ID Q4GVU8_HUMAN Unreviewed; 513 AA. AC Q4GVU8; DT 30-AUG-2005, integrated into UniProtKB/TrEMBL. DT 30-AUG-2005, sequence version 1. DT 14-DEC-2022, entry version 120. DE RecName: Full=Cytochrome c oxidase subunit 1 {ECO:0000256|ARBA:ARBA00015947, ECO:0000256|RuleBase:RU000369}; DE EC=7.1.1.9 {ECO:0000256|ARBA:ARBA00012949, ECO:0000256|RuleBase:RU000369}; GN Name=COI {ECO:0000313|EMBL:BAE07443.1}; GN Synonyms=COX1 {ECO:0000313|EMBL:ACA22373.1}, coxI GN {ECO:0000313|EMBL:BAN79832.1}; OS Homo sapiens (Human). OG Mitochondrion {ECO:0000313|EMBL:BAE07443.1}. OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606 {ECO:0000313|EMBL:BAE07443.1}; RN [1] {ECO:0000313|EMBL:BAE07443.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=HNsq0219 {ECO:0000313|EMBL:BAE13022.1}, PDsq0056 RC {ECO:0000313|EMBL:BAE09016.1}, and TCsq0007 RC {ECO:0000313|EMBL:BAE07443.1}; 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:BAG39021.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=Mdmd25 {ECO:0000313|EMBL:BAG39021.1}; 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 [3] {ECO:0000313|EMBL:BAE07443.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=HNsq0219 {ECO:0000313|EMBL:BAE13022.1}, PDsq0056 RC {ECO:0000313|EMBL:BAE09016.1}, and TCsq0007 RC {ECO:0000313|EMBL:BAE07443.1}; RA Tanaka M.; RT "Human mitochondrial genome polymorphism database (mtSNP)."; RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases. RN [4] {ECO:0000313|EMBL:BAG39021.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=Mdmd25 {ECO:0000313|EMBL:BAG39021.1}; 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 [5] {ECO:0000313|EMBL:ACA22373.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=Chuk101 {ECO:0000313|EMBL:ACA22373.1}; RX PubMed=18452887; DOI=10.1016/j.ajhg.2008.03.019; RA Volodko N.V., Starikovskaya E.B., Mazunin I.O., Eltsov N.P., Naidenko P.V., RA Wallace D.C., Sukernik R.I.; RT "Mitochondrial genome diversity in arctic Siberians, with particular RT reference to the evolutionary history of Beringia and Pleistocenic peopling RT of the Americas."; RL Am. J. Hum. Genet. 82:1084-1100(2008). RN [6] {ECO:0000313|EMBL:BAG39021.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=Mdmd25 {ECO:0000313|EMBL:BAG39021.1}; 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 [7] {ECO:0000313|EMBL:BAG39021.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=Mdmd25 {ECO:0000313|EMBL:BAG39021.1}; 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 [8] {ECO:0000313|EMBL:BAG39021.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=Mdmd25 {ECO:0000313|EMBL:BAG39021.1}; 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 [9] {ECO:0000313|EMBL:ACM69780.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=GL37 {ECO:0000313|EMBL:ACM69780.1}; RX PubMed=19624810; DOI=10.1186/1471-2148-9-173; RA Kumar S., Ravuri R.R., Koneru P., Urade B.P., Sarkar B.N., Chandrasekar A., RA Rao V.R.; RT "Reconstructing Indian-Australian phylogenetic link."; RL BMC Evol. Biol. 9:173-173(2009). RN [10] {ECO:0000313|EMBL:ACM69780.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=GL37 {ECO:0000313|EMBL:ACM69780.1}; RX PubMed=19823670; DOI=10.1371/journal.pone.0007447; RA Chandrasekar A., Kumar S., Sreenath J., Sarkar B.N., Urade B.P., RA Mallick S., Bandopadhyay S.S., Barua P., Barik S.S., Basu D., Kiran U., RA Gangopadhyay P., Sahani R., Prasad B.V., Gangopadhyay S., Lakshmi G.R., RA Ravuri R.R., Padmaja K., Venugopal P.N., Sharma M.B., Rao V.R.; RT "Updating phylogeny of mitochondrial DNA macrohaplogroup m in India: RT dispersal of modern human in South Asian corridor."; RL PLoS ONE 4:E7447-E7447(2009). RN [11] {ECO:0000313|EMBL:ADG46466.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=20587512; DOI=10.1101/gr.109231.110; RA Perego U.A., Angerhofer N., Pala M., Olivieri A., Lancioni H., RA Kashani B.H., Carossa V., Ekins J.E., Gomez-Carballa A., Huber G., RA Zimmermann B., Corach D., Babudri N., Panara F., Myres N.M., Parson W., RA Semino O., Salas A., Woodward S.R., Achilli A., Torroni A.; RT "The initial peopling of the Americas: a growing number of founding RT mitochondrial genomes from Beringia."; RL Genome Res. 20:1174-1179(2010). RN [12] {ECO:0000313|EMBL:AFF96408.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=22482806; DOI=10.1016/j.ajhg.2012.03.002; RA Behar D.M., van Oven M., Rosset S., Metspalu M., Loogvali E.L., Silva N.M., RA Kivisild T., Torroni A., Villems R.; RT "A "Copernican" reassessment of the human mitochondrial DNA tree from its RT root."; RL Am. J. Hum. Genet. 90:675-684(2012). RN [13] {ECO:0000313|EMBL:AGC16424.1} RP NUCLEOTIDE SEQUENCE. RA Duggan A.T., Stoneking M.; RT "A Highly Unstable Recent Mutation in Human mtDNA."; RL Am. J. Hum. Genet. 0:0-0(2013). RN [14] {ECO:0000313|EMBL:BAN79832.1} RP NUCLEOTIDE SEQUENCE. RA Mikami E., Fuku N., Kong Q.P., Takahashi H., Ohiwa N., Murakami H., RA Miyachi M., Pitsiladis Y.P., Higuchi M., Kawahara T., Tanaka M.; RT "Comprehensive analysis of common and rare mitochondrial DNA variants in RT elite Japanese athletes: Case-control study."; RL Submitted (AUG-2013) to the EMBL/GenBank/DDBJ databases. RN [15] {ECO:0000313|EMBL:AID12811.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=24901532; RA Barbieri C., Vicente M., Oliveira S., Bostoen K., Rocha J., Stoneking M., RA Pakendorf B.; RT "Migration and Interaction in a Contact Zone: mtDNA Variation among Bantu- RT Speakers in Southern Africa."; RL PLoS ONE 9:E99117-E99117(2014). RN [16] {ECO:0000313|EMBL:AID61001.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=25757516; RA Gomes S.M., Bodner M., Souto L., Zimmermann B., Huber G., Strobl C., RA Roeck A.W., Achilli A., Olivieri A., Torroni A., Corte-Real F., Parson W.; RT "Human settlement history between Sunda and Sahul: a focus on East Timor RT (Timor-Leste) and the Pleistocenic mtDNA diversity."; RL BMC Genomics 16:70-70(2015). RN [17] {ECO:0000313|EMBL:ALM03578.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=26509580; RA Hernandez C.L., Soares P., Dugoujon J.M., Novelletto A., Rodriguez J.N., RA Rito T., Oliveira M., Melhaoui M., Baali A., Pereira L., Calderon R.; RT "Early Holocenic and Historic mtDNA African Signatures in the Iberian RT Peninsula: The Andalusian Region as a Paradigm."; RL PLoS ONE 10:E0139784-E0139784(2015). RN [18] {ECO:0000313|EMBL:AGA55911.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=26781090; DOI=10.1007/s00439-015-1620-z; RA Soares P.A., Trejaut J.A., Rito T., Cavadas B., Hill C., Eng K.K., RA Mormina M., Brandao A., Fraser R.M., Wang T.Y., Loo J.H., Snell C., RA Ko T.M., Amorim A., Pala M., Macaulay V., Bulbeck D., Wilson J.F., RA Gusmao L., Pereira L., Oppenheimer S., Lin M., Richards M.B.; RT "Resolving the ancestry of Austronesian-speaking populations."; RL Hum. Genet. 135:309-326(2016). RN [19] {ECO:0000313|EMBL:AOT80857.1} RP NUCLEOTIDE SEQUENCE. RA Gomez-Carballa A., Pardo-Seco J., Martinon-Torres F., Salas A.; RT "Analyses of mitogenomes do not support a role of mitochondrial DNA RT variation in sperm motility."; RL Submitted (MAR-2016) to the EMBL/GenBank/DDBJ databases. RN [20] {ECO:0000313|EMBL:AUT78487.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=29304377; DOI=10.1016/j.ajhg.2017.11.011; RA Brucato N., Fernandes V., Mazieres S., Kusuma P., Cox M.P., Ng'ang'a J.W., RA Omar M., Simeone-Senelle M.C., Frassati C., Alshamali F., Fin B., RA Boland A., Deleuze J.F., Stoneking M., Adelaar A., Crowther A., Boivin N., RA Pereira L., Bailly P., Chiaroni J., Ricaut F.X.; RT "The Comoros Show the Earliest Austronesian Gene Flow into the Swahili RT Corridor."; RL Am. J. Hum. Genet. 102:58-68(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:0000256|RuleBase:RU000369}. 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 -!- COFACTOR: CC Name=Cu cation; Xref=ChEBI:CHEBI:23378; CC Evidence={ECO:0000256|ARBA:ARBA00001935}; CC -!- COFACTOR: CC Name=heme; Xref=ChEBI:CHEBI:30413; CC Evidence={ECO:0000256|ARBA:ARBA00001971}; CC -!- PATHWAY: Energy metabolism; oxidative phosphorylation. CC {ECO:0000256|ARBA:ARBA00004673, ECO:0000256|RuleBase:RU000369}. CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000256|ARBA:ARBA00004141}; Multi- CC pass membrane protein {ECO:0000256|ARBA:ARBA00004141}. Mitochondrion CC inner membrane {ECO:0000256|RuleBase:RU000369}; Multi-pass membrane CC protein {ECO:0000256|RuleBase:RU000369}. CC -!- SIMILARITY: Belongs to the heme-copper respiratory oxidase family. CC {ECO:0000256|ARBA:ARBA00009578, ECO:0000256|RuleBase:RU000369}. 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; EU482342; ACA22373.1; -; Genomic_DNA. DR EMBL; FJ383204; ACM69780.1; -; Genomic_DNA. DR EMBL; HM107337; ADG46466.1; -; Genomic_DNA. DR EMBL; JQ704496; AFF96408.1; -; Genomic_DNA. DR EMBL; JX987459; AGA55911.1; -; Genomic_DNA. DR EMBL; JX900416; AGC16424.1; -; Genomic_DNA. DR EMBL; KJ185800; AID12811.1; -; Genomic_DNA. DR EMBL; KJ185801; AID12824.1; -; Genomic_DNA. DR EMBL; KJ676782; AID61001.1; -; Genomic_DNA. DR EMBL; KJ676784; AID61027.1; -; Genomic_DNA. DR EMBL; KT819233; ALM03578.1; -; Genomic_DNA. DR EMBL; KU867580; AOT80857.1; -; Genomic_DNA. DR EMBL; KU867608; AOT81221.1; -; Genomic_DNA. DR EMBL; MF695952; AUT78487.1; -; Genomic_DNA. DR EMBL; AP008266; BAE07443.1; -; Genomic_DNA. DR EMBL; AP008387; BAE09016.1; -; Genomic_DNA. DR EMBL; AP008695; BAE13022.1; -; Genomic_DNA. DR EMBL; AP009443; BAG39021.1; -; Genomic_DNA. DR EMBL; AP013148; BAN79832.1; -; Genomic_DNA. DR EMBL; AP013289; BAN81524.1; -; Genomic_DNA. DR AlphaFoldDB; Q4GVU8; -. DR PeptideAtlas; Q4GVU8; -. DR UniPathway; UPA00705; -. DR ChiTaRS; MT-CO1; human. DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell. DR GO; GO:0045277; C:respiratory chain complex IV; IEA:InterPro. DR GO; GO:0004129; F:cytochrome-c oxidase activity; IEA:UniProtKB-EC. DR GO; GO:0020037; F:heme binding; IEA:InterPro. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0006119; P:oxidative phosphorylation; IEA:UniProtKB-UniPathway. DR CDD; cd01663; Cyt_c_Oxidase_I; 1. DR Gene3D; 1.20.210.10; -; 1. DR InterPro; IPR023616; Cyt_c_oxase-like_su1_dom. DR InterPro; IPR036927; Cyt_c_oxase-like_su1_sf. DR InterPro; IPR000883; Cyt_C_Oxase_1. DR InterPro; IPR023615; Cyt_c_Oxase_su1_BS. DR InterPro; IPR033944; Cyt_c_oxase_su1_dom. DR PANTHER; PTHR10422; CYTOCHROME C OXIDASE SUBUNIT 1; 1. DR Pfam; PF00115; COX1; 1. DR PRINTS; PR01165; CYCOXIDASEI. DR SUPFAM; SSF81442; Cytochrome c oxidase subunit I-like; 1. DR PROSITE; PS50855; COX1; 1. DR PROSITE; PS00077; COX1_CUB; 1. PE 3: Inferred from homology; KW Calcium {ECO:0000256|ARBA:ARBA00022837}; KW Copper {ECO:0000256|ARBA:ARBA00023008, ECO:0000256|RuleBase:RU000369}; KW Electron transport {ECO:0000256|ARBA:ARBA00022982, KW ECO:0000256|RuleBase:RU000369}; Heme {ECO:0000256|RuleBase:RU000369}; KW Iron {ECO:0000256|RuleBase:RU000369}; KW Magnesium {ECO:0000256|ARBA:ARBA00022842}; KW Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|RuleBase:RU000369}; KW Metal-binding {ECO:0000256|RuleBase:RU000369}; KW Mitochondrion {ECO:0000256|RuleBase:RU000369, ECO:0000313|EMBL:BAE07443.1}; KW Mitochondrion inner membrane {ECO:0000256|ARBA:ARBA00022792, KW ECO:0000256|RuleBase:RU000369}; KW Respiratory chain {ECO:0000256|ARBA:ARBA00022660, KW ECO:0000256|RuleBase:RU000369}; Sodium {ECO:0000256|ARBA:ARBA00023053}; KW Translocase {ECO:0000256|ARBA:ARBA00022967}; KW Transmembrane {ECO:0000256|ARBA:ARBA00022692, KW ECO:0000256|RuleBase:RU000369}; KW Transmembrane helix {ECO:0000256|ARBA:ARBA00022989, KW ECO:0000256|SAM:Phobius}; KW Transport {ECO:0000256|ARBA:ARBA00022448, ECO:0000256|RuleBase:RU000369}. FT TRANSMEM 18..37 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 57..83 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 104..128 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 148..171 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 183..210 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 243..261 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 268..291 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 303..325 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 337..359 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 379..400 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 412..430 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 450..473 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT DOMAIN 1..511 FT /note="COX1" FT /evidence="ECO:0000259|PROSITE:PS50855" SQ SEQUENCE 513 AA; 57071 MW; 766088D9F783F77C CRC64; MFADRWLFST NHKDIGTLYL LFGAWAGVLG TALSLLIRTE LGQPGNLLGN DHIYNVIVTA HAFVMIFFMV MPIMIGGFGN WLVPLMIGAP DMAFPRMNNM SFWLLPPSLL LLLASAMVEA GAGTGWTVYP PLAGNYSHPG ASVDLTIFSL HLAGVSSILG AINFITTIIN MKPPAMTQYQ TPLFVWSVLI TAVLLLLSLP VLAAGITMLL TDRNLNTTFF DPAGGGDPIL YQHLFWFFGH PEVYILILPG FGMISHIVTY YSGKKEPFGY MGMVWAMMSI GFLGFIVWAH HMFTVGMDVD TRAYFTSATM IIAIPTGVKV FSWLATLHGS NMKWSAAVLW ALGFIFLFTV GGLTGIVLAN SSLDIVLHDT YYVVAHFHYV LSMGAVFAIM GGFIHWFPLF SGYTLDQTYA KIHFTIMFIG VNLTFFPQHF LGLSGMPRRY SDYPDAYTTW NILSSVGSFI SLTAVMLMIF MIWEAFASKR KVLMVEEPSM NLEWLYGCPP PYHTFEEPVY MKS //