SCO2_HUMAN
ID SCO2_HUMAN Reviewed; 266 AA.
AC O43819; Q3T1B5; Q9UK87;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 3.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=Protein SCO2 homolog, mitochondrial;
DE Flags: Precursor;
GN Name=SCO2;
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 [GENOMIC DNA], AND VARIANTS MC4DN2 LYS-140 AND PHE-225.
RX PubMed=10545952; DOI=10.1038/15513;
RA Papadopoulou L.C., Sue C.M., Davidson M.M., Tanji K., Nishino I.,
RA Sadlock J.E., Krishna S., Walker W., Selby J., Glerum D.M., Van Coster R.,
RA Lyon G., Scalais E., Lebel R., Kaplan P., Shanske S., De Vivo D.C.,
RA Bonilla E., Hirano M., DiMauro S., Schon E.A.;
RT "Fatal infantile cardioencephalomyopathy with COX deficiency and mutations
RT in SCO2, a COX assembly gene.";
RL Nat. Genet. 23:333-337(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Monocyte;
RX PubMed=12529303; DOI=10.1101/gr.695703;
RA Collins J.E., Goward M.E., Cole C.G., Smink L.J., Huckle E.J., Knowles S.,
RA Bye J.M., Beare D.M., Dunham I.;
RT "Reevaluating human gene annotation: a second-generation analysis of
RT chromosome 22.";
RL Genome Res. 13:27-36(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PRO-20.
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, AND SUBUNIT.
RX PubMed=15229189; DOI=10.1093/hmg/ddh197;
RA Leary S.C., Kaufman B.A., Pellecchia G., Guercin G.H., Mattman A.,
RA Jaksch M., Shoubridge E.A.;
RT "Human SCO1 and SCO2 have independent, cooperative functions in copper
RT delivery to cytochrome c oxidase.";
RL Hum. Mol. Genet. 13:1839-1848(2004).
RN [6]
RP FUNCTION, AND CHARACTERIZATION OF VARIANT MC4DN2 LYS-140.
RX PubMed=17189203; DOI=10.1016/j.cmet.2006.12.001;
RA Leary S.C., Cobine P.A., Kaufman B.A., Guercin G.H., Mattman A., Palaty J.,
RA Lockitch G., Winge D.R., Rustin P., Horvath R., Shoubridge E.A.;
RT "The human cytochrome c oxidase assembly factors SCO1 and SCO2 have
RT regulatory roles in the maintenance of cellular copper homeostasis.";
RL Cell Metab. 5:9-20(2007).
RN [7]
RP FUNCTION, AND CHARACTERIZATION OF VARIANT MC4DN2 LYS-140.
RX PubMed=19336478; DOI=10.1093/hmg/ddp158;
RA Leary S.C., Sasarman F., Nishimura T., Shoubridge E.A.;
RT "Human SCO2 is required for the synthesis of CO II and as a thiol-
RT disulphide oxidoreductase for SCO1.";
RL Hum. Mol. Genet. 18:2230-2240(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP INTERACTION WITH COX20.
RX PubMed=24403053; DOI=10.1093/hmg/ddu003;
RA Bourens M., Boulet A., Leary S.C., Barrientos A.;
RT "Human COX20 cooperates with SCO1 and SCO2 to mature COX2 and promote the
RT assembly of cytochrome c oxidase.";
RL Hum. Mol. Genet. 23:2901-2913(2014).
RN [10]
RP INTERACTION WITH COA6, CHARACTERIZATION OF VARIANT MYP6 HIS-114, AND
RP CHARACTERIZATION OF VARIANT MC4DN2 TRP-171.
RX PubMed=25959673; DOI=10.1016/j.cmet.2015.04.012;
RA Pacheu-Grau D., Bareth B., Dudek J., Juris L., Voegtle F.N., Wissel M.,
RA Leary S.C., Dennerlein S., Rehling P., Deckers M.;
RT "Cooperation between COA6 and SCO2 in COX2 maturation during cytochrome c
RT oxidase assembly links two mitochondrial cardiomyopathies.";
RL Cell Metab. 21:823-833(2015).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [12]
RP IDENTIFICATION IN A COMPLEX WITH TMEM177; COA6; MT-CO2; COX20; COX18 AND
RP SCO1, AND INTERACTION WITH TMEM177 AND COX20.
RX PubMed=29154948; DOI=10.1016/j.bbamcr.2017.11.010;
RA Lorenzi I., Oeljeklaus S., Aich A., Ronsoer C., Callegari S., Dudek J.,
RA Warscheid B., Dennerlein S., Rehling P.;
RT "The mitochondrial TMEM177 associates with COX20 during COX2 biogenesis.";
RL Biochim. Biophys. Acta 1865:323-333(2017).
RN [13]
RP INTERACTION WITH COX20.
RX PubMed=28330871; DOI=10.1074/jbc.m117.778514;
RA Bourens M., Barrientos A.;
RT "Human mitochondrial cytochrome c oxidase assembly factor COX18 acts
RT transiently as a membrane insertase within the subunit 2 maturation
RT module.";
RL J. Biol. Chem. 292:7774-7783(2017).
RN [14]
RP VARIANTS MC4DN2 SER-193 AND THR-258.
RX PubMed=26741492; DOI=10.1371/journal.pgen.1005679;
RA Kohda M., Tokuzawa Y., Kishita Y., Nyuzuki H., Moriyama Y., Mizuno Y.,
RA Hirata T., Yatsuka Y., Yamashita-Sugahara Y., Nakachi Y., Kato H.,
RA Okuda A., Tamaru S., Borna N.N., Banshoya K., Aigaki T., Sato-Miyata Y.,
RA Ohnuma K., Suzuki T., Nagao A., Maehata H., Matsuda F., Higasa K.,
RA Nagasaki M., Yasuda J., Yamamoto M., Fushimi T., Shimura M.,
RA Kaiho-Ichimoto K., Harashima H., Yamazaki T., Mori M., Murayama K.,
RA Ohtake A., Okazaki Y.;
RT "A comprehensive genomic analysis reveals the genetic landscape of
RT mitochondrial respiratory chain complex deficiencies.";
RL PLoS Genet. 12:E1005679-E1005679(2016).
RN [15]
RP INTERACTION WITH COX16.
RX PubMed=29381136; DOI=10.7554/elife.32572;
RA Aich A., Wang C., Chowdhury A., Ronsoer C., Pacheu-Grau D.,
RA Richter-Dennerlein R., Dennerlein S., Rehling P.;
RT "COX16 promotes COX2 metallation and assembly during respiratory complex IV
RT biogenesis.";
RL Elife 7:0-0(2018).
RN [16]
RP STRUCTURE BY NMR OF 100-266 ALONE AND IN COMPLEX WITH COPPER, AND
RP COPPER-BINDING SITES.
RX PubMed=17850752; DOI=10.1016/j.str.2007.07.011;
RA Banci L., Bertini I., Ciofi-Baffoni S., Gerothanassis I.P., Leontari I.,
RA Martinelli M., Wang S.;
RT "A structural characterization of human SCO2.";
RL Structure 15:1132-1140(2007).
RN [17]
RP VARIANTS MC4DN2 LYS-140 AND TRP-171.
RX PubMed=10749987; DOI=10.1093/hmg/9.5.795;
RA Jaksch M., Ogilvie I., Yao J., Kortenhaus G., Bresser H.G., Gerbitz K.D.,
RA Shoubridge E.A.;
RT "Mutations in SCO2 are associated with a distinct form of hypertrophic
RT cardiomyopathy and cytochrome c oxidase deficiency.";
RL Hum. Mol. Genet. 9:795-801(2000).
RN [18]
RP VARIANT MC4DN2 LYS-140.
RX PubMed=11673586; DOI=10.1212/wnl.57.8.1440;
RA Jaksch M., Horvath R., Horn N., Auer D.P., Macmillan C., Peters J.,
RA Gerbitz K.D., Kraegeloh-Mann I., Muntau A., Karcagi V., Kalmanchey R.,
RA Lochmuller H., Shoubridge E.A., Freisinger P.;
RT "Homozygosity (E140K) in SCO2 causes delayed infantile onset of
RT cardiomyopathy and neuropathy.";
RL Neurology 57:1440-1446(2001).
RN [19]
RP VARIANTS MC4DN2 TYR-133 AND LYS-140.
RX PubMed=14994243; DOI=10.1002/ajmg.a.20466;
RA Tarnopolsky M.A., Bourgeois J.M., Fu M.H., Kataeva G., Shah J., Simon D.K.,
RA Mahoney D., Johns D., MacKay N., Robinson B.H.;
RT "Novel SCO2 mutation (G1521A) presenting as a spinal muscular atrophy type
RT I phenotype.";
RL Am. J. Med. Genet. A 125A:310-314(2004).
RN [20]
RP VARIANT PRO-20, AND VARIANT MC4DN2 SER-193.
RX PubMed=19353847; DOI=10.5414/npp28143;
RA Mobley B.C., Enns G.M., Wong L.J., Vogel H.;
RT "A novel homozygous SCO2 mutation, p.G193S, causing fatal infantile
RT cardioencephalomyopathy.";
RL Clin. Neuropathol. 28:143-149(2009).
RN [21]
RP VARIANTS MYP6 HIS-114; LYS-140 AND VAL-259.
RX PubMed=23643385; DOI=10.1016/j.ajhg.2013.04.005;
RA Tran-Viet K.N., Powell C., Barathi V.A., Klemm T., Maurer-Stroh S.,
RA Limviphuvadh V., Soler V., Ho C., Yanovitch T., Schneider G., Li Y.J.,
RA Nading E., Metlapally R., Saw S.M., Goh L., Rozen S., Young T.L.;
RT "Mutations in SCO2 are associated with autosomal-dominant high-grade
RT myopia.";
RL Am. J. Hum. Genet. 92:820-826(2013).
RN [22]
RP VARIANTS MYP6 TRP-112 AND TRP-120.
RX PubMed=25525168; DOI=10.1167/iovs.14-14850;
RA Jiang D., Li J., Xiao X., Li S., Jia X., Sun W., Guo X., Zhang Q.;
RT "Detection of mutations in LRPAP1, CTSH, LEPREL1, ZNF644, SLC39A5, and SCO2
RT in 298 families with early-onset high myopia by exome sequencing.";
RL Invest. Ophthalmol. Vis. Sci. 56:339-345(2015).
CC -!- FUNCTION: Copper metallochaperone essential for the synthesis and
CC maturation of cytochrome c oxidase subunit II (MT-CO2/COX2). Involved
CC in transporting copper to the Cu(A) site on MT-CO2/COX2
CC (PubMed:15229189, PubMed:17189203). Also acts as a thiol-disulfide
CC oxidoreductase to regulate the redox state of the cysteines in SCO1
CC during maturation of MT-CO2/COX2 (PubMed:19336478).
CC {ECO:0000269|PubMed:15229189, ECO:0000269|PubMed:17189203,
CC ECO:0000269|PubMed:19336478}.
CC -!- SUBUNIT: Homodimer (PubMed:15229189). Interacts with COA6
CC (PubMed:25959673). Found in a complex with TMEM177, COX20, COA6, MT-
CC CO2/COX2, COX18 and SCO1 (PubMed:29154948). Interacts with TMEM177 in a
CC COX20-dependent manner (PubMed:29154948). Interacts with COX20 in a MT-
CC CO2/COX2- and COX18-dependent manner (PubMed:29154948, PubMed:24403053,
CC PubMed:28330871). Interacts with COX16 (PubMed:29381136).
CC {ECO:0000269|PubMed:15229189, ECO:0000269|PubMed:24403053,
CC ECO:0000269|PubMed:25959673, ECO:0000269|PubMed:28330871,
CC ECO:0000269|PubMed:29154948, ECO:0000269|PubMed:29381136}.
CC -!- INTERACTION:
CC O43819; Q9UHD4: CIDEB; NbExp=3; IntAct=EBI-357012, EBI-7062247;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:15229189}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- DISEASE: Mitochondrial complex IV deficiency, nuclear type 2 (MC4DN2)
CC [MIM:604377]: An autosomal recessive, severe mitochondrial disorder
CC characterized by hypotonia, global developmental delay, hypertrophic
CC cardiomyopathy, lactic acidosis, gliosis, and neuronal loss in basal
CC ganglia, brainstem and spinal cord. Serum lactate is increased, and
CC laboratory studies show decreased mitochondrial complex IV protein and
CC activity levels in various tissues, including heart and skeletal
CC muscle. Most patients die in infancy of cardiorespiratory failure.
CC {ECO:0000269|PubMed:10545952, ECO:0000269|PubMed:10749987,
CC ECO:0000269|PubMed:11673586, ECO:0000269|PubMed:14994243,
CC ECO:0000269|PubMed:17189203, ECO:0000269|PubMed:19336478,
CC ECO:0000269|PubMed:19353847, ECO:0000269|PubMed:25959673,
CC ECO:0000269|PubMed:26741492}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Myopia 6 (MYP6) [MIM:608908]: A refractive error of the eye,
CC in which parallel rays from a distant object come to focus in front of
CC the retina, vision being better for near objects than for far.
CC {ECO:0000269|PubMed:23643385, ECO:0000269|PubMed:25525168,
CC ECO:0000269|PubMed:25959673}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the SCO1/2 family. {ECO:0000305}.
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DR EMBL; AF177385; AAF05313.1; -; Genomic_DNA.
DR EMBL; AL021683; CAA16671.1; -; mRNA.
DR EMBL; CR456569; CAG30455.1; -; mRNA.
DR EMBL; BC102024; AAI02025.1; -; mRNA.
DR EMBL; BC102025; AAI02026.1; -; mRNA.
DR CCDS; CCDS14095.1; -.
DR RefSeq; NP_001162580.1; NM_001169109.1.
DR RefSeq; NP_001162581.1; NM_001169110.1.
DR RefSeq; NP_001162582.1; NM_001169111.1.
DR RefSeq; NP_005129.2; NM_005138.2.
DR PDB; 2RLI; NMR; -; A=100-266.
DR PDBsum; 2RLI; -.
DR AlphaFoldDB; O43819; -.
DR BMRB; O43819; -.
DR SMR; O43819; -.
DR BioGRID; 115317; 107.
DR DIP; DIP-46088N; -.
DR IntAct; O43819; 46.
DR MINT; O43819; -.
DR STRING; 9606.ENSP00000444433; -.
DR GlyGen; O43819; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O43819; -.
DR PhosphoSitePlus; O43819; -.
DR BioMuta; SCO2; -.
DR EPD; O43819; -.
DR jPOST; O43819; -.
DR MassIVE; O43819; -.
DR MaxQB; O43819; -.
DR PaxDb; O43819; -.
DR PeptideAtlas; O43819; -.
DR PRIDE; O43819; -.
DR ProteomicsDB; 49182; -.
DR Antibodypedia; 78977; 175 antibodies from 31 providers.
DR DNASU; 9997; -.
DR Ensembl; ENST00000252785.3; ENSP00000252785.3; ENSG00000284194.3.
DR Ensembl; ENST00000395693.8; ENSP00000379046.4; ENSG00000284194.3.
DR Ensembl; ENST00000535425.5; ENSP00000444242.1; ENSG00000284194.3.
DR Ensembl; ENST00000543927.6; ENSP00000444433.1; ENSG00000284194.3.
DR GeneID; 9997; -.
DR KEGG; hsa:9997; -.
DR MANE-Select; ENST00000395693.8; ENSP00000379046.4; NM_005138.3; NP_005129.2.
DR UCSC; uc003blz.5; human.
DR CTD; 9997; -.
DR DisGeNET; 9997; -.
DR GeneCards; SCO2; -.
DR GeneReviews; SCO2; -.
DR HGNC; HGNC:10604; SCO2.
DR HPA; ENSG00000284194; Low tissue specificity.
DR MalaCards; SCO2; -.
DR MIM; 604272; gene.
DR MIM; 604377; phenotype.
DR MIM; 608908; phenotype.
DR neXtProt; NX_O43819; -.
DR Orphanet; 521411; Autosomal recessive axonal Charcot-Marie-Tooth disease due to copper metabolism defect.
DR Orphanet; 1561; Fatal infantile cytochrome C oxidase deficiency.
DR Orphanet; 70474; Leigh syndrome with cardiomyopathy.
DR Orphanet; 98619; Rare isolated myopia.
DR PharmGKB; PA35013; -.
DR VEuPathDB; HostDB:ENSG00000284194; -.
DR eggNOG; KOG2792; Eukaryota.
DR GeneTree; ENSGT00390000004323; -.
DR HOGENOM; CLU_050131_0_3_1; -.
DR InParanoid; O43819; -.
DR OMA; KHAGRDY; -.
DR OrthoDB; 1462537at2759; -.
DR PhylomeDB; O43819; -.
DR TreeFam; TF313752; -.
DR PathwayCommons; O43819; -.
DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-HSA-611105; Respiratory electron transport.
DR Reactome; R-HSA-9707564; Cytoprotection by HMOX1.
DR SignaLink; O43819; -.
DR SIGNOR; O43819; -.
DR BioGRID-ORCS; 9997; 169 hits in 1093 CRISPR screens.
DR ChiTaRS; SCO2; human.
DR EvolutionaryTrace; O43819; -.
DR GeneWiki; SCO2; -.
DR GenomeRNAi; 9997; -.
DR Pharos; O43819; Tbio.
DR PRO; PR:O43819; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; O43819; protein.
DR Bgee; ENSG00000284194; Expressed in right uterine tube and 174 other tissues.
DR ExpressionAtlas; O43819; baseline and differential.
DR Genevisible; O43819; HS.
DR GO; GO:0031305; C:integral component of mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0030016; C:myofibril; IDA:MGI.
DR GO; GO:0016531; F:copper chaperone activity; IEA:InterPro.
DR GO; GO:0005507; F:copper ion binding; NAS:UniProtKB.
DR GO; GO:0015035; F:protein-disulfide reductase activity; IDA:UniProtKB.
DR GO; GO:0006878; P:cellular copper ion homeostasis; IEA:InterPro.
DR GO; GO:0001654; P:eye development; IMP:UniProtKB.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0033617; P:mitochondrial cytochrome c oxidase assembly; IMP:UniProtKB.
DR GO; GO:0003012; P:muscle system process; IEA:Ensembl.
DR GO; GO:0022904; P:respiratory electron transport chain; IEA:Ensembl.
DR GO; GO:0014823; P:response to activity; IEA:Ensembl.
DR CDD; cd02968; SCO; 1.
DR InterPro; IPR003782; SCO1/SenC.
DR InterPro; IPR017276; Synth_of_cyt-c-oxidase_Sco1/2.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR InterPro; IPR013766; Thioredoxin_domain.
DR PANTHER; PTHR12151; PTHR12151; 1.
DR Pfam; PF02630; SCO1-SenC; 1.
DR PIRSF; PIRSF037736; SCO1; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
DR PROSITE; PS51352; THIOREDOXIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cardiomyopathy; Chaperone; Copper; Disease variant;
KW Disulfide bond; Leigh syndrome; Membrane; Metal-binding; Mitochondrion;
KW Mitochondrion inner membrane; Primary mitochondrial disease;
KW Reference proteome; Transit peptide; Transmembrane; Transmembrane helix.
FT TRANSIT 1..41
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 42..266
FT /note="Protein SCO2 homolog, mitochondrial"
FT /id="PRO_0000031922"
FT TOPO_DOM 42..60
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305|PubMed:15229189"
FT TRANSMEM 61..78
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 79..266
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305|PubMed:15229189"
FT DOMAIN 85..259
FT /note="Thioredoxin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT BINDING 133
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000269|PubMed:17850752"
FT BINDING 137
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000269|PubMed:17850752"
FT BINDING 224
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000269|PubMed:17850752"
FT DISULFID 133..137
FT /note="Redox-active"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT VARIANT 20
FT /note="R -> P (in dbSNP:rs140523)"
FT /evidence="ECO:0000269|PubMed:15461802,
FT ECO:0000269|PubMed:19353847"
FT /id="VAR_011738"
FT VARIANT 112
FT /note="R -> W (in MYP6; unknown pathological significance;
FT dbSNP:rs370130010)"
FT /evidence="ECO:0000269|PubMed:25525168"
FT /id="VAR_074010"
FT VARIANT 114
FT /note="R -> H (in MYP6; remains stable in mitochondria;
FT reduces the level of the protein copurifying with COA6 by
FT 80%; dbSNP:rs145100473)"
FT /evidence="ECO:0000269|PubMed:23643385,
FT ECO:0000269|PubMed:25959673"
FT /id="VAR_070053"
FT VARIANT 120
FT /note="R -> W (in MYP6; unknown pathological significance;
FT dbSNP:rs375954523)"
FT /evidence="ECO:0000269|PubMed:25525168"
FT /id="VAR_074011"
FT VARIANT 133
FT /note="C -> Y (in MC4DN2; dbSNP:rs28937868)"
FT /evidence="ECO:0000269|PubMed:14994243"
FT /id="VAR_070054"
FT VARIANT 140
FT /note="E -> K (in MC4DN2 and MYP6; reduced cytochrome c
FT oxidase subunit II synthesis and reduced ability to
FT regulate cellular copper homeostasis; dbSNP:rs74315511)"
FT /evidence="ECO:0000269|PubMed:10545952,
FT ECO:0000269|PubMed:10749987, ECO:0000269|PubMed:11673586,
FT ECO:0000269|PubMed:14994243, ECO:0000269|PubMed:17189203,
FT ECO:0000269|PubMed:19336478, ECO:0000269|PubMed:23643385"
FT /id="VAR_008874"
FT VARIANT 171
FT /note="R -> W (in MC4DN2; renders the protein unstable;
FT dbSNP:rs28937598)"
FT /evidence="ECO:0000269|PubMed:10749987,
FT ECO:0000269|PubMed:25959673"
FT /id="VAR_013238"
FT VARIANT 193
FT /note="G -> S (in MC4DN2; dbSNP:rs759452074)"
FT /evidence="ECO:0000269|PubMed:19353847,
FT ECO:0000269|PubMed:26741492"
FT /id="VAR_076281"
FT VARIANT 225
FT /note="S -> F (in MC4DN2; dbSNP:rs80358232)"
FT /evidence="ECO:0000269|PubMed:10545952"
FT /id="VAR_008875"
FT VARIANT 258
FT /note="M -> T (in MC4DN2; dbSNP:rs1352878283)"
FT /evidence="ECO:0000269|PubMed:26741492"
FT /id="VAR_076282"
FT VARIANT 259
FT /note="A -> V (in MYP6; likely benign variant;
FT dbSNP:rs8139305)"
FT /evidence="ECO:0000269|PubMed:23643385"
FT /id="VAR_051912"
FT STRAND 105..108
FT /evidence="ECO:0007829|PDB:2RLI"
FT STRAND 113..115
FT /evidence="ECO:0007829|PDB:2RLI"
FT TURN 116..121
FT /evidence="ECO:0007829|PDB:2RLI"
FT STRAND 122..129
FT /evidence="ECO:0007829|PDB:2RLI"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:2RLI"
FT HELIX 137..153
FT /evidence="ECO:0007829|PDB:2RLI"
FT STRAND 160..167
FT /evidence="ECO:0007829|PDB:2RLI"
FT HELIX 174..182
FT /evidence="ECO:0007829|PDB:2RLI"
FT STRAND 190..192
FT /evidence="ECO:0007829|PDB:2RLI"
FT HELIX 195..204
FT /evidence="ECO:0007829|PDB:2RLI"
FT STRAND 227..231
FT /evidence="ECO:0007829|PDB:2RLI"
FT STRAND 237..244
FT /evidence="ECO:0007829|PDB:2RLI"
FT HELIX 247..261
FT /evidence="ECO:0007829|PDB:2RLI"
SQ SEQUENCE 266 AA; 29810 MW; BC2F40E057329BF3 CRC64;
MLLLTRSPTA WHRLSQLKPR VLPGTLGGQA LHLRSWLLSR QGPAETGGQG QPQGPGLRTR
LLITGLFGAG LGGAWLALRA EKERLQQQKR TEALRQAAVG QGDFHLLDHR GRARCKADFR
GQWVLMYFGF THCPDICPDE LEKLVQVVRQ LEAEPGLPPV QPVFITVDPE RDDVEAMARY
VQDFHPRLLG LTGSTKQVAQ ASHSYRVYYN AGPKDEDQDY IVDHSIAIYL LNPDGLFTDY
YGRSRSAEQI SDSVRRHMAA FRSVLS
