COX20_HUMAN
ID COX20_HUMAN Reviewed; 118 AA.
AC Q5RI15; Q8WV86;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 2.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Cytochrome c oxidase assembly protein COX20, mitochondrial;
GN Name=COX20; Synonyms=FAM36A;
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 [LARGE SCALE GENOMIC DNA] (ISOFORMS 1 AND 2).
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, Prostate, and Uterus;
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 [3]
RP IDENTIFICATION.
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 [4]
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 [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [6]
RP FUNCTION, INTERACTION WITH MT-CO2; SCO1 AND SCO2, AND SUBCELLULAR LOCATION.
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 [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [8]
RP INTERACTION WITH MT-CO2; SCO1; SCO2; COA6 AND COX18.
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 [9]
RP VARIANT MC4DN11 PRO-52, CHARACTERIZATION OF VARIANT MC4DN11 PRO-52,
RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, AND INTERACTION WITH MT-CO2.
RX PubMed=23125284; DOI=10.1093/hmg/dds473;
RA Szklarczyk R., Wanschers B.F., Nijtmans L.G., Rodenburg R.J., Zschocke J.,
RA Dikow N., van den Brand M.A., Hendriks-Franssen M.G., Gilissen C.,
RA Veltman J.A., Nooteboom M., Koopman W.J., Willems P.H., Smeitink J.A.,
RA Huynen M.A., van den Heuvel L.P.;
RT "A mutation in the FAM36A gene, the human ortholog of COX20, impairs
RT cytochrome c oxidase assembly and is associated with ataxia and muscle
RT hypotonia.";
RL Hum. Mol. Genet. 22:656-667(2013).
RN [10]
RP VARIANT MC4DN11 PRO-52, AND VARIANT SER-118.
RX PubMed=24202787; DOI=10.1007/s00415-013-7177-7;
RA Doss S., Lohmann K., Seibler P., Arns B., Klopstock T., Zuehlke C.,
RA Freimann K., Winkler S., Lohnau T., Drungowski M., Nuernberg P.,
RA Wiegers K., Lohmann E., Naz S., Kasten M., Bohner G., Ramirez A.,
RA Endres M., Klein C.;
RT "Recessive dystonia-ataxia syndrome in a Turkish family caused by a COX20
RT (FAM36A) mutation.";
RL J. Neurol. 261:207-212(2014).
RN [11]
RP CHARACTERIZATION OF VARIANT MC4DN11 PRO-52, IDENTIFICATION IN A COMPLEX
RP WITH TMEM177; COA6; MT-CO2; COX18; SCO1 AND SCO2, AND INTERACTION WITH
RP TMEM177; COA6; MT-CO2; SCO1 AND SCO2.
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).
CC -!- FUNCTION: Essential for the assembly of the mitochondrial respiratory
CC chain complex IV (CIV), also known as cytochrome c oxidase
CC (PubMed:23125284). Acts as a chaperone in the early steps of cytochrome
CC c oxidase subunit II (MT-CO2/COX2) maturation, stabilizing the newly
CC synthesized protein and presenting it to metallochaperones SCO1/2 which
CC in turn facilitates the incorporation of the mature MT-CO2/COX2 into
CC the assembling CIV holoenzyme (PubMed:24403053).
CC {ECO:0000269|PubMed:23125284, ECO:0000269|PubMed:24403053}.
CC -!- SUBUNIT: Found in a complex with TMEM177, COA6, MT-CO2/COX2, COX18,
CC SCO1 and SCO2. Interacts with SCO1, SCO2 and COA6 in a MT-CO2/COX2- and
CC COX18-dependent manner (PubMed:29154948, PubMed:24403053,
CC PubMed:28330871). Interacts with COX18 in a MT-CO2/COX2-dependent
CC manner (PubMed:28330871). Interacts with MT-CO2/COX2 (PubMed:29154948,
CC PubMed:24403053, PubMed:23125284, PubMed:28330871). Interacts with
CC TMEM177 (PubMed:29154948). {ECO:0000269|PubMed:23125284,
CC ECO:0000269|PubMed:24403053, ECO:0000269|PubMed:28330871,
CC ECO:0000269|PubMed:29154948}.
CC -!- INTERACTION:
CC Q5RI15; Q13520: AQP6; NbExp=3; IntAct=EBI-2834035, EBI-13059134;
CC Q5RI15; Q9BZP6: CHIA; NbExp=3; IntAct=EBI-2834035, EBI-14357960;
CC Q5RI15; Q96BA8: CREB3L1; NbExp=3; IntAct=EBI-2834035, EBI-6942903;
CC Q5RI15; Q6P2H7: DYNC1H1; NbExp=3; IntAct=EBI-2834035, EBI-17590191;
CC Q5RI15; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-2834035, EBI-781551;
CC Q5RI15; Q9BWH2: FUNDC2; NbExp=3; IntAct=EBI-2834035, EBI-714482;
CC Q5RI15; O00258: GET1; NbExp=3; IntAct=EBI-2834035, EBI-18908258;
CC Q5RI15; P48165: GJA8; NbExp=3; IntAct=EBI-2834035, EBI-17458373;
CC Q5RI15; Q6ZVE7: GOLT1A; NbExp=3; IntAct=EBI-2834035, EBI-17231387;
CC Q5RI15; Q8N5M9: JAGN1; NbExp=3; IntAct=EBI-2834035, EBI-10266796;
CC Q5RI15; P27338: MAOB; NbExp=3; IntAct=EBI-2834035, EBI-3911344;
CC Q5RI15; Q9BUN1: MENT; NbExp=3; IntAct=EBI-2834035, EBI-12022316;
CC Q5RI15; Q69YL0: NCBP2AS2; NbExp=3; IntAct=EBI-2834035, EBI-10986258;
CC Q5RI15; O15173: PGRMC2; NbExp=3; IntAct=EBI-2834035, EBI-1050125;
CC Q5RI15; Q14973: SLC10A1; NbExp=3; IntAct=EBI-2834035, EBI-3923031;
CC Q5RI15; Q3KNW5: SLC10A6; NbExp=3; IntAct=EBI-2834035, EBI-18159983;
CC Q5RI15; Q15560: TCEA2; NbExp=3; IntAct=EBI-2834035, EBI-710310;
CC Q5RI15; Q53QW1: TEX44; NbExp=3; IntAct=EBI-2834035, EBI-10278496;
CC Q5RI15; Q53FP2: TMEM35A; NbExp=3; IntAct=EBI-2834035, EBI-11722971;
CC Q5RI15; Q9Y320: TMX2; NbExp=3; IntAct=EBI-2834035, EBI-6447886;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:23125284, ECO:0000269|PubMed:29154948}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5RI15-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5RI15-2; Sequence=VSP_014855;
CC -!- DISEASE: Mitochondrial complex IV deficiency, nuclear type 11 (MC4DN11)
CC [MIM:619054]: An autosomal recessive mitochondrial disorder with onset
CC in childhood or adolescence. MC4DN11 is characterized by walking
CC difficulties, cerebellar ataxia, dystonia, choreoathetotic movements
CC and dysarthria. Additional features may include sensory axonal
CC neuropathy, cerebellar atrophy, and mild speech delay. Cognitive
CC function is normal. Serum lactate levels are increased. Patient tissues
CC show decreased levels and activity of mitochondrial respiratory complex
CC IV. {ECO:0000269|PubMed:23125284, ECO:0000269|PubMed:24202787,
CC ECO:0000269|PubMed:29154948}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the COX20 family. {ECO:0000305}.
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DR EMBL; BX323046; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC018519; AAH18519.1; -; mRNA.
DR EMBL; BC062419; AAH62419.1; -; mRNA.
DR EMBL; BC095486; AAH95486.1; -; mRNA.
DR CCDS; CCDS31080.1; -. [Q5RI15-1]
DR CCDS; CCDS81434.1; -. [Q5RI15-2]
DR RefSeq; NP_001299800.1; NM_001312871.1. [Q5RI15-1]
DR RefSeq; NP_932342.1; NM_198076.5. [Q5RI15-1]
DR AlphaFoldDB; Q5RI15; -.
DR SMR; Q5RI15; -.
DR BioGRID; 125491; 51.
DR IntAct; Q5RI15; 39.
DR MINT; Q5RI15; -.
DR STRING; 9606.ENSP00000406327; -.
DR TCDB; 8.A.182.1.1; the mitochondrial cytochrome c oxidase assembly protein, cox20 (cox20) family.
DR GlyGen; Q5RI15; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q5RI15; -.
DR PhosphoSitePlus; Q5RI15; -.
DR SwissPalm; Q5RI15; -.
DR BioMuta; COX20; -.
DR DMDM; 71151875; -.
DR EPD; Q5RI15; -.
DR jPOST; Q5RI15; -.
DR MassIVE; Q5RI15; -.
DR MaxQB; Q5RI15; -.
DR PaxDb; Q5RI15; -.
DR PeptideAtlas; Q5RI15; -.
DR PRIDE; Q5RI15; -.
DR ProteomicsDB; 63739; -. [Q5RI15-1]
DR ProteomicsDB; 63740; -. [Q5RI15-2]
DR Antibodypedia; 34716; 78 antibodies from 17 providers.
DR DNASU; 116228; -.
DR Ensembl; ENST00000366528.3; ENSP00000355486.3; ENSG00000203667.10. [Q5RI15-2]
DR Ensembl; ENST00000411948.7; ENSP00000406327.2; ENSG00000203667.10. [Q5RI15-1]
DR GeneID; 116228; -.
DR KEGG; hsa:116228; -.
DR MANE-Select; ENST00000411948.7; ENSP00000406327.2; NM_198076.6; NP_932342.1.
DR UCSC; uc001iar.5; human. [Q5RI15-1]
DR CTD; 116228; -.
DR DisGeNET; 116228; -.
DR GeneCards; COX20; -.
DR HGNC; HGNC:26970; COX20.
DR HPA; ENSG00000203667; Low tissue specificity.
DR MalaCards; COX20; -.
DR MIM; 614698; gene.
DR MIM; 619054; phenotype.
DR neXtProt; NX_Q5RI15; -.
DR OpenTargets; ENSG00000203667; -.
DR Orphanet; 254905; Isolated cytochrome C oxidase deficiency.
DR PharmGKB; PA134976890; -.
DR VEuPathDB; HostDB:ENSG00000203667; -.
DR eggNOG; ENOG502S3BD; Eukaryota.
DR GeneTree; ENSGT00390000016158; -.
DR HOGENOM; CLU_101495_1_1_1; -.
DR InParanoid; Q5RI15; -.
DR OMA; VSQIPCF; -.
DR PhylomeDB; Q5RI15; -.
DR TreeFam; TF323844; -.
DR PathwayCommons; Q5RI15; -.
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; Q5RI15; -.
DR BioGRID-ORCS; 116228; 217 hits in 1011 CRISPR screens.
DR ChiTaRS; COX20; human.
DR GenomeRNAi; 116228; -.
DR Pharos; Q5RI15; Tbio.
DR PRO; PR:Q5RI15; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q5RI15; protein.
DR Bgee; ENSG00000203667; Expressed in kidney epithelium and 183 other tissues.
DR ExpressionAtlas; Q5RI15; baseline and differential.
DR Genevisible; Q5RI15; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0033617; P:mitochondrial cytochrome c oxidase assembly; IMP:UniProtKB.
DR InterPro; IPR022533; Cox20.
DR PANTHER; PTHR31586; PTHR31586; 1.
DR Pfam; PF12597; DUF3767; 1.
DR PRINTS; PR02049; PROTEINF36A.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Disease variant; Membrane;
KW Mitochondrion; Mitochondrion inner membrane; Primary mitochondrial disease;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:25944712"
FT CHAIN 2..118
FT /note="Cytochrome c oxidase assembly protein COX20,
FT mitochondrial"
FT /id="PRO_0000186815"
FT TOPO_DOM 2..33
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305|PubMed:23125284"
FT TRANSMEM 34..51
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 52..60
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305|PubMed:23125284"
FT TRANSMEM 61..77
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 78..118
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305|PubMed:23125284"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:25944712"
FT VAR_SEQ 14
FT /note="K -> KASCTSLHLSYWK (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_014855"
FT VARIANT 52
FT /note="T -> P (in MC4DN11; reduced protein expression;
FT defective mitochondrial respiratory chain complex IV
FT assembly; decreased interaction with MT-CO2/COX2; increased
FT interaction with TMEM177; dbSNP:rs587777004)"
FT /evidence="ECO:0000269|PubMed:23125284,
FT ECO:0000269|PubMed:24202787, ECO:0000269|PubMed:29154948"
FT /id="VAR_080123"
FT VARIANT 118
FT /note="N -> S (in dbSNP:rs61749963)"
FT /evidence="ECO:0000269|PubMed:24202787"
FT /id="VAR_080124"
SQ SEQUENCE 118 AA; 13291 MW; 8D413FD148382A94 CRC64;
MAAPPEPGEP EERKSLKLLG FLDVENTPCA RHSILYGSLG SVVAGFGHFL FTSRIRRSCD
VGVGGFILVT LGCWFHCRYN YAKQRIQERI AREEIKKKIL YEGTHLDPER KHNGSSSN
