COX17_HUMAN
ID COX17_HUMAN Reviewed; 63 AA.
AC Q14061; B2R5D2; D3DN84; Q3MHD6;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Cytochrome c oxidase copper chaperone;
GN Name=COX17;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9050918; DOI=10.1007/s004390050367;
RA Amaravadi R., Glerum D.M., Tzagoloff A.;
RT "Isolation of a cDNA encoding the human homolog of COX17, a yeast gene
RT essential for mitochondrial copper recruitment.";
RL Hum. Genet. 99:329-333(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RX PubMed=10982038; DOI=10.1007/s004390000339;
RA Punter F.A., Adams D.L., Glerum D.M.;
RT "Characterization and localization of human COX17, a gene involved in
RT mitochondrial copper transport.";
RL Hum. Genet. 107:69-74(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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 [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19393246; DOI=10.1016/j.jmb.2009.04.034;
RA Oswald C., Krause-Buchholz U., Roedel G.;
RT "Knockdown of human COX17 affects assembly and supramolecular organization
RT of cytochrome c oxidase.";
RL J. Mol. Biol. 389:470-479(2009).
RN [7]
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 [8]
RP INTERACTION WITH COA1.
RX PubMed=22356826; DOI=10.1186/gb-2012-13-2-r12;
RA Szklarczyk R., Wanschers B.F., Cuypers T.D., Esseling J.J., Riemersma M.,
RA van den Brand M.A., Gloerich J., Lasonder E., van den Heuvel L.P.,
RA Nijtmans L.G., Huynen M.A.;
RT "Iterative orthology prediction uncovers new mitochondrial proteins and
RT identifies C12orf62 as the human ortholog of COX14, a protein involved in
RT the assembly of cytochrome c oxidase.";
RL Genome Biol. 13:RESEARCH0012.1-RESEARCH0012.14(2012).
RN [9]
RP CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14, AND IDENTIFICATION BY
RP 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 [11]
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 [12]
RP STRUCTURE BY NMR IN APO AND COPPER-BOUND FORMS, AND DISULFIDE BONDS.
RX PubMed=18093982; DOI=10.1074/jbc.m708016200;
RA Banci L., Bertini I., Ciofi-Baffoni S., Janicka A., Martinelli M.,
RA Kozlowski H., Palumaa P.;
RT "A structural-dynamical characterization of human Cox17.";
RL J. Biol. Chem. 283:7912-7920(2008).
RN [13]
RP STRUCTURE BY NMR IN COMPLEX WITH CHCHD4, AND DISULFIDE BONDS.
RX PubMed=21059946; DOI=10.1073/pnas.1010095107;
RA Banci L., Bertini I., Cefaro C., Cenacchi L., Ciofi-Baffoni S., Felli I.C.,
RA Gallo A., Gonnelli L., Luchinat E., Sideris D., Tokatlidis K.;
RT "Molecular chaperone function of Mia40 triggers consecutive induced folding
RT steps of the substrate in mitochondrial protein import.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:20190-20195(2010).
RN [14]
RP STRUCTURE BY NMR, COPPER-BINDING, AND DISULFIDE BONDS.
RX PubMed=21816817; DOI=10.1074/jbc.m111.246223;
RA Banci L., Bertini I., Cefaro C., Ciofi-Baffoni S., Gallo A.;
RT "Functional role of two interhelical disulfide bonds in human Cox17 protein
RT from a structural perspective.";
RL J. Biol. Chem. 286:34382-34390(2011).
CC -!- FUNCTION: Copper metallochaperone essential for the assembly of the
CC mitochondrial respiratory chain complex IV (CIV), also known as
CC cytochrome c oxidase. Binds two copper ions and delivers them to the
CC metallochaperone SCO1 which transports the copper ions to the Cu(A)
CC site on the cytochrome c oxidase subunit II (MT-CO2/COX2).
CC {ECO:0000269|PubMed:19393246}.
CC -!- SUBUNIT: Interacts with COA1. Interacts with the chaperone CHCHD4; this
CC is important for correct folding and the formation of disulfide bonds
CC that stabilize the structure. {ECO:0000269|PubMed:21059946,
CC ECO:0000269|PubMed:22356826}.
CC -!- INTERACTION:
CC Q14061; Q8N4Q1-1: CHCHD4; NbExp=2; IntAct=EBI-711311, EBI-15755238;
CC Q14061; Q9BW62: KATNAL1; NbExp=4; IntAct=EBI-711311, EBI-743591;
CC Q14061; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-711311, EBI-10171774;
CC Q14061; O75880: SCO1; NbExp=3; IntAct=EBI-711311, EBI-6656171;
CC Q14061; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-711311, EBI-5235340;
CC -!- SUBCELLULAR LOCATION: Mitochondrion intermembrane space
CC {ECO:0000269|PubMed:19393246}. Cytoplasm {ECO:0000269|PubMed:19393246}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:10982038}.
CC -!- SIMILARITY: Belongs to the COX17 family. {ECO:0000305}.
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DR EMBL; L77701; AAA98114.1; -; mRNA.
DR EMBL; AF269244; AAF82569.1; -; Genomic_DNA.
DR EMBL; AF269243; AAF82569.1; JOINED; Genomic_DNA.
DR EMBL; AK312143; BAG35079.1; -; mRNA.
DR EMBL; CH471052; EAW79545.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79547.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79548.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79550.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79551.1; -; Genomic_DNA.
DR EMBL; BC010933; AAH10933.1; -; mRNA.
DR EMBL; BC105280; AAI05281.1; -; mRNA.
DR EMBL; BC108317; AAI08318.1; -; mRNA.
DR CCDS; CCDS2993.1; -.
DR PIR; T09533; T09533.
DR RefSeq; NP_005685.1; NM_005694.1.
DR PDB; 2L0Y; NMR; -; B=1-63.
DR PDB; 2LGQ; NMR; -; A=1-63.
DR PDB; 2RN9; NMR; -; A=1-63.
DR PDB; 2RNB; NMR; -; A=1-63.
DR PDBsum; 2L0Y; -.
DR PDBsum; 2LGQ; -.
DR PDBsum; 2RN9; -.
DR PDBsum; 2RNB; -.
DR AlphaFoldDB; Q14061; -.
DR BMRB; Q14061; -.
DR SMR; Q14061; -.
DR BioGRID; 115374; 59.
DR DIP; DIP-46087N; -.
DR IntAct; Q14061; 22.
DR STRING; 9606.ENSP00000261070; -.
DR DrugBank; DB09130; Copper.
DR iPTMnet; Q14061; -.
DR PhosphoSitePlus; Q14061; -.
DR BioMuta; COX17; -.
DR DMDM; 2493873; -.
DR EPD; Q14061; -.
DR jPOST; Q14061; -.
DR MassIVE; Q14061; -.
DR MaxQB; Q14061; -.
DR PaxDb; Q14061; -.
DR PeptideAtlas; Q14061; -.
DR PRIDE; Q14061; -.
DR ProteomicsDB; 59805; -.
DR Antibodypedia; 32759; 237 antibodies from 30 providers.
DR DNASU; 10063; -.
DR Ensembl; ENST00000261070.7; ENSP00000261070.2; ENSG00000138495.7.
DR Ensembl; ENST00000468918.5; ENSP00000417805.1; ENSG00000138495.7.
DR Ensembl; ENST00000497116.1; ENSP00000417923.1; ENSG00000138495.7.
DR GeneID; 10063; -.
DR KEGG; hsa:10063; -.
DR MANE-Select; ENST00000261070.7; ENSP00000261070.2; NM_005694.2; NP_005685.1.
DR UCSC; uc003ecz.2; human.
DR CTD; 10063; -.
DR DisGeNET; 10063; -.
DR GeneCards; COX17; -.
DR HGNC; HGNC:2264; COX17.
DR HPA; ENSG00000138495; Low tissue specificity.
DR MIM; 604813; gene.
DR neXtProt; NX_Q14061; -.
DR OpenTargets; ENSG00000138495; -.
DR PharmGKB; PA26780; -.
DR VEuPathDB; HostDB:ENSG00000138495; -.
DR eggNOG; KOG3496; Eukaryota.
DR GeneTree; ENSGT00390000002329; -.
DR InParanoid; Q14061; -.
DR OMA; EACTKWI; -.
DR OrthoDB; 1621529at2759; -.
DR PhylomeDB; Q14061; -.
DR TreeFam; TF105074; -.
DR PathwayCommons; Q14061; -.
DR Reactome; R-HSA-1268020; Mitochondrial protein import.
DR SignaLink; Q14061; -.
DR BioGRID-ORCS; 10063; 627 hits in 1086 CRISPR screens.
DR ChiTaRS; COX17; human.
DR EvolutionaryTrace; Q14061; -.
DR GeneWiki; COX17; -.
DR GenomeRNAi; 10063; -.
DR Pharos; Q14061; Tbio.
DR PRO; PR:Q14061; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q14061; protein.
DR Bgee; ENSG00000138495; Expressed in pituitary gland and 98 other tissues.
DR ExpressionAtlas; Q14061; baseline and differential.
DR Genevisible; Q14061; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:CAFA.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:CAFA.
DR GO; GO:0016531; F:copper chaperone activity; IMP:CAFA.
DR GO; GO:0005507; F:copper ion binding; TAS:ProtInc.
DR GO; GO:1903136; F:cuprous ion binding; IDA:CAFA.
DR GO; GO:0008047; F:enzyme activator activity; IEA:Ensembl.
DR GO; GO:0006825; P:copper ion transport; TAS:ProtInc.
DR GO; GO:0006091; P:generation of precursor metabolites and energy; TAS:ProtInc.
DR GO; GO:0033617; P:mitochondrial cytochrome c oxidase assembly; IMP:CAFA.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:CAFA.
DR GO; GO:1904960; P:positive regulation of cytochrome-c oxidase activity; IMP:CAFA.
DR DisProt; DP00543; -.
DR InterPro; IPR009069; Cys_alpha_HP_mot_SF.
DR InterPro; IPR007745; Cyt_c_oxidase_Cu-chaperone.
DR PANTHER; PTHR16719; PTHR16719; 1.
DR Pfam; PF05051; COX17; 1.
DR SUPFAM; SSF47072; SSF47072; 1.
DR PROSITE; PS51808; CHCH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chaperone; Copper; Cytoplasm; Disulfide bond; Metal-binding;
KW Mitochondrion; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22223895"
FT CHAIN 2..63
FT /note="Cytochrome c oxidase copper chaperone"
FT /id="PRO_0000213538"
FT DOMAIN 23..63
FT /note="CHCH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 26..36
FT /note="Cx9C motif 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150"
FT MOTIF 45..55
FT /note="Cx9C motif 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150"
FT BINDING 23
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000269|PubMed:18093982,
FT ECO:0000269|PubMed:21816817, ECO:0007744|PDB:2RNB"
FT BINDING 24
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000269|PubMed:18093982,
FT ECO:0000269|PubMed:21816817, ECO:0007744|PDB:2RNB"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT DISULFID 26..55
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150,
FT ECO:0000269|PubMed:18093982, ECO:0000269|PubMed:21059946,
FT ECO:0007744|PDB:2L0Y, ECO:0007744|PDB:2RN9,
FT ECO:0007744|PDB:2RNB"
FT DISULFID 36..45
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150,
FT ECO:0000269|PubMed:18093982, ECO:0000269|PubMed:21816817,
FT ECO:0007744|PDB:2LGQ, ECO:0007744|PDB:2RN9,
FT ECO:0007744|PDB:2RNB"
FT STRAND 22..24
FT /evidence="ECO:0007829|PDB:2LGQ"
FT HELIX 27..39
FT /evidence="ECO:0007829|PDB:2LGQ"
FT HELIX 42..44
FT /evidence="ECO:0007829|PDB:2LGQ"
FT HELIX 49..62
FT /evidence="ECO:0007829|PDB:2L0Y"
SQ SEQUENCE 63 AA; 6915 MW; E97090F939E78276 CRC64;
MPGLVDSNPA PPESQEKKPL KPCCACPETK KARDACIIEK GEEHCGHLIE AHKECMRALG
FKI
