COX8A_HUMAN
ID COX8A_HUMAN Reviewed; 69 AA.
AC P10176; P15955;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 2.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Cytochrome c oxidase subunit 8A, mitochondrial;
DE AltName: Full=Cytochrome c oxidase polypeptide VIII-liver/heart;
DE AltName: Full=Cytochrome c oxidase subunit 8-2;
DE Flags: Precursor;
GN Name=COX8A; Synonyms=COX8, COX8L;
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=Liver;
RX PubMed=2543673; DOI=10.1016/s0021-9258(18)81662-3;
RA Rizzuto R., Nakase H., Darras B., Francke U., Fabrizi G.M., Mengel T.,
RA Walsh F., Kadenbach B., Dimauro S., Schon E.A.;
RT "A gene specifying subunit VIII of human cytochrome c oxidase is localized
RT to chromosome 11 and is expressed in both muscle and non-muscle tissues.";
RL J. Biol. Chem. 264:10595-10600(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
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 [3]
RP PROTEIN SEQUENCE OF 26-69.
RC TISSUE=Heart;
RX PubMed=2847943; DOI=10.1016/0014-5793(88)80353-3;
RA van Kuilenburg A.B.P., Muijsers A.O., Demol H., Dekker H.L.,
RA van Beeumen J.J.;
RT "Human heart cytochrome c oxidase subunit VIII. Purification and
RT determination of the complete amino acid sequence.";
RL FEBS Lett. 240:127-132(1988).
RN [4]
RP TISSUE SPECIFICITY, AND INVOLVEMENT IN MC4DN15.
RX PubMed=26685157; DOI=10.1093/brain/awv357;
RA Hallmann K., Kudin A.P., Zsurka G., Kornblum C., Reimann J., Stueve B.,
RA Waltz S., Hattingen E., Thiele H., Nuernberg P., Rueb C., Voos W.,
RA Kopatz J., Neumann H., Kunz W.S.;
RT "Loss of the smallest subunit of cytochrome c oxidase, COX8A, causes Leigh-
RT like syndrome and epilepsy.";
RL Brain 139:338-345(2016).
RN [5]
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 [6]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS).
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).
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:P10175}.
CC -!- PATHWAY: Energy metabolism; oxidative phosphorylation.
CC {ECO:0000250|UniProtKB:P10175}.
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 {ECO:0000269|PubMed:28844695, ECO:0000269|PubMed:30030519}.
CC -!- INTERACTION:
CC P10176; Q16520: BATF; NbExp=3; IntAct=EBI-3904738, EBI-749503;
CC P10176; P56851: EDDM3B; NbExp=3; IntAct=EBI-3904738, EBI-10215665;
CC P10176; P43358: MAGEA4; NbExp=3; IntAct=EBI-3904738, EBI-743122;
CC P10176; P06748: NPM1; NbExp=3; IntAct=EBI-3904738, EBI-78579;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:30030519}; Single-pass membrane protein
CC {ECO:0000269|PubMed:30030519}.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:26685157}.
CC -!- DISEASE: Mitochondrial complex IV deficiency, nuclear type 15 (MC4DN15)
CC [MIM:619059]: An autosomal recessive mitochondrial disorder with onset
CC in infancy. MC4DN15 is characterized by global developmental delay,
CC poor feeding, metabolic acidosis, short stature, microcephaly, proximal
CC muscle weakness, and distal spasticity. Additional manifestations
CC include scoliosis, primary pulmonary hypertension, refractory seizures,
CC and inability to walk. Serum and CSF lactate levels are increased.
CC Patient tissues show decreased levels and activity of mitochondrial
CC respiratory complex IV. {ECO:0000269|PubMed:26685157}. Note=The disease
CC may be caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the cytochrome c oxidase VIII family.
CC {ECO:0000305}.
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DR EMBL; J04823; AAA99313.1; -; mRNA.
DR EMBL; BC063025; AAH63025.1; -; mRNA.
DR CCDS; CCDS8054.1; -.
DR PIR; A34103; OSHU8.
DR RefSeq; NP_004065.1; NM_004074.2.
DR PDB; 5Z62; EM; 3.60 A; M=26-68.
DR PDBsum; 5Z62; -.
DR AlphaFoldDB; P10176; -.
DR SMR; P10176; -.
DR BioGRID; 107744; 322.
DR ComplexPortal; CPX-6123; Mitochondrial respiratory chain complex IV.
DR IntAct; P10176; 9.
DR STRING; 9606.ENSP00000321260; -.
DR DrugBank; DB02659; Cholic Acid.
DR DrugBank; DB04464; N-Formylmethionine.
DR TCDB; 3.D.4.11.1; the proton-translocating cytochrome oxidase (cox) superfamily.
DR PhosphoSitePlus; P10176; -.
DR SwissPalm; P10176; -.
DR BioMuta; COX8A; -.
DR EPD; P10176; -.
DR jPOST; P10176; -.
DR MassIVE; P10176; -.
DR PaxDb; P10176; -.
DR PeptideAtlas; P10176; -.
DR PRIDE; P10176; -.
DR ProteomicsDB; 52577; -.
DR TopDownProteomics; P10176; -.
DR Antibodypedia; 43917; 83 antibodies from 22 providers.
DR DNASU; 1351; -.
DR Ensembl; ENST00000314133.4; ENSP00000321260.3; ENSG00000176340.4.
DR GeneID; 1351; -.
DR KEGG; hsa:1351; -.
DR MANE-Select; ENST00000314133.4; ENSP00000321260.3; NM_004074.3; NP_004065.1.
DR CTD; 1351; -.
DR DisGeNET; 1351; -.
DR GeneCards; COX8A; -.
DR HGNC; HGNC:2294; COX8A.
DR HPA; ENSG00000176340; Low tissue specificity.
DR MalaCards; COX8A; -.
DR MIM; 123870; gene.
DR MIM; 619059; phenotype.
DR neXtProt; NX_P10176; -.
DR OpenTargets; ENSG00000176340; -.
DR Orphanet; 254905; Isolated cytochrome C oxidase deficiency.
DR PharmGKB; PA26814; -.
DR VEuPathDB; HostDB:ENSG00000176340; -.
DR eggNOG; ENOG502SA62; Eukaryota.
DR GeneTree; ENSGT00390000006255; -.
DR HOGENOM; CLU_203368_0_0_1; -.
DR InParanoid; P10176; -.
DR OMA; MPPEQKL; -.
DR OrthoDB; 1632471at2759; -.
DR PhylomeDB; P10176; -.
DR TreeFam; TF105070; -.
DR BioCyc; MetaCyc:HS11040-MON; -.
DR PathwayCommons; P10176; -.
DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-HSA-611105; Respiratory electron transport.
DR Reactome; R-HSA-9707564; Cytoprotection by HMOX1.
DR SignaLink; P10176; -.
DR SIGNOR; P10176; -.
DR UniPathway; UPA00705; -.
DR BioGRID-ORCS; 1351; 55 hits in 1078 CRISPR screens.
DR ChiTaRS; COX8A; human.
DR GenomeRNAi; 1351; -.
DR Pharos; P10176; Tbio.
DR PRO; PR:P10176; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P10176; protein.
DR Bgee; ENSG00000176340; Expressed in apex of heart and 213 other tissues.
DR ExpressionAtlas; P10176; baseline and differential.
DR Genevisible; P10176; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
DR GO; GO:0031966; C:mitochondrial membrane; IDA:ComplexPortal.
DR GO; GO:0005751; C:mitochondrial respiratory chain complex IV; IPI:ComplexPortal.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0045277; C:respiratory chain complex IV; IBA:GO_Central.
DR GO; GO:0004129; F:cytochrome-c oxidase activity; TAS:ProtInc.
DR GO; GO:0045333; P:cellular respiration; IC:ComplexPortal.
DR GO; GO:0006091; P:generation of precursor metabolites and energy; TAS:ProtInc.
DR GO; GO:0006123; P:mitochondrial electron transport, cytochrome c to oxygen; IC:ComplexPortal.
DR Gene3D; 4.10.81.10; -; 1.
DR InterPro; IPR003205; Cyt_c_oxidase_su8.
DR InterPro; IPR036548; Cyt_c_oxidase_su8_sf.
DR PANTHER; PTHR16717; PTHR16717; 1.
DR Pfam; PF02285; COX8; 1.
DR SUPFAM; SSF81431; SSF81431; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Primary mitochondrial disease;
KW Reference proteome; Transit peptide; Transmembrane; Transmembrane helix.
FT TRANSIT 1..25
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:2847943"
FT CHAIN 26..69
FT /note="Cytochrome c oxidase subunit 8A, mitochondrial"
FT /id="PRO_0000006186"
FT TOPO_DOM 26..36
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000269|PubMed:30030519"
FT TRANSMEM 37..60
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P10175"
FT TOPO_DOM 61..69
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000269|PubMed:30030519"
SQ SEQUENCE 69 AA; 7579 MW; E1736E52AD0F76E2 CRC64;
MSVLTPLLLR GLTGSARRLP VPRAKIHSLP PEGKLGIMEL AVGLTSCFVT FLLPAGWILS
HLETYRRPE
