ID   COX5A_YEAST             Reviewed;         153 AA.
AC   P00424; D6W1C7;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   13-AUG-1987, sequence version 1.
DT   27-MAR-2024, entry version 204.
DE   RecName: Full=Cytochrome c oxidase subunit 5A, mitochondrial;
DE   AltName: Full=Cytochrome c oxidase polypeptide Va;
DE   Flags: Precursor;
GN   Name=COX5A; OrderedLocusNames=YNL052W; ORFNames=N2474, YNL2474W;
OS   Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX   NCBI_TaxID=559292;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2836092; DOI=10.1007/bf00434047;
RA   Seraphin B., Simon M., Faye G.;
RT   "Primary structure of a gene for subunit V of the cytochrome c oxidase from
RT   Saccharomyces cerevisiae.";
RL   Curr. Genet. 9:435-439(1985).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2991248; DOI=10.1016/s0021-9258(17)39261-x;
RA   Koerner T.J., Hill J., Tzagoloff A.;
RT   "Cloning and characterization of the yeast nuclear gene for subunit 5 of
RT   cytochrome oxidase.";
RL   J. Biol. Chem. 260:9513-9515(1985).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2824989; DOI=10.1128/mcb.7.10.3511-3519.1987;
RA   Cumsky M.G., Trueblood C.E., Ko C., Poyton R.O.;
RT   "Structural analysis of two genes encoding divergent forms of yeast
RT   cytochrome c oxidase subunit V.";
RL   Mol. Cell. Biol. 7:3511-3519(1987).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=S288c / FY1676;
RX   PubMed=8533472; DOI=10.1002/yea.320111008;
RA   Bergez P., Doignon F., Crouzet M.;
RT   "The sequence of a 44 420 bp fragment located on the left arm of chromosome
RT   XIV from Saccharomyces cerevisiae.";
RL   Yeast 11:967-974(1995).
RN   [5]
RP   ERRATUM OF PUBMED:8533472.
RX   PubMed=8904343;
RX   DOI=10.1002/(sici)1097-0061(19960315)12:3<297::aid-yea940>3.0.co;2-d;
RA   Bergez P., Doignon F., Crouzet M.;
RL   Yeast 12:297-297(1996).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169873;
RA   Philippsen P., Kleine K., Poehlmann R., Duesterhoeft A., Hamberg K.,
RA   Hegemann J.H., Obermaier B., Urrestarazu L.A., Aert R., Albermann K.,
RA   Altmann R., Andre B., Baladron V., Ballesta J.P.G., Becam A.-M.,
RA   Beinhauer J.D., Boskovic J., Buitrago M.J., Bussereau F., Coster F.,
RA   Crouzet M., D'Angelo M., Dal Pero F., De Antoni A., del Rey F., Doignon F.,
RA   Domdey H., Dubois E., Fiedler T.A., Fleig U., Floeth M., Fritz C.,
RA   Gaillardin C., Garcia-Cantalejo J.M., Glansdorff N., Goffeau A.,
RA   Gueldener U., Herbert C.J., Heumann K., Heuss-Neitzel D., Hilbert H.,
RA   Hinni K., Iraqui Houssaini I., Jacquet M., Jimenez A., Jonniaux J.-L.,
RA   Karpfinger-Hartl L., Lanfranchi G., Lepingle A., Levesque H., Lyck R.,
RA   Maftahi M., Mallet L., Maurer C.T.C., Messenguy F., Mewes H.-W., Moestl D.,
RA   Nasr F., Nicaud J.-M., Niedenthal R.K., Pandolfo D., Pierard A.,
RA   Piravandi E., Planta R.J., Pohl T.M., Purnelle B., Rebischung C.,
RA   Remacha M.A., Revuelta J.L., Rinke M., Saiz J.E., Sartorello F.,
RA   Scherens B., Sen-Gupta M., Soler-Mira A., Urbanus J.H.M., Valle G.,
RA   Van Dyck L., Verhasselt P., Vierendeels F., Vissers S., Voet M.,
RA   Volckaert G., Wach A., Wambutt R., Wedler H., Zollner A., Hani J.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its
RT   evolutionary implications.";
RL   Nature 387:93-98(1997).
RN   [7]
RP   GENOME REANNOTATION.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=24374639; DOI=10.1534/g3.113.008995;
RA   Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA   Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA   Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT   "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL   G3 (Bethesda) 4:389-398(2014).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=17322287; DOI=10.1101/gr.6037607;
RA   Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA   Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA   Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA   Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA   LaBaer J.;
RT   "Approaching a complete repository of sequence-verified protein-encoding
RT   clones for Saccharomyces cerevisiae.";
RL   Genome Res. 17:536-543(2007).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 21-98.
RX   PubMed=2986105; DOI=10.1073/pnas.82.8.2235;
RA   Cumsky M.G., Ko C., Trueblood C.E., Poyton R.O.;
RT   "Two nonidentical forms of subunit V are functional in yeast cytochrome c
RT   oxidase.";
RL   Proc. Natl. Acad. Sci. U.S.A. 82:2235-2239(1985).
RN   [10]
RP   PROTEIN SEQUENCE OF 21-69.
RX   PubMed=6327686; DOI=10.1016/s0021-9258(20)82180-2;
RA   Power S.D., Lochrie M.A., Poyton R.O.;
RT   "The nuclear-coded subunits of yeast cytochrome c oxidase. III.
RT   Identification of homologous subunits in yeast, bovine heart, and
RT   Neurospora crassa cytochrome c oxidases.";
RL   J. Biol. Chem. 259:6575-6578(1984).
RN   [11]
RP   PROTEIN SEQUENCE OF 21-35.
RX   PubMed=6300105; DOI=10.1016/s0021-9258(18)32519-5;
RA   Cerletti N., Bohni P.C., Suda K.;
RT   "Import of proteins into mitochondria. Isolated yeast mitochondria and a
RT   solubilized matrix protease correctly process cytochrome c oxidase subunit
RT   V precursor at the NH2 terminus.";
RL   J. Biol. Chem. 258:4944-4949(1983).
RN   [12]
RP   PROTEIN SEQUENCE OF 21-34, AND COMPOSITION OF THE CYTOCHROME C OXIDASE
RP   COMPLEX.
RX   PubMed=1331058; DOI=10.1016/s0021-9258(18)41697-3;
RA   Taanman J.-W., Capaldi R.A.;
RT   "Purification of yeast cytochrome c oxidase with a subunit composition
RT   resembling the mammalian enzyme.";
RL   J. Biol. Chem. 267:22481-22485(1992).
RN   [13]
RP   PROTEIN SEQUENCE OF 21-23, AND COMPOSITION OF THE CYTOCHROME C OXIDASE
RP   COMPLEX.
RX   PubMed=7851399; DOI=10.1111/j.1432-1033.1995.tb20388.x;
RA   Geier B.M., Schagger H., Ortwein C., Link T.A., Hagen W.R., Brandt U.,
RA   Von Jagow G.;
RT   "Kinetic properties and ligand binding of the eleven-subunit cytochrome-c
RT   oxidase from Saccharomyces cerevisiae isolated with a novel large-scale
RT   purification method.";
RL   Eur. J. Biochem. 227:296-302(1995).
RN   [14]
RP   SUBUNIT, AND INDUCTION.
RX   PubMed=2546055; DOI=10.1128/mcb.9.5.1958-1964.1989;
RA   Hodge M.R., Kim G., Singh K., Cumsky M.G.;
RT   "Inverse regulation of the yeast COX5 genes by oxygen and heme.";
RL   Mol. Cell. Biol. 9:1958-1964(1989).
RN   [15]
RP   INDUCTION.
RX   PubMed=9169434; DOI=10.1074/jbc.272.23.14705;
RA   Burke P.V., Raitt D.C., Allen L.A., Kellogg E.A., Poyton R.O.;
RT   "Effects of oxygen concentration on the expression of cytochrome c and
RT   cytochrome c oxidase genes in yeast.";
RL   J. Biol. Chem. 272:14705-14712(1997).
RN   [16]
RP   FORMATION OF CYTOCHROME BC1-CYTOCHROME C OXIDASE SUPERCOMPLEX.
RX   PubMed=10775262; DOI=10.1093/emboj/19.8.1777;
RA   Schaegger H., Pfeiffer K.;
RT   "Supercomplexes in the respiratory chains of yeast and mammalian
RT   mitochondria.";
RL   EMBO J. 19:1777-1783(2000).
RN   [17]
RP   FORMATION OF CYTOCHROME BC1-CYTOCHROME C OXIDASE SUPERCOMPLEX.
RX   PubMed=10764779; DOI=10.1074/jbc.m001901200;
RA   Cruciat C.M., Brunner S., Baumann F., Neupert W., Stuart R.A.;
RT   "The cytochrome bc1 and cytochrome c oxidase complexes associate to form a
RT   single supracomplex in yeast mitochondria.";
RL   J. Biol. Chem. 275:18093-18098(2000).
RN   [18]
RP   LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX   PubMed=14562106; DOI=10.1038/nature02046;
RA   Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA   O'Shea E.K., Weissman J.S.;
RT   "Global analysis of protein expression in yeast.";
RL   Nature 425:737-741(2003).
RN   [19]
RP   STRUCTURE BY ELECTRON MICROSCOPY (3.23 ANGSTROMS) OF 1-153.
RX   PubMed=30598556; DOI=10.1038/s41594-018-0169-7;
RA   Rathore S., Berndtsson J., Marin-Buera L., Conrad J., Carroni M.,
RA   Brzezinski P., Ott M.;
RT   "Cryo-EM structure of the yeast respiratory supercomplex.";
RL   Nat. Struct. Mol. Biol. 26:50-57(2019).
RN   [20]
RP   STRUCTURE BY ELECTRON MICROSCOPY (3.35 ANGSTROMS), AND FUNCTION.
RX   PubMed=30598554; DOI=10.1038/s41594-018-0172-z;
RA   Hartley A.M., Lukoyanova N., Zhang Y., Cabrera-Orefice A., Arnold S.,
RA   Meunier B., Pinotsis N., Marechal A.;
RT   "Structure of yeast cytochrome c oxidase in a supercomplex with cytochrome
RT   bc1.";
RL   Nat. Struct. Mol. Biol. 26:78-83(2019).
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 COX2 and heme A of COX1 to the
CC       active site in COX1, a binuclear center (BNC) formed by heme A3 and
CC       copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules
CC       using 4 electrons from cytochrome c in the IMS and 4 protons from the
CC       mitochondrial matrix. {ECO:0000305|PubMed:30598554}.
CC   -!- PATHWAY: Energy metabolism; oxidative phosphorylation.
CC   -!- SUBUNIT: Component of the cytochrome c oxidase (complex IV, CIV), a
CC       multisubunit enzyme composed of 12 subunits. The complex is composed of
CC       a catalytic core of 3 subunits COX1, COX2 and COX3, encoded in the
CC       mitochondrial DNA, and 9 supernumerary subunits COX4, COX5A (or COX5B),
CC       COX6, COX7, COX8, COX9, COX12, COX13 and COX26, which are encoded in
CC       the nuclear genome (PubMed:7851399, PubMed:30598556, PubMed:30598554).
CC       COX5A is the predominant subunit V during aerobic/normoxic growth, it
CC       gets replaced by COX5B under anaerobic/hypoxic conditions
CC       (PubMed:2546055). The complex exists as a monomer or a dimer and forms
CC       supercomplexes (SCs) in the inner mitochondrial membrane with a dimer
CC       of ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex,
CC       complex III, CIII), resulting in 2 different assemblies (supercomplexes
CC       III(2)IV and III(2)IV(2)) (PubMed:10775262, PubMed:10764779,
CC       PubMed:30598556, PubMed:30598554). COX5A interacts with COR1, CYT1 and
CC       QCR6 at the CIII-CIV interface (PubMed:30598556, PubMed:30598554).
CC       {ECO:0000269|PubMed:10764779, ECO:0000269|PubMed:10775262,
CC       ECO:0000269|PubMed:2546055, ECO:0000269|PubMed:30598554,
CC       ECO:0000269|PubMed:30598556, ECO:0000269|PubMed:7851399}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC       {ECO:0000269|PubMed:30598554}; Single-pass membrane protein
CC       {ECO:0000269|PubMed:30598554}.
CC   -!- INDUCTION: By oxygen at the level of transcription through heme
CC       (PubMed:2546055). Expression drops rapidly when the oxygen
CC       concentration falls below 0.5 uM O(2) (PubMed:9169434).
CC       {ECO:0000269|PubMed:2546055, ECO:0000269|PubMed:9169434}.
CC   -!- MISCELLANEOUS: Present with 3670 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the cytochrome c oxidase IV family.
CC       {ECO:0000305}.
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; X02561; CAA26403.1; -; Genomic_DNA.
DR   EMBL; M11770; AAA34518.1; -; Genomic_DNA.
DR   EMBL; M17800; AAA34520.1; -; Genomic_DNA.
DR   EMBL; U12141; AAA99660.1; -; Genomic_DNA.
DR   EMBL; Z71328; CAA95921.1; -; Genomic_DNA.
DR   EMBL; AY558131; AAS56457.1; -; Genomic_DNA.
DR   EMBL; M11141; AAA34519.1; -; Genomic_DNA.
DR   EMBL; BK006947; DAA10493.1; -; Genomic_DNA.
DR   PIR; S05833; OTBY5A.
DR   RefSeq; NP_014346.1; NM_001182891.1.
DR   PDB; 6GIQ; EM; 3.23 A; e=1-153.
DR   PDB; 6HU9; EM; 3.35 A; e/q=21-153.
DR   PDB; 6YMX; EM; 3.17 A; e=25-152.
DR   PDB; 6YMY; EM; 3.41 A; e=25-152.
DR   PDB; 7Z10; EM; 3.87 A; e=21-153.
DR   PDB; 8DH6; EM; 2.94 A; e=21-153.
DR   PDB; 8E7S; EM; 3.20 A; W/w=1-153.
DR   PDB; 8EC0; EM; 3.30 A; W=1-153.
DR   PDBsum; 6GIQ; -.
DR   PDBsum; 6HU9; -.
DR   PDBsum; 6YMX; -.
DR   PDBsum; 6YMY; -.
DR   PDBsum; 7Z10; -.
DR   PDBsum; 8DH6; -.
DR   PDBsum; 8E7S; -.
DR   PDBsum; 8EC0; -.
DR   AlphaFoldDB; P00424; -.
DR   EMDB; EMD-0004; -.
DR   EMDB; EMD-10375; -.
DR   EMDB; EMD-10376; -.
DR   EMDB; EMD-10847; -.
DR   EMDB; EMD-10848; -.
DR   EMDB; EMD-14436; -.
DR   EMDB; EMD-27430; -.
DR   SMR; P00424; -.
DR   BioGRID; 35772; 244.
DR   ComplexPortal; CPX-1721; Mitochondrial respiratory chain complex IV, COX5A variant.
DR   DIP; DIP-6820N; -.
DR   IntAct; P00424; 5.
DR   MINT; P00424; -.
DR   STRING; 4932.YNL052W; -.
DR   TCDB; 3.D.4.8.1; the proton-translocating cytochrome oxidase (cox) superfamily.
DR   MaxQB; P00424; -.
DR   PaxDb; 4932-YNL052W; -.
DR   PeptideAtlas; P00424; -.
DR   EnsemblFungi; YNL052W_mRNA; YNL052W; YNL052W.
DR   GeneID; 855675; -.
DR   KEGG; sce:YNL052W; -.
DR   AGR; SGD:S000004997; -.
DR   SGD; S000004997; COX5A.
DR   VEuPathDB; FungiDB:YNL052W; -.
DR   eggNOG; KOG4075; Eukaryota.
DR   GeneTree; ENSGT00390000002407; -.
DR   HOGENOM; CLU_070101_2_0_1; -.
DR   InParanoid; P00424; -.
DR   OMA; YVIHLFA; -.
DR   OrthoDB; 36553at2759; -.
DR   BioCyc; MetaCyc:YNL052W-MONOMER; -.
DR   BioCyc; YEAST:YNL052W-MONOMER; -.
DR   UniPathway; UPA00705; -.
DR   BioGRID-ORCS; 855675; 3 hits in 10 CRISPR screens.
DR   PRO; PR:P00424; -.
DR   Proteomes; UP000002311; Chromosome XIV.
DR   RNAct; P00424; Protein.
DR   GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
DR   GO; GO:0005758; C:mitochondrial intermembrane space; TAS:Reactome.
DR   GO; GO:0005751; C:mitochondrial respiratory chain complex IV; IDA:SGD.
DR   GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   GO; GO:0006123; P:mitochondrial electron transport, cytochrome c to oxygen; IDA:SGD.
DR   GO; GO:1902600; P:proton transmembrane transport; IEA:GOC.
DR   CDD; cd00922; Cyt_c_Oxidase_IV; 1.
DR   Gene3D; 1.10.442.10; Cytochrome c oxidase subunit IV; 1.
DR   InterPro; IPR004203; Cyt_c_oxidase_su4_fam.
DR   InterPro; IPR036639; Cyt_c_oxidase_su4_sf.
DR   PANTHER; PTHR10707:SF10; CYTOCHROME C OXIDASE SUBUNIT 4; 1.
DR   PANTHER; PTHR10707; CYTOCHROME C OXIDASE SUBUNIT IV; 1.
DR   Pfam; PF02936; COX4; 1.
DR   SUPFAM; SSF81406; Mitochondrial cytochrome c oxidase subunit IV; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; Membrane; Mitochondrion;
KW   Mitochondrion inner membrane; Oxidoreductase; Reference proteome;
KW   Transit peptide; Transmembrane; Transmembrane helix.
FT   TRANSIT         1..20
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000269|PubMed:1331058,
FT                   ECO:0000269|PubMed:6300105, ECO:0000269|PubMed:6327686,
FT                   ECO:0000269|PubMed:7851399"
FT   CHAIN           21..153
FT                   /note="Cytochrome c oxidase subunit 5A, mitochondrial"
FT                   /id="PRO_0000006097"
FT   TOPO_DOM        21..88
FT                   /note="Mitochondrial matrix"
FT                   /evidence="ECO:0000269|PubMed:30598554"
FT   TRANSMEM        89..111
FT                   /note="Helical"
FT                   /evidence="ECO:0000269|PubMed:30598554"
FT   TOPO_DOM        112..153
FT                   /note="Mitochondrial intermembrane"
FT                   /evidence="ECO:0000269|PubMed:30598554"
FT   CONFLICT        51
FT                   /note="Missing (in Ref. 10; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   HELIX           28..31
FT                   /evidence="ECO:0007829|PDB:8DH6"
FT   HELIX           34..37
FT                   /evidence="ECO:0007829|PDB:8DH6"
FT   TURN            38..40
FT                   /evidence="ECO:0007829|PDB:8DH6"
FT   HELIX           43..57
FT                   /evidence="ECO:0007829|PDB:8DH6"
FT   HELIX           61..63
FT                   /evidence="ECO:0007829|PDB:8DH6"
FT   HELIX           66..77
FT                   /evidence="ECO:0007829|PDB:8DH6"
FT   STRAND          78..80
FT                   /evidence="ECO:0007829|PDB:6HU9"
FT   HELIX           81..83
FT                   /evidence="ECO:0007829|PDB:8DH6"
FT   HELIX           91..115
FT                   /evidence="ECO:0007829|PDB:8DH6"
FT   HELIX           122..125
FT                   /evidence="ECO:0007829|PDB:6GIQ"
FT   HELIX           126..138
FT                   /evidence="ECO:0007829|PDB:8DH6"
FT   STRAND          142..145
FT                   /evidence="ECO:0007829|PDB:8DH6"
SQ   SEQUENCE   153 AA;  17140 MW;  1B1F8A3FE12CF783 CRC64;
     MLRNTFTRAG GLSRITSVRF AQTHALSNAA VMDLQSRWEN MPSTEQQDIV SKLSERQKLP
     WAQLTEPEKQ AVWYISYGEW GPRRPVLNKG DSSFIAKGVA AGLLFSVGLF AVVRMAGGQD
     AKTMNKEWQL KSDEYLKSKN ANPWGGYSQV QSK
//