CX7A2_HUMAN
ID CX7A2_HUMAN Reviewed; 83 AA.
AC P14406; B2R5E1; Q3MIH5; Q5TF59; Q6FGI2;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Cytochrome c oxidase subunit 7A2, mitochondrial;
DE AltName: Full=Cytochrome c oxidase subunit VIIa-liver/heart;
DE Short=Cytochrome c oxidase subunit VIIa-L;
DE Short=Cytochrome c oxidase subunit VIIaL;
DE Flags: Precursor;
GN Name=COX7A2; Synonyms=COX7AL;
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].
RC TISSUE=Endothelial cell;
RX PubMed=2550906; DOI=10.1093/nar/17.17.7107;
RA Fabrizi G.M., Rizzuto R., Nakase H., Mita S., Lomax M.I., Grossman L.I.,
RA Schon E.A.;
RT "Sequence of a cDNA specifying subunit VIIa of human cytochrome c
RT oxidase.";
RL Nucleic Acids Res. 17:7107-7107(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Blood;
RX PubMed=11004498; DOI=10.1016/s0167-4781(00)00087-7;
RA Huettemann M., Muehlenbein N., Schmidt T.R., Grossman L.I., Kadenbach B.;
RT "Isolation and sequence of the human cytochrome c oxidase subunit VIIaL
RT gene.";
RL Biochim. Biophys. Acta 1492:252-258(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hippocampus;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [8]
RP PROTEIN SEQUENCE OF 24-53.
RC TISSUE=Heart, and Liver;
RX PubMed=1309697; DOI=10.1111/j.1432-1033.1992.tb19847.x;
RA van Kuilenburg A.B.P., van Beeumen J.J., van der Meer N.M., Muijsers A.O.;
RT "Subunits VIIa,b,c of human cytochrome c oxidase. Identification of both
RT 'heart-type' and 'liver-type' isoforms of subunit VIIa in human heart.";
RL Eur. J. Biochem. 203:193-199(1992).
RN [9]
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 [10]
RP INTERACTION WITH PET100.
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 [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 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 STRUCTURE BY ELECTRON MICROSCOPY (3.90 ANGSTROMS), AND SUBUNIT.
RX PubMed=28844695; DOI=10.1016/j.cell.2017.07.050;
RA Guo R., Zong S., Wu M., Gu J., Yang M.;
RT "Architecture of human mitochondrial respiratory megacomplex I2III2IV2.";
RL Cell 170:1247-1257(2017).
RN [14]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS) OF 25-80.
RX PubMed=30030519; DOI=10.1038/s41422-018-0071-1;
RA Zong S., Wu M., Gu J., Liu T., Guo R., Yang M.;
RT "Structure of the intact 14-subunit human cytochrome c oxidase.";
RL Cell Res. 28:1026-1034(2018).
RN [15]
RP VARIANT ASP-40.
RA Devreese B.;
RL Submitted (DEC-2001) to UniProtKB.
CC -!- FUNCTION: Component of the cytochrome c oxidase, the last enzyme in the
CC mitochondrial electron transport chain which drives oxidative
CC phosphorylation. The respiratory chain contains 3 multisubunit
CC complexes succinate dehydrogenase (complex II, CII), ubiquinol-
CC cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III,
CC CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to
CC transfer electrons derived from NADH and succinate to molecular oxygen,
CC creating an electrochemical gradient over the inner membrane that
CC drives transmembrane transport and the ATP synthase. Cytochrome c
CC oxidase is the component of the respiratory chain that catalyzes the
CC reduction of oxygen to water. Electrons originating from reduced
CC cytochrome c in the intermembrane space (IMS) are transferred via the
CC dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1
CC to the active site in subunit 1, a binuclear center (BNC) formed by
CC heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2
CC water molecules using 4 electrons from cytochrome c in the IMS and 4
CC protons from the mitochondrial matrix. {ECO:0000250|UniProtKB:P10174}.
CC -!- PATHWAY: Energy metabolism; oxidative phosphorylation.
CC {ECO:0000250|UniProtKB:P10174}.
CC -!- SUBUNIT: Component of the cytochrome c oxidase (complex IV, CIV), a
CC multisubunit enzyme composed of 14 subunits. The complex is composed of
CC a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in
CC the mitochondrial DNA, and 11 supernumerary subunits COX4I1 (or
CC COX4I2), COX5A, COX5B, COX6A1 (or COX6A2), COX6B1 (or COX6B2), COX6C,
CC COX7A2 (or COX7A1), COX7B, COX7C, COX8A and NDUFA4, which are encoded
CC in the nuclear genome (PubMed:30030519). The complex exists as a
CC monomer or a dimer and forms supercomplexes (SCs) in the inner
CC mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I,
CC CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex,
CC complex III, CIII), resulting in different assemblies (supercomplex
CC SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)) (PubMed:28844695).
CC Interacts with PET100 (PubMed:22356826). {ECO:0000269|PubMed:22356826,
CC ECO:0000269|PubMed:28844695, ECO:0000269|PubMed:30030519}.
CC -!- INTERACTION:
CC P14406; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-2606666, EBI-16439278;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:30030519}; Single-pass membrane protein
CC {ECO:0000269|PubMed:30030519}.
CC -!- SIMILARITY: Belongs to the cytochrome c oxidase VIIa family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X15822; CAA33820.1; -; mRNA.
DR EMBL; AF134406; AAF61396.1; -; Genomic_DNA.
DR EMBL; CR407646; CAG28574.1; -; mRNA.
DR EMBL; CR542125; CAG46922.1; -; mRNA.
DR EMBL; AK312154; BAG35088.1; -; mRNA.
DR EMBL; AL080250; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC101826; AAI01827.1; -; mRNA.
DR EMBL; BC101828; AAI01829.1; -; mRNA.
DR CCDS; CCDS34486.2; -.
DR PIR; S06897; OSHU7L.
DR RefSeq; NP_001856.2; NM_001865.3.
DR PDB; 5Z62; EM; 3.60 A; J=25-80.
DR PDBsum; 5Z62; -.
DR AlphaFoldDB; P14406; -.
DR SMR; P14406; -.
DR BioGRID; 107740; 97.
DR ComplexPortal; CPX-6123; Mitochondrial respiratory chain complex IV.
DR IntAct; P14406; 32.
DR MINT; P14406; -.
DR STRING; 9606.ENSP00000359098; -.
DR TCDB; 3.D.4.11.1; the proton-translocating cytochrome oxidase (cox) superfamily.
DR GlyGen; P14406; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P14406; -.
DR PhosphoSitePlus; P14406; -.
DR BioMuta; COX7A2; -.
DR EPD; P14406; -.
DR jPOST; P14406; -.
DR MassIVE; P14406; -.
DR MaxQB; P14406; -.
DR PaxDb; P14406; -.
DR PeptideAtlas; P14406; -.
DR PRIDE; P14406; -.
DR ProteomicsDB; 53050; -.
DR TopDownProteomics; P14406; -.
DR DNASU; 1347; -.
DR Ensembl; ENST00000684430.2; ENSP00000506727.1; ENSG00000112695.13.
DR GeneID; 1347; -.
DR KEGG; hsa:1347; -.
DR MANE-Select; ENST00000684430.2; ENSP00000506727.1; NM_001366293.2; NP_001353222.1.
DR CTD; 1347; -.
DR DisGeNET; 1347; -.
DR GeneCards; COX7A2; -.
DR HGNC; HGNC:2288; COX7A2.
DR MIM; 123996; gene.
DR neXtProt; NX_P14406; -.
DR OpenTargets; ENSG00000112695; -.
DR PharmGKB; PA26806; -.
DR eggNOG; ENOG502S4DT; Eukaryota.
DR GeneTree; ENSGT00940000154550; -.
DR InParanoid; P14406; -.
DR PhylomeDB; P14406; -.
DR BioCyc; MetaCyc:HS03606-MON; -.
DR PathwayCommons; P14406; -.
DR SignaLink; P14406; -.
DR SIGNOR; P14406; -.
DR UniPathway; UPA00705; -.
DR BioGRID-ORCS; 1347; 32 hits in 1043 CRISPR screens.
DR ChiTaRS; COX7A2; human.
DR GeneWiki; COX7A2; -.
DR GenomeRNAi; 1347; -.
DR Pharos; P14406; Tbio.
DR PRO; PR:P14406; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P14406; protein.
DR Bgee; ENSG00000112695; Expressed in endothelial cell and 206 other tissues.
DR ExpressionAtlas; P14406; baseline and differential.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031966; C:mitochondrial membrane; IDA:ComplexPortal.
DR GO; GO:0005746; C:mitochondrial respirasome; IBA:GO_Central.
DR GO; GO:0005751; C:mitochondrial respiratory chain complex IV; IPI:ComplexPortal.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0045333; P:cellular respiration; IC:ComplexPortal.
DR GO; GO:0006123; P:mitochondrial electron transport, cytochrome c to oxygen; IC:ComplexPortal.
DR GO; GO:0097250; P:mitochondrial respirasome assembly; IBA:GO_Central.
DR GO; GO:0002082; P:regulation of oxidative phosphorylation; IBA:GO_Central.
DR CDD; cd00928; Cyt_c_Oxidase_VIIa; 1.
DR Gene3D; 4.10.91.10; -; 1.
DR InterPro; IPR039297; COX7a.
DR InterPro; IPR036539; Cyt_c_oxidase_su7a_sf.
DR InterPro; IPR003177; Cytc_oxidase_su7a_met.
DR PANTHER; PTHR10510; PTHR10510; 1.
DR Pfam; PF02238; COX7a; 1.
DR SUPFAM; SSF81419; SSF81419; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Direct protein sequencing; Membrane;
KW Mitochondrion; Mitochondrion inner membrane; Oxidoreductase;
KW Reference proteome; Transit peptide; Transmembrane; Transmembrane helix.
FT TRANSIT 1..23
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:1309697"
FT CHAIN 24..83
FT /note="Cytochrome c oxidase subunit 7A2, mitochondrial"
FT /id="PRO_0000006145"
FT TOPO_DOM 24..48
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000269|PubMed:30030519"
FT TRANSMEM 49..77
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P07470"
FT TOPO_DOM 78..83
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000269|PubMed:30030519"
FT MOD_RES 33
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P48771"
FT VARIANT 40
FT /note="E -> D (in dbSNP:rs769314754)"
FT /evidence="ECO:0000269|Ref.15"
FT /id="VAR_012319"
SQ SEQUENCE 83 AA; 9396 MW; 490F45059CAF971F CRC64;
MLRNLLALRQ IGQRTISTAS RRHFKNKVPE KQKLFQEDDE IPLYLKGGVA DALLYRATMI
LTVGGTAYAI YELAVASFPK KQE
