ID CX6A2_BOVIN Reviewed; 97 AA. AC P07471; Q3SZ61; DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1992, sequence version 2. DT 24-JAN-2024, entry version 174. DE RecName: Full=Cytochrome c oxidase subunit 6A2, mitochondrial; DE AltName: Full=Cytochrome c oxidase polypeptide VIa-heart; DE Short=COXVIAH; DE AltName: Full=Cytochrome c oxidase polypeptide VIb; DE Flags: Precursor; GN Name=COX6A2; Synonyms=COX6A; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Heart; RX PubMed=1647214; DOI=10.1016/0167-4781(91)90022-e; RA Smith E.O., Bement D.M., Grossman L.I., Lomax M.I.; RT "The cDNA for the heart/muscle isoform of bovine cytochrome c oxidase RT subunit VIa encodes a presequence."; RL Biochim. Biophys. Acta 1089:266-268(1991). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=7687470; DOI=10.1016/0167-4781(93)90092-r; RA Smith E.O., Lomax M.I.; RT "Structural organization of the bovine gene for the heart/muscle isoform of RT cytochrome c oxidase subunit VIa."; RL Biochim. Biophys. Acta 1174:63-71(1993). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Hereford; TISSUE=Heart ventricle; RG NIH - Mammalian Gene Collection (MGC) project; RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP PROTEIN SEQUENCE OF 13-96. RC TISSUE=Heart; RX PubMed=2994692; DOI=10.1515/bchm3.1985.366.2.687; RA Meinecke L., Buse G.; RT "Studies on cytochrome c oxidase, XII. Isolation and primary structure of RT polypeptide VIb from bovine heart."; RL Biol. Chem. Hoppe-Seyler 366:687-694(1985). RN [5] RP SUBUNIT. RX PubMed=26698328; DOI=10.1074/jbc.m115.680553; RA Shinzawa-Itoh K., Shimomura H., Yanagisawa S., Shimada S., Takahashi R., RA Oosaki M., Ogura T., Tsukihara T.; RT "Purification of active respiratory supercomplex from bovine heart RT mitochondria enables functional studies."; RL J. Biol. Chem. 291:4178-4184(2016). RN [6] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS). RX PubMed=8638158; DOI=10.1126/science.272.5265.1136; RA Tsukihara T., Aoyama H., Yamashita E., Tomizaki T., Yamaguchi H., RA Shinzawa-Itoh K., Nakashima R., Yaono R., Yoshikawa S.; RT "The whole structure of the 13-subunit oxidized cytochrome c oxidase at 2.8 RT A."; RL Science 272:1136-1144(1996). RN [7] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS). RC TISSUE=Heart; RX PubMed=10089392; DOI=10.1107/s0907444998006362; RA Tomizaki T., Yamashita E., Yamaguchi H., Aoyama H., Tsukihara T., RA Shinzawa-Itoh K., Nakashima R., Yaono R., Yoshikawa S.; RT "Structure analysis of bovine heart cytochrome c oxidase at 2.8 A RT resolution."; RL Acta Crystallogr. D 55:31-45(1999). RN [8] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS). RC TISSUE=Heart; RX PubMed=10771420; DOI=10.1107/s0907444900002213; RA Fei M.J., Yamashita E., Inoue N., Yao M., Yamaguchi H., Tsukihara T., RA Shinzawa-Itoh K., Nakashima R., Yoshikawa S.; RT "X-ray structure of azide-bound fully oxidized cytochrome c oxidase from RT bovine heart at 2.9 A resolution."; RL Acta Crystallogr. D 56:529-535(2000). RN [9] RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS). RX PubMed=20385840; DOI=10.1073/pnas.0910410107; RA Muramoto K., Ohta K., Shinzawa-Itoh K., Kanda K., Taniguchi M., RA Nabekura H., Yamashita E., Tsukihara T., Yoshikawa S.; RT "Bovine cytochrome c oxidase structures enable O2 reduction with RT minimization of reactive oxygens and provide a proton-pumping gate."; RL Proc. Natl. Acad. Sci. U.S.A. 107:7740-7745(2010). RN [10] RP STRUCTURE BY ELECTRON MICROSCOPY (9.10 ANGSTROMS) OF 13-96. RX PubMed=27830641; DOI=10.7554/elife.21290; RA Sousa J.S., Mills D.J., Vonck J., Kuehlbrandt W.; RT "Functional asymmetry and electron flow in the bovine respirasome."; RL Elife 5:0-0(2016). RN [11] RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS). RX PubMed=27605664; DOI=10.1074/jbc.m115.711770; RA Yano N., Muramoto K., Shimada A., Takemura S., Baba J., Fujisawa H., RA Mochizuki M., Shinzawa-Itoh K., Yamashita E., Tsukihara T., Yoshikawa S.; RT "The Mg2+-containing water cluster of mammalian cytochrome c oxidase RT collects four pumping proton equivalents in each catalytic cycle."; RL J. Biol. Chem. 291:23882-23894(2016). RN [12] RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS). RX PubMed=31533957; DOI=10.1073/pnas.1907183116; RA Shinzawa-Itoh K., Sugimura T., Misaki T., Tadehara Y., Yamamoto S., RA Hanada M., Yano N., Nakagawa T., Uene S., Yamada T., Aoyama H., RA Yamashita E., Tsukihara T., Yoshikawa S., Muramoto K.; RT "Monomeric structure of an active form of bovine cytochrome c oxidase."; RL Proc. Natl. Acad. Sci. U.S.A. 116:19945-19951(2019). 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 unsing 4 electrons from cytochrome c in the IMS and 4 CC protons from the mitochondrial matrix. Plays a role in the assembly and CC stabilization of complex IV (By similarity). CC {ECO:0000250|UniProtKB:P32799, ECO:0000250|UniProtKB:P43023}. CC -!- PATHWAY: Energy metabolism; oxidative phosphorylation. CC {ECO:0000250|UniProtKB:P32799}. 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, COX6A2 (or COX6A1), COX6B1 (or COX6B2), COX6C, CC COX7A1 (or COX7A2), COX7B, COX7C, COX8B and NDUFA4, which are encoded CC in the nuclear genome (PubMed:8638158). The complex exists as a monomer CC or a dimer and forms supercomplexes (SCs) in the inner mitochondrial CC membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and CC ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex CC III, CIII), resulting in different assemblies (supercomplex CC SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)) (PubMed:26698328, CC PubMed:27830641). {ECO:0000269|PubMed:26698328, CC ECO:0000269|PubMed:27830641, ECO:0000269|PubMed:8638158}. CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:27605664, ECO:0000269|PubMed:31533957}; Single-pass CC membrane protein {ECO:0000269|PubMed:27605664, CC ECO:0000269|PubMed:31533957}. CC -!- TISSUE SPECIFICITY: Heart/muscle specific isoform. CC -!- SIMILARITY: Belongs to the cytochrome c oxidase subunit 6A 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; X56857; CAA40183.1; -; mRNA. DR EMBL; S64127; AAB27605.1; -; Genomic_DNA. DR EMBL; BC103117; AAI03118.1; -; mRNA. DR PIR; S35702; OGBO6. DR RefSeq; NP_776947.1; NM_174522.3. DR PDB; 1OCC; X-ray; 2.80 A; G/T=13-96. DR PDB; 1OCO; X-ray; 2.80 A; G/T=13-96. DR PDB; 1OCR; X-ray; 2.35 A; G/T=13-96. DR PDB; 1OCZ; X-ray; 2.90 A; G/T=13-96. DR PDB; 1V54; X-ray; 1.80 A; G/T=13-97. DR PDB; 1V55; X-ray; 1.90 A; G/T=13-97. DR PDB; 2DYR; X-ray; 1.80 A; G/T=13-97. DR PDB; 2DYS; X-ray; 2.20 A; G/T=13-97. DR PDB; 2EIJ; X-ray; 1.90 A; G/T=13-97. DR PDB; 2EIK; X-ray; 2.10 A; G/T=13-97. DR PDB; 2EIL; X-ray; 2.10 A; G/T=13-97. DR PDB; 2EIM; X-ray; 2.60 A; G/T=13-97. DR PDB; 2EIN; X-ray; 2.70 A; G/T=13-97. DR PDB; 2OCC; X-ray; 2.30 A; G/T=13-96. DR PDB; 2Y69; X-ray; 1.95 A; G/T=1-97. DR PDB; 2YBB; EM; 19.00 A; R=13-96. DR PDB; 2ZXW; X-ray; 2.50 A; G/T=13-97. DR PDB; 3ABK; X-ray; 2.00 A; G/T=13-97. DR PDB; 3ABL; X-ray; 2.10 A; G/T=13-97. DR PDB; 3ABM; X-ray; 1.95 A; G/T=13-97. DR PDB; 3AG1; X-ray; 2.20 A; G/T=13-97. DR PDB; 3AG2; X-ray; 1.80 A; G/T=13-97. DR PDB; 3AG3; X-ray; 1.80 A; G/T=13-97. DR PDB; 3AG4; X-ray; 2.05 A; G/T=13-97. DR PDB; 3ASN; X-ray; 3.00 A; G/T=13-97. DR PDB; 3ASO; X-ray; 2.30 A; G/T=13-97. DR PDB; 3WG7; X-ray; 1.90 A; G/T=13-97. DR PDB; 3X2Q; X-ray; 2.00 A; G/T=13-97. DR PDB; 5B1A; X-ray; 1.50 A; G/T=13-97. DR PDB; 5B1B; X-ray; 1.60 A; G/T=13-97. DR PDB; 5B3S; X-ray; 1.68 A; G/T=13-97. DR PDB; 5GPN; EM; 5.40 A; 4=13-96. DR PDB; 5IY5; X-ray; 2.00 A; G/T=13-96. DR PDB; 5LUF; EM; 9.10 A; 4=13-96. DR PDB; 5W97; X-ray; 2.30 A; G/g=13-97. DR PDB; 5WAU; X-ray; 1.95 A; G/g=13-97. DR PDB; 5X19; X-ray; 2.20 A; G/T=13-97. DR PDB; 5X1B; X-ray; 2.40 A; G/T=13-97. DR PDB; 5X1F; X-ray; 2.20 A; G/T=13-97. DR PDB; 5XDQ; X-ray; 1.77 A; G/T=13-97. DR PDB; 5XDX; X-ray; 1.99 A; G/T=13-97. DR PDB; 5XTH; EM; 3.90 A; 3=13-96. DR PDB; 5XTI; EM; 17.40 A; 3/B3=13-96. DR PDB; 5Z84; X-ray; 1.85 A; G/T=13-97. DR PDB; 5Z85; X-ray; 1.85 A; G/T=13-97. DR PDB; 5Z86; X-ray; 1.85 A; G/T=13-97. DR PDB; 5ZCO; X-ray; 1.90 A; G/T=13-97. DR PDB; 5ZCP; X-ray; 1.65 A; G/T=13-97. DR PDB; 5ZCQ; X-ray; 1.65 A; G/T=13-97. DR PDB; 6J8M; X-ray; 1.90 A; G/T=13-97. DR PDB; 6JUW; X-ray; 1.80 A; G/T=13-96. DR PDB; 6JY3; X-ray; 1.85 A; G=13-97. DR PDB; 6JY4; X-ray; 1.95 A; G=13-97. DR PDB; 6NKN; X-ray; 2.50 A; G/T=13-97. DR PDB; 6NMF; X-ray; 2.80 A; G/T=13-97. DR PDB; 6NMP; X-ray; 2.90 A; G/T=13-97. DR PDB; 7COH; X-ray; 1.30 A; G/T=13-97. DR PDB; 7CP5; X-ray; 1.76 A; G/T=13-96. DR PDB; 7D5W; X-ray; 1.84 A; G/T=13-96. DR PDB; 7D5X; X-ray; 1.74 A; G/T=13-96. DR PDB; 7DGQ; EM; 5.00 A; A6=1-97. DR PDB; 7DGR; EM; 4.60 A; A4=1-97. DR PDB; 7DGS; EM; 7.80 A; A4=1-97. DR PDB; 7DKF; EM; 8.30 A; G3=1-97. DR PDB; 7EV7; X-ray; 1.70 A; G/T=13-97. DR PDB; 7THU; X-ray; 1.93 A; GGG/TTT=13-97. DR PDB; 7TIE; X-ray; 1.90 A; GGG/TTT=13-97. DR PDB; 7TIH; X-ray; 2.35 A; GGG/TTT=13-97. DR PDB; 7TII; X-ray; 2.45 A; GGG/TTT=13-97. DR PDB; 7VUW; X-ray; 1.60 A; G/T=13-96. DR PDB; 7VVR; X-ray; 1.65 A; G/T=13-96. DR PDB; 7W3E; X-ray; 1.45 A; G/T=13-96. DR PDB; 7XMA; X-ray; 2.20 A; G/T=13-96. DR PDB; 7XMB; X-ray; 2.20 A; G/T=13-96. DR PDB; 7Y44; X-ray; 1.90 A; G/T=13-97. DR PDB; 7YPY; X-ray; 1.50 A; G/T=13-97. DR PDB; 8D4T; EM; 3.10 A; T=24-95. DR PDB; 8GBT; X-ray; 2.80 A; G/T=13-97. DR PDB; 8GCQ; X-ray; 2.38 A; G/T=13-97. DR PDB; 8GVM; X-ray; 1.85 A; G/T=13-97. DR PDB; 8H8R; X-ray; 1.70 A; G/T=13-97. DR PDB; 8H8S; X-ray; 1.70 A; G/T=13-97. DR PDB; 8IJN; X-ray; 1.80 A; G/T=13-97. DR PDBsum; 1OCC; -. DR PDBsum; 1OCO; -. DR PDBsum; 1OCR; -. DR PDBsum; 1OCZ; -. DR PDBsum; 1V54; -. DR PDBsum; 1V55; -. DR PDBsum; 2DYR; -. DR PDBsum; 2DYS; -. DR PDBsum; 2EIJ; -. DR PDBsum; 2EIK; -. DR PDBsum; 2EIL; -. DR PDBsum; 2EIM; -. DR PDBsum; 2EIN; -. DR PDBsum; 2OCC; -. DR PDBsum; 2Y69; -. DR PDBsum; 2YBB; -. DR PDBsum; 2ZXW; -. DR PDBsum; 3ABK; -. DR PDBsum; 3ABL; -. DR PDBsum; 3ABM; -. DR PDBsum; 3AG1; -. DR PDBsum; 3AG2; -. DR PDBsum; 3AG3; -. DR PDBsum; 3AG4; -. DR PDBsum; 3ASN; -. DR PDBsum; 3ASO; -. DR PDBsum; 3WG7; -. DR PDBsum; 3X2Q; -. DR PDBsum; 5B1A; -. DR PDBsum; 5B1B; -. DR PDBsum; 5B3S; -. DR PDBsum; 5GPN; -. DR PDBsum; 5IY5; -. DR PDBsum; 5LUF; -. DR PDBsum; 5W97; -. DR PDBsum; 5WAU; -. DR PDBsum; 5X19; -. DR PDBsum; 5X1B; -. DR PDBsum; 5X1F; -. DR PDBsum; 5XDQ; -. DR PDBsum; 5XDX; -. DR PDBsum; 5XTH; -. DR PDBsum; 5XTI; -. DR PDBsum; 5Z84; -. DR PDBsum; 5Z85; -. DR PDBsum; 5Z86; -. DR PDBsum; 5ZCO; -. DR PDBsum; 5ZCP; -. DR PDBsum; 5ZCQ; -. DR PDBsum; 6J8M; -. DR PDBsum; 6JUW; -. DR PDBsum; 6JY3; -. DR PDBsum; 6JY4; -. DR PDBsum; 6NKN; -. DR PDBsum; 6NMF; -. DR PDBsum; 6NMP; -. DR PDBsum; 7COH; -. DR PDBsum; 7CP5; -. DR PDBsum; 7D5W; -. DR PDBsum; 7D5X; -. DR PDBsum; 7DGQ; -. DR PDBsum; 7DGR; -. DR PDBsum; 7DGS; -. DR PDBsum; 7DKF; -. DR PDBsum; 7EV7; -. DR PDBsum; 7THU; -. DR PDBsum; 7TIE; -. DR PDBsum; 7TIH; -. DR PDBsum; 7TII; -. DR PDBsum; 7VUW; -. DR PDBsum; 7VVR; -. DR PDBsum; 7W3E; -. DR PDBsum; 7XMA; -. DR PDBsum; 7XMB; -. DR PDBsum; 7Y44; -. DR PDBsum; 7YPY; -. DR PDBsum; 8D4T; -. DR PDBsum; 8GBT; -. DR PDBsum; 8GCQ; -. DR PDBsum; 8GVM; -. DR PDBsum; 8H8R; -. DR PDBsum; 8H8S; -. DR PDBsum; 8IJN; -. DR AlphaFoldDB; P07471; -. DR EMDB; EMD-27196; -. DR EMDB; EMD-30673; -. DR EMDB; EMD-30674; -. DR EMDB; EMD-30675; -. DR EMDB; EMD-30706; -. DR EMDB; EMD-4107; -. DR EMDB; EMD-9534; -. DR SMR; P07471; -. DR CORUM; P07471; -. DR DIP; DIP-39018N; -. DR IntAct; P07471; 2. DR STRING; 9913.ENSBTAP00000026002; -. DR PaxDb; 9913-ENSBTAP00000026002; -. DR Ensembl; ENSBTAT00000026002.4; ENSBTAP00000026002.3; ENSBTAG00000019521.4. DR GeneID; 282200; -. DR KEGG; bta:282200; -. DR CTD; 1339; -. DR VEuPathDB; HostDB:ENSBTAG00000019521; -. DR VGNC; VGNC:27637; COX6A2. DR eggNOG; KOG3469; Eukaryota. DR GeneTree; ENSGT00940000162257; -. DR HOGENOM; CLU_122515_1_1_1; -. DR InParanoid; P07471; -. DR OMA; IRTKPYC; -. DR OrthoDB; 2912771at2759; -. DR TreeFam; TF105064; -. DR BRENDA; 7.1.1.9; 908. DR UniPathway; UPA00705; -. DR EvolutionaryTrace; P07471; -. DR Proteomes; UP000009136; Chromosome 25. DR Bgee; ENSBTAG00000019521; Expressed in laryngeal cartilage and 44 other cell types or tissues. DR GO; GO:0005751; C:mitochondrial respiratory chain complex IV; IBA:GO_Central. DR GO; GO:0045277; C:respiratory chain complex IV; IDA:UniProtKB. DR GO; GO:0030234; F:enzyme regulator activity; IBA:GO_Central. DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW. DR GO; GO:0006123; P:mitochondrial electron transport, cytochrome c to oxygen; IBA:GO_Central. DR CDD; cd00925; Cyt_c_Oxidase_VIa; 1. DR Gene3D; 4.10.95.10; Cytochrome c oxidase, subunit VIa; 1. DR InterPro; IPR001349; Cyt_c_oxidase_su6a. DR InterPro; IPR018507; Cyt_c_oxidase_su6a_CS. DR InterPro; IPR036418; Cyt_c_oxidase_su6a_sf. DR PANTHER; PTHR11504; CYTOCHROME C OXIDASE POLYPEPTIDE VIA; 1. DR PANTHER; PTHR11504:SF1; CYTOCHROME C OXIDASE SUBUNIT 6A2, MITOCHONDRIAL; 1. DR Pfam; PF02046; COX6A; 1. DR PIRSF; PIRSF000277; COX6A1; 1. DR SUPFAM; SSF81411; Mitochondrial cytochrome c oxidase subunit VIa; 1. DR PROSITE; PS01329; COX6A; 1. PE 1: Evidence at protein level; KW 3D-structure; Direct protein sequencing; Membrane; Mitochondrion; KW Mitochondrion inner membrane; Oxidoreductase; Reference proteome; KW Transit peptide; Transmembrane; Transmembrane helix. FT TRANSIT 1..12 FT /note="Mitochondrion" FT /evidence="ECO:0000269|PubMed:2994692" FT CHAIN 13..97 FT /note="Cytochrome c oxidase subunit 6A2, mitochondrial" FT /id="PRO_0000006115" FT TOPO_DOM 13..24 FT /note="Mitochondrial matrix" FT /evidence="ECO:0000269|PubMed:27605664" FT TRANSMEM 25..49 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:27605664" FT TOPO_DOM 50..97 FT /note="Mitochondrial intermembrane" FT /evidence="ECO:0000269|PubMed:27605664" FT STRAND 21..23 FT /evidence="ECO:0007829|PDB:1OCR" FT HELIX 25..34 FT /evidence="ECO:0007829|PDB:7COH" FT HELIX 36..50 FT /evidence="ECO:0007829|PDB:7COH" FT STRAND 77..79 FT /evidence="ECO:0007829|PDB:7COH" FT TURN 85..87 FT /evidence="ECO:0007829|PDB:7COH" FT STRAND 91..93 FT /evidence="ECO:0007829|PDB:1OCC" SQ SEQUENCE 97 AA; 10800 MW; 59B408A1B9B6AF4F CRC64; MALPLKSLSR GLASAAKGDH GGTGARTWRF LTFGLALPSV ALCTLNSWLH SGHRERPAFI PYHHLRIRTK PFSWGDGNHT FFHNPRVNPL PTGYEKP //