CX6A2_MOUSE
ID CX6A2_MOUSE Reviewed; 97 AA.
AC P43023;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Cytochrome c oxidase subunit 6A2, mitochondrial;
DE AltName: Full=Cytochrome c oxidase polypeptide VIa-heart;
DE Short=COXVIAH;
DE Flags: Precursor;
GN Name=Cox6a2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=BALB/cJ;
RA Newton D., Bowman L.H.;
RL Submitted (APR-1994) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/Sv;
RX PubMed=7592858; DOI=10.1074/jbc.270.44.26433;
RA Wan B., Moreadith R.W.;
RT "Structural characterization and regulatory element analysis of the heart
RT isoform of cytochrome c oxidase VIa.";
RL J. Biol. Chem. 270:26433-26440(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE.
RA Schmidt T.A., Jaradat S.A., Goodman M., Lomax M.I., Grossman L.I.;
RL Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=31155743; DOI=10.1002/ana.25517;
RA Inoue M., Uchino S., Iida A., Noguchi S., Hayashi S., Takahashi T.,
RA Fujii K., Komaki H., Takeshita E., Nonaka I., Okada Y., Yoshizawa T.,
RA Van Lommel L., Schuit F., Goto Y.I., Mimaki M., Nishino I.;
RT "COX6A2 variants cause a muscle-specific cytochrome c oxidase deficiency.";
RL Ann. Neurol. 86:193-202(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 (PubMed:31155743).
CC {ECO:0000250|UniProtKB:P32799, ECO:0000269|PubMed:31155743}.
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 COX4I, COX5A,
CC COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and NDUFA4, which
CC are encoded in the nuclear genome. The complex exists as a monomer or a
CC 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)).
CC {ECO:0000250|UniProtKB:P07471}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:P07471}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:P07471}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice show significant decline of COX
CC activity and assembly in skeletal muscle. In particular, complexes IV,
CC IV(2) and III(2)IV(2), and supercomplex I(1)III(2)IV(1) are reduced,
CC whereas levels of complexes I, II, and III are normal.
CC {ECO:0000269|PubMed:31155743}.
CC -!- SIMILARITY: Belongs to the cytochrome c oxidase subunit 6A family.
CC {ECO:0000305}.
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DR EMBL; U08439; AAA17835.1; -; mRNA.
DR EMBL; U34801; AAC52280.1; -; Genomic_DNA.
DR EMBL; U63716; AAB41683.1; -; Genomic_DNA.
DR EMBL; AK002506; BAB22151.1; -; mRNA.
DR CCDS; CCDS21891.1; -.
DR PIR; I49360; I49360.
DR RefSeq; NP_034073.2; NM_009943.2.
DR PDB; 7O37; EM; 3.20 A; g=13-97.
DR PDB; 7O3C; EM; 3.30 A; g=13-97.
DR PDB; 7O3E; EM; 3.60 A; g=13-97.
DR PDBsum; 7O37; -.
DR PDBsum; 7O3C; -.
DR PDBsum; 7O3E; -.
DR AlphaFoldDB; P43023; -.
DR SMR; P43023; -.
DR IntAct; P43023; 1.
DR STRING; 10090.ENSMUSP00000033049; -.
DR iPTMnet; P43023; -.
DR PhosphoSitePlus; P43023; -.
DR MaxQB; P43023; -.
DR PaxDb; P43023; -.
DR PeptideAtlas; P43023; -.
DR PRIDE; P43023; -.
DR ProteomicsDB; 279213; -.
DR Antibodypedia; 27872; 106 antibodies from 29 providers.
DR DNASU; 12862; -.
DR Ensembl; ENSMUST00000033049; ENSMUSP00000033049; ENSMUSG00000030785.
DR GeneID; 12862; -.
DR KEGG; mmu:12862; -.
DR UCSC; uc009jyi.1; mouse.
DR CTD; 1339; -.
DR MGI; MGI:104649; Cox6a2.
DR VEuPathDB; HostDB:ENSMUSG00000030785; -.
DR eggNOG; KOG3469; Eukaryota.
DR GeneTree; ENSGT00940000162257; -.
DR HOGENOM; CLU_122515_1_1_1; -.
DR InParanoid; P43023; -.
DR OMA; IRTKPYC; -.
DR OrthoDB; 1591077at2759; -.
DR PhylomeDB; P43023; -.
DR TreeFam; TF105064; -.
DR UniPathway; UPA00705; -.
DR BioGRID-ORCS; 12862; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Cox6a2; mouse.
DR PRO; PR:P43023; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P43023; protein.
DR Bgee; ENSMUSG00000030785; Expressed in digastric muscle group and 138 other tissues.
DR Genevisible; P43023; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005751; C:mitochondrial respiratory chain complex IV; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0004129; F:cytochrome-c oxidase activity; IEA:InterPro.
DR GO; GO:0030234; F:enzyme regulator activity; IBA:GO_Central.
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; -; 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; PTHR11504; 1.
DR Pfam; PF02046; COX6A; 1.
DR PIRSF; PIRSF000277; COX6A1; 1.
DR SUPFAM; SSF81411; SSF81411; 1.
DR PROSITE; PS01329; COX6A; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Oxidoreductase; Reference proteome; Transit peptide; Transmembrane;
KW Transmembrane helix.
FT TRANSIT 1..12
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:P07471"
FT CHAIN 13..97
FT /note="Cytochrome c oxidase subunit 6A2, mitochondrial"
FT /id="PRO_0000006117"
FT TOPO_DOM 13..24
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000250|UniProtKB:P07471"
FT TRANSMEM 25..49
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P07471"
FT TOPO_DOM 50..97
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000250|UniProtKB:P07471"
FT CONFLICT 39
FT /note="G -> S (in Ref. 1; AAA17835)"
FT /evidence="ECO:0000305"
FT HELIX 26..49
FT /evidence="ECO:0007829|PDB:7O37"
FT STRAND 63..66
FT /evidence="ECO:0007829|PDB:7O37"
FT STRAND 73..79
FT /evidence="ECO:0007829|PDB:7O37"
FT TURN 85..87
FT /evidence="ECO:0007829|PDB:7O37"
SQ SEQUENCE 97 AA; 10749 MW; CECCAC26D332A47F CRC64;
MALPLKVLSR SMASAAKGDH GGAGANTWRL LTFVLALPGV ALCSLNCWMH AGHHERPEFI
PYHHLRIRTK PFAWGDGNHT LFHNPHVNPL PTGYEHP
