copper ion transport; IDA:UniProtKB. DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI. DR GO; GO:0006878; P:intracellular copper ion homeostasis; IGI:MGI. DR GO; GO:0015679; P:plasma membrane copper ion transport; ISS:UniProtKB. DR GO; GO:0051259; P:protein complex oligomerization; ISS:UniProtKB. DR GO; GO:1902601; P:silver ion transmembrane transport; IDA:UniProtKB. DR GO; GO:0055085; P:transmembrane transport; ISO:MGI. DR GO; GO:0036324; P:vascular endothelial growth factor receptor-2 signaling pathway; ISS:UniProtKB. DR GO; GO:0042908; P:xenobiotic transport; IMP:UniProtKB. DR InterPro; IPR007274; Cop_transporter. DR PANTHER; PTHR12483:SF22; HIGH AFFINITY COPPER UPTAKE PROTEIN 1; 1. DR PANTHER; PTHR12483; SOLUTE CARRIER FAMILY 31 COPPER TRANSPORTERS; 1. DR Pfam; PF04145; Ctr; 1. DR Genevisible; Q8K211; MM. PE 1: Evidence at protein level; KW Cell membrane; Copper; Copper transport; Disulfide bond; Endosome; KW Glycoprotein; Ion transport; Membrane; Oxidation; Phosphoprotein; KW Reference proteome; Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..196 FT /note="High affinity copper uptake protein 1" FT /id="PRO_0000195041" FT CHAIN 49..196 FT /note="Truncated CTR1 form" FT /evidence="ECO:0000269|PubMed:24167251" FT /id="PRO_0000458009" FT TOPO_DOM 1..74 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 75..95 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 96..138 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 139..159 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 160..162 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 163..183 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 184..196 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 19..41 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 13..14 FT /note="Bis-His motif" FT /evidence="ECO:0000250|UniProtKB:O15431" FT COMPBIAS 27..41 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 48..49 FT /note="Cleavage" FT /evidence="ECO:0000269|PubMed:24167251" FT MOD_RES 120 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:O15431" FT MOD_RES 195 FT /note="Cysteine sulfenic acid (-SOH)" FT /evidence="ECO:0000250|UniProtKB:O15431" FT CARBOHYD 23 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000250|UniProtKB:O15431" FT CARBOHYD 34 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000250|UniProtKB:O15431" FT DISULFID 195 FT /note="Interchain (with C-1208 in KDR)" FT /evidence="ECO:0000250|UniProtKB:O15431" FT MUTAGEN 195 FT /note="C->A: Inhibition of VEGF-induced VEGFR2 signaling. FT Inhibition of endothelial cell migration." FT /evidence="ECO:0000269|PubMed:35027734" FT CONFLICT 18 FT /note="N -> Y (in Ref. 1; BAC32891)" FT /evidence="ECO:0000305" SQ SEQUENCE 196 AA; 21961 MW; A4EDDD2A9E51AF10 CRC64; MNHMGMNHME MHHHMGMNHT DDNITMPPHH HPTTSASHSH GGGDSMMMMP MTFYFDFKNV NLLFSGLVIN TPGEMAGAFV AVFLLAMFYE GLKIAREGLL RKSQVSIRYN SMPVPGPNGT ILMETHKTVG QQMLSFPHLL QTVLHIIQVV ISYFLMLIFM TYNGYLCIAV AAGAGTGYFL FSWKKAVVVD ITEHCH //