ID ATX1_YEAST Reviewed; 73 AA. AC P38636; D6W0T4; E9P8W0; DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1994, sequence version 1. DT 27-MAR-2024, entry version 175. DE RecName: Full=Copper chaperone ATX1 {ECO:0000303|PubMed:9346482}; DE AltName: Full=Antioxidant protein 1 {ECO:0000303|PubMed:7731983}; DE AltName: Full=Metal homeostasis protein ATX1 {ECO:0000303|PubMed:7731983}; GN Name=ATX1 {ECO:0000303|PubMed:7731983}; OrderedLocusNames=YNL259C; GN ORFNames=N0840; OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; OC Saccharomycetales; Saccharomycetaceae; Saccharomyces. OX NCBI_TaxID=559292; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND INDUCTION. RX PubMed=7731983; DOI=10.1073/pnas.92.9.3784; RA Lin S.-J., Culotta V.L.; RT "The ATX1 gene of Saccharomyces cerevisiae encodes a small metal RT homeostasis factor that protects cells against reactive oxygen toxicity."; RL Proc. Natl. Acad. Sci. U.S.A. 92:3784-3788(1995). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 96604 / S288c / FY1679; RX PubMed=9234673; RX DOI=10.1002/(sici)1097-0061(199707)13:9<849::aid-yea106>3.0.co;2-n; RA Sen-Gupta M., Gueldener U., Beinhauer J.D., Fiedler T.A., Hegemann J.H.; RT "Sequence analysis of the 33 kb long region between ORC5 and SUI1 from the RT left arm of chromosome XIV from Saccharomyces cerevisiae."; RL Yeast 13:849-860(1997). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=9169873; RA Philippsen P., Kleine K., Poehlmann R., Duesterhoeft A., Hamberg K., RA Hegemann J.H., Obermaier B., Urrestarazu L.A., Aert R., Albermann K., RA Altmann R., Andre B., Baladron V., Ballesta J.P.G., Becam A.-M., RA Beinhauer J.D., Boskovic J., Buitrago M.J., Bussereau F., Coster F., RA Crouzet M., D'Angelo M., Dal Pero F., De Antoni A., del Rey F., Doignon F., RA Domdey H., Dubois E., Fiedler T.A., Fleig U., Floeth M., Fritz C., RA Gaillardin C., Garcia-Cantalejo J.M., Glansdorff N., Goffeau A., RA Gueldener U., Herbert C.J., Heumann K., Heuss-Neitzel D., Hilbert H., RA Hinni K., Iraqui Houssaini I., Jacquet M., Jimenez A., Jonniaux J.-L., RA Karpfinger-Hartl L., Lanfranchi G., Lepingle A., Levesque H., Lyck R., RA Maftahi M., Mallet L., Maurer C.T.C., Messenguy F., Mewes H.-W., Moestl D., RA Nasr F., Nicaud J.-M., Niedenthal R.K., Pandolfo D., Pierard A., RA Piravandi E., Planta R.J., Pohl T.M., Purnelle B., Rebischung C., RA Remacha M.A., Revuelta J.L., Rinke M., Saiz J.E., Sartorello F., RA Scherens B., Sen-Gupta M., Soler-Mira A., Urbanus J.H.M., Valle G., RA Van Dyck L., Verhasselt P., Vierendeels F., Vissers S., Voet M., RA Volckaert G., Wach A., Wambutt R., Wedler H., Zollner A., Hani J.; RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its RT evolutionary implications."; RL Nature 387:93-98(1997). RN [4] RP GENOME REANNOTATION. RC STRAIN=ATCC 204508 / S288c; RX PubMed=24374639; DOI=10.1534/g3.113.008995; RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.; RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now."; RL G3 (Bethesda) 4:389-398(2014). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=17322287; DOI=10.1101/gr.6037607; RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F., RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J., RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J., RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D., RA LaBaer J.; RT "Approaching a complete repository of sequence-verified protein-encoding RT clones for Saccharomyces cerevisiae."; RL Genome Res. 17:536-543(2007). RN [6] RP FUNCTON. RX PubMed=9083054; RA Lin S.J., Pufahl R.A., Dancis A., O'Halloran T.V., Culotta V.C.; RT "A role for the Saccharomyces cerevisiae ATX1 gene in copper trafficking RT and iron transport."; RL J. Biol. Chem. 272:9215-9220(1997). RN [7] RP FUNCTION, COPPER-BINDING, AND SUBCELLULAR LOCATION. RX PubMed=9346482; DOI=10.1126/science.278.5339.853; RA Pufahl R.A., Singer C.P., Peariso K.L., Lin S.J., Schmidt P.J., RA Fahrni C.J., Culotta V.C., Penner-Hahn J.E., O'Halloran T.V.; RT "Metal ion chaperone function of the soluble Cu(I) receptor Atx1."; RL Science 278:853-856(1997). RN [8] {ECO:0007744|PDB:1CC7, ECO:0007744|PDB:1CC8} RP X-RAY CRYSTALLOGRAPHY (1.02 ANGSTROMS). RX PubMed=10404590; DOI=10.1016/s0969-2126(99)80082-3; RA Rosenzweig A.C., Huffman D.L., Hou M.Y., Wernimont A.K., Pufahl R.A., RA O'Halloran T.V.; RT "Crystal structure of the Atx1 metallochaperone protein at 1.02 A RT resolution."; RL Structure 7:605-617(1999). RN [9] {ECO:0007744|PDB:1FD8, ECO:0007744|PDB:1FES} RP STRUCTURE BY NMR IN COMPLEX WITH COPPER. RX PubMed=11327811; DOI=10.1021/bi0014711; RA Arnesano F., Banci L., Bertini I., Huffman D.L., O'Halloran T.V.; RT "Solution structure of the Cu(I) and apo forms of the yeast RT metallochaperone, Atx1."; RL Biochemistry 40:1528-1539(2001). RN [10] {ECO:0007744|PDB:2GGP} RP STRUCTURE BY NMR, FUNCTION, AND INTERACTION WITH CCC2. RX PubMed=16732294; DOI=10.1038/nchembio797; RA Banci L., Bertini I., Cantini F., Felli I.C., Gonnelli L., Hadjiliadis N., RA Pierattelli R., Rosato A., Voulgaris P.; RT "The Atx1-Ccc2 complex is a metal-mediated protein-protein interaction."; RL Nat. Chem. Biol. 2:367-368(2006). RN [11] {ECO:0007744|PDB:3K7R} RP X-RAY CRYSTALLOGRAPHY (2.28 ANGSTROMS) IN COMPLEX WITH COPPER AND RP TETRATHIOMOLYBDATE. RX PubMed=19965379; DOI=10.1126/science.1179907; RA Alvarez H.M., Xue Y., Robinson C.D., Canalizo-Hernandez M.A., Marvin R.G., RA Kelly R.A., Mondragon A., Penner-Hahn J.E., O'Halloran T.V.; RT "Tetrathiomolybdate inhibits copper trafficking proteins through metal RT cluster formation."; RL Science 327:331-334(2010). RN [12] {ECO:0007744|PDB:5VDE, ECO:0007744|PDB:5VDF} RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS)IN COMPLEX WITH COPPER, AND SUBUNIT. RX PubMed=28865724; DOI=10.1016/j.jinorgbio.2017.08.009; RA Lee M., Cooray N.D.G., Maher M.J.; RT "The crystal structures of a copper-bound metallochaperone from RT Saccharomyces cerevisiae."; RL J. Inorg. Biochem. 177:368-374(2017). CC -!- FUNCTION: Copper homeostasis factor that specifically transports copper CC to the secretory pathway for incorporation into copper enzymes destined CC for the cell surface or extracellular milieu (PubMed:9346482). Shuttles CC copper to the transport ATPase CCC2 on a post-Golgi vesicle for CC eventual targeting to the cell-surface high-affinity iron uptake CC protein FET3 (PubMed:9083054, PubMed:9346482, PubMed:11327811, CC PubMed:16732294). Protects against oxygen toxicity (PubMed:7731983). CC {ECO:0000269|PubMed:11327811, ECO:0000269|PubMed:16732294, CC ECO:0000269|PubMed:7731983, ECO:0000269|PubMed:9083054, CC ECO:0000269|PubMed:9346482}. CC -!- ACTIVITY REGULATION: Tetrathiomolybdate directly and reversibly down- CC regulates copper delivery to secreted metalloenzymes. CC {ECO:0000269|PubMed:19965379}. CC -!- SUBUNIT: Homodimer (PubMed:28865724). Interacts with CCC2 via the CC copper anion (PubMed:16732294). {ECO:0000269|PubMed:16732294, CC ECO:0000269|PubMed:28865724}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9346482}. CC -!- INDUCTION: Expression is induced by oxygen (PubMed:7731983). Expression CC is also induced by the iron-sensing trans-activator AFT1 CC (PubMed:9083054). {ECO:0000269|PubMed:7731983, CC ECO:0000269|PubMed:9083054}. CC -!- SIMILARITY: Belongs to the ATX1 family. {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; L35270; AAC37428.1; -; Genomic_DNA. DR EMBL; X96722; CAA65485.1; -; Genomic_DNA. DR EMBL; Z71535; CAA96166.1; -; Genomic_DNA. DR EMBL; AY558367; AAS56693.1; -; Genomic_DNA. DR EMBL; BK006947; DAA10300.1; -; Genomic_DNA. DR PIR; S47930; S47930. DR RefSeq; NP_014140.1; NM_001183097.1. DR PDB; 1CC7; X-ray; 1.20 A; A=1-73. DR PDB; 1CC8; X-ray; 1.02 A; A=1-73. DR PDB; 1FD8; NMR; -; A=1-73. DR PDB; 1FES; NMR; -; A=1-73. DR PDB; 2GGP; NMR; -; A=1-73. DR PDB; 3K7R; X-ray; 2.28 A; A/B/C/D/E/F/G/H/I/J/K/L=1-73. DR PDB; 5VDE; X-ray; 1.65 A; A/B/C/D=1-73. DR PDB; 5VDF; X-ray; 1.93 A; A/B/C/D/E/F/G/H=1-73. DR PDBsum; 1CC7; -. DR PDBsum; 1CC8; -. DR PDBsum; 1FD8; -. DR PDBsum; 1FES; -. DR PDBsum; 2GGP; -. DR PDBsum; 3K7R; -. DR PDBsum; 5VDE; -. DR PDBsum; 5VDF; -. DR AlphaFoldDB; P38636; -. DR SMR; P38636; -. DR BioGRID; 35580; 80. DR DIP; DIP-813N; -. DR IntAct; P38636; 5. DR MINT; P38636; -. DR STRING; 4932.YNL259C; -. DR MaxQB; P38636; -. DR PaxDb; 4932-YNL259C; -. DR PeptideAtlas; P38636; -. DR EnsemblFungi; YNL259C_mRNA; YNL259C; YNL259C. DR GeneID; 855462; -. DR KEGG; sce:YNL259C; -. DR AGR; SGD:S000005203; -. DR SGD; S000005203; ATX1. DR VEuPathDB; FungiDB:YNL259C; -. DR eggNOG; KOG1603; Eukaryota. DR HOGENOM; CLU_134973_3_1_1; -. DR InParanoid; P38636; -. DR OMA; YEFDIAM; -. DR OrthoDB; 1107952at2759; -. DR BioCyc; YEAST:G3O-33255-MONOMER; -. DR BioGRID-ORCS; 855462; 0 hits in 10 CRISPR screens. DR ChiTaRS; ATX1; yeast. DR EvolutionaryTrace; P38636; -. DR PRO; PR:P38636; -. DR Proteomes; UP000002311; Chromosome XIV. DR RNAct; P38636; Protein. DR GO; GO:0005829; C:cytosol; IDA:SGD. DR GO; GO:0016531; F:copper chaperone activity; IDA:SGD. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0034599; P:cellular response to oxidative stress; IMP:SGD. DR GO; GO:0006825; P:copper ion transport; IMP:SGD. DR GO; GO:0006879; P:intracellular iron ion homeostasis; IMP:SGD. DR CDD; cd00371; HMA; 1. DR Gene3D; 3.30.70.100; -; 1. DR InterPro; IPR017969; Heavy-metal-associated_CS. DR InterPro; IPR006121; HMA_dom. DR InterPro; IPR036163; HMA_dom_sf. DR PANTHER; PTHR46365; COPPER TRANSPORT PROTEIN ATOX1; 1. DR PANTHER; PTHR46365:SF1; COPPER TRANSPORT PROTEIN ATOX1; 1. DR Pfam; PF00403; HMA; 1. DR SUPFAM; SSF55008; HMA, heavy metal-associated domain; 1. DR PROSITE; PS01047; HMA_1; 1. DR PROSITE; PS50846; HMA_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Chaperone; Copper; Copper transport; Cytoplasm; KW Ion transport; Metal-binding; Reference proteome; Transport. FT CHAIN 1..73 FT /note="Copper chaperone ATX1" FT /id="PRO_0000212535" FT DOMAIN 4..68 FT /note="HMA" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280" FT BINDING 15 FT /ligand="Cu(+)" FT /ligand_id="ChEBI:CHEBI:49552" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280, FT ECO:0000269|PubMed:11327811, ECO:0000269|PubMed:19965379, FT ECO:0000269|PubMed:28865724, ECO:0007744|PDB:1FD8, FT ECO:0007744|PDB:3K7R, ECO:0007744|PDB:5VDE, FT ECO:0007744|PDB:5VDF" FT BINDING 18 FT /ligand="Cu(+)" FT /ligand_id="ChEBI:CHEBI:49552" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280, FT ECO:0000269|PubMed:11327811, ECO:0000269|PubMed:19965379, FT ECO:0000269|PubMed:28865724, ECO:0007744|PDB:1FD8, FT ECO:0007744|PDB:3K7R, ECO:0007744|PDB:5VDE, FT ECO:0007744|PDB:5VDF" FT CONFLICT 8 FT /note="Q -> H (in Ref. 5; AAS56693)" FT /evidence="ECO:0000305" FT STRAND 5..11 FT /evidence="ECO:0007829|PDB:1CC8" FT HELIX 16..27 FT /evidence="ECO:0007829|PDB:1CC8" FT TURN 28..31 FT /evidence="ECO:0007829|PDB:1CC8" FT STRAND 32..39 FT /evidence="ECO:0007829|PDB:1CC8" FT TURN 40..43 FT /evidence="ECO:0007829|PDB:1CC8" FT STRAND 44..51 FT /evidence="ECO:0007829|PDB:1CC8" FT HELIX 53..61 FT /evidence="ECO:0007829|PDB:1CC8" FT TURN 62..64 FT /evidence="ECO:0007829|PDB:5VDE" FT STRAND 67..73 FT /evidence="ECO:0007829|PDB:1CC8" SQ SEQUENCE 73 AA; 8221 MW; 9BDF0B542F80EA83 CRC64; MAEIKHYQFN VVMTCSGCSG AVNKVLTKLE PDVSKIDISL EKQLVDVYTT LPYDFILEKI KKTGKEVRSG KQL //