ATP7A_HUMAN
ID ATP7A_HUMAN Reviewed; 1500 AA.
AC Q04656; B1AT72; O00227; O00745; Q9BYY8;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 12-SEP-2018, sequence version 4.
DT 03-AUG-2022, entry version 238.
DE RecName: Full=Copper-transporting ATPase 1;
DE EC=7.2.2.8 {ECO:0000269|PubMed:10419525, ECO:0000305|PubMed:28389643};
DE AltName: Full=Copper pump 1;
DE AltName: Full=Menkes disease-associated protein;
GN Name=ATP7A {ECO:0000303|PubMed:28389643, ECO:0000312|HGNC:HGNC:869};
GN Synonyms=MC1, MNK;
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] (ISOFORM 4), VARIANT THR-669, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Fibroblast;
RX PubMed=8490659; DOI=10.1038/ng0193-7;
RA Vulpe C.D., Levinson B., Whitney S., Packman S., Gitschier J.;
RT "Isolation of a candidate gene for Menkes disease and evidence that it
RT encodes a copper-transporting ATPase.";
RL Nat. Genet. 3:7-13(1993).
RN [2]
RP ERRATUM OF PUBMED:8490659.
RA Vulpe C.D., Levinson B., Whitney S., Packman S., Gitschier J.;
RL Nat. Genet. 3:273-273(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 4), AND VARIANT THR-669.
RX PubMed=7607665; DOI=10.1016/0888-7543(95)80160-n;
RA Tuemer Z., Vural B., Toennesen T., Chelly J., Monaco A.P., Horn N.;
RT "Characterization of the exon structure of the Menkes disease gene using
RT vectorette PCR.";
RL Genomics 26:437-442(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND TISSUE SPECIFICITY (ISOFORM 3).
RC TISSUE=Fibroblast;
RX PubMed=9693104; DOI=10.1042/bj3340071;
RA Reddy M.C., Harris E.D.;
RT "Multiple transcripts coding for the menkes gene: evidence for alternative
RT splicing of Menkes mRNA.";
RL Biochem. J. 334:71-77(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Colon carcinoma, and Fibroblast;
RX PubMed=10079814; DOI=10.1007/978-1-4615-4859-1_4;
RA Harris E.D., Reddy M.C., Qian Y., Tiffany-Castiglioni E., Majumdar S.,
RA Nelson J.;
RT "Multiple forms of the Menkes Cu-ATPase.";
RL Adv. Exp. Med. Biol. 448:39-51(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLU-1350.
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLU-1350.
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-1447 (ISOFORM 4).
RX PubMed=7490081; DOI=10.1006/geno.1995.1175;
RA Dierick H.A., Ambrosini L., Spencer J., Glover T.W., Mercer J.F.B.;
RT "Molecular structure of the Menkes disease gene (ATP7A).";
RL Genomics 28:462-469(1995).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-626 (ISOFORM 4), AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=8490646; DOI=10.1038/ng0193-14;
RA Chelly J., Tuemer Z., Toennesen T., Petterson A., Ishikawa-Brush Y.,
RA Tommerup N., Horn N., Monaco A.P.;
RT "Isolation of a candidate gene for Menkes disease that encodes a potential
RT heavy metal binding protein.";
RL Nat. Genet. 3:14-19(1993).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 12-529 (ISOFORM 4).
RC TISSUE=Endothelial cell;
RX PubMed=8490647; DOI=10.1038/ng0193-20;
RA Mercer J.F.B., Livingston J., Hall B., Paynter J.A., Begy C.,
RA Chandrasekharappa S., Lockhart P., Grimes A., Bhave M., Siemieniak D.,
RA Glover T.W.;
RT "Isolation of a partial candidate gene for Menkes disease by positional
RT cloning.";
RL Nat. Genet. 3:20-25(1993).
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 213-437.
RX PubMed=11214319; DOI=10.1038/35054550;
RA Murphy W.J., Eizirik E., Johnson W.E., Zhang Y.-P., Ryder O.A.,
RA O'Brien S.J.;
RT "Molecular phylogenetics and the origins of placental mammals.";
RL Nature 409:614-618(2001).
RN [12]
RP ALTERNATIVE SPLICING (ISOFORM 5), AND SUBCELLULAR LOCATION.
RX PubMed=9467005; DOI=10.1093/hmg/7.3.465;
RA Qi M., Byers P.H.;
RT "Constitutive skipping of alternatively spliced exon 10 in the ATP7A gene
RT abolishes Golgi localization of the menkes protein and produces the
RT occipital horn syndrome.";
RL Hum. Mol. Genet. 7:465-469(1998).
RN [13]
RP ALTERNATIVE SPLICING (ISOFORM 6).
RC TISSUE=Neuroblastoma;
RX PubMed=10970802; DOI=10.1042/bj3500855;
RA Reddy M.C., Majumdar S., Harris E.D.;
RT "Evidence for a Menkes-like protein with a nuclear targeting sequence.";
RL Biochem. J. 350:855-863(2000).
RN [14]
RP SUBCELLULAR LOCATION.
RX PubMed=9147644; DOI=10.1093/hmg/6.3.409;
RA Dierick H.A., Adam A.N., Escara-Wilke J.F., Glover T.W.;
RT "Immunocytochemical localization of the Menkes copper transport protein
RT (ATP7A) to the trans-Golgi network.";
RL Hum. Mol. Genet. 6:409-416(1997).
RN [15]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF LEUCINE RESIDUES.
RX PubMed=10484781; DOI=10.1093/hmg/8.11.2107;
RA Petris M.J., Mercer J.F.B.;
RT "The Menkes protein (ATP7A; MNK) cycles via the plasma membrane both in
RT basal and elevated extracellular copper using a C-terminal di-leucine
RT endocytic signal.";
RL Hum. Mol. Genet. 8:2107-2115(1999).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND DOMAIN.
RX PubMed=10419525; DOI=10.1074/jbc.274.31.22008;
RA Voskoboinik I., Strausak D., Greenough M., Brooks H., Petris M., Smith S.,
RA Mercer J.F., Camakaris J.;
RT "Functional analysis of the N-terminal CXXC metal-binding motifs in the
RT human Menkes copper-transporting P-type ATPase expressed in cultured
RT mammalian cells.";
RL J. Biol. Chem. 274:22008-22012(1999).
RN [17]
RP FUNCTION, AND MUTAGENESIS OF ASP-1044.
RX PubMed=11092760; DOI=10.1093/hmg/9.19.2845;
RA Petris M.J., Strausak D., Mercer J.F.;
RT "The Menkes copper transporter is required for the activation of
RT tyrosinase.";
RL Hum. Mol. Genet. 9:2845-2851(2000).
RN [18]
RP INTERACTION WITH PDZD11.
RX PubMed=16051599; DOI=10.1074/jbc.m505889200;
RA Stephenson S.E., Dubach D., Lim C.M., Mercer J.F., La Fontaine S.;
RT "A single PDZ domain protein interacts with the Menkes copper ATPase,
RT ATP7A. A new protein implicated in copper homeostasis.";
RL J. Biol. Chem. 280:33270-33279(2005).
RN [19]
RP TISSUE SPECIFICITY, AND INTERACTION WITH SOD3.
RX PubMed=16371425; DOI=10.1096/fj.05-4564fje;
RA Qin Z., Itoh S., Jeney V., Ushio-Fukai M., Fukai T.;
RT "Essential role for the Menkes ATPase in activation of extracellular
RT superoxide dismutase: implication for vascular oxidative stress.";
RL FASEB J. 20:334-336(2006).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-339, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [22]
RP INTERACTION WITH ATOX1 AND COMMD1, CHARACTERIZATION OF VARIANT OHS
RP SER-1304, AND CHARACTERIZATION OF VARIANTS MNK ARG-873; ARG-1000 AND
RP ASP-1362.
RX PubMed=21667063; DOI=10.1007/s00018-011-0743-1;
RA Vonk W.I., de Bie P., Wichers C.G., van den Berghe P.V., van der Plaats R.,
RA Berger R., Wijmenga C., Klomp L.W., van de Sluis B.;
RT "The copper-transporting capacity of ATP7A mutants associated with Menkes
RT disease is ameliorated by COMMD1 as a result of improved protein
RT expression.";
RL Cell. Mol. Life Sci. 69:149-163(2012).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-152; SER-270; THR-327;
RP SER-339; SER-357; SER-1460; SER-1463; SER-1466; SER-1469 AND SER-1473, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1430 AND SER-1432, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [25]
RP STRUCTURE BY NMR OF 375-446.
RX PubMed=9437429; DOI=10.1038/nsb0198-47;
RA Gitschier J., Moffat B., Reilly D., Wood W.I., Fairbrother W.J.;
RT "Solution structure of the fourth metal-binding domain from the Menkes
RT copper-transporting ATPase.";
RL Nat. Struct. Biol. 5:47-54(1998).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 7-77, DOMAIN, INTERACTION WITH
RP ATOX1, AND FUNCTION.
RX PubMed=19453293; DOI=10.1042/bj20090422;
RA Banci L., Bertini I., Calderone V., Della-Malva N., Felli I.C., Neri S.,
RA Pavelkova A., Rosato A.;
RT "Copper(I)-mediated protein-protein interactions result from suboptimal
RT interaction surfaces.";
RL Biochem. J. 422:37-42(2009).
RN [27]
RP STRUCTURE BY NMR OF 1051-1231, DOMAIN, AND FUNCTION.
RX PubMed=19917612; DOI=10.1074/jbc.m109.054262;
RA Banci L., Bertini I., Cantini F., Inagaki S., Migliardi M., Rosato A.;
RT "The binding mode of ATP revealed by the solution structure of the N-domain
RT of human ATP7A.";
RL J. Biol. Chem. 285:2537-2544(2010).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (2.83 ANGSTROMS) OF 7-77 IN COMPLEX WITH COPPER AND
RP ATOX1, DOMAIN, FUNCTION, AND MUTAGENESIS OF CYS-22.
RX PubMed=31283225; DOI=10.1021/jacs.9b05550;
RA Lasorsa A., Nardella M.I., Rosato A., Mirabelli V., Caliandro R.,
RA Caliandro R., Natile G., Arnesano F.;
RT "Mechanistic and Structural Basis for Inhibition of Copper Trafficking by
RT Platinum Anticancer Drugs.";
RL J. Am. Chem. Soc. 141:12109-12120(2019).
RN [29]
RP REVIEW, AND VARIANTS MNK.
RX PubMed=10079817; DOI=10.1007/978-1-4615-4859-1_7;
RA Tuemer Z., Moeller L.B., Horn N.;
RT "Mutation spectrum of ATP7A, the gene defective in Menkes disease.";
RL Adv. Exp. Med. Biol. 448:83-95(1999).
RN [30]
RP VARIANT LEU-767, AND VARIANT MNK ARG-1302.
RX PubMed=7977350;
RA Das S., Levinson B., Whitney S., Vulpe C., Packman S., Gitschier J.;
RT "Diverse mutations in patients with Menkes disease often lead to exon
RT skipping.";
RL Am. J. Hum. Genet. 55:883-889(1994).
RN [31]
RP VARIANTS MNK PRO-629; ARG-727; PRO-1006 AND ASP-1019.
RX PubMed=8981948;
RA Tuemer Z., Lund C., Tolshave J., Vural B., Toennesen T., Horn N.;
RT "Identification of point mutations in 41 unrelated patients affected with
RT Menkes disease.";
RL Am. J. Hum. Genet. 60:63-71(1997).
RN [32]
RP VARIANT OHS LEU-637.
RX PubMed=9246006; DOI=10.1086/516852;
RA Ronce N., Moizard M.P., Robb L., Toutain A., Villard L., Moraine C.;
RT "A C2055T transition in exon 8 of the ATP7A gene is associated with exon
RT skipping in an occipital horn syndrome family.";
RL Am. J. Hum. Genet. 61:233-238(1997).
RN [33]
RP VARIANT MNK VAL-1362.
RX PubMed=10401004; DOI=10.1093/hmg/8.8.1547;
RA Ambrosini L., Mercer J.F.B.;
RT "Defective copper-induced trafficking and localization of the Menkes
RT protein in patients with mild and copper-treated classical Menkes
RT disease.";
RL Hum. Mol. Genet. 8:1547-1555(1999).
RN [34]
RP VARIANT MNK ARG-873.
RX PubMed=10319589; DOI=10.1007/s100380050144;
RA Ogawa A., Yamamoto S., Takayanagi M., Kogo T., Kanazawa M., Kohno Y.;
RT "Identification of three novel mutations in the MNK gene in three unrelated
RT Japanese patients with classical Menkes disease.";
RL J. Hum. Genet. 44:206-209(1999).
RN [35]
RP INVOLVEMENT IN OCCIPITAL HORN SYNDROME.
RX PubMed=11431706; DOI=10.1086/321290;
RA Dagenais S.L., Adam A.N., Innis J.W., Glover T.W.;
RT "A novel frameshift mutation in exon 23 of ATP7A (MNK) results in occipital
RT horn syndrome and not in Menkes disease.";
RL Am. J. Hum. Genet. 69:420-427(2001).
RN [36]
RP VARIANTS MNK ARG-1344 AND PHE-1345.
RX PubMed=11241493;
RX DOI=10.1002/1096-8628(2001)9999:9999<::aid-ajmg1167>3.0.co;2-r;
RA Gu Y.-H., Kodama H., Murata Y., Mochizuki D., Yanagawa Y., Ushijima H.,
RA Shiba T., Lee C.-C.;
RT "ATP7A gene mutations in 16 patients with Menkes disease and a patient with
RT occipital horn syndrome.";
RL Am. J. Med. Genet. 99:217-222(2001).
RN [37]
RP VARIANTS MNK ARG-706; ASP-1118 AND ARG-1255.
RX PubMed=11350187; DOI=10.1006/mgme.2001.3169;
RA Hahn S., Cho K., Ryu K., Kim J., Pai K., Kim M., Park H., Yoo O.;
RT "Identification of four novel mutations in classical Menkes disease and
RT successful prenatal DNA diagnosis.";
RL Mol. Genet. Metab. 73:86-90(2001).
RN [38]
RP VARIANTS MNK HIS-844; ARG-853; VAL-860; ARG-876; GLU-876; ARG-924;
RP ARG-1000; VAL-1007; ASP-1015; GLY-1044; PRO-1100; GLU-1282; GLU-1300;
RP VAL-1302; LYS-1304; ALA-1305; ARG-1315; VAL-1325; ARG-1369 AND PHE-1397.
RX PubMed=15981243; DOI=10.1002/humu.20190;
RA Moeller L.B., Bukrinsky J.T., Moelgaard A., Paulsen M., Lund C., Tuemer Z.,
RA Larsen S., Horn N.;
RT "Identification and analysis of 21 novel disease-causing amino acid
RT substitutions in the conserved part of ATP7A.";
RL Hum. Mutat. 26:84-93(2005).
RN [39]
RP VARIANT OHS SER-1304, AND CHARACTERIZATION OF VARIANT OHS SER-1304.
RX PubMed=17108763; DOI=10.1097/01.gim.0000245578.94312.1e;
RA Tang J., Robertson S., Lem K.E., Godwin S.C., Kaler S.G.;
RT "Functional copper transport explains neurologic sparing in occipital horn
RT syndrome.";
RL Genet. Med. 8:711-718(2006).
RN [40]
RP VARIANTS DSMAX3 ILE-994 AND SER-1386, AND CHARACTERIZATION OF VARIANTS
RP DSMAX3 ILE-994 AND SER-1386.
RX PubMed=20170900; DOI=10.1016/j.ajhg.2010.01.027;
RA Kennerson M.L., Nicholson G.A., Kaler S.G., Kowalski B., Mercer J.F.B.,
RA Tang J., Llanos R.M., Chu S., Takata R.I., Speck-Martins C.E., Baets J.,
RA Almeida-Souza L., Fischer D., Timmerman V., Taylor P.E., Scherer S.S.,
RA Ferguson T.A., Bird T.D., De Jonghe P., Feely S.M.E., Shy M.E.,
RA Garbern J.Y.;
RT "Missense mutations in the copper transporter gene ATP7A cause X-linked
RT distal hereditary motor neuropathy.";
RL Am. J. Hum. Genet. 86:343-352(2010).
RN [41]
RP VARIANT MNK ILE-1048.
RX PubMed=22992316; DOI=10.1186/1471-2431-12-150;
RA De Leon-Garcia G., Santana A., Villegas-Sepulveda N., Perez-Gonzalez C.,
RA Henrriquez-Esquiroz J.M., De Leon-Garcia C., Wong C., Baeza I.;
RT "The T1048I mutation in ATP7A gene causes an unusual Menkes disease
RT presentation.";
RL BMC Pediatr. 12:150-150(2012).
RN [42]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, CHARACTERIZATION OF
RP VARIANTS MNK VAL-628; ARG-633; TYR-653; ARG-666; ARG-727; ASP-728; PRO-761;
RP ASN-802; HIS-844; VAL-860; ARG-876; GLU-876; ARG-1000; ARG-1005; VAL-1007;
RP ASP-1015; ASN-1037; GLY-1044; ARG-1255; GLU-1282; GLU-1300; GLY-1301;
RP GLU-1302; VAL-1302; LYS-1304; ALA-1305; GLY-1305; ASP-1308; ARG-1315;
RP VAL-1325; VAL-1362; ARG-1369; PRO-1373; THR-1393 AND PHE-1397, AND
RP CHARACTERIZATION OF VARIANT OHS ARG-924.
RX PubMed=28389643; DOI=10.1038/s41598-017-00618-6;
RA Skjoerringe T., Amstrup Pedersen P., Salling Thorborg S., Nissen P.,
RA Gourdon P., Birk Moeller L.;
RT "Characterization of ATP7A missense mutants suggests a correlation between
RT intracellular trafficking and severity of Menkes disease.";
RL Sci. Rep. 7:757-757(2017).
CC -!- FUNCTION: ATP-driven copper (Cu(+)) ion pump that plays an important
CC role in intracellular copper ion homeostasis (PubMed:10419525,
CC PubMed:11092760, PubMed:28389643). Within a catalytic cycle, acquires
CC Cu(+) ion from donor protein on the cytoplasmic side of the membrane
CC and delivers it to acceptor protein on the lumenal side. The transfer
CC of Cu(+) ion across the membrane is coupled to ATP hydrolysis and is
CC associated with a transient phosphorylation that shifts the pump
CC conformation from inward-facing to outward-facing state
CC (PubMed:10419525, PubMed:19453293, PubMed:19917612, PubMed:31283225,
CC PubMed:28389643). Under physiological conditions, at low cytosolic
CC copper concentration, it is localized at the trans-Golgi network (TGN)
CC where it transfers Cu(+) ions to cuproenzymes of the secretory pathway
CC (PubMed:28389643, PubMed:11092760). Upon elevated cytosolic copper
CC concentrations, it relocalizes to the plasma membrane where it is
CC responsible for the export of excess Cu(+) ions (PubMed:10419525,
CC PubMed:28389643). May play a dual role in neuron function and survival
CC by regulating cooper efflux and neuronal transmission at the synapse as
CC well as by supplying Cu(+) ions to enzymes such as PAM, TYR and SOD3
CC (PubMed:28389643) (By similarity). In the melanosomes of pigmented
CC cells, provides copper cofactor to TYR to form an active TYR holoenzyme
CC for melanin biosynthesis (By similarity).
CC {ECO:0000250|UniProtKB:Q64430, ECO:0000269|PubMed:10419525,
CC ECO:0000269|PubMed:11092760, ECO:0000269|PubMed:19453293,
CC ECO:0000269|PubMed:19917612, ECO:0000269|PubMed:28389643,
CC ECO:0000269|PubMed:31283225}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + Cu(+)(in) + H2O = ADP + Cu(+)(out) + H(+) + phosphate;
CC Xref=Rhea:RHEA:25792, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:49552,
CC ChEBI:CHEBI:456216; EC=7.2.2.8;
CC Evidence={ECO:0000269|PubMed:10419525};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25793;
CC Evidence={ECO:0000305|PubMed:10419525, ECO:0000305|PubMed:28389643};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4 uM for Cu(+) ion {ECO:0000269|PubMed:10419525};
CC Vmax=1.15 nmol/min/mg enzyme toward Cu(+) ion
CC {ECO:0000269|PubMed:10419525};
CC -!- SUBUNIT: Monomer. Interacts with PDZD11 (PubMed:16051599). Interacts
CC with ATOX1 and COMMD1 (PubMed:21667063, PubMed:19453293,
CC PubMed:31283225). Interacts with TYRP1 (By similarity). Directly
CC interacts with SOD3; this interaction is copper-dependent and is
CC required for SOD3 activity. {ECO:0000250|UniProtKB:Q64430,
CC ECO:0000269|PubMed:16051599, ECO:0000269|PubMed:16371425,
CC ECO:0000269|PubMed:21667063, ECO:0000269|PubMed:31283225}.
CC -!- INTERACTION:
CC Q04656; P09172: DBH; NbExp=2; IntAct=EBI-7706409, EBI-8589586;
CC Q04656; Q5EBL8: PDZD11; NbExp=4; IntAct=EBI-7706409, EBI-1644207;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane
CC {ECO:0000269|PubMed:10484781, ECO:0000269|PubMed:28389643,
CC ECO:0000269|PubMed:9147644, ECO:0000269|PubMed:9467005}; Multi-pass
CC membrane protein {ECO:0000255}. Cell membrane
CC {ECO:0000269|PubMed:10484781, ECO:0000269|PubMed:28389643,
CC ECO:0000269|PubMed:9147644}; Multi-pass membrane protein {ECO:0000255}.
CC Melanosome membrane {ECO:0000250|UniProtKB:Q64430}; Multi-pass membrane
CC protein {ECO:0000255}. Early endosome membrane
CC {ECO:0000250|UniProtKB:Q64430}; Multi-pass membrane protein
CC {ECO:0000255}. Cell projection, axon {ECO:0000250|UniProtKB:P70705}.
CC Cell projection, dendrite {ECO:0000250|UniProtKB:P70705}. Postsynaptic
CC density {ECO:0000250|UniProtKB:P70705}. Note=Cycles constitutively
CC between the TGN and the plasma membrane (PubMed:9147644). Predominantly
CC found in the TGN and relocalized to the plasma membrane in response to
CC elevated copper levels. Targeting into melanosomes is regulated by
CC BLOC-1 complex (By similarity). In response to glutamate, translocates
CC to neuron processes with a minor fraction at extrasynaptic sites (By
CC similarity). {ECO:0000250|UniProtKB:P70705,
CC ECO:0000250|UniProtKB:Q64430, ECO:0000269|PubMed:9147644}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm, cytosol {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 5]: Endoplasmic reticulum
CC {ECO:0000269|PubMed:9467005}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=4;
CC IsoId=Q04656-1; Sequence=Displayed;
CC Name=1;
CC IsoId=Q04656-2; Sequence=VSP_000419;
CC Name=2;
CC IsoId=Q04656-3; Sequence=VSP_000420;
CC Name=3; Synonyms=2-16;
CC IsoId=Q04656-4; Sequence=VSP_000424;
CC Name=5;
CC IsoId=Q04656-5; Sequence=VSP_000425;
CC Name=6; Synonyms=NML45;
CC IsoId=Q04656-6; Sequence=VSP_000421, VSP_000422, VSP_000423;
CC -!- TISSUE SPECIFICITY: Widely expressed including in heart, brain, lung,
CC muscle, kidney, pancreas, and to a lesser extent placenta
CC (PubMed:8490646, PubMed:8490659). Expressed in fibroblasts, aortic
CC smooth muscle cells, aortic endothelial cells and umbilical vein
CC endothelial cells (at protein level) (PubMed:16371425).
CC {ECO:0000269|PubMed:16371425, ECO:0000269|PubMed:8490646,
CC ECO:0000269|PubMed:8490659}.
CC -!- TISSUE SPECIFICITY: [Isoform 3]: Expressed in cerebellum and brain
CC cortex. {ECO:0000269|PubMed:9693104}.
CC -!- DOMAIN: The nucleotide-binding domain consists of a twisted six-
CC stranded antiparallel beta-sheet flanked by two pairs of alpha-helices,
CC forming an hydrophobic pocket that interacts with the adenine ring of
CC ATP. The ATP binding site comprises residues located in alpha-1 and
CC alpha-2 helices and beta-2 and beta-3 strands, which are involved in
CC van der Waal's interactions, and Glu-1081 which forms an hydrogen bond
CC with the adenine ring. {ECO:0000269|PubMed:19917612}.
CC -!- DOMAIN: The heavy-metal-associated domain (HMA) coordinates a Cu(+) ion
CC via the cysteine residues within the CXXC motif. The transfer of Cu(+)
CC ion from ATOX1 to ATP7A involves the formation of a three-coordinate
CC Cu(+)-bridged heterodimer where the metal is shared between the two
CC metal binding sites of ATOX1 and ATP7A. The Cu(+) ion appears to switch
CC between two coordination modes, forming two links with one protein and
CC one with the other. Cisplatin, a chemotherapeutic drug, can bind the
CC CXXC motif and hinder the release of Cu(+) ion.
CC {ECO:0000269|PubMed:10419525, ECO:0000269|PubMed:19453293,
CC ECO:0000269|PubMed:31283225}.
CC -!- DOMAIN: Contains three di-leucine motifs in the C-terminus which are
CC required for recycling from the plasma membrane to the TGN. The di-
CC leucine 1487-Leu-Leu-1488 motif mediates endocytosis at the plasma
CC membrane, whereas the di-leucine 1467-Leu-Leu-1468 motif is a sorting
CC signal for retrograde trafficking to TGN via early endosomes.
CC {ECO:0000250|UniProtKB:Q64430}.
CC -!- DISEASE: Menkes disease (MNK) [MIM:309400]: An X-linked recessive
CC disorder of copper metabolism characterized by generalized copper
CC deficiency. MNKD results in progressive neurodegeneration and
CC connective-tissue disturbances: focal cerebral and cerebellar
CC degeneration, early growth retardation, peculiar hair,
CC hypopigmentation, cutis laxa, vascular complications and death in early
CC childhood. The clinical features result from the dysfunction of several
CC copper-dependent enzymes. A mild form of the disease has been
CC described, in which cerebellar ataxia and moderate developmental delay
CC predominate. {ECO:0000269|PubMed:10079817, ECO:0000269|PubMed:10319589,
CC ECO:0000269|PubMed:10401004, ECO:0000269|PubMed:11241493,
CC ECO:0000269|PubMed:11350187, ECO:0000269|PubMed:15981243,
CC ECO:0000269|PubMed:21667063, ECO:0000269|PubMed:22992316,
CC ECO:0000269|PubMed:28389643, ECO:0000269|PubMed:7977350,
CC ECO:0000269|PubMed:8981948}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Occipital horn syndrome (OHS) [MIM:304150]: An X-linked
CC recessive disorder of copper metabolism. Common features are unusual
CC facial appearance, skeletal abnormalities, chronic diarrhea and
CC genitourinary defects. The skeletal abnormalities include occipital
CC horns, short, broad clavicles, deformed radii, ulnae and humeri,
CC narrowing of the rib cage, undercalcified long bones with thin cortical
CC walls and coxa valga. {ECO:0000269|PubMed:11431706,
CC ECO:0000269|PubMed:17108763, ECO:0000269|PubMed:21667063,
CC ECO:0000269|PubMed:28389643, ECO:0000269|PubMed:9246006}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Distal spinal muscular atrophy, X-linked, 3 (DSMAX3)
CC [MIM:300489]: A neuromuscular disorder. Distal spinal muscular atrophy,
CC also known as distal hereditary motor neuronopathy, represents a
CC heterogeneous group of neuromuscular disorders caused by selective
CC degeneration of motor neurons in the anterior horn of the spinal cord,
CC without sensory deficit in the posterior horn. The overall clinical
CC picture consists of a classical distal muscular atrophy syndrome in the
CC legs without clinical sensory loss. The disease starts with weakness
CC and wasting of distal muscles of the anterior tibial and peroneal
CC compartments of the legs. Later on, weakness and atrophy may expand to
CC the proximal muscles of the lower limbs and/or to the distal upper
CC limbs. {ECO:0000269|PubMed:20170900}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 3]: Lacks 6 transmembrane regions and 5 heavy-
CC metal-associated (HMA) domains. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 5]: Lacks the transmembrane domains 3 and 4.
CC Expressed at a low level in several tissues of normal individuals and
CC is the only isoform found in patients with OHS. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 6]: Lacks all transmembrane regions and 5
CC heavy-metal-associated (HMA) domains, but has a putative nuclear
CC localization signal attached at the N-terminus. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3)
CC family. Type IB subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Heavy metal - Issue 79 of
CC February 2007;
CC URL="https://web.expasy.org/spotlight/back_issues/079";
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DR EMBL; L06133; AAA35580.1; -; mRNA.
DR EMBL; X82336; CAB94714.1; -; Genomic_DNA.
DR EMBL; X82337; CAB94714.1; JOINED; Genomic_DNA.
DR EMBL; X82338; CAB94714.1; JOINED; Genomic_DNA.
DR EMBL; X82339; CAB94714.1; JOINED; Genomic_DNA.
DR EMBL; X82340; CAB94714.1; JOINED; Genomic_DNA.
DR EMBL; X82341; CAB94714.1; JOINED; Genomic_DNA.
DR EMBL; X82342; CAB94714.1; JOINED; Genomic_DNA.
DR EMBL; X82343; CAB94714.1; JOINED; Genomic_DNA.
DR EMBL; X82344; CAB94714.1; JOINED; Genomic_DNA.
DR EMBL; X82345; CAB94714.1; JOINED; Genomic_DNA.
DR EMBL; X82346; CAB94714.1; JOINED; Genomic_DNA.
DR EMBL; X82347; CAB94714.1; JOINED; Genomic_DNA.
DR EMBL; X82348; CAB94714.1; JOINED; Genomic_DNA.
DR EMBL; X82349; CAB94714.1; JOINED; Genomic_DNA.
DR EMBL; X82350; CAB94714.1; JOINED; Genomic_DNA.
DR EMBL; X82351; CAB94714.1; JOINED; Genomic_DNA.
DR EMBL; X82352; CAB94714.1; JOINED; Genomic_DNA.
DR EMBL; X82353; CAB94714.1; JOINED; Genomic_DNA.
DR EMBL; X82354; CAB94714.1; JOINED; Genomic_DNA.
DR EMBL; X82355; CAB94714.1; JOINED; Genomic_DNA.
DR EMBL; X82356; CAB94714.1; JOINED; Genomic_DNA.
DR EMBL; AL645821; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z94753; CAB08160.1; -; Genomic_DNA.
DR EMBL; Z94801; CAB08162.2; -; Genomic_DNA.
DR EMBL; CH471104; EAW98605.1; -; Genomic_DNA.
DR EMBL; U27381; AAA96010.1; -; Genomic_DNA.
DR EMBL; U27361; AAA96010.1; JOINED; Genomic_DNA.
DR EMBL; U27362; AAA96010.1; JOINED; Genomic_DNA.
DR EMBL; U27363; AAA96010.1; JOINED; Genomic_DNA.
DR EMBL; U27365; AAA96010.1; JOINED; Genomic_DNA.
DR EMBL; U27366; AAA96010.1; JOINED; Genomic_DNA.
DR EMBL; U27367; AAA96010.1; JOINED; Genomic_DNA.
DR EMBL; U27368; AAA96010.1; JOINED; Genomic_DNA.
DR EMBL; U27369; AAA96010.1; JOINED; Genomic_DNA.
DR EMBL; U27370; AAA96010.1; JOINED; Genomic_DNA.
DR EMBL; U27371; AAA96010.1; JOINED; Genomic_DNA.
DR EMBL; U27372; AAA96010.1; JOINED; Genomic_DNA.
DR EMBL; U27373; AAA96010.1; JOINED; Genomic_DNA.
DR EMBL; U27374; AAA96010.1; JOINED; Genomic_DNA.
DR EMBL; U27375; AAA96010.1; JOINED; Genomic_DNA.
DR EMBL; U27376; AAA96010.1; JOINED; Genomic_DNA.
DR EMBL; U27377; AAA96010.1; JOINED; Genomic_DNA.
DR EMBL; U27378; AAA96010.1; JOINED; Genomic_DNA.
DR EMBL; U27379; AAA96010.1; JOINED; Genomic_DNA.
DR EMBL; U27380; AAA96010.1; JOINED; Genomic_DNA.
DR EMBL; X69208; CAA49145.1; -; mRNA.
DR EMBL; L06476; AAA16974.1; -; mRNA.
DR EMBL; AY011418; AAG47452.1; -; Genomic_DNA.
DR CCDS; CCDS35339.1; -. [Q04656-1]
DR CCDS; CCDS75997.1; -. [Q04656-5]
DR PIR; S36149; S36149.
DR RefSeq; NP_000043.4; NM_000052.6. [Q04656-1]
DR RefSeq; NP_001269153.1; NM_001282224.1. [Q04656-5]
DR PDB; 1AW0; NMR; -; A=375-446.
DR PDB; 1KVI; NMR; -; A=1-79.
DR PDB; 1KVJ; NMR; -; A=1-79.
DR PDB; 1Q8L; NMR; -; A=164-246.
DR PDB; 1S6O; NMR; -; A=169-240.
DR PDB; 1S6U; NMR; -; A=169-240.
DR PDB; 1Y3J; NMR; -; A=486-558.
DR PDB; 1Y3K; NMR; -; A=486-558.
DR PDB; 1YJR; NMR; -; A=562-633.
DR PDB; 1YJT; NMR; -; A=562-633.
DR PDB; 1YJU; NMR; -; A=562-633.
DR PDB; 1YJV; NMR; -; A=562-633.
DR PDB; 2AW0; NMR; -; A=375-446.
DR PDB; 2G9O; NMR; -; A=275-352.
DR PDB; 2GA7; NMR; -; A=275-352.
DR PDB; 2K1R; NMR; -; A=5-77.
DR PDB; 2KIJ; NMR; -; A=806-924.
DR PDB; 2KMV; NMR; -; A=1051-1231.
DR PDB; 2KMX; NMR; -; A=1051-1231.
DR PDB; 3CJK; X-ray; 1.80 A; B=7-77.
DR PDB; 5T7L; X-ray; 2.83 A; B=7-77.
DR PDB; 7LU8; NMR; -; A=84-156.
DR PDBsum; 1AW0; -.
DR PDBsum; 1KVI; -.
DR PDBsum; 1KVJ; -.
DR PDBsum; 1Q8L; -.
DR PDBsum; 1S6O; -.
DR PDBsum; 1S6U; -.
DR PDBsum; 1Y3J; -.
DR PDBsum; 1Y3K; -.
DR PDBsum; 1YJR; -.
DR PDBsum; 1YJT; -.
DR PDBsum; 1YJU; -.
DR PDBsum; 1YJV; -.
DR PDBsum; 2AW0; -.
DR PDBsum; 2G9O; -.
DR PDBsum; 2GA7; -.
DR PDBsum; 2K1R; -.
DR PDBsum; 2KIJ; -.
DR PDBsum; 2KMV; -.
DR PDBsum; 2KMX; -.
DR PDBsum; 3CJK; -.
DR PDBsum; 5T7L; -.
DR PDBsum; 7LU8; -.
DR AlphaFoldDB; Q04656; -.
DR BMRB; Q04656; -.
DR SMR; Q04656; -.
DR BioGRID; 107020; 89.
DR ELM; Q04656; -.
DR IntAct; Q04656; 25.
DR MINT; Q04656; -.
DR STRING; 9606.ENSP00000345728; -.
DR DrugBank; DB00958; Carboplatin.
DR DrugBank; DB00515; Cisplatin.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB00526; Oxaliplatin.
DR TCDB; 3.A.3.5.6; the p-type atpase (p-atpase) superfamily.
DR GlyGen; Q04656; 3 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q04656; -.
DR PhosphoSitePlus; Q04656; -.
DR BioMuta; ATP7A; -.
DR DMDM; 223590241; -.
DR EPD; Q04656; -.
DR jPOST; Q04656; -.
DR MassIVE; Q04656; -.
DR PaxDb; Q04656; -.
DR PeptideAtlas; Q04656; -.
DR PRIDE; Q04656; -.
DR ProteomicsDB; 58255; -. [Q04656-1]
DR ProteomicsDB; 58256; -. [Q04656-2]
DR ProteomicsDB; 58257; -. [Q04656-3]
DR ProteomicsDB; 58258; -. [Q04656-4]
DR ProteomicsDB; 58259; -. [Q04656-5]
DR ABCD; Q04656; 1 sequenced antibody.
DR Antibodypedia; 536; 418 antibodies from 35 providers.
DR DNASU; 538; -.
DR Ensembl; ENST00000341514.11; ENSP00000345728.6; ENSG00000165240.22. [Q04656-1]
DR Ensembl; ENST00000685264.1; ENSP00000510136.1; ENSG00000165240.22. [Q04656-1]
DR Ensembl; ENST00000686133.1; ENSP00000509233.1; ENSG00000165240.22. [Q04656-1]
DR Ensembl; ENST00000686543.1; ENSP00000509477.1; ENSG00000165240.22. [Q04656-5]
DR Ensembl; ENST00000687086.1; ENSP00000509566.1; ENSG00000165240.22. [Q04656-1]
DR Ensembl; ENST00000692908.1; ENSP00000508627.1; ENSG00000165240.22. [Q04656-5]
DR GeneID; 538; -.
DR KEGG; hsa:538; -.
DR MANE-Select; ENST00000341514.11; ENSP00000345728.6; NM_000052.7; NP_000043.4.
DR UCSC; uc004ecx.6; human. [Q04656-1]
DR CTD; 538; -.
DR DisGeNET; 538; -.
DR GeneCards; ATP7A; -.
DR GeneReviews; ATP7A; -.
DR HGNC; HGNC:869; ATP7A.
DR HPA; ENSG00000165240; Low tissue specificity.
DR MalaCards; ATP7A; -.
DR MIM; 300011; gene.
DR MIM; 300489; phenotype.
DR MIM; 304150; phenotype.
DR MIM; 309400; phenotype.
DR neXtProt; NX_Q04656; -.
DR OpenTargets; ENSG00000165240; -.
DR Orphanet; 388; Hirschsprung disease.
DR Orphanet; 565; Menkes disease.
DR Orphanet; 198; Occipital horn syndrome.
DR Orphanet; 139557; X-linked distal spinal muscular atrophy type 3.
DR PharmGKB; PA72; -.
DR VEuPathDB; HostDB:ENSG00000165240; -.
DR eggNOG; KOG0207; Eukaryota.
DR GeneTree; ENSGT00940000159568; -.
DR HOGENOM; CLU_001771_0_1_1; -.
DR InParanoid; Q04656; -.
DR OMA; IEKTGYE; -.
DR OrthoDB; 649559at2759; -.
DR PhylomeDB; Q04656; -.
DR TreeFam; TF300460; -.
DR BRENDA; 7.2.2.8; 2681.
DR BRENDA; 7.2.2.9; 2681.
DR PathwayCommons; Q04656; -.
DR Reactome; R-HSA-3299685; Detoxification of Reactive Oxygen Species.
DR Reactome; R-HSA-6803544; Ion influx/efflux at host-pathogen interface.
DR Reactome; R-HSA-936837; Ion transport by P-type ATPases.
DR SABIO-RK; Q04656; -.
DR SignaLink; Q04656; -.
DR BioGRID-ORCS; 538; 15 hits in 701 CRISPR screens.
DR ChiTaRS; ATP7A; human.
DR EvolutionaryTrace; Q04656; -.
DR GeneWiki; ATP7A; -.
DR GenomeRNAi; 538; -.
DR Pharos; Q04656; Tbio.
DR PRO; PR:Q04656; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q04656; protein.
DR Bgee; ENSG00000165240; Expressed in buccal mucosa cell and 199 other tissues.
DR ExpressionAtlas; Q04656; baseline and differential.
DR Genevisible; Q04656; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0031526; C:brush border membrane; IEA:Ensembl.
DR GO; GO:0031252; C:cell leading edge; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR GO; GO:0033162; C:melanosome membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0005902; C:microvillus; IEA:Ensembl.
DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0043204; C:perikaryon; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0030670; C:phagocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IEA:UniProtKB-SubCell.
DR GO; GO:0030141; C:secretory granule; IEA:Ensembl.
DR GO; GO:0005802; C:trans-Golgi network; IDA:UniProtKB.
DR GO; GO:0032588; C:trans-Golgi network membrane; ISS:UniProtKB.
DR GO; GO:0030140; C:trans-Golgi network transport vesicle; IMP:HGNC-UCL.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0051087; F:chaperone binding; IEA:Ensembl.
DR GO; GO:0005507; F:copper ion binding; IDA:UniProtKB.
DR GO; GO:0005375; F:copper ion transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0032767; F:copper-dependent protein binding; IDA:UniProtKB.
DR GO; GO:1903136; F:cuprous ion binding; IDA:UniProtKB.
DR GO; GO:0043682; F:P-type divalent copper transporter activity; ISS:UniProtKB.
DR GO; GO:0140581; F:P-type monovalent copper transporter activity; IDA:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IEA:Ensembl.
DR GO; GO:0016532; F:superoxide dismutase copper chaperone activity; ISS:UniProtKB.
DR GO; GO:0001568; P:blood vessel development; ISS:UniProtKB.
DR GO; GO:0001974; P:blood vessel remodeling; ISS:UniProtKB.
DR GO; GO:0051216; P:cartilage development; ISS:UniProtKB.
DR GO; GO:0006584; P:catecholamine metabolic process; ISS:UniProtKB.
DR GO; GO:0006878; P:cellular copper ion homeostasis; IMP:UniProtKB.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; IEA:Ensembl.
DR GO; GO:0071236; P:cellular response to antibiotic; IEA:Ensembl.
DR GO; GO:0071276; P:cellular response to cadmium ion; IEA:Ensembl.
DR GO; GO:0071279; P:cellular response to cobalt ion; IEA:Ensembl.
DR GO; GO:0071280; P:cellular response to copper ion; IEA:Ensembl.
DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR GO; GO:0071281; P:cellular response to iron ion; IEA:Ensembl.
DR GO; GO:0071284; P:cellular response to lead ion; IEA:Ensembl.
DR GO; GO:0036120; P:cellular response to platelet-derived growth factor stimulus; IEA:Ensembl.
DR GO; GO:0021954; P:central nervous system neuron development; ISS:UniProtKB.
DR GO; GO:0021702; P:cerebellar Purkinje cell differentiation; ISS:UniProtKB.
DR GO; GO:0030199; P:collagen fibril organization; ISS:UniProtKB.
DR GO; GO:0060003; P:copper ion export; IDA:UniProtKB.
DR GO; GO:0055070; P:copper ion homeostasis; IBA:GO_Central.
DR GO; GO:0015677; P:copper ion import; ISS:UniProtKB.
DR GO; GO:0006825; P:copper ion transport; IMP:UniProtKB.
DR GO; GO:0010273; P:detoxification of copper ion; ISS:UniProtKB.
DR GO; GO:0042417; P:dopamine metabolic process; ISS:UniProtKB.
DR GO; GO:0048251; P:elastic fiber assembly; ISS:UniProtKB.
DR GO; GO:0051542; P:elastin biosynthetic process; ISS:UniProtKB.
DR GO; GO:0042414; P:epinephrine metabolic process; ISS:UniProtKB.
DR GO; GO:0030198; P:extracellular matrix organization; ISS:UniProtKB.
DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR GO; GO:0031069; P:hair follicle morphogenesis; ISS:UniProtKB.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0007595; P:lactation; IEA:Ensembl.
DR GO; GO:0001889; P:liver development; IEA:Ensembl.
DR GO; GO:0007626; P:locomotory behavior; ISS:UniProtKB.
DR GO; GO:0048286; P:lung alveolus development; ISS:UniProtKB.
DR GO; GO:0007005; P:mitochondrion organization; ISS:UniProtKB.
DR GO; GO:0034760; P:negative regulation of iron ion transmembrane transport; IEA:Ensembl.
DR GO; GO:0048812; P:neuron projection morphogenesis; ISS:UniProtKB.
DR GO; GO:0042415; P:norepinephrine metabolic process; ISS:UniProtKB.
DR GO; GO:0018205; P:peptidyl-lysine modification; ISS:UniProtKB.
DR GO; GO:0043473; P:pigmentation; ISS:UniProtKB.
DR GO; GO:0043085; P:positive regulation of catalytic activity; ISS:UniProtKB.
DR GO; GO:0045793; P:positive regulation of cell size; IEA:Ensembl.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0010592; P:positive regulation of lamellipodium assembly; IEA:Ensembl.
DR GO; GO:0048023; P:positive regulation of melanin biosynthetic process; IMP:UniProtKB.
DR GO; GO:1903036; P:positive regulation of response to wounding; IEA:Ensembl.
DR GO; GO:0032773; P:positive regulation of tyrosinase activity; IMP:UniProtKB.
DR GO; GO:1904754; P:positive regulation of vascular associated smooth muscle cell migration; IEA:Ensembl.
DR GO; GO:0021860; P:pyramidal neuron development; ISS:UniProtKB.
DR GO; GO:1904959; P:regulation of cytochrome-c oxidase activity; IEA:Ensembl.
DR GO; GO:0010468; P:regulation of gene expression; IEA:Ensembl.
DR GO; GO:0002082; P:regulation of oxidative phosphorylation; ISS:UniProtKB.
DR GO; GO:0019430; P:removal of superoxide radicals; ISS:UniProtKB.
DR GO; GO:0010041; P:response to iron(III) ion; IEA:Ensembl.
DR GO; GO:0010042; P:response to manganese ion; IEA:Ensembl.
DR GO; GO:0010043; P:response to zinc ion; IEA:Ensembl.
DR GO; GO:0042428; P:serotonin metabolic process; ISS:UniProtKB.
DR GO; GO:0043588; P:skin development; ISS:UniProtKB.
DR GO; GO:0042093; P:T-helper cell differentiation; ISS:UniProtKB.
DR GO; GO:0006568; P:tryptophan metabolic process; ISS:UniProtKB.
DR CDD; cd00371; HMA; 6.
DR DisProt; DP00282; -.
DR Gene3D; 3.40.1110.10; -; 1.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR023299; ATPase_P-typ_cyto_dom_N.
DR InterPro; IPR018303; ATPase_P-typ_P_site.
DR InterPro; IPR023298; ATPase_P-typ_TM_dom_sf.
DR InterPro; IPR008250; ATPase_P-typ_transduc_dom_A_sf.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR023214; HAD_sf.
DR InterPro; IPR017969; Heavy-metal-associated_CS.
DR InterPro; IPR006122; HMA_Cu_ion-bd.
DR InterPro; IPR006121; HMA_dom.
DR InterPro; IPR036163; HMA_dom_sf.
DR InterPro; IPR027256; P-typ_ATPase_IB.
DR InterPro; IPR001757; P_typ_ATPase.
DR InterPro; IPR044492; P_typ_ATPase_HD_dom.
DR Pfam; PF00403; HMA; 6.
DR SFLD; SFLDF00027; p-type_atpase; 1.
DR SUPFAM; SSF55008; SSF55008; 6.
DR SUPFAM; SSF56784; SSF56784; 1.
DR SUPFAM; SSF81653; SSF81653; 1.
DR SUPFAM; SSF81660; SSF81660; 1.
DR SUPFAM; SSF81665; SSF81665; 1.
DR TIGRFAMs; TIGR01525; ATPase-IB_hvy; 1.
DR TIGRFAMs; TIGR01494; ATPase_P-type; 2.
DR TIGRFAMs; TIGR00003; TIGR00003; 6.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
DR PROSITE; PS01047; HMA_1; 6.
DR PROSITE; PS50846; HMA_2; 7.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane;
KW Cell projection; Copper; Copper transport; Cytoplasm; Disease variant;
KW Endoplasmic reticulum; Endosome; Glycoprotein; Golgi apparatus;
KW Ion transport; Magnesium; Membrane; Metal-binding; Neurodegeneration;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat; Synapse;
KW Translocase; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1500
FT /note="Copper-transporting ATPase 1"
FT /id="PRO_0000046311"
FT TOPO_DOM 1..653
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 654..675
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 676..714
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 715..734
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 735..741
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 742..762
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 763..781
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 782..802
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 803..936
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 937..959
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 960..989
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 990..1011
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1012..1356
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1357..1374
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1375..1385
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1386..1405
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1406..1500
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 8..74
FT /note="HMA 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT DOMAIN 85..151
FT /note="HMA 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT DOMAIN 171..237
FT /note="HMA 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT DOMAIN 277..343
FT /note="HMA 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT DOMAIN 377..443
FT /note="HMA 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT DOMAIN 488..554
FT /note="HMA 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT DOMAIN 564..630
FT /note="HMA 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT REGION 1486..1500
FT /note="PDZD11-binding"
FT MOTIF 1467..1468
FT /note="Endocytosis signal"
FT /evidence="ECO:0000250|UniProtKB:Q64430"
FT MOTIF 1487..1488
FT /note="Endocytosis signal"
FT /evidence="ECO:0000250|UniProtKB:Q64430"
FT ACT_SITE 1044
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000250"
FT BINDING 18
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:31283225,
FT ECO:0007744|PDB:5T7L"
FT BINDING 19
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280,
FT ECO:0000269|PubMed:31283225, ECO:0007744|PDB:5T7L"
FT BINDING 22
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280,
FT ECO:0000269|PubMed:31283225, ECO:0007744|PDB:5T7L"
FT BINDING 182
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 185
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 288
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 291
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 388
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 391
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 499
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 502
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 575
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 578
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 1081
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:19917612"
FT BINDING 1301
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT BINDING 1305
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT MOD_RES 152
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 270
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 327
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 339
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 353
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70705"
FT MOD_RES 357
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 362
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64430"
FT MOD_RES 1212
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P70705"
FT MOD_RES 1430
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1432
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1460
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1463
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1466
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1469
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1473
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1476
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64430"
FT MOD_RES 1486
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64430"
FT CARBOHYD 686
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 975
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1
FT /note="M -> MRKLSIRKRDNNLLK (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:10079814"
FT /id="VSP_000419"
FT VAR_SEQ 1
FT /note="M -> MRKLSIRKRDNNLLKPSSASSLGIAVSLGRPVLSRSSSGTVNLLEEV
FT GLHIRDTAFSSTKLLEAISTVSAQVEELAVHNECY (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10079814"
FT /id="VSP_000420"
FT VAR_SEQ 1
FT /note="M -> MRKLSIRKRDNNLLKECNEEIK (in isoform 6)"
FT /evidence="ECO:0000305"
FT /id="VSP_000421"
FT VAR_SEQ 42..1038
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10079814,
FT ECO:0000303|PubMed:9693104"
FT /id="VSP_000424"
FT VAR_SEQ 53..81
FT /note="DPKLQTPKTLQEAIDDMGFDAVIHNPDPL -> AHWFGFAALDGICSNGCFI
FT CFCSTFFSSL (in isoform 6)"
FT /evidence="ECO:0000305"
FT /id="VSP_000422"
FT VAR_SEQ 82..1499
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000305"
FT /id="VSP_000423"
FT VAR_SEQ 725..802
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_000425"
FT VARIANT 628
FT /note="E -> V (in MNK; loss of protein expression)"
FT /evidence="ECO:0000269|PubMed:28389643"
FT /id="VAR_084344"
FT VARIANT 629
FT /note="A -> P (in MNK; dbSNP:rs72554639)"
FT /evidence="ECO:0000269|PubMed:8981948"
FT /id="VAR_000699"
FT VARIANT 633
FT /note="K -> R (in MNK; loss of protein expression)"
FT /evidence="ECO:0000269|PubMed:28389643"
FT /id="VAR_084345"
FT VARIANT 637
FT /note="S -> L (in OHS; dbSNP:rs151340631)"
FT /evidence="ECO:0000269|PubMed:9246006"
FT /id="VAR_009999"
FT VARIANT 653
FT /note="S -> Y (in MNK; impaired copper-dependent
FT trafficking from TGN to post-TGN compartments; subcellular
FT location restricted to TGN; impaired copper transport
FT activity)"
FT /evidence="ECO:0000269|PubMed:28389643"
FT /id="VAR_084346"
FT VARIANT 666
FT /note="G -> R (in MNK; subcellular location restricted to
FT post-TGN compartments; impaired copper transport activity;
FT dbSNP:rs797045344)"
FT /evidence="ECO:0000269|PubMed:28389643"
FT /id="VAR_084347"
FT VARIANT 669
FT /note="I -> T (in dbSNP:rs2234935)"
FT /evidence="ECO:0000269|PubMed:7607665,
FT ECO:0000269|PubMed:8490659"
FT /id="VAR_016119"
FT VARIANT 703
FT /note="R -> H (in dbSNP:rs2234936)"
FT /id="VAR_016120"
FT VARIANT 706
FT /note="L -> R (in MNK; dbSNP:rs72554642)"
FT /evidence="ECO:0000269|PubMed:11350187"
FT /id="VAR_023261"
FT VARIANT 727
FT /note="G -> R (in MNK; impaired copper-dependent
FT trafficking from TGN to post-TGN compartments; subcellular
FT location restricted to TGN; impaired copper transport
FT activity; dbSNP:rs72554644)"
FT /evidence="ECO:0000269|PubMed:28389643,
FT ECO:0000269|PubMed:8981948"
FT /id="VAR_000700"
FT VARIANT 728
FT /note="G -> D (in MNK; impaired copper-dependent
FT trafficking from TGN to post-TGN compartments; subcellular
FT location restricted to TGN; impaired copper transport
FT activity; dbSNP:rs797045350)"
FT /evidence="ECO:0000269|PubMed:28389643"
FT /id="VAR_084348"
FT VARIANT 761
FT /note="S -> P (in MNK; has no effect on copper-dependent
FT trafficking from TGN to post-TGN compartments; impaired
FT copper transport activity)"
FT /evidence="ECO:0000269|PubMed:28389643"
FT /id="VAR_084349"
FT VARIANT 767
FT /note="V -> L (in dbSNP:rs2227291)"
FT /evidence="ECO:0000269|PubMed:7977350"
FT /id="VAR_010000"
FT VARIANT 802
FT /note="K -> N (in MNK; loss of protein expression)"
FT /evidence="ECO:0000269|PubMed:28389643"
FT /id="VAR_084350"
FT VARIANT 844
FT /note="R -> H (in MNK; loss of protein expression;
FT dbSNP:rs367775730)"
FT /evidence="ECO:0000269|PubMed:15981243,
FT ECO:0000269|PubMed:28389643"
FT /id="VAR_023262"
FT VARIANT 853
FT /note="G -> R (in MNK)"
FT /evidence="ECO:0000269|PubMed:15981243"
FT /id="VAR_023263"
FT VARIANT 860
FT /note="G -> V (in MNK; decreased protein abundance;
FT impaired copper transport activity)"
FT /evidence="ECO:0000269|PubMed:15981243,
FT ECO:0000269|PubMed:28389643"
FT /id="VAR_023264"
FT VARIANT 873
FT /note="L -> R (in MNK; increased protein abundance; does
FT not affect interaction with ATOX1; does not affect
FT interaction with COMMD1; increased localization at the
FT plasma membrane; does not cycle back to TGN under
FT conditions of copper depletion; dbSNP:rs72554646)"
FT /evidence="ECO:0000269|PubMed:10319589,
FT ECO:0000269|PubMed:21667063"
FT /id="VAR_010001"
FT VARIANT 876
FT /note="G -> E (in MNK; subcellular location restricted to
FT post-TGN compartments; impaired copper transport activity)"
FT /evidence="ECO:0000269|PubMed:15981243,
FT ECO:0000269|PubMed:28389643"
FT /id="VAR_010002"
FT VARIANT 876
FT /note="G -> R (in MNK; loss of protein expression)"
FT /evidence="ECO:0000269|PubMed:15981243,
FT ECO:0000269|PubMed:28389643"
FT /id="VAR_023265"
FT VARIANT 924
FT /note="Q -> R (in OHS; has no effect on copper-dependent
FT trafficking; impaired copper transport activity)"
FT /evidence="ECO:0000269|PubMed:15981243,
FT ECO:0000269|PubMed:28389643"
FT /id="VAR_023266"
FT VARIANT 994
FT /note="T -> I (in DSMAX3; demonstrates impaired
FT intracellular trafficking compared to control with some of
FT the mutant protein remaining in the Golgi apparatus after
FT exposure to copper; dbSNP:rs267606673)"
FT /evidence="ECO:0000269|PubMed:20170900"
FT /id="VAR_063882"
FT VARIANT 1000
FT /note="C -> R (in MNK; decreased protein abundance;
FT increased protein degradation; does not affect interaction
FT with ATOX1; does not affect interaction with COMMD1;
FT subcellular location restricted to TGN; does not localizes
FT to the plasma membrane in response to elevated copper
FT levels; impaired copper transport activity)"
FT /evidence="ECO:0000269|PubMed:15981243,
FT ECO:0000269|PubMed:21667063, ECO:0000269|PubMed:28389643"
FT /id="VAR_010003"
FT VARIANT 1005
FT /note="G -> R (in MNK; impaired copper-dependent
FT trafficking from TGN to post-TGN compartments; subcellular
FT location restricted to TGN; impaired copper transport
FT activity; dbSNP:rs1569550143)"
FT /evidence="ECO:0000269|PubMed:28389643"
FT /id="VAR_084351"
FT VARIANT 1006
FT /note="L -> P (in MNK; dbSNP:rs72554651)"
FT /evidence="ECO:0000269|PubMed:8981948"
FT /id="VAR_000701"
FT VARIANT 1007
FT /note="A -> V (in MNK; impaired copper-dependent
FT trafficking from TGN to post-TGN compartments; subcellular
FT location restricted to TGN; impaired copper transport
FT activity)"
FT /evidence="ECO:0000269|PubMed:15981243,
FT ECO:0000269|PubMed:28389643"
FT /id="VAR_023267"
FT VARIANT 1015
FT /note="G -> D (in MNK; subcellular location restricted to
FT post-TGN compartments; impaired copper transport activity)"
FT /evidence="ECO:0000269|PubMed:15981243,
FT ECO:0000269|PubMed:28389643"
FT /id="VAR_023268"
FT VARIANT 1019
FT /note="G -> D (in MNK; dbSNP:rs72554652)"
FT /evidence="ECO:0000269|PubMed:8981948"
FT /id="VAR_000702"
FT VARIANT 1037
FT /note="K -> N (in MNK; loss of protein expression)"
FT /evidence="ECO:0000269|PubMed:28389643"
FT /id="VAR_084352"
FT VARIANT 1044
FT /note="D -> G (in MNK; impaired copper-dependent
FT trafficking from TGN to post-TGN compartments; subcellular
FT location restricted to TGN; impaired copper transport
FT activity)"
FT /evidence="ECO:0000269|PubMed:15981243,
FT ECO:0000269|PubMed:28389643"
FT /id="VAR_023269"
FT VARIANT 1048
FT /note="T -> I (in MNK)"
FT /evidence="ECO:0000269|PubMed:22992316"
FT /id="VAR_068831"
FT VARIANT 1100
FT /note="L -> P (in MNK)"
FT /evidence="ECO:0000269|PubMed:15981243"
FT /id="VAR_023270"
FT VARIANT 1118
FT /note="G -> D (in MNK; dbSNP:rs72554654)"
FT /evidence="ECO:0000269|PubMed:11350187"
FT /id="VAR_023271"
FT VARIANT 1255
FT /note="G -> R (in MNK; decreased protein abundance;
FT impaired copper-dependent trafficking from TGN to post-TGN
FT compartments; subcellular location restricted to TGN;
FT impaired copper transport activity; dbSNP:rs72554655)"
FT /evidence="ECO:0000269|PubMed:11350187,
FT ECO:0000269|PubMed:28389643"
FT /id="VAR_023272"
FT VARIANT 1282
FT /note="K -> E (in MNK; impaired copper-dependent
FT trafficking from TGN to post-TGN compartments; subcellular
FT location restricted to TGN; impaired copper transport
FT activity)"
FT /evidence="ECO:0000269|PubMed:15981243,
FT ECO:0000269|PubMed:28389643"
FT /id="VAR_023273"
FT VARIANT 1300
FT /note="G -> E (in MNK; impaired copper-dependent
FT trafficking from TGN to post-TGN compartments; subcellular
FT location restricted to TGN; impaired copper transport
FT activity)"
FT /evidence="ECO:0000269|PubMed:15981243,
FT ECO:0000269|PubMed:28389643"
FT /id="VAR_010004"
FT VARIANT 1301
FT /note="D -> G (in MNK; impaired copper-dependent
FT trafficking from TGN to post-TGN compartments; subcellular
FT location restricted to TGN; impaired copper transport
FT activity; dbSNP:rs1557238588)"
FT /evidence="ECO:0000269|PubMed:28389643"
FT /id="VAR_084353"
FT VARIANT 1302
FT /note="G -> E (in MNK; impaired copper-dependent
FT trafficking from TGN to post-TGN compartments; subcellular
FT location restricted to TGN; impaired copper transport
FT activity)"
FT /evidence="ECO:0000269|PubMed:28389643"
FT /id="VAR_084354"
FT VARIANT 1302
FT /note="G -> R (in MNK; dbSNP:rs72554657)"
FT /evidence="ECO:0000269|PubMed:7977350"
FT /id="VAR_010005"
FT VARIANT 1302
FT /note="G -> V (in MNK; impaired copper-dependent
FT trafficking from TGN to post-TGN compartments; subcellular
FT location restricted to TGN; impaired copper transport
FT activity)"
FT /evidence="ECO:0000269|PubMed:15981243,
FT ECO:0000269|PubMed:28389643"
FT /id="VAR_010006"
FT VARIANT 1304
FT /note="N -> K (in MNK; impaired copper-dependent
FT trafficking from TGN to post-TGN compartments; subcellular
FT location restricted to TGN; impaired copper transport
FT activity)"
FT /evidence="ECO:0000269|PubMed:15981243,
FT ECO:0000269|PubMed:28389643"
FT /id="VAR_023274"
FT VARIANT 1304
FT /note="N -> S (in OHS; has approximately 33% residual
FT copper transport; increased protein abundance; increased
FT localization at the plasma membrane; does not cycle back to
FT TGN under conditions of copper depletion; does not affect
FT interaction with ATOX1; does not affect interaction with
FT COMMD1; dbSNP:rs151340632)"
FT /evidence="ECO:0000269|PubMed:17108763,
FT ECO:0000269|PubMed:21667063"
FT /id="VAR_063883"
FT VARIANT 1305
FT /note="D -> A (in MNK; impaired copper-dependent
FT trafficking from TGN to post-TGN compartments; subcellular
FT location restricted to TGN; impaired copper transport
FT activity)"
FT /evidence="ECO:0000269|PubMed:15981243,
FT ECO:0000269|PubMed:28389643"
FT /id="VAR_010007"
FT VARIANT 1305
FT /note="D -> G (in MNK; impaired copper-dependent
FT trafficking from TGN to post-TGN compartments; subcellular
FT location restricted to TGN; impaired copper transport
FT activity)"
FT /evidence="ECO:0000269|PubMed:28389643"
FT /id="VAR_084355"
FT VARIANT 1308
FT /note="A -> D (in MNK; impaired copper-dependent
FT trafficking from TGN to post-TGN compartments; subcellular
FT location restricted to TGN; impaired copper transport
FT activity)"
FT /evidence="ECO:0000269|PubMed:28389643"
FT /id="VAR_084356"
FT VARIANT 1315
FT /note="G -> R (in MNK; impaired copper-dependent
FT trafficking from TGN to post-TGN compartments; subcellular
FT location restricted to TGN; impaired copper transport
FT activity; dbSNP:rs797045390)"
FT /evidence="ECO:0000269|PubMed:15981243,
FT ECO:0000269|PubMed:28389643"
FT /id="VAR_023275"
FT VARIANT 1325
FT /note="A -> V (in MNK; subcellular location restricted to
FT post-TGN compartments; impaired copper transport activity)"
FT /evidence="ECO:0000269|PubMed:15981243,
FT ECO:0000269|PubMed:28389643"
FT /id="VAR_023276"
FT VARIANT 1344
FT /note="S -> R (in MNK)"
FT /evidence="ECO:0000269|PubMed:11241493"
FT /id="VAR_023277"
FT VARIANT 1345
FT /note="I -> F (in MNK)"
FT /evidence="ECO:0000269|PubMed:11241493"
FT /id="VAR_023278"
FT VARIANT 1350
FT /note="K -> E (in dbSNP:rs4826245)"
FT /evidence="ECO:0000269|PubMed:15772651, ECO:0000269|Ref.7"
FT /id="VAR_080663"
FT VARIANT 1362
FT /note="A -> V (in MNK; decreased protein abundance;
FT increased protein degradation; does not affect interaction
FT with ATOX1; does not affect interaction with COMMD1;
FT subcellular location restricted to TGN; does not localizes
FT to the plasma membrane in response to elevated copper
FT levels; impaired copper transport activity)"
FT /evidence="ECO:0000269|PubMed:10401004,
FT ECO:0000269|PubMed:21667063, ECO:0000269|PubMed:28389643"
FT /id="VAR_010008"
FT VARIANT 1369
FT /note="G -> R (in MNK; loss of protein expression)"
FT /evidence="ECO:0000269|PubMed:15981243,
FT ECO:0000269|PubMed:28389643"
FT /id="VAR_023279"
FT VARIANT 1373
FT /note="A -> P (in MNK; loss of protein expression)"
FT /evidence="ECO:0000269|PubMed:28389643"
FT /id="VAR_084357"
FT VARIANT 1386
FT /note="P -> S (in DSMAX3; demonstrates impaired
FT intracellular trafficking compared to control with some
FT mutant protein remaining in the Golgi apparatus after
FT exposure to copper; dbSNP:rs267606672)"
FT /evidence="ECO:0000269|PubMed:20170900"
FT /id="VAR_063884"
FT VARIANT 1393
FT /note="M -> T (in MNK; impaired copper-dependent
FT trafficking from TGN to post-TGN compartments; subcellular
FT location restricted to TGN; impaired copper transport
FT activity)"
FT /evidence="ECO:0000269|PubMed:28389643"
FT /id="VAR_084358"
FT VARIANT 1397
FT /note="S -> F (in MNK; impaired copper-dependent
FT trafficking from TGN to post-TGN compartments; subcellular
FT location restricted to TGN; impaired copper transport
FT activity)"
FT /evidence="ECO:0000269|PubMed:15981243,
FT ECO:0000269|PubMed:28389643"
FT /id="VAR_023280"
FT VARIANT 1464
FT /note="I -> V (in dbSNP:rs2234938)"
FT /id="VAR_016121"
FT MUTAGEN 22
FT /note="C->A: Impairs Cu(+)-bridged heterodimer formation
FT with ATOX1 while increasing the reactivity toward
FT cisplatin."
FT /evidence="ECO:0000269|PubMed:31283225"
FT MUTAGEN 1044
FT /note="D->E: Impairs tyrosinase activity involved in
FT melanin synthesis."
FT /evidence="ECO:0000269|PubMed:11092760"
FT MUTAGEN 1487..1488
FT /note="LL->AA: Loss of relocalization to the trans-Golgi."
FT /evidence="ECO:0000269|PubMed:10484781"
FT CONFLICT 10
FT /note="V -> A (in Ref. 4; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 36
FT /note="V -> E (in Ref. 10; AAA16974)"
FT /evidence="ECO:0000305"
FT CONFLICT 336
FT /note="E -> V (in Ref. 1; AAA35580 and 8; AAA96010)"
FT /evidence="ECO:0000305"
FT CONFLICT 446
FT /note="D -> G (in Ref. 6; CAB08162)"
FT /evidence="ECO:0000305"
FT CONFLICT 624
FT /note="S -> G (in Ref. 6; CAB08162)"
FT /evidence="ECO:0000305"
FT CONFLICT 725
FT /note="F -> V (in Ref. 6; CAB08162)"
FT /evidence="ECO:0000305"
FT CONFLICT 833
FT /note="S -> R (in Ref. 6; CAB08162)"
FT /evidence="ECO:0000305"
FT CONFLICT 1099
FT /note="E -> K (in Ref. 4; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 1171
FT /note="N -> S (in Ref. 6; CAB08162)"
FT /evidence="ECO:0000305"
FT CONFLICT 1178
FT /note="Y -> C (in Ref. 4; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 1178
FT /note="Y -> H (in Ref. 1; AAA35580, 3; CAB94714 and 8;
FT AAA96010)"
FT /evidence="ECO:0000305"
FT CONFLICT 1220
FT /note="D -> G (in Ref. 6; CAB08162)"
FT /evidence="ECO:0000305"
FT CONFLICT 1295
FT /note="R -> W (in Ref. 4; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 1313
FT /note="N -> D (in Ref. 4; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 1336
FT /note="N -> D (in Ref. 6; CAB08162)"
FT /evidence="ECO:0000305"
FT CONFLICT 1376
FT /note="V -> M (in Ref. 6; CAB08162)"
FT /evidence="ECO:0000305"
FT CONFLICT 1396
FT /note="S -> P (in Ref. 4; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 1409
FT /note="L -> R (in Ref. 6; CAB08160)"
FT /evidence="ECO:0000305"
FT CONFLICT 1455
FT /note="R -> W (in Ref. 4; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT TURN 4..6
FT /evidence="ECO:0007829|PDB:1KVI"
FT STRAND 8..14
FT /evidence="ECO:0007829|PDB:3CJK"
FT HELIX 20..31
FT /evidence="ECO:0007829|PDB:3CJK"
FT STRAND 33..35
FT /evidence="ECO:0007829|PDB:1KVI"
FT STRAND 36..42
FT /evidence="ECO:0007829|PDB:3CJK"
FT TURN 43..46
FT /evidence="ECO:0007829|PDB:3CJK"
FT STRAND 47..52
FT /evidence="ECO:0007829|PDB:3CJK"
FT TURN 54..56
FT /evidence="ECO:0007829|PDB:3CJK"
FT HELIX 59..68
FT /evidence="ECO:0007829|PDB:3CJK"
FT STRAND 73..77
FT /evidence="ECO:0007829|PDB:3CJK"
FT STRAND 84..91
FT /evidence="ECO:0007829|PDB:7LU8"
FT HELIX 100..109
FT /evidence="ECO:0007829|PDB:7LU8"
FT STRAND 113..119
FT /evidence="ECO:0007829|PDB:7LU8"
FT TURN 120..123
FT /evidence="ECO:0007829|PDB:7LU8"
FT STRAND 124..129
FT /evidence="ECO:0007829|PDB:7LU8"
FT TURN 131..133
FT /evidence="ECO:0007829|PDB:7LU8"
FT HELIX 136..142
FT /evidence="ECO:0007829|PDB:7LU8"
FT STRAND 165..169
FT /evidence="ECO:0007829|PDB:1Q8L"
FT STRAND 171..177
FT /evidence="ECO:0007829|PDB:1Q8L"
FT TURN 180..182
FT /evidence="ECO:0007829|PDB:1Q8L"
FT HELIX 187..194
FT /evidence="ECO:0007829|PDB:1Q8L"
FT STRAND 199..204
FT /evidence="ECO:0007829|PDB:1Q8L"
FT TURN 207..209
FT /evidence="ECO:0007829|PDB:1Q8L"
FT STRAND 210..215
FT /evidence="ECO:0007829|PDB:1Q8L"
FT TURN 217..219
FT /evidence="ECO:0007829|PDB:1S6O"
FT HELIX 222..231
FT /evidence="ECO:0007829|PDB:1Q8L"
FT STRAND 236..238
FT /evidence="ECO:0007829|PDB:1S6U"
FT TURN 242..244
FT /evidence="ECO:0007829|PDB:1Q8L"
FT STRAND 277..285
FT /evidence="ECO:0007829|PDB:2G9O"
FT HELIX 288..299
FT /evidence="ECO:0007829|PDB:2G9O"
FT STRAND 305..311
FT /evidence="ECO:0007829|PDB:2G9O"
FT TURN 312..315
FT /evidence="ECO:0007829|PDB:2G9O"
FT STRAND 316..321
FT /evidence="ECO:0007829|PDB:2G9O"
FT STRAND 324..326
FT /evidence="ECO:0007829|PDB:2GA7"
FT HELIX 329..336
FT /evidence="ECO:0007829|PDB:2G9O"
FT TURN 340..342
FT /evidence="ECO:0007829|PDB:2G9O"
FT STRAND 344..346
FT /evidence="ECO:0007829|PDB:2G9O"
FT STRAND 377..384
FT /evidence="ECO:0007829|PDB:1AW0"
FT HELIX 388..400
FT /evidence="ECO:0007829|PDB:1AW0"
FT STRAND 408..411
FT /evidence="ECO:0007829|PDB:1AW0"
FT TURN 412..415
FT /evidence="ECO:0007829|PDB:1AW0"
FT STRAND 416..421
FT /evidence="ECO:0007829|PDB:1AW0"
FT TURN 423..425
FT /evidence="ECO:0007829|PDB:1AW0"
FT HELIX 428..438
FT /evidence="ECO:0007829|PDB:1AW0"
FT STRAND 441..446
FT /evidence="ECO:0007829|PDB:1AW0"
FT STRAND 488..495
FT /evidence="ECO:0007829|PDB:1Y3J"
FT HELIX 497..499
FT /evidence="ECO:0007829|PDB:1Y3J"
FT HELIX 502..510
FT /evidence="ECO:0007829|PDB:1Y3J"
FT STRAND 513..518
FT /evidence="ECO:0007829|PDB:1Y3J"
FT TURN 523..526
FT /evidence="ECO:0007829|PDB:1Y3J"
FT STRAND 527..532
FT /evidence="ECO:0007829|PDB:1Y3J"
FT TURN 534..536
FT /evidence="ECO:0007829|PDB:1Y3J"
FT HELIX 539..549
FT /evidence="ECO:0007829|PDB:1Y3J"
FT STRAND 553..557
FT /evidence="ECO:0007829|PDB:1Y3J"
FT STRAND 566..571
FT /evidence="ECO:0007829|PDB:1YJR"
FT TURN 575..577
FT /evidence="ECO:0007829|PDB:1YJR"
FT HELIX 578..586
FT /evidence="ECO:0007829|PDB:1YJR"
FT STRAND 592..598
FT /evidence="ECO:0007829|PDB:1YJR"
FT TURN 599..602
FT /evidence="ECO:0007829|PDB:1YJR"
FT STRAND 603..608
FT /evidence="ECO:0007829|PDB:1YJR"
FT TURN 610..613
FT /evidence="ECO:0007829|PDB:1YJR"
FT HELIX 614..626
FT /evidence="ECO:0007829|PDB:1YJR"
FT STRAND 628..633
FT /evidence="ECO:0007829|PDB:1YJR"
FT HELIX 808..814
FT /evidence="ECO:0007829|PDB:2KIJ"
FT STRAND 818..824
FT /evidence="ECO:0007829|PDB:2KIJ"
FT STRAND 826..828
FT /evidence="ECO:0007829|PDB:2KIJ"
FT STRAND 833..838
FT /evidence="ECO:0007829|PDB:2KIJ"
FT TURN 839..841
FT /evidence="ECO:0007829|PDB:2KIJ"
FT STRAND 847..849
FT /evidence="ECO:0007829|PDB:2KIJ"
FT STRAND 860..862
FT /evidence="ECO:0007829|PDB:2KIJ"
FT STRAND 868..870
FT /evidence="ECO:0007829|PDB:2KIJ"
FT TURN 872..875
FT /evidence="ECO:0007829|PDB:2KIJ"
FT STRAND 887..889
FT /evidence="ECO:0007829|PDB:2KIJ"
FT STRAND 894..898
FT /evidence="ECO:0007829|PDB:2KIJ"
FT STRAND 901..904
FT /evidence="ECO:0007829|PDB:2KIJ"
FT TURN 908..910
FT /evidence="ECO:0007829|PDB:2KIJ"
FT HELIX 912..919
FT /evidence="ECO:0007829|PDB:2KIJ"
FT TURN 920..923
FT /evidence="ECO:0007829|PDB:2KIJ"
FT STRAND 1055..1061
FT /evidence="ECO:0007829|PDB:2KMV"
FT TURN 1065..1067
FT /evidence="ECO:0007829|PDB:2KMV"
FT HELIX 1070..1079
FT /evidence="ECO:0007829|PDB:2KMV"
FT HELIX 1080..1082
FT /evidence="ECO:0007829|PDB:2KMV"
FT STRAND 1083..1085
FT /evidence="ECO:0007829|PDB:2KMV"
FT HELIX 1087..1100
FT /evidence="ECO:0007829|PDB:2KMV"
FT STRAND 1112..1114
FT /evidence="ECO:0007829|PDB:2KMV"
FT TURN 1115..1117
FT /evidence="ECO:0007829|PDB:2KMV"
FT STRAND 1118..1123
FT /evidence="ECO:0007829|PDB:2KMV"
FT HELIX 1127..1129
FT /evidence="ECO:0007829|PDB:2KMV"
FT TURN 1135..1139
FT /evidence="ECO:0007829|PDB:2KMX"
FT TURN 1150..1153
FT /evidence="ECO:0007829|PDB:2KMV"
FT STRAND 1161..1166
FT /evidence="ECO:0007829|PDB:2KMX"
FT TURN 1167..1171
FT /evidence="ECO:0007829|PDB:2KMV"
FT HELIX 1172..1174
FT /evidence="ECO:0007829|PDB:2KMV"
FT STRAND 1178..1183
FT /evidence="ECO:0007829|PDB:2KMV"
FT HELIX 1185..1191
FT /evidence="ECO:0007829|PDB:2KMV"
FT HELIX 1197..1208
FT /evidence="ECO:0007829|PDB:2KMV"
FT STRAND 1212..1218
FT /evidence="ECO:0007829|PDB:2KMV"
FT STRAND 1221..1229
FT /evidence="ECO:0007829|PDB:2KMV"
SQ SEQUENCE 1500 AA; 163373 MW; A54F17EA08FDACDB CRC64;
MDPSMGVNSV TISVEGMTCN SCVWTIEQQI GKVNGVHHIK VSLEEKNATI IYDPKLQTPK
TLQEAIDDMG FDAVIHNPDP LPVLTDTLFL TVTASLTLPW DHIQSTLLKT KGVTDIKIYP
QKRTVAVTII PSIVNANQIK ELVPELSLDT GTLEKKSGAC EDHSMAQAGE VVLKMKVEGM
TCHSCTSTIE GKIGKLQGVQ RIKVSLDNQE ATIVYQPHLI SVEEMKKQIE AMGFPAFVKK
QPKYLKLGAI DVERLKNTPV KSSEGSQQRS PSYTNDSTAT FIIDGMHCKS CVSNIESTLS
ALQYVSSIVV SLENRSAIVK YNASSVTPES LRKAIEAVSP GLYRVSITSE VESTSNSPSS
SSLQKIPLNV VSQPLTQETV INIDGMTCNS CVQSIEGVIS KKPGVKSIRV SLANSNGTVE
YDPLLTSPET LRGAIEDMGF DATLSDTNEP LVVIAQPSSE MPLLTSTNEF YTKGMTPVQD
KEEGKNSSKC YIQVTGMTCA SCVANIERNL RREEGIYSIL VALMAGKAEV RYNPAVIQPP
MIAEFIRELG FGATVIENAD EGDGVLELVV RGMTCASCVH KIESSLTKHR GILYCSVALA
TNKAHIKYDP EIIGPRDIIH TIESLGFEAS LVKKDRSASH LDHKREIRQW RRSFLVSLFF
CIPVMGLMIY MMVMDHHFAT LHHNQNMSKE EMINLHSSMF LERQILPGLS VMNLLSFLLC
VPVQFFGGWY FYIQAYKALK HKTANMDVLI VLATTIAFAY SLIILLVAMY ERAKVNPITF
FDTPPMLFVF IALGRWLEHI AKGKTSEALA KLISLQATEA TIVTLDSDNI LLSEEQVDVE
LVQRGDIIKV VPGGKFPVDG RVIEGHSMVD ESLITGEAMP VAKKPGSTVI AGSINQNGSL
LICATHVGAD TTLSQIVKLV EEAQTSKAPI QQFADKLSGY FVPFIVFVSI ATLLVWIVIG
FLNFEIVETY FPGYNRSISR TETIIRFAFQ ASITVLCIAC PCSLGLATPT AVMVGTGVGA
QNGILIKGGE PLEMAHKVKV VVFDKTGTIT HGTPVVNQVK VLTESNRISH HKILAIVGTA
ESNSEHPLGT AITKYCKQEL DTETLGTCID FQVVPGCGIS CKVTNIEGLL HKNNWNIEDN
NIKNASLVQI DASNEQSSTS SSMIIDAQIS NALNAQQYKV LIGNREWMIR NGLVINNDVN
DFMTEHERKG RTAVLVAVDD ELCGLIAIAD TVKPEAELAI HILKSMGLEV VLMTGDNSKT
ARSIASQVGI TKVFAEVLPS HKVAKVKQLQ EEGKRVAMVG DGINDSPALA MANVGIAIGT
GTDVAIEAAD VVLIRNDLLD VVASIDLSRK TVKRIRINFV FALIYNLVGI PIAAGVFMPI
GLVLQPWMGS AAMAASSVSV VLSSLFLKLY RKPTYESYEL PARSQIGQKS PSEISVHVGI
DDTSRNSPKL GLLDRIVNYS RASINSLLSD KRSLNSVVTS EPDKHSLLVG DFREDDDTAL
