ID Q4G6P4_HUMAN Unreviewed; 261 AA. AC Q4G6P4; DT 30-AUG-2005, integrated into UniProtKB/TrEMBL. DT 30-AUG-2005, sequence version 1. DT 29-MAY-2024, entry version 101. DE RecName: Full=Cytochrome c oxidase subunit 3 {ECO:0000256|ARBA:ARBA00015944, ECO:0000256|RuleBase:RU003375}; GN Name=COIII {ECO:0000313|EMBL:BAE15899.1}; GN Synonyms=COX3 {ECO:0000313|EMBL:ABN13452.2}; OS Homo sapiens (Human). OG Mitochondrion {ECO:0000313|EMBL:BAE15899.1}. OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606 {ECO:0000313|EMBL:BAE15899.1}; RN [1] {ECO:0000313|EMBL:BAE15899.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=JDsq0100 {ECO:0000313|EMBL:BAE15899.1}, and NDsq0117 RC {ECO:0000313|EMBL:BAE14092.1}; RX PubMed=15466285; DOI=10.1101/gr.2286304; RA Tanaka M., Cabrera V.M., Gonzalez A.M., Larruga J.M., Takeyasu T., Fuku N., RA Guo L., Hirose R., Fujita Y., Kurata M., Shinoda K., Umetsu K., Yamada Y., RA Oshida Y., Sato Y., Hattori N., Mizuno Y., Arai Y., Hirose N., Ohta S., RA Ogawa O., Tanaka Y., Kawamori R., Shamoto-Nagai M., Maruyama W., RA Shimokata H., Suzuki R., Shimodaira H.; RT "Mitochondrial genome variation in eastern Asia and the peopling of RT Japan."; RL Genome Res. 14:1832-1850(2004). RN [2] {ECO:0000313|EMBL:BAE14092.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=NDsq0117 {ECO:0000313|EMBL:BAE14092.1}; RA Guo L., Oshida Y., Fuku N., Takeyasu T., Fujita Y., Kurata M., Sato Y., RA Ito M., Tanaka M.; RT "Mitochondrial genome polymorphisms associated with type-2 diabetes or RT obesity."; RL Mitochondrion 0:0-0(2004). RN [3] {ECO:0000313|EMBL:BAG39298.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=Mdmd46 {ECO:0000313|EMBL:BAG39298.1}; RX PubMed=16048457; DOI=10.1111/j.1440-1819.2005.01404.x; RA Kazuno A., Munakata K., Mori K., Tanaka M., Nanko S., Kunugi H., RA Umekage T., Tochigi M., Kohda K., Sasaki T., Akiyama T., Washizuka S., RA Kato N., Kato T.; RT "Mitochondrial DNA sequence analysis of patients with 'atypical RT psychosis'."; RL Psychiatry Clin. Neurosci. 59:497-503(2005). RN [4] {ECO:0000313|EMBL:BAE15899.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=JDsq0100 {ECO:0000313|EMBL:BAE15899.1}, and NDsq0117 RC {ECO:0000313|EMBL:BAE14092.1}; RA Tanaka M.; RT "Human mitochondrial genome polymorphism database (mtSNP)."; RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases. RN [5] {ECO:0000313|EMBL:BAG39298.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=Mdmd46 {ECO:0000313|EMBL:BAG39298.1}; RX PubMed=16895436; DOI=10.1371/journal.pgen.0020128; RA Kazuno A., Munakata K., Nagai T., Shimozono S., Tanaka M., Yoneda M., RA Kato N., Miyawaki A., Kato T.; RT "Identification of mitochondrial DNA polymorphisms that alter mitochondrial RT matrix pH and intracellular calcium dynamics."; RL PLoS Genet. 2:e128-e128(2006). RN [6] {ECO:0000313|EMBL:ABN13452.2} RP NUCLEOTIDE SEQUENCE. RA Greenspan B.; RL Submitted (JAN-2007) to the EMBL/GenBank/DDBJ databases. RN [7] {ECO:0000313|EMBL:BAG39298.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=Mdmd46 {ECO:0000313|EMBL:BAG39298.1}; RA Kazuno A., Munakata K., Mori K., Nanko S., Kunugi H., Nakamura K., Mori N., RA Yamada K., Yoshikawa T., Kato N., Kato T.; RT "Mitochondrial DNA haplogroup analysis in patients with Bipolar Disorder."; RL Am. J. Med. Genet. B Neuropsychiatr. Genet. 0:0-0(2008). RN [8] {ECO:0000313|EMBL:BAG39298.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=Mdmd46 {ECO:0000313|EMBL:BAG39298.1}; RX PubMed=17288645; RA Kazuno A., Munakata K., Kato N., Kato T.; RT "Mitochondrial DNA-dependent effects of valproate on mitochondrial calcium RT levels in transmitochondrial cybrids."; RL Int. J. Neuropsychopharmacol. 11:71-78(2008). RN [9] {ECO:0000313|EMBL:BAG39298.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=Mdmd46 {ECO:0000313|EMBL:BAG39298.1}; RX PubMed=18226984; DOI=10.1016/j.mito.2007.12.002; RA Kazuno A., Munakata K., Tanaka M., Kato N., Kato T.; RT "Relationships between mitochondrial DNA subhaplogroups and intracellular RT calcium dynamics."; RL Mitochondrion 8:164-169(2008). RN [10] {ECO:0000313|EMBL:ADL15367.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=21041797; DOI=10.1093/molbev/msq294; RA Batini C., Lopes J., Behar D.M., Calafell F., Jorde L.B., van der Veen L., RA Quintana-Murci L., Spedini G., Destro-Bisol G., Comas D.; RT "Insights into the demographic history of African Pygmies from complete RT mitochondrial genomes."; RL Mol. Biol. Evol. 28:1099-1110(2011). RN [11] {ECO:0000313|EMBL:AFV56906.1} RP NUCLEOTIDE SEQUENCE. RC TISSUE=Saliva {ECO:0000313|EMBL:AFV56906.1}; RA Tito R.Y., Polo S.I., Lewis C.M.Jr.; RT "Mitochondrial Genomes and Founder Effects within the Americas."; RL Submitted (SEP-2012) to the EMBL/GenBank/DDBJ databases. RN [12] {ECO:0000313|EMBL:AGZ66938.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=25254093; DOI=10.1186/2041-2223-5-13; RA Lippold S., Xu H., Ko A., Li M., Renaud G., Butthof A., Schroder R., RA Stoneking M.; RT "Human paternal and maternal demographic histories: insights from high- RT resolution Y chromosome and mtDNA sequences."; RL Investig Genet 5:13-13(2014). RN [13] {ECO:0000313|EMBL:AHX43278.1} RP NUCLEOTIDE SEQUENCE. RA Zheng H.-X., Qin Z.-D., Jin L., Jin L.; RT "The mitochondrial DNA diversity of HGDP populations."; RL Submitted (FEB-2014) to the EMBL/GenBank/DDBJ databases. RN [14] {ECO:0000313|EMBL:AKH35845.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=26640946; RA De Fanti S., Barbieri C., Sarno S., Sevini F., Vianello D., Tamm E., RA Metspalu E., van Oven M., Hubner A., Sazzini M., Franceschi C., RA Pettener D., Luiselli D.; RT "Fine Dissection of Human Mitochondrial DNA Haplogroup HV Lineages Reveals RT Paleolithic Signatures from European Glacial Refugia."; RL PLoS ONE 10:E0144391-E0144391(2015). RN [15] {ECO:0000313|EMBL:ASS04564.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=28716916; DOI=10.1073/pnas.1704906114; RA Pierron D., Heiske M., Razafindrazaka H., Rakoto I., Rabetokotany N., RA Ravololomanga B., Rakotozafy L.M., Rakotomalala M.M., Razafiarivony M., RA Rasoarifetra B., Raharijesy M.A., Razafindralambo L., Ramilisonina, RA Fanony F., Lejamble S., Thomas O., Mohamed Abdallah A., Rocher C., RA Arachiche A., Tonaso L., Pereda-Loth V., Schiavinato S., Brucato N., RA Ricaut F.X., Kusuma P., Sudoyo H., Ni S., Boland A., Deleuze J.F., RA Beaujard P., Grange P., Adelaar S., Stoneking M., Rakotoarisoa J.A., RA Radimilahy C., Letellier T.; RT "Genomic landscape of human diversity across Madagascar."; RL Proc. Natl. Acad. Sci. U.S.A. 114:E6498-E6506(2017). RN [16] {ECO:0000313|EMBL:ASU93649.1} RP NUCLEOTIDE SEQUENCE. RC TISSUE=Peripheral blood {ECO:0000313|EMBL:ASU93649.1}; RA Afonso C.L., Miller P.J., Scott M.A., Spackman E., Goraichik I., RA Dimitrov K.M., Suarez D.L., Swayne D.E.; RL Submitted (APR-2017) to the EMBL/GenBank/DDBJ databases. RN [17] {ECO:0000313|EMBL:ATW75525.1} RP NUCLEOTIDE SEQUENCE. RA Han C.G.; RL Submitted (NOV-2017) to the EMBL/GenBank/DDBJ databases. 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:0000256|RuleBase:RU003375}. CC -!- CATALYTIC ACTIVITY: CC Reaction=4 Fe(II)-[cytochrome c] + 8 H(+)(in) + O2 = 4 Fe(III)- CC [cytochrome c] + 4 H(+)(out) + 2 H2O; Xref=Rhea:RHEA:11436, CC Rhea:RHEA-COMP:10350, Rhea:RHEA-COMP:14399, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:29033, CC ChEBI:CHEBI:29034; EC=7.1.1.9; CC Evidence={ECO:0000256|ARBA:ARBA00029331}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11437; CC Evidence={ECO:0000256|ARBA:ARBA00029331}; CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000256|ARBA:ARBA00004141}; Multi- CC pass membrane protein {ECO:0000256|ARBA:ARBA00004141}. CC -!- SIMILARITY: Belongs to the cytochrome c oxidase subunit 3 family. CC {ECO:0000256|ARBA:ARBA00010581, ECO:0000256|RuleBase:RU003375}. 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; EF417833; ABN13452.2; -; Genomic_DNA. DR EMBL; HM771154; ADL15367.1; -; Genomic_DNA. DR EMBL; HM771155; ADL15380.1; -; Genomic_DNA. DR EMBL; JX669399; AFV56906.1; -; Genomic_DNA. DR EMBL; KC765917; AGH20733.1; -; Genomic_DNA. DR EMBL; KF451023; AGZ66938.1; -; Genomic_DNA. DR EMBL; KF451033; AGZ67068.1; -; Genomic_DNA. DR EMBL; KJ445786; AHX43278.1; -; Genomic_DNA. DR EMBL; KJ445787; AHX43291.1; -; Genomic_DNA. DR EMBL; KP340171; AKH35845.1; -; Genomic_DNA. DR EMBL; MF056587; ASS04564.1; -; Genomic_DNA. DR EMBL; KY941906; ASU93649.1; -; Genomic_DNA. DR EMBL; MG546008; ATW75525.1; -; Genomic_DNA. DR EMBL; AP008777; BAE14092.1; -; Genomic_DNA. DR EMBL; AP008916; BAE15899.1; -; Genomic_DNA. DR EMBL; AP009464; BAG39298.1; -; Genomic_DNA. DR AlphaFoldDB; Q4G6P4; -. DR PeptideAtlas; Q4G6P4; -. DR ChiTaRS; COX3; human. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-KW. DR GO; GO:0004129; F:cytochrome-c oxidase activity; IEA:UniProtKB-EC. DR GO; GO:0006123; P:mitochondrial electron transport, cytochrome c to oxygen; IEA:TreeGrafter. DR CDD; cd01665; Cyt_c_Oxidase_III; 1. DR Gene3D; 1.10.287.70; -; 1. DR Gene3D; 1.20.120.80; Cytochrome c oxidase, subunit III, four-helix bundle; 1. DR InterPro; IPR024791; Cyt_c/ubiquinol_Oxase_su3. DR InterPro; IPR033945; Cyt_c_oxase_su3_dom. DR InterPro; IPR000298; Cyt_c_oxidase-like_su3. DR InterPro; IPR035973; Cyt_c_oxidase_su3-like_sf. DR InterPro; IPR013833; Cyt_c_oxidase_su3_a-hlx. DR PANTHER; PTHR11403:SF7; CYTOCHROME C OXIDASE SUBUNIT 3; 1. DR PANTHER; PTHR11403; CYTOCHROME C OXIDASE SUBUNIT III; 1. DR Pfam; PF00510; COX3; 1. DR SUPFAM; SSF81452; Cytochrome c oxidase subunit III-like; 1. DR PROSITE; PS50253; COX3; 1. PE 3: Inferred from homology; KW Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|SAM:Phobius}; KW Mitochondrion {ECO:0000256|RuleBase:RU003375, ECO:0000313|EMBL:BAE15899.1}; KW Translocase {ECO:0000256|ARBA:ARBA00022967}; KW Transmembrane {ECO:0000256|ARBA:ARBA00022692, KW ECO:0000256|RuleBase:RU003375}; KW Transmembrane helix {ECO:0000256|ARBA:ARBA00022989, KW ECO:0000256|SAM:Phobius}. FT TRANSMEM 16..35 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 41..58 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 79..102 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 159..177 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 197..220 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 240..260 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT DOMAIN 4..261 FT /note="Heme-copper oxidase subunit III family profile" FT /evidence="ECO:0000259|PROSITE:PS50253" SQ SEQUENCE 261 AA; 29924 MW; 0DA1A437A7A55B31 CRC64; MTHQSHAYHM VKPSPWPLTG ALSALLMTSG LAMWFHFHSM TLLMLGLLTS TLTMYQWWRD VTRESTYQGH HTPPVQKGLR YGMILFITSE VFFFAGFFWA FYHSSLAPTP QLGGHWPPTG ITPLNPLEVP LLNTSVLLAS GVSITWAHHS LMENNRNQMI QALLITILLG LYFTLLQASE YFESPFTISD GIYGSTFFVA TGFHGLHVII GSTFLTICFI RQLMFHFTSK HHFGFEAAAW YWHFVDVVWL FLYVSIYWWG S //