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-SEP-2021, entry version 94.
DE   RecName: Full=Cytochrome c oxidase subunit 3 {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: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   [7] {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   [8] {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   [9] {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   [10] {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   [11] {ECO:0000313|EMBL:AGH20733.1}
RP   NUCLEOTIDE SEQUENCE.
RA   Greenspan B.;
RL   Submitted (MAR-2013) 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
CC         [Fe(III)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:ARBA00000049};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11437;
CC         Evidence={ECO:0000256|ARBA:ARBA00000049};
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000256|ARBA:ARBA00004141}; Multi-
CC       pass membrane protein {ECO:0000256|ARBA:ARBA00004141}. Mitochondrion
CC       inner membrane {ECO:0000256|ARBA:ARBA00004448}; Multi-pass membrane
CC       protein {ECO:0000256|ARBA:ARBA00004448}.
CC   -!- SIMILARITY: Belongs to the cytochrome c oxidase subunit 3 family.
CC       {ECO:0000256|ARBA:ARBA00010581, ECO:0000256|RuleBase:RU003375}.
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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   OMA; SIYWWGS; -.
DR   ChiTaRS; COX3; human.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0004129; F:cytochrome-c oxidase activity; IEA:UniProtKB-EC.
DR   GO; GO:0019646; P:aerobic electron transport chain; IEA:InterPro.
DR   CDD; cd01665; Cyt_c_Oxidase_III; 1.
DR   Gene3D; 1.20.120.80; -; 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; PTHR11403; 1.
DR   Pfam; PF00510; COX3; 1.
DR   SUPFAM; SSF81452; SSF81452; 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="COX3"
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
//