CX6A1_MOUSE
ID CX6A1_MOUSE Reviewed; 111 AA.
AC P43024;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 2.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Cytochrome c oxidase subunit 6A1, mitochondrial;
DE AltName: Full=Cytochrome c oxidase polypeptide VIa-liver;
DE Flags: Precursor;
GN Name=Cox6a1; Synonyms=Cox6al;
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 [MRNA].
RC TISSUE=Liver;
RX PubMed=7873616; DOI=10.1016/0167-4781(94)00232-r;
RA Grossman L.I., Rosenthal N.H., Akamatsu M., Erickson R.P.;
RT "Cloning, sequence analysis, and expression of a mouse cDNA encoding
RT cytochrome c oxidase subunit VIa liver isoform.";
RL Biochim. Biophys. Acta 1260:361-364(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-111.
RC STRAIN=BALB/cJ;
RA Newton D., Bowman L.H.;
RL Submitted (APR-1994) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PROTEIN SEQUENCE OF 63-80 AND 83-111, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Hippocampus;
RA Lubec G., Klug S.;
RL Submitted (MAR-2007) to UniProtKB.
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
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 [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=25152455; DOI=10.1016/j.ajhg.2014.07.013;
RA Tamiya G., Makino S., Hayashi M., Abe A., Numakura C., Ueki M., Tanaka A.,
RA Ito C., Toshimori K., Ogawa N., Terashima T., Maegawa H., Yanagisawa D.,
RA Tooyama I., Tada M., Onodera O., Hayasaka K.;
RT "A mutation of COX6A1 causes a recessive axonal or mixed form of Charcot-
RT Marie-Tooth disease.";
RL Am. J. Hum. Genet. 95:294-300(2014).
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. {ECO:0000250|UniProtKB:P32799}.
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:P12074}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:P12074}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:P12074}.
CC -!- DISRUPTION PHENOTYPE: Mice have walking difficulties. Histologic
CC examination shows thinned sciatic nerves and neurogenic muscular
CC changes, including small angular fibers and small group atrophy.
CC Electrophysiologic studies show delayed motor nerve conduction
CC velocities compared to controls. COX activity and ATP contents in liver
CC cells are decreased. {ECO:0000269|PubMed:25152455}.
CC -!- SIMILARITY: Belongs to the cytochrome c oxidase subunit 6A family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA17836.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAA53066.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; L06465; AAA53066.1; ALT_INIT; mRNA.
DR EMBL; U08440; AAA17836.1; ALT_INIT; mRNA.
DR CCDS; CCDS19590.1; -.
DR RefSeq; NP_031774.1; NM_007748.3.
DR AlphaFoldDB; P43024; -.
DR SMR; P43024; -.
DR BioGRID; 198843; 21.
DR CORUM; P43024; -.
DR IntAct; P43024; 2.
DR MINT; P43024; -.
DR STRING; 10090.ENSMUSP00000047661; -.
DR PhosphoSitePlus; P43024; -.
DR SWISS-2DPAGE; P43024; -.
DR EPD; P43024; -.
DR jPOST; P43024; -.
DR MaxQB; P43024; -.
DR PaxDb; P43024; -.
DR PeptideAtlas; P43024; -.
DR PRIDE; P43024; -.
DR ProteomicsDB; 279242; -.
DR TopDownProteomics; P43024; -.
DR DNASU; 12861; -.
DR Ensembl; ENSMUST00000040154; ENSMUSP00000047661; ENSMUSG00000041697.
DR GeneID; 12861; -.
DR KEGG; mmu:12861; -.
DR CTD; 1337; -.
DR MGI; MGI:103099; Cox6a1.
DR eggNOG; KOG3469; Eukaryota.
DR InParanoid; P43024; -.
DR OMA; GYEGHDE; -.
DR OrthoDB; 1591077at2759; -.
DR Reactome; R-MMU-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-MMU-611105; Respiratory electron transport.
DR Reactome; R-MMU-9707564; Cytoprotection by HMOX1.
DR UniPathway; UPA00705; -.
DR BioGRID-ORCS; 12861; 6 hits in 74 CRISPR screens.
DR ChiTaRS; Cox6a1; mouse.
DR PRO; PR:P43024; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; P43024; protein.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031966; C:mitochondrial membrane; ISO:MGI.
DR GO; GO:0005751; C:mitochondrial respiratory chain complex IV; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0043209; C:myelin sheath; HDA:UniProtKB.
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 Direct protein sequencing; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Oxidoreductase; Reference proteome;
KW Transit peptide; Transmembrane; Transmembrane helix.
FT TRANSIT 1..26
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:P12074"
FT CHAIN 27..111
FT /note="Cytochrome c oxidase subunit 6A1, mitochondrial"
FT /id="PRO_0000006120"
FT TOPO_DOM 27..36
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000250|UniProtKB:P07471"
FT TRANSMEM 37..61
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P07471"
FT TOPO_DOM 62..111
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000250|UniProtKB:P07471"
SQ SEQUENCE 111 AA; 12352 MW; 76D5EDA5F79EC5E7 CRC64;
MASAVLSASR VSRPLGRALP GLRRPMSSGA HGEEGSARMW KALTYFVALP GVGVSMLNVF
LKSRHEEHER PPFVAYPHLR IRTKPFPWGD GNHTLFHNPH VNPLPTGYED E
