ID COPT1_HUMAN Reviewed; 190 AA. AC O15431; A8K8Z6; Q53GR5; Q5T1M4; DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 08-NOV-2023, entry version 183. DE RecName: Full=High affinity copper uptake protein 1 {ECO:0000305}; DE AltName: Full=Copper transporter 1 {ECO:0000303|PubMed:9207117}; DE Short=hCTR1 {ECO:0000303|PubMed:9207117}; DE AltName: Full=Solute carrier family 31 member 1; DE Contains: DE RecName: Full=Truncated CTR1 form {ECO:0000303|PubMed:24167251}; GN Name=SLC31A1 {ECO:0000312|HGNC:HGNC:11016}; GN Synonyms=COPT1, CTR1 {ECO:0000303|PubMed:9207117}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9207117; DOI=10.1073/pnas.94.14.7481; RA Zhou B., Gitschier J.; RT "hCTR1: a human gene for copper uptake identified by complementation in RT yeast."; RL Proc. Natl. Acad. Sci. U.S.A. 94:7481-7486(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Liver; RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Skeletal muscle; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung; 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 [8] RP SUBCELLULAR LOCATION. RX PubMed=12023893; DOI=10.1042/bj20011803; RA Klomp A.E., Tops B.B., Van Denberg I.E., Berger R., Klomp L.W.; RT "Biochemical characterization and subcellular localization of human copper RT transporter 1 (hCTR1)."; RL Biochem. J. 364:497-505(2002). RN [9] RP FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND RP SUBCELLULAR LOCATION. RX PubMed=11734551; DOI=10.1074/jbc.m104728200; RA Lee J., Pena M.M., Nose Y., Thiele D.J.; RT "Biochemical characterization of the human copper transporter Ctr1."; RL J. Biol. Chem. 277:4380-4387(2002). RN [10] RP SUBCELLULAR LOCATION, SUBUNIT, MUTAGENESIS OF 7-MET--MET-12 AND RP 40-MET--MET-45, AND MOTIF. RX PubMed=15326162; DOI=10.1074/jbc.m407777200; RA Guo Y., Smith K., Petris M.J.; RT "Cisplatin stabilizes a multimeric complex of the human Ctr1 copper RT transporter: requirement for the extracellular methionine-rich clusters."; RL J. Biol. Chem. 279:46393-46399(2004). RN [11] RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, TRANSPORTER ACTIVITY, AND RP MUTAGENESIS OF HIS-139; MET-150; MET-154; TYR-156; CYS-161; RP 179-LYS--HIS-190; 185-ILE--HIS-190 AND CYS-189. RX PubMed=16135512; DOI=10.1074/jbc.m508822200; RA Eisses J.F., Kaplan J.H.; RT "The mechanism of copper uptake mediated by human CTR1: a mutational RT analysis."; RL J. Biol. Chem. 280:37159-37168(2005). RN [12] RP FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, AND GLYCOSYLATION AT RP ASN-15 AND THR-27. RX PubMed=17525160; DOI=10.1074/jbc.m701806200; RA Maryon E.B., Molloy S.A., Kaplan J.H.; RT "O-linked glycosylation at threonine 27 protects the copper transporter RT hCTR1 from proteolytic cleavage in mammalian cells."; RL J. Biol. Chem. 282:20376-20387(2007). RN [13] RP FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, AND ACTIVITY RP REGULATION. RX PubMed=19740744; DOI=10.1074/jbc.m109.000166; RA Molloy S.A., Kaplan J.H.; RT "Copper-dependent recycling of hCTR1, the human high affinity copper RT transporter."; RL J. Biol. Chem. 284:29704-29713(2009). RN [14] RP FUNCTION, TRANSPORTER ACTIVITY, AND SUBCELLULAR LOCATION. RX PubMed=20451502; DOI=10.1016/j.bcp.2010.04.030; RA Larson C.A., Adams P.L., Jandial D.D., Blair B.G., Safaei R., Howell S.B.; RT "The role of the N-terminus of mammalian copper transporter 1 in the RT cellular accumulation of cisplatin."; RL Biochem. Pharmacol. 80:448-454(2010). RN [15] RP FUNCTION, TRANSPORTER ACTIVITY, AND MUTAGENESIS OF MET-150 AND MET-154. 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 [16] RP FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR RP LOCATION, MUTAGENESIS OF HIS-139; MET-150; MET-154; 180-ALA--HIS-190; RP 184-ASP--HIS-190 AND 188-HIS--HIS-190, AND DOMAIN. RX PubMed=23658018; DOI=10.1074/jbc.m112.442426; RA Maryon E.B., Molloy S.A., Ivy K., Yu H., Kaplan J.H.; RT "Rate and regulation of copper transport by human copper transporter 1 RT (hCTR1)."; RL J. Biol. Chem. 288:18035-18046(2013). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-114, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [18] RP PROTEOLYTIC CLEAVAGE, AND SITE. 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 [19] RP INTERACTION WITH ATOX1, AND DOMAIN. RX PubMed=24837030; DOI=10.1021/jp412589b; RA Levy A.R., Yarmiayev V., Moskovitz Y., Ruthstein S.; RT "Probing the structural flexibility of the human copper metallochaperone RT Atox1 dimer and its interaction with the CTR1 c-terminal domain."; RL J. Phys. Chem. B 118:5832-5842(2014). RN [20] RP INTERACTION WITH SLC31A2, AND SUBCELLULAR LOCATION. RX PubMed=26205368; DOI=10.1039/c5mt00131e; RA Tsai C.Y., Liebig J.K., Tsigelny I.F., Howell S.B.; RT "The copper transporter 1 (CTR1) is required to maintain the stability of RT copper transporter 2 (CTR2)."; RL Metallomics 7:1477-1487(2015). RN [21] RP FUNCTION, DOMAIN, MUTAGENESIS OF 188-HIS--HIS-190 AND CYS-189, AND RP INTERACTION WITH ATOX1. RX PubMed=26745413; DOI=10.1016/j.bpj.2015.11.016; RA Kahra D., Kovermann M., Wittung-Stafshede P.; RT "The C-Terminus of Human Copper Importer Ctr1 Acts as a Binding Site and RT Transfers Copper to Atox1."; RL Biophys. J. 110:95-102(2016). RN [22] 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 [23] RP SUBCELLULAR LOCATION. RX PubMed=26945057; DOI=10.1242/jcs.173351; RA Clifford R.J., Maryon E.B., Kaplan J.H.; RT "Dynamic internalization and recycling of a metal ion transporter: Cu RT homeostasis and CTR1, the human Cu(+) uptake system."; RL J. Cell Sci. 129:1711-1721(2016). RN [24] RP MUTAGENESIS OF HIS-3; HIS-5 AND HIS-6, DOMAIN, AND MOTIF. RA Shenberger Y., Marciano O., Gottlieb H.E., Ruthstein S.; RT "Insights into the N-terminal Cu(II) and Cu(I) binding sites of the human RT copper transporter CTR1."; RL J. Coord. Chem. 71:1985-2002(2018). RN [25] RP FUNCTION, MOTIF, AND DOMAIN. RX PubMed=30489586; DOI=10.1039/c8mt00274f; RA Stefaniak E., Plonka D., Drew S.C., Bossak-Ahmad K., Haas K.L., RA Pushie M.J., Faller P., Wezynfeld N.E., Bal W.; RT "The N-terminal 14-mer model peptide of human Ctr1 can collect Cu(ii) from RT albumin. Implications for copper uptake by Ctr1."; RL Metallomics 10:1723-1727(2018). RN [26] RP INTERACTION WITH CCS, AND SUBUNIT. RX PubMed=31292775; DOI=10.1007/s10534-019-00206-3; RA Skopp A., Boyd S.D., Ullrich M.S., Liu L., Winkler D.D.; RT "Copper-zinc superoxide dismutase (Sod1) activation terminates interaction RT between its copper chaperone (Ccs) and the cytosolic metal-binding domain RT of the copper importer Ctr1."; RL BioMetals 32:695-705(2019). RN [27] RP SUBUNIT, AND DOMAIN. RX PubMed=32914794; DOI=10.1039/d0cc04693k; RA Galler T., Lebrun V., Raibaut L., Faller P., Wezynfeld N.E.; RT "How trimerization of CTR1 N-terminal model peptides tunes Cu-binding and RT redox-chemistry."; RL Chem. Commun. (Camb.) 56:12194-12197(2020). RN [28] RP FUNCTION. RX PubMed=33294387; DOI=10.1016/j.toxrep.2020.11.005; RA Kwok M.L., Li Z.P., Law T.Y.S., Chan K.M.; RT "Promotion of cadmium uptake and cadmium-induced toxicity by the copper RT transporter CTR1 in HepG2 and ZFL cells."; RL Toxicol. Rep. 7:1564-1570(2020). RN [29] RP FUNCTION, OXIDATION AT CYS-189, MUTAGENESIS OF MET-154 AND CYS-189, RP INTERACTION WITH KDR, AND DISULFIDE BOND. 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 [30] RP DOMAIN. RX PubMed=35601835; DOI=10.3389/fmolb.2022.897621; RA Nardella M.I., Fortino M., Barbanente A., Natile G., Pietropaolo A., RA Arnesano F.; RT "Multinuclear Metal-Binding Ability of the N-Terminal Region of Human RT Copper Transporter Ctr1: Dependence Upon pH and Metal Oxidation State."; RL Front. Mol. Biosci. 9:897621-897621(2022). RN [31] RP STRUCTURE BY ELECTRON MICROSCOPY (6 ANGSTROMS) IN A NATIVE PHOSPHOLIPID RP BILAYER, AND SUBUNIT. RX PubMed=16501047; DOI=10.1073/pnas.0509929103; RA Aller S.G., Unger V.M.; RT "Projection structure of the human copper transporter CTR1 at 6-A RT resolution reveals a compact trimer with a novel channel-like RT architecture."; RL Proc. Natl. Acad. Sci. U.S.A. 103:3627-3632(2006). RN [32] {ECO:0007744|PDB:2LS2, ECO:0007744|PDB:2LS3, ECO:0007744|PDB:2LS4} RP STRUCTURE BY NMR OF 132-157. RX PubMed=22615137; DOI=10.1002/psc.2415; RA Yang L., Huang Z., Li F.; RT "Structural insights into the transmembrane domains of human copper RT transporter 1."; RL J. Pept. Sci. 18:449-455(2012). RN [33] RP VARIANT NSCT HIS-95, CHARACTERIZATION OF VARIANT NSCT HIS-95, INVOLVEMENT RP IN NSCT, AND SUBCELLULAR LOCATION. RX PubMed=35913762; DOI=10.1093/hmg/ddac156; RA Batzios S., Tal G., DiStasio A.T., Peng Y., Charalambous C., Nicolaides P., RA Kamsteeg E.J., Korman S.H., Mandel H., Steinbach P.J., Yi L., Fair S.R., RA Hester M.E., Drousiotou A., Kaler S.G.; RT "Newly identified disorder of copper metabolism caused by variants in CTR1, RT a high-affinity copper transporter."; RL Hum. Mol. Genet. 31:4121-4130(2022). RN [34] RP VARIANT NSCT PRO-79, AND INVOLVEMENT IN NSCT. RX PubMed=36562171; DOI=10.1111/cge.14289; RA Dame C., Horn D., Schomburg L., Gruenhagen J., Chillon T.S., Tietze A., RA Vogt A., Buehrer C.; RT "Fatal congenital copper transport defect caused by a homozygous likely RT pathogenic variant of SLC31A1."; RL Clin. Genet. 103:585-589(2023). 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:11734551, CC PubMed:16135512, PubMed:17525160, PubMed:19740744, PubMed:20451502, CC PubMed:20569931, PubMed:23658018) and delivers directly copper(1+) to CC specific chaperone such as ATOX1, via a copper(1+)- mediated transient CC interaction between the C-terminal domain and a copper(1+) chaperone, CC thus controlling intracellular copper(1+) levels (PubMed:26745413, CC PubMed:11734551, PubMed:17525160, PubMed:20451502, PubMed:19740744, CC PubMed:16135512, PubMed:23658018, PubMed:20569931). May function in CC copper(1+) import from the apical membrane thus may drive intestinal CC copper absorption (By similarity). The copper(1+) transport mechanism CC is sodium-independent, saturable and of high-affinity CC (PubMed:11734551). Also mediates the uptake of silver(1+) CC (PubMed:20569931). May function in the influx of the platinum- CC containing chemotherapeutic agents (PubMed:20451502, PubMed:20569931). CC The platinum-containing chemotherapeutic agents uptake is saturable (By CC similarity). In vitro, mediates the transport of cadmium(2+) into cells CC (PubMed:33294387). Also participates in the first step of copper(2+) CC acquisition by cells through a direct transfer of copper(2+) from CC copper(2+) carriers in blood, such as ALB to the N-terminal domain of CC SLC31A1, leading to copper(2+) reduction and probably followed by CC copper(1+) stabilization (PubMed:30489586). In addition, functions as a CC redox sensor to promote angiogenesis in endothelial cells, in a CC copper(1+) transport independent manner, by transmitting the VEGF- CC induced ROS signal through a sulfenylation at Cys-189 leadin g to a CC subsequent disulfide bond formation between SLC31A1 and KDR CC (PubMed:35027734). The SLC31A1-KDR complex is then co-internalized to CC early endosomes, driving a sustained VEGFR2 signaling CC (PubMed:35027734). {ECO:0000250|UniProtKB:Q8K211, CC ECO:0000250|UniProtKB:Q9JK41, ECO:0000269|PubMed:11734551, CC ECO:0000269|PubMed:16135512, ECO:0000269|PubMed:17525160, CC ECO:0000269|PubMed:19740744, ECO:0000269|PubMed:20451502, CC ECO:0000269|PubMed:20569931, ECO:0000269|PubMed:23658018, CC ECO:0000269|PubMed:26745413, ECO:0000269|PubMed:30489586, CC ECO:0000269|PubMed:33294387, 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:0000250|UniProtKB:Q8K211}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Ag(+)(out) = Ag(+)(in); Xref=Rhea:RHEA:75207, CC ChEBI:CHEBI:49468; Evidence={ECO:0000269|PubMed:20569931}; CC -!- CATALYTIC ACTIVITY: CC Reaction=Cu(+)(out) = Cu(+)(in); Xref=Rhea:RHEA:75211, CC ChEBI:CHEBI:49552; Evidence={ECO:0000269|PubMed:11734551, CC ECO:0000269|PubMed:16135512, ECO:0000269|PubMed:17525160, CC ECO:0000269|PubMed:19740744, ECO:0000269|PubMed:20451502, CC ECO:0000269|PubMed:20569931, ECO:0000269|PubMed:23658018}; CC -!- ACTIVITY REGULATION: Copper(1+) transport is stimulated by CC extracellular acidic pH and high potassium ions concentrations CC (PubMed:11734551). Copper(1+) import is regulated by a copper(1+)- CC dependent recycling of SLC31A1 (PubMed:19740744). CC {ECO:0000269|PubMed:11734551, ECO:0000269|PubMed:19740744}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=1.71 uM for copper(1+) {ECO:0000269|PubMed:11734551}; CC KM=8.9 uM for copper(1+) {ECO:0000269|PubMed:16135512}; CC KM=9.2 uM for copper(1+) (in Sf9 cells expressing SLC31A1) CC {ECO:0000269|PubMed:16135512}; CC KM=4.4 uM for copper(1+) {ECO:0000269|PubMed:23658018}; CC Vmax=6.76 pmol/min/mg protein toward copper(1+) CC {ECO:0000269|PubMed:11734551}; CC Vmax=75.7 pmol/min/mg protein toward copper(1+) CC {ECO:0000269|PubMed:16135512}; CC Vmax=59.5 pmol/min/mg protein toward copper(1+) (in Sf9 cells CC expressing SLC31A1) {ECO:0000269|PubMed:16135512}; CC -!- SUBUNIT: Homotrimer (PubMed:11734551, PubMed:15326162, CC PubMed:16501047); is stabilized by cisplatin (PubMed:15326162) via CC interactions between cisplatin and the methionine-rich CC clusters(PubMed:15326162), and could be crucial for the copper(2+) CC reduction process and copper(1+) stabilization (PubMed:32914794, CC PubMed:11734551, PubMed:16501047, PubMed:15326162). Heterotrimer CC between SLC31A1, CCS and SOD1; this heterotrimer is copper(1+)-mediated CC and its maintenance is regulated through SOD1 activation CC (PubMed:31292775). Interacts with KDR; this interaction is induced upon CC VEGFA stimulation leading to SLC31A1 and KDR subsequent co- CC internalization to early endosomes, thereby activating KDR downstream CC signaling in endothelial cells (PubMed:35027734). Interacts (via C- CC terminal domain) with ATOX1 (via dimer form); this interaction improves CC ATOX1 stability and controls intracellular copper(1+) levels CC (PubMed:24837030, PubMed:26745413). Interacts with SLC31A2; this CC interaction stabilizes SLC31A2 and protects its from ubiquitination and CC degradation (PubMed:26205368). Interacts (via C-terminal domain) with CC CCS; this interaction is copper(1+)-mediated (PubMed:31292775). CC {ECO:0000269|PubMed:11734551, ECO:0000269|PubMed:15326162, CC ECO:0000269|PubMed:16501047, ECO:0000269|PubMed:24837030, CC ECO:0000269|PubMed:26205368, ECO:0000269|PubMed:26745413, CC ECO:0000269|PubMed:31292775, ECO:0000269|PubMed:32914794, CC ECO:0000269|PubMed:35027734}. CC -!- INTERACTION: CC O15431; O15431: SLC31A1; NbExp=6; IntAct=EBI-15571835, EBI-15571835; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11734551, CC ECO:0000269|PubMed:12023893, ECO:0000269|PubMed:15326162, CC ECO:0000269|PubMed:17525160, ECO:0000269|PubMed:20451502, CC ECO:0000269|PubMed:26205368, ECO:0000269|PubMed:26945057, CC ECO:0000269|PubMed:35913762}; Multi-pass membrane protein CC {ECO:0000255}. Early endosome membrane {ECO:0000269|PubMed:26945057}; CC Multi-pass membrane protein {ECO:0000255}. Recycling endosome membrane CC {ECO:0000269|PubMed:26945057}; Multi-pass membrane protein CC {ECO:0000255}. Apical cell membrane {ECO:0000250|UniProtKB:Q8K211}; CC Multi-pass membrane protein {ECO:0000255}. Late endosome membrane CC {ECO:0000250|UniProtKB:Q8K211}; Multi-pass membrane protein CC {ECO:0000255}. Basolateral cell membrane CC {ECO:0000250|UniProtKB:Q8K211}; Multi-pass membrane protein CC {ECO:0000255}. Note=The localization is controlled by the intra and CC extra-cellular copper concentration (PubMed:19740744, PubMed:15326162, CC PubMed:26205368, PubMed:23658018, PubMed:26945057). Under conditions of CC elevated extracellular copper concentrations, it is rapidly CC internalized by endocytosis from the plasma membrane by a clathrin- and CC dynamin-mediated process and degradated in order to prevent CC intracellular copper accumulation and to reduce the transport of the CC copper across the membrane (PubMed:19740744, PubMed:15326162, CC PubMed:26205368, PubMed:23658018, PubMed:26945057). The internalized CC SLC31A1 is then localized in early endosomes, and, upon a low CC extracellular copper concentrations, it is transported back to the CC plasma membrane in a RAB11A-dependent recycling pathway CC (PubMed:26945057). Localizes to the apical membrane in intestinal CC epithelial cells (By similarity). Mainly localized on the basolateral CC side of renal tubular cells (By similarity). Localizes to the neuronal CC cell body plasma membranes (By similarity). CC {ECO:0000250|UniProtKB:Q8K211, ECO:0000250|UniProtKB:Q9JK41, CC ECO:0000269|PubMed:15326162, ECO:0000269|PubMed:19740744, CC ECO:0000269|PubMed:23658018, ECO:0000269|PubMed:26205368, CC ECO:0000269|PubMed:26945057}. CC -!- DOMAIN: The C-terminal domain mediates copper(1+) binding CC (PubMed:26745413) and is involved in the copper(1+)-dependent-ATOX1 CC interaction (PubMed:26745413, PubMed:24837030). The C-terminal domain CC appears to act to limit transport through the pore by regulating the CC rate of exit of copper ions at the intracellular side CC (PubMed:23658018). The N-terminal domain can collect copper(2+) from CC copper(2+) carriers in blood (PubMed:30489586). The N-terminal domain, CC in the trimeric arrangement, tunes its reactivity with copper, CC promoting copper(2+) reduction and copper(1+) stabilization thanks to CC the presence of histidine (His) and methionine (Met) motifs CC (PubMed:32914794, Ref.24). The bis-His motif directly coordinate to CC copper(2+), whereas the Mets motif is involved in copper(1+) binding CC (Ref.24). The ligand switching between the bis-His motif and the Mets CC motif is regulated by pH (PubMed:35601835). CC {ECO:0000269|PubMed:23658018, ECO:0000269|PubMed:24837030, CC ECO:0000269|PubMed:26745413, ECO:0000269|PubMed:30489586, CC ECO:0000269|PubMed:32914794, ECO:0000269|PubMed:35601835, CC ECO:0000269|Ref.24}. CC -!- PTM: O-Glycosylation at Thr-27 protects from proteolytic cleavage in CC the N-terminal extracellular domain. {ECO:0000269|PubMed:17525160}. 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). In vitro, is cleaved by CC CTSL/cathepsin L between residues 8 and 9 from the amino terminus CC (PubMed:27143361). A post-CTSL/cathepsin L processing occurs to yield CC to the fully truncated form (PubMed:27143361). CC {ECO:0000269|PubMed:24167251, ECO:0000269|PubMed:27143361}. CC -!- PTM: Sulfenylated at Cys-189 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:0000269|PubMed:35027734}. CC -!- DISEASE: Neurodegeneration and seizures due to copper transport defect CC (NSCT) [MIM:620306]: An autosomal recessive disorder of copper CC metabolism characterized by global developmental delay, seizures, CC cortical and cerebellar atrophy, and axial hypotonia. Death in infancy CC may occur. {ECO:0000269|PubMed:35913762, ECO:0000269|PubMed:36562171}. CC Note=The disease may be caused by variants affecting the gene CC represented in this entry. 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; U83460; AAB66306.1; -; mRNA. DR EMBL; AK222866; BAD96586.1; -; mRNA. DR EMBL; AK292511; BAF85200.1; -; mRNA. DR EMBL; AL831843; CAD38549.1; -; mRNA. DR EMBL; AL449305; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471090; EAW87357.1; -; Genomic_DNA. DR EMBL; BC013611; AAH13611.1; -; mRNA. DR CCDS; CCDS6789.1; -. DR RefSeq; NP_001850.1; NM_001859.3. DR PDB; 2LS2; NMR; -; A=64-87. DR PDB; 2LS3; NMR; -; A=132-157. DR PDB; 2LS4; NMR; -; A=156-179. DR PDBsum; 2LS2; -. DR PDBsum; 2LS3; -. DR PDBsum; 2LS4; -. DR AlphaFoldDB; O15431; -. DR BMRB; O15431; -. DR SMR; O15431; -. DR BioGRID; 107712; 189. DR DIP; DIP-48727N; -. DR IntAct; O15431; 9. DR STRING; 9606.ENSP00000363329; -. DR DrugBank; DB00958; Carboplatin. DR DrugBank; DB00515; Cisplatin. DR DrugBank; DB09130; Copper. DR DrugBank; DB00526; Oxaliplatin. DR TCDB; 1.A.56.1.2; the copper transporter (ctr) family. DR GlyCosmos; O15431; 2 sites, No reported glycans. DR GlyGen; O15431; 2 sites. DR iPTMnet; O15431; -. DR PhosphoSitePlus; O15431; -. DR BioMuta; SLC31A1; -. DR EPD; O15431; -. DR jPOST; O15431; -. DR MassIVE; O15431; -. DR MaxQB; O15431; -. DR PaxDb; 9606-ENSP00000363329; -. DR PeptideAtlas; O15431; -. DR ProteomicsDB; 48657; -. DR Pumba; O15431; -. DR Antibodypedia; 3008; 281 antibodies from 31 providers. DR CPTC; O15431; 1 antibody. DR DNASU; 1317; -. DR Ensembl; ENST00000374212.5; ENSP00000363329.4; ENSG00000136868.11. DR GeneID; 1317; -. DR KEGG; hsa:1317; -. DR MANE-Select; ENST00000374212.5; ENSP00000363329.4; NM_001859.4; NP_001850.1. DR UCSC; uc004bgu.4; human. DR AGR; HGNC:11016; -. DR CTD; 1317; -. DR DisGeNET; 1317; -. DR GeneCards; SLC31A1; -. DR HGNC; HGNC:11016; SLC31A1. DR HPA; ENSG00000136868; Tissue enhanced (liver). DR MalaCards; SLC31A1; -. DR MIM; 603085; gene. DR MIM; 620306; phenotype. DR neXtProt; NX_O15431; -. DR OpenTargets; ENSG00000136868; -. DR PharmGKB; PA118; -. DR VEuPathDB; HostDB:ENSG00000136868; -. DR eggNOG; KOG3386; Eukaryota. DR GeneTree; ENSGT00940000155147; -. DR HOGENOM; CLU_079690_2_0_1; -. DR InParanoid; O15431; -. DR OMA; GPKCNMN; -. DR OrthoDB; 3399710at2759; -. DR PhylomeDB; O15431; -. DR TreeFam; TF315142; -. DR BRENDA; 7.2.2.8; 2681. DR PathwayCommons; O15431; -. DR Reactome; R-HSA-425410; Metal ion SLC transporters. DR SignaLink; O15431; -. DR BioGRID-ORCS; 1317; 91 hits in 1153 CRISPR screens. DR ChiTaRS; SLC31A1; human. DR GeneWiki; SLC31A1; -. DR GenomeRNAi; 1317; -. DR Pharos; O15431; Tbio. DR PRO; PR:O15431; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; O15431; Protein. DR Bgee; ENSG00000136868; Expressed in parotid gland and 179 other tissues. DR ExpressionAtlas; O15431; baseline and differential. DR Genevisible; O15431; HS. DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB. DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB. DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB. DR GO; GO:0014704; C:intercalated disc; IEA:Ensembl. DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0055038; C:recycling endosome membrane; IDA:UniProtKB. DR GO; GO:0005507; F:copper ion binding; IDA:UniProtKB. DR GO; GO:0005375; F:copper ion transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0015080; F:silver ion transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0042910; F:xenobiotic transmembrane transporter activity; ISS:UniProtKB. DR GO; GO:0001525; P:angiogenesis; IMP:UniProtKB. DR GO; GO:0015677; P:copper ion import; IDA:UniProtKB. DR GO; GO:0006825; P:copper ion transport; TAS:ProtInc. DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl. DR GO; GO:0006878; P:intracellular copper ion homeostasis; IEA:Ensembl. DR GO; GO:0015679; P:plasma membrane copper ion transport; IDA:UniProtKB. DR GO; GO:0051259; P:protein complex oligomerization; IDA:UniProtKB. DR GO; GO:1902601; P:silver ion transmembrane transport; IDA:UniProtKB. DR GO; GO:0036324; P:vascular endothelial growth factor receptor-2 signaling pathway; IMP:UniProtKB. DR GO; GO:0042908; P:xenobiotic transport; IDA: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. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Copper; Copper transport; Disulfide bond; KW Endosome; Epilepsy; Glycoprotein; Ion transport; Membrane; KW Neurodegeneration; Oxidation; Phosphoprotein; Reference proteome; KW Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..190 FT /note="High affinity copper uptake protein 1" FT /id="PRO_0000195040" FT CHAIN 43..190 FT /note="Truncated CTR1 form" FT /evidence="ECO:0000269|PubMed:24167251" FT /id="PRO_0000458008" FT TOPO_DOM 1..61 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 62..82 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 83..132 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 133..153 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 154..156 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 157..177 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 178..190 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 1..35 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 5..6 FT /note="Bis-His motif" FT /evidence="ECO:0000269|Ref.24" FT MOTIF 7..12 FT /note="Methionine segments (Mets) motif" FT /evidence="ECO:0000269|Ref.24" FT COMPBIAS 9..35 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 42..43 FT /note="Cleavage" FT /evidence="ECO:0000269|PubMed:24167251" FT MOD_RES 114 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 189 FT /note="Cysteine sulfenic acid (-SOH)" FT /evidence="ECO:0000269|PubMed:35027734" FT CARBOHYD 15 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:17525160" FT CARBOHYD 27 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000269|PubMed:17525160" FT DISULFID 189 FT /note="Interchain (with C-1208 in KDR)" FT /evidence="ECO:0000269|PubMed:35027734" FT VARIANT 25 FT /note="P -> A (in dbSNP:rs2233915)" FT /id="VAR_029338" FT VARIANT 79 FT /note="L -> P (in NSCT; unknown pathological significance)" FT /evidence="ECO:0000269|PubMed:36562171" FT /id="VAR_088353" FT VARIANT 95 FT /note="R -> H (in NSCT; unknown pathological significance; FT does not affect localization at the plasma membrane)" FT /evidence="ECO:0000269|PubMed:35913762" FT /id="VAR_088354" FT MUTAGEN 3 FT /note="H->A: Decreases affinity towards copper(1+)." FT /evidence="ECO:0000269|Ref.24" FT MUTAGEN 5 FT /note="H->A: Affects copper(2+) binding. Increases the FT efficiency of the reduction." FT /evidence="ECO:0000269|Ref.24" FT MUTAGEN 6 FT /note="H->A: Increases the efficiency of the reduction." FT /evidence="ECO:0000269|Ref.24" FT MUTAGEN 7..12 FT /note="MGMSYM->AGASYA: Affects homotrimer formation; when FT associated with 40-A--A-45. Does not affect localization at FT the plasma membrane; when associated with 40-A--A-45." FT /evidence="ECO:0000269|PubMed:15326162" FT MUTAGEN 40..45 FT /note="MMMMPM->AAAAPA: Affects homotrimer formation; when FT associated with 7-A--A-12. Does not affect localization at FT the plasma membrane; when associated with 7-A--A-12." FT /evidence="ECO:0000269|PubMed:15326162" FT MUTAGEN 139 FT /note="H->A: Decreases of about 40% the copper(1+) FT transport activity." FT /evidence="ECO:0000269|PubMed:16135512" FT MUTAGEN 139 FT /note="H->R: Dramatically decreases copper(1+) affinity. FT Reduces copper(1+) uptake; when associated with L-150 and FT L-154. Does not affect cell membrane expression." FT /evidence="ECO:0000269|PubMed:16135512, FT ECO:0000269|PubMed:23658018" FT MUTAGEN 150 FT /note="M->I: Reduces of about 30% the copper(1+) transport FT activity; when associated with I-154. Does not affect FT copper(1+) affinity; when associated with I-154. Abolishes FT silver(1+) transport activity; when associated with I-154." FT /evidence="ECO:0000269|PubMed:16135512, FT ECO:0000269|PubMed:20569931" FT MUTAGEN 150 FT /note="M->L: Reduces copper(1+) uptake; when associated FT with L-154. Reduces copper(1+) uptake; when associated with FT L-154 and R-139. Reduces copper(1+) uptake; when associated FT with L-154 and 188-A--A-190." FT /evidence="ECO:0000269|PubMed:23658018" FT MUTAGEN 154 FT /note="M->A: Inhibits copper(1+)-induced MAPK activation. FT Loss of copper(1+)-induced endothelil cell (EC) migration FT and capillary formation." FT /evidence="ECO:0000269|PubMed:35027734" FT MUTAGEN 154 FT /note="M->I: Reduces of about 30% the copper(1+) transport FT activity; when associated with I-150. Does not affect FT copper(1+) affinity; when associated with I-150. Abolishes FT silver(1+) transport activity when associated with I-150." FT /evidence="ECO:0000269|PubMed:16135512, FT ECO:0000269|PubMed:20569931" FT MUTAGEN 154 FT /note="M->L: Reduces copper(1+) uptake; when associated FT with L-150. Reduces copper(1+) uptake; when associated with FT L-150 and R-139. Reduces copper(1+) uptake; when associated FT with L-150 and 188-A--A-190." FT /evidence="ECO:0000269|PubMed:23658018" FT MUTAGEN 156 FT /note="Y->A: Dramatically affects copper(1+) transport FT activity." FT /evidence="ECO:0000269|PubMed:16135512" FT MUTAGEN 161 FT /note="C->S: Markedly decreases the copper(1+) transport FT activity; when associated with S-189." FT /evidence="ECO:0000269|PubMed:16135512" FT MUTAGEN 179..190 FT /note="Missing: Does not affect expression. Does not affect FT cell membrane localization. Significantly reduces FT copper(1+) transport activity." FT /evidence="ECO:0000269|PubMed:16135512" FT MUTAGEN 180..190 FT /note="Missing: Increases copper(1+) uptake. Reduces FT affinity for copper(1+)." FT /evidence="ECO:0000269|PubMed:23658018" FT MUTAGEN 184..190 FT /note="Missing: Increases copper(1+) uptake." FT /evidence="ECO:0000269|PubMed:23658018" FT MUTAGEN 185..190 FT /note="Missing: Does not affect expression. Does not affect FT cell membrane localization. Moderately affects copper(1+) FT transport activity." FT /evidence="ECO:0000269|PubMed:16135512" FT MUTAGEN 188..190 FT /note="HCH->AAA: Increases copper(1+) uptake. Reduces FT affinity for copper(1+). Reduces copper(1+) uptake; when FT associated with L-150 and L-154. Impairs endocytosis in FT response to higher extracellular copper(1+) concentration." FT /evidence="ECO:0000269|PubMed:23658018, FT ECO:0000269|PubMed:26745413" FT MUTAGEN 188..190 FT /note="HCH->ACA: Decreases of 45-fold copper(1+) affinity." FT /evidence="ECO:0000269|PubMed:26745413" FT MUTAGEN 189 FT /note="C->A: Does not affect copper(1+)-induced MAPK FT activation. Does not affect copper(1+)-induced endothelial FT cells migration and capillary formation. Almost completely FT loss of VEGFA-induced internalization of KDR and SLC31A1. FT Almost completely loss of VEGFA-induced interaction between FT KDR and SLC31A1. Decreases of 200-fold affinity for FT copper(1+) ion. Loss of ATOX1 interaction in the absence of FT copper(1+)." FT /evidence="ECO:0000269|PubMed:26745413, FT ECO:0000269|PubMed:35027734" FT MUTAGEN 189 FT /note="C->S: Markedly decreases the copper(1+) transport FT activity; when associated with S-161." FT /evidence="ECO:0000269|PubMed:16135512" FT CONFLICT 168 FT /note="A -> G (in Ref. 3; BAD96586)" FT /evidence="ECO:0000305" FT HELIX 67..82 FT /evidence="ECO:0007829|PDB:2LS2" FT TURN 83..85 FT /evidence="ECO:0007829|PDB:2LS2" FT HELIX 134..155 FT /evidence="ECO:0007829|PDB:2LS3" FT STRAND 160..162 FT /evidence="ECO:0007829|PDB:2LS4" FT HELIX 163..168 FT /evidence="ECO:0007829|PDB:2LS4" FT HELIX 174..177 FT /evidence="ECO:0007829|PDB:2LS4" SQ SEQUENCE 190 AA; 21091 MW; 1E08FBAB72A9C014 CRC64; MDHSHHMGMS YMDSNSTMQP SHHHPTTSAS HSHGGGDSSM MMMPMTFYFG FKNVELLFSG LVINTAGEMA GAFVAVFLLA MFYEGLKIAR ESLLRKSQVS IRYNSMPVPG PNGTILMETH KTVGQQMLSF PHLLQTVLHI IQVVISYFLM LIFMTYNGYL CIAVAAGAGT GYFLFSWKKA VVVDITEHCH //