COX4_YEAST
ID COX4_YEAST Reviewed; 155 AA.
AC P04037; A2TBN6; D6VTW7;
DT 01-NOV-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1986, sequence version 1.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Cytochrome c oxidase subunit 4, mitochondrial;
DE AltName: Full=Cytochrome c oxidase polypeptide IV;
DE Flags: Precursor;
GN Name=COX4; OrderedLocusNames=YGL187C; ORFNames=G1362;
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=6098449; DOI=10.1002/j.1460-2075.1984.tb02216.x;
RA Maarse A.C., van Loon A.P.G.M., Riezman H., Gregor I., Schatz G.,
RA Grivell L.A.;
RT "Subunit IV of yeast cytochrome c oxidase: cloning and nucleotide
RT sequencing of the gene and partial amino acid sequencing of the mature
RT protein.";
RL EMBO J. 3:2831-2837(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 96604 / S288c / FY1679;
RX PubMed=9046087;
RX DOI=10.1002/(sici)1097-0061(199701)13:1<55::aid-yea48>3.0.co;2-9;
RA Coglievina M., Klima R., Bertani I., Delneri D., Zaccaria P., Bruschi C.V.;
RT "Sequencing of a 40.5 kb fragment located on the left arm of chromosome VII
RT from Saccharomyces cerevisiae.";
RL Yeast 13:55-64(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169869;
RA Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J.,
RA Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M.,
RA Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L.,
RA Coblenz A., Coglievina M., Coissac E., Defoor E., Del Bino S., Delius H.,
RA Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P.,
RA Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M.,
RA Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A.,
RA Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K.,
RA Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P.,
RA Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E.,
RA Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K.,
RA Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A.,
RA Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S.,
RA Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M.,
RA Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C.,
RA Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M.,
RA Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M.,
RA Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y.,
RA Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L.,
RA Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D.,
RA Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F.,
RA Zaccaria P., Zimmermann M., Zollner A., Kleine K.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome VII.";
RL Nature 387:81-84(1997).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-33.
RC STRAIN=ATCC 201390 / BY4743;
RX PubMed=17244705; DOI=10.1073/pnas.0610354104;
RA Juneau K., Palm C., Miranda M., Davis R.W.;
RT "High-density yeast-tiling array reveals previously undiscovered introns
RT and extensive regulation of meiotic splicing.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1522-1527(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-3.
RX PubMed=3033605; DOI=10.1093/nar/15.8.3515;
RA Schneider J.C., Guarente L.;
RT "The untranslated leader of nuclear COX4 gene of Saccharomyces cerevisiae
RT contains an intron.";
RL Nucleic Acids Res. 15:3515-3529(1987).
RN [7]
RP PROTEIN SEQUENCE OF 26-79.
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 [8]
RP PROTEIN SEQUENCE OF 26-30, 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 [9]
RP PROTEIN SEQUENCE OF 26-28, 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 [10]
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 [11]
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-55, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 76625 / YPH499;
RX PubMed=17761666; DOI=10.1074/mcp.m700098-mcp200;
RA Reinders J., Wagner K., Zahedi R.P., Stojanovski D., Eyrich B.,
RA van der Laan M., Rehling P., Sickmann A., Pfanner N., Meisinger C.;
RT "Profiling phosphoproteins of yeast mitochondria reveals a role of
RT phosphorylation in assembly of the ATP synthase.";
RL Mol. Cell. Proteomics 6:1896-1906(2007).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 2-25 IN COMPLEX WITH MAS1/MAS2
RP HETERODIMER.
RX PubMed=11470436; DOI=10.1016/s0969-2126(01)00621-9;
RA Taylor A.B., Smith B.S., Kitada S., Kojima K., Miyaura H., Otwinowski Z.,
RA Ito A., Deisenhofer J.;
RT "Crystal structures of mitochondrial processing peptidase reveal the mode
RT for specific cleavage of import signal sequences.";
RL Structure 9:615-625(2001).
RN [14]
RP STRUCTURE BY NMR OF 79-155 IN COMPLEX WITH ZINC.
RX PubMed=17215247; DOI=10.1074/jbc.m610303200;
RA Coyne H.J. III, Ciofi-Baffoni S., Banci L., Bertini I., Zhang L.,
RA George G.N., Winge D.R.;
RT "The characterization and role of zinc binding in yeast Cox4.";
RL J. Biol. Chem. 282:8926-8934(2007).
RN [15]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.23 ANGSTROMS) OF 1-155.
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 [16]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.35 ANGSTROMS) IN COMPLEX WITH ZINC, AND
RP 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 The complex exists as a monomer or a dimer and forms supercomplexes
CC (SCs) in the inner mitochondrial membrane with a dimer of ubiquinol-
CC cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III,
CC CIII), resulting in 2 different assemblies (supercomplexes III(2)IV and
CC III(2)IV(2)) (PubMed:10775262, PubMed:10764779, PubMed:30598556,
CC PubMed:30598554). {ECO:0000269|PubMed:10764779,
CC ECO:0000269|PubMed:10775262, ECO:0000269|PubMed:30598554,
CC ECO:0000269|PubMed:30598556, ECO:0000269|PubMed:7851399}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:30598554}; Peripheral membrane protein
CC {ECO:0000269|PubMed:30598554}; Matrix side
CC {ECO:0000269|PubMed:30598554}.
CC -!- MISCELLANEOUS: Present with 9410 molecules/cell in log phase SD medium.
CC -!- SIMILARITY: Belongs to the cytochrome c oxidase subunit 5B family.
CC {ECO:0000305}.
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DR EMBL; X01418; CAA25665.1; -; Genomic_DNA.
DR EMBL; X91489; CAA62787.1; -; Genomic_DNA.
DR EMBL; Z72709; CAA96899.1; -; Genomic_DNA.
DR EMBL; EF123139; ABM97483.1; -; mRNA.
DR EMBL; Y00152; CAA68347.1; -; Genomic_DNA.
DR EMBL; BK006941; DAA07928.1; -; Genomic_DNA.
DR PIR; A22786; OLBY4.
DR RefSeq; NP_011328.1; NM_001181052.1.
DR PDB; 1HR8; X-ray; 2.70 A; O/P/Q/R=2-25.
DR PDB; 2ODX; NMR; -; A=79-155.
DR PDB; 6GIQ; EM; 3.23 A; d=1-155.
DR PDB; 6HU9; EM; 3.35 A; d/p=26-155.
DR PDB; 6T0B; EM; 2.80 A; d/q=26-155.
DR PDB; 6T15; EM; 3.29 A; d=26-155.
DR PDB; 6YMX; EM; 3.17 A; d=30-146.
DR PDB; 6YMY; EM; 3.41 A; d=30-146.
DR PDB; 7CLV; NMR; -; C=1-25.
DR PDBsum; 1HR8; -.
DR PDBsum; 2ODX; -.
DR PDBsum; 6GIQ; -.
DR PDBsum; 6HU9; -.
DR PDBsum; 6T0B; -.
DR PDBsum; 6T15; -.
DR PDBsum; 6YMX; -.
DR PDBsum; 6YMY; -.
DR PDBsum; 7CLV; -.
DR AlphaFoldDB; P04037; -.
DR BMRB; P04037; -.
DR SMR; P04037; -.
DR BioGRID; 33068; 241.
DR ComplexPortal; CPX-1721; Mitochondrial respiratory chain complex IV, COX5A variant.
DR ComplexPortal; CPX-1722; Mitochondrial respiratory chain complex IV, COX5B variant.
DR DIP; DIP-2763N; -.
DR IntAct; P04037; 13.
DR MINT; P04037; -.
DR STRING; 4932.YGL187C; -.
DR TCDB; 3.D.4.8.1; the proton-translocating cytochrome oxidase (cox) superfamily.
DR iPTMnet; P04037; -.
DR MaxQB; P04037; -.
DR PaxDb; P04037; -.
DR PRIDE; P04037; -.
DR EnsemblFungi; YGL187C_mRNA; YGL187C; YGL187C.
DR GeneID; 852688; -.
DR KEGG; sce:YGL187C; -.
DR SGD; S000003155; COX4.
DR VEuPathDB; FungiDB:YGL187C; -.
DR eggNOG; KOG3352; Eukaryota.
DR GeneTree; ENSGT00390000011010; -.
DR HOGENOM; CLU_091071_2_0_1; -.
DR InParanoid; P04037; -.
DR OMA; DSHDTIY; -.
DR BioCyc; MetaCyc:YGL187C-MON; -.
DR BioCyc; YEAST:YGL187C-MON; -.
DR UniPathway; UPA00705; -.
DR ChiTaRS; COX4; yeast.
DR EvolutionaryTrace; P04037; -.
DR PRO; PR:P04037; -.
DR Proteomes; UP000002311; Chromosome VII.
DR RNAct; P04037; protein.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
DR GO; GO:0005758; C:mitochondrial intermembrane space; TAS:Reactome.
DR GO; GO:0031966; C:mitochondrial membrane; IDA:ComplexPortal.
DR GO; GO:0005751; C:mitochondrial respiratory chain complex IV; IDA:SGD.
DR GO; GO:0005739; C:mitochondrion; IDA:SGD.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IDA:SGD.
DR GO; GO:0045333; P:cellular respiration; IDA:ComplexPortal.
DR GO; GO:0033617; P:mitochondrial cytochrome c oxidase assembly; IMP:CACAO.
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; cd00924; Cyt_c_Oxidase_Vb; 1.
DR Gene3D; 2.60.11.10; -; 1.
DR InterPro; IPR002124; Cyt_c_oxidase_su5b.
DR InterPro; IPR036972; Cyt_c_oxidase_su5b_sf.
DR PANTHER; PTHR10122; PTHR10122; 1.
DR Pfam; PF01215; COX5B; 1.
DR PROSITE; PS00848; COX5B_1; 1.
DR PROSITE; PS51359; COX5B_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Membrane; Metal-binding;
KW Mitochondrion; Mitochondrion inner membrane; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Transit peptide; Zinc.
FT TRANSIT 1..25
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:1331058,
FT ECO:0000269|PubMed:6327686, ECO:0000269|PubMed:7851399"
FT CHAIN 26..155
FT /note="Cytochrome c oxidase subunit 4, mitochondrial"
FT /id="PRO_0000006114"
FT BINDING 111
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:17215247,
FT ECO:0000269|PubMed:30598554"
FT BINDING 119
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:17215247,
FT ECO:0000269|PubMed:30598554"
FT BINDING 134
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:17215247,
FT ECO:0000269|PubMed:30598554"
FT BINDING 137
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:17215247,
FT ECO:0000269|PubMed:30598554"
FT MOD_RES 55
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17761666"
FT CONFLICT 26
FT /note="Q -> E (in Ref. 7; AA sequence, 8; AA sequence and
FT 9; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 73
FT /note="G -> C (in Ref. 7; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 15..17
FT /evidence="ECO:0007829|PDB:1HR8"
FT STRAND 35..37
FT /evidence="ECO:0007829|PDB:6T0B"
FT STRAND 42..44
FT /evidence="ECO:0007829|PDB:6T0B"
FT STRAND 53..55
FT /evidence="ECO:0007829|PDB:6T15"
FT STRAND 59..62
FT /evidence="ECO:0007829|PDB:6YMX"
FT HELIX 65..75
FT /evidence="ECO:0007829|PDB:6T0B"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:6YMX"
FT STRAND 98..106
FT /evidence="ECO:0007829|PDB:6T0B"
FT STRAND 109..111
FT /evidence="ECO:0007829|PDB:6T0B"
FT STRAND 114..119
FT /evidence="ECO:0007829|PDB:6T0B"
FT STRAND 122..124
FT /evidence="ECO:0007829|PDB:6T0B"
FT STRAND 127..129
FT /evidence="ECO:0007829|PDB:6T0B"
FT STRAND 131..133
FT /evidence="ECO:0007829|PDB:2ODX"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:6T0B"
FT STRAND 141..145
FT /evidence="ECO:0007829|PDB:6T0B"
SQ SEQUENCE 155 AA; 17143 MW; AB2EE69878819E0F CRC64;
MLSLRQSIRF FKPATRTLCS SRYLLQQKPV VKTAQNLAEV NGPETLIGPG AKEGTVPTDL
DQETGLARLE LLGKLEGIDV FDTKPLDSSR KGTMKDPIII ESYDDYRYVG CTGSPAGSHT
IMWLKPTVNE VARCWECGSV YKLNPVGVPN DDHHH
