COA3_HUMAN
ID COA3_HUMAN Reviewed; 106 AA.
AC Q9Y2R0; A8K498;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Cytochrome c oxidase assembly factor 3 homolog, mitochondrial;
DE AltName: Full=Coiled-coil domain-containing protein 56;
DE AltName: Full=Mitochondrial translation regulation assembly intermediate of cytochrome c oxidase protein of 12 kDa;
GN Name=COA3; Synonyms=CCDC56, MITRAC12; ORFNames=HSPC009;
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 MRNA].
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for 300
RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT cells.";
RL Genome Res. 10:1546-1560(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary gland;
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 [3]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [6]
RP PROTEIN SEQUENCE OF 40-48 AND 84-93, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (JUN-2005) to UniProtKB.
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=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(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 FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN MITRAC COMPLEX, AND
RP TOPOLOGY.
RX PubMed=23260140; DOI=10.1016/j.cell.2012.11.053;
RA Mick D.U., Dennerlein S., Wiese H., Reinhold R., Pacheu-Grau D.,
RA Lorenzi I., Sasarman F., Weraarpachai W., Shoubridge E.A., Warscheid B.,
RA Rehling P.;
RT "MITRAC links mitochondrial protein translocation to respiratory-chain
RT assembly and translational regulation.";
RL Cell 151:1528-1541(2012).
RN [10]
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=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [11]
RP INTERACTION WITH MT-CO1; SMIM20; SURF1 AND TIMM21.
RX PubMed=26321642; DOI=10.1016/j.celrep.2015.08.009;
RA Dennerlein S., Oeljeklaus S., Jans D., Hellwig C., Bareth B., Jakobs S.,
RA Deckers M., Warscheid B., Rehling P.;
RT "MITRAC7 acts as a COX1-specific chaperone and reveals a checkpoint during
RT cytochrome c oxidase assembly.";
RL Cell Rep. 12:1644-1655(2015).
RN [12]
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 [13]
RP INVOLVEMENT IN MC4DN14, AND VARIANT MC4DN14 CYS-72.
RX PubMed=25604084; DOI=10.1136/jmedgenet-2014-102914;
RA Ostergaard E., Weraarpachai W., Ravn K., Born A.P., Joenson L., Duno M.,
RA Wibrand F., Shoubridge E.A., Vissing J.;
RT "Mutations in COA3 cause isolated complex IV deficiency associated with
RT neuropathy, exercise intolerance, obesity, and short stature.";
RL J. Med. Genet. 52:203-207(2015).
CC -!- FUNCTION: Core component of the MITRAC (mitochondrial translation
CC regulation assembly intermediate of cytochrome c oxidase complex)
CC complex, that regulates cytochrome c oxidase assembly. MITRAC complexes
CC regulate both translation of mitochondrial encoded components and
CC assembly of nuclear-encoded components imported in mitochondrion.
CC Required for efficient translation of MT-CO1 and mitochondrial
CC respiratory chain complex IV assembly. {ECO:0000269|PubMed:23260140}.
CC -!- SUBUNIT: Along with COX14, core component of the MITRAC (mitochondrial
CC translation regulation assembly intermediate of cytochrome c oxidase
CC complex) complex (Probable) (PubMed:23260140). Interacts with MT-
CC CO1/COX1, SMIM20, SURF1 and TIMM21 (PubMed:26321642).
CC {ECO:0000269|PubMed:23260140, ECO:0000269|PubMed:26321642,
CC ECO:0000305|PubMed:26321642}.
CC -!- INTERACTION:
CC Q9Y2R0; P00395: MT-CO1; NbExp=11; IntAct=EBI-6570446, EBI-2117234;
CC Q9Y2R0; Q15526: SURF1; NbExp=6; IntAct=EBI-6570446, EBI-3915286;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:23260140}; Single-pass membrane protein
CC {ECO:0000269|PubMed:23260140}.
CC -!- DISEASE: Mitochondrial complex IV deficiency, nuclear type 14 (MC4DN14)
CC [MIM:619058]: An autosomal recessive mitochondrial disorder with onset
CC in early childhood. MC4DN14 is characterized by developmental delay,
CC cognitive impairment, motor delay, abnormal gait, sensorimotor
CC demyelinating polyneuropathy, exercise intolerance, obesity, and short
CC stature. Serum lactate levels are marginally increased. Patient tissues
CC show decreased levels and activity of mitochondrial respiratory complex
CC IV. {ECO:0000269|PubMed:25604084}. Note=The disease may be caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the COA3 family. {ECO:0000305}.
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DR EMBL; AF070665; AAD20971.1; -; mRNA.
DR EMBL; AK290863; BAF83552.1; -; mRNA.
DR EMBL; AC016889; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471152; EAW60884.1; -; Genomic_DNA.
DR EMBL; BC002698; AAH02698.1; -; mRNA.
DR CCDS; CCDS32660.1; -.
DR RefSeq; NP_001035521.1; NM_001040431.2.
DR AlphaFoldDB; Q9Y2R0; -.
DR BioGRID; 118785; 100.
DR CORUM; Q9Y2R0; -.
DR IntAct; Q9Y2R0; 45.
DR MINT; Q9Y2R0; -.
DR STRING; 9606.ENSP00000354762; -.
DR iPTMnet; Q9Y2R0; -.
DR MetOSite; Q9Y2R0; -.
DR PhosphoSitePlus; Q9Y2R0; -.
DR BioMuta; COA3; -.
DR DMDM; 74735238; -.
DR EPD; Q9Y2R0; -.
DR jPOST; Q9Y2R0; -.
DR MassIVE; Q9Y2R0; -.
DR MaxQB; Q9Y2R0; -.
DR PaxDb; Q9Y2R0; -.
DR PeptideAtlas; Q9Y2R0; -.
DR PRIDE; Q9Y2R0; -.
DR ProteomicsDB; 85873; -.
DR TopDownProteomics; Q9Y2R0; -.
DR Antibodypedia; 29425; 74 antibodies from 17 providers.
DR DNASU; 28958; -.
DR Ensembl; ENST00000328434.8; ENSP00000354762.5; ENSG00000183978.8.
DR GeneID; 28958; -.
DR KEGG; hsa:28958; -.
DR MANE-Select; ENST00000328434.8; ENSP00000354762.5; NM_001040431.3; NP_001035521.1.
DR UCSC; uc002ibl.5; human.
DR CTD; 28958; -.
DR DisGeNET; 28958; -.
DR GeneCards; COA3; -.
DR HGNC; HGNC:24990; COA3.
DR HPA; ENSG00000183978; Low tissue specificity.
DR MalaCards; COA3; -.
DR MIM; 614775; gene.
DR MIM; 619058; phenotype.
DR neXtProt; NX_Q9Y2R0; -.
DR OpenTargets; ENSG00000183978; -.
DR Orphanet; 254905; Isolated cytochrome C oxidase deficiency.
DR PharmGKB; PA142672172; -.
DR VEuPathDB; HostDB:ENSG00000183978; -.
DR eggNOG; KOG4782; Eukaryota.
DR GeneTree; ENSGT00390000016262; -.
DR HOGENOM; CLU_167761_0_1_1; -.
DR InParanoid; Q9Y2R0; -.
DR OMA; MHFIRQV; -.
DR OrthoDB; 1515241at2759; -.
DR PhylomeDB; Q9Y2R0; -.
DR TreeFam; TF314703; -.
DR PathwayCommons; Q9Y2R0; -.
DR SignaLink; Q9Y2R0; -.
DR BioGRID-ORCS; 28958; 149 hits in 1085 CRISPR screens.
DR ChiTaRS; COA3; human.
DR GenomeRNAi; 28958; -.
DR Pharos; Q9Y2R0; Tbio.
DR PRO; PR:Q9Y2R0; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9Y2R0; protein.
DR Bgee; ENSG00000183978; Expressed in mucosa of transverse colon and 197 other tissues.
DR ExpressionAtlas; Q9Y2R0; baseline and differential.
DR Genevisible; Q9Y2R0; HS.
DR GO; GO:0031305; C:integral component of 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 GO; GO:0070131; P:positive regulation of mitochondrial translation; IMP:UniProtKB.
DR InterPro; IPR041752; Coa3.
DR InterPro; IPR018628; Coa3_cc.
DR PANTHER; PTHR15642; PTHR15642; 1.
DR Pfam; PF09813; Coiled-coil_56; 1.
PE 1: Evidence at protein level;
KW Acetylation; Coiled coil; Direct protein sequencing; 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:19413330,
FT ECO:0007744|PubMed:22814378"
FT CHAIN 2..106
FT /note="Cytochrome c oxidase assembly factor 3 homolog,
FT mitochondrial"
FT /id="PRO_0000239438"
FT TOPO_DOM 2..57
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000255"
FT TRANSMEM 58..78
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 79..106
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT REGION 1..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 78..104
FT /evidence="ECO:0000255"
FT COMPBIAS 15..34
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22814378"
FT VARIANT 72
FT /note="Y -> C (in MC4DN14; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:25604084"
FT /id="VAR_084180"
SQ SEQUENCE 106 AA; 11731 MW; ED6E73527E9B6C3C CRC64;
MASSGAGDPL DSKRGEAPFA QRIDPTREKL TPEQLHSMRQ AELAQWQKVL PRRRTRNIVT
GLGIGALVLA IYGYTFYSIS QERFLDELED EAKAARARAL ARASGS
