COX2_RAT
ID COX2_RAT Reviewed; 227 AA.
AC P00406; Q37738; Q80WI7;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-2015, sequence version 3.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Cytochrome c oxidase subunit 2;
DE EC=7.1.1.9;
DE AltName: Full=Cytochrome c oxidase polypeptide II;
GN Name=Mtco2; Synonyms=Coii, COX2, mt-Co2;
OS Rattus norvegicus (Rat).
OG Mitochondrion.
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=R.norvegicus, and R.rattus;
RX PubMed=6285344; DOI=10.1073/pnas.79.10.3246;
RA Brown G.G., Simpson M.V.;
RT "Novel features of animal mtDNA evolution as shown by sequences of two rat
RT cytochrome oxidase subunit II genes.";
RL Proc. Natl. Acad. Sci. U.S.A. 79:3246-3250(1982).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Wistar;
RX PubMed=6091655;
RA Pepe G., Holtrop M., Gadaleta G., Kroon A.M., Cantatore P., Gallerani R.,
RA de Benedetto C., Quagliariello C., Sbisa E., Saccone C.;
RT "Non-random patterns of nucleotide substitutions and codon strategy in the
RT mammalian mitochondrial genes coding for identified and unidentified
RT reading frames.";
RL Biochem. Int. 6:553-563(1983).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Wistar;
RX PubMed=2504926; DOI=10.1007/bf02602930;
RA Gadaleta G., Pepe G., de Candia G., Quagliariello C., Sbisa E., Saccone C.;
RT "The complete nucleotide sequence of the Rattus norvegicus mitochondrial
RT genome: cryptic signals revealed by comparative analysis between
RT vertebrates.";
RL J. Mol. Evol. 28:497-516(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RA Grosskopf R., Feldmann H.;
RT "Analysis of a DNA segment from rat liver mitochondria containing the genes
RT for the cytochrome oxidase subunits I, II, II, ATPase subunit 6, and
RT several tRNA genes.";
RL Curr. Genet. 4:151-158(1981).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1848093; DOI=10.1021/bi00224a012;
RA Cao J.L., Revzin A., Ferguson-Miller S.;
RT "Conversion of a mitochondrial gene for mammalian cytochrome c oxidase
RT subunit II into its universal codon equivalent and expression in vivo and
RT in vitro.";
RL Biochemistry 30:2642-2650(1991).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 7-56.
RX PubMed=7981121; DOI=10.1016/0960-0760(94)90085-x;
RA Law S.W., Apostolakis E.M., Samora P.J., O'Malley B.W., Clark J.H.;
RT "Hormonal regulation of hypothalamic gene expression: identification of
RT multiple novel estrogen induced genes.";
RL J. Steroid Biochem. Mol. Biol. 51:131-136(1994).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-218, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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:0000250|UniProtKB:P00410}.
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:0000250|UniProtKB:P00410};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11437;
CC Evidence={ECO:0000250|UniProtKB:P00410};
CC -!- COFACTOR:
CC Name=Cu cation; Xref=ChEBI:CHEBI:23378;
CC Evidence={ECO:0000250|UniProtKB:P68530};
CC Note=Binds a dinuclear copper A center per subunit.
CC {ECO:0000250|UniProtKB:P68530};
CC -!- SUBUNIT: Component of the cytochrome c oxidase (complex IV, CIV), a
CC multisubunit enzyme composed of 14 subunits. The complex is composed of
CC a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in
CC the mitochondrial DNA, and 11 supernumerary subunits COX4I, COX5A,
CC COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and NDUFA4, which
CC are encoded in the nuclear genome. The complex exists as a monomer or a
CC dimer and forms supercomplexes (SCs) in the inner mitochondrial
CC membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and
CC ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex
CC III, CIII), resulting in different assemblies (supercomplex
CC SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)) (By similarity).
CC Found in a complex with TMEM177, COA6, COX18, COX20, SCO1 and SCO2.
CC Interacts with TMEM177 in a COX20-dependent manner. Interacts with
CC COX20. Interacts with COX16 (By similarity).
CC {ECO:0000250|UniProtKB:P00403, ECO:0000250|UniProtKB:P68530}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:P68530}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P68530}.
CC -!- SIMILARITY: Belongs to the cytochrome c oxidase subunit 2 family.
CC {ECO:0000305}.
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DR EMBL; J01434; AAA67374.1; -; Genomic_DNA.
DR EMBL; M27315; AAB00992.1; -; Genomic_DNA.
DR EMBL; X14848; CAA32957.1; -; Genomic_DNA.
DR EMBL; M64496; AAA67314.1; -; Genomic_DNA.
DR EMBL; AY172581; AAN77597.1; -; Genomic_DNA.
DR EMBL; S74342; AAP31514.1; -; mRNA.
DR PIR; A93914; OBRT2.
DR PIR; B93914; OBRT2B.
DR RefSeq; AP_004895.1; AC_000022.2.
DR RefSeq; YP_665632.1; NC_001665.2.
DR AlphaFoldDB; P00406; -.
DR SMR; P00406; -.
DR CORUM; P00406; -.
DR IntAct; P00406; 1.
DR MINT; P00406; -.
DR STRING; 10116.ENSRNOP00000046414; -.
DR iPTMnet; P00406; -.
DR SwissPalm; P00406; -.
DR jPOST; P00406; -.
DR PaxDb; P00406; -.
DR PRIDE; P00406; -.
DR Ensembl; ENSRNOT00000043693; ENSRNOP00000046414; ENSRNOG00000030371.
DR GeneID; 26198; -.
DR KEGG; rno:26198; -.
DR CTD; 4513; -.
DR RGD; 621872; mt-Co2.
DR eggNOG; KOG4767; Eukaryota.
DR GeneTree; ENSGT00390000017410; -.
DR HOGENOM; CLU_036876_2_3_1; -.
DR InParanoid; P00406; -.
DR OMA; WSYEYTD; -.
DR OrthoDB; 1432833at2759; -.
DR Reactome; R-RNO-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-RNO-611105; Respiratory electron transport.
DR Reactome; R-RNO-9707564; Cytoprotection by HMOX1.
DR PRO; PR:P00406; -.
DR Proteomes; UP000002494; Mitochondrion.
DR Bgee; ENSRNOG00000030371; Expressed in ovary and 19 other tissues.
DR ExpressionAtlas; P00406; baseline and differential.
DR Genevisible; P00406; RN.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISO:RGD.
DR GO; GO:0031966; C:mitochondrial membrane; ISO:RGD.
DR GO; GO:0005751; C:mitochondrial respiratory chain complex IV; ISO:RGD.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR GO; GO:0045277; C:respiratory chain complex IV; ISS:UniProtKB.
DR GO; GO:0005507; F:copper ion binding; IEA:InterPro.
DR GO; GO:0004129; F:cytochrome-c oxidase activity; IEA:UniProtKB-EC.
DR GO; GO:0042773; P:ATP synthesis coupled electron transport; IBA:GO_Central.
DR GO; GO:0007595; P:lactation; IEP:RGD.
DR GO; GO:2001171; P:positive regulation of ATP biosynthetic process; IMP:RGD.
DR GO; GO:0010729; P:positive regulation of hydrogen peroxide biosynthetic process; IMP:RGD.
DR GO; GO:0010940; P:positive regulation of necrotic cell death; IMP:RGD.
DR GO; GO:0009409; P:response to cold; IEP:RGD.
DR CDD; cd13912; CcO_II_C; 1.
DR Gene3D; 1.10.287.90; -; 1.
DR Gene3D; 2.60.40.420; -; 1.
DR InterPro; IPR045187; CcO_II.
DR InterPro; IPR002429; CcO_II-like_C.
DR InterPro; IPR034210; CcO_II_C.
DR InterPro; IPR001505; Copper_CuA.
DR InterPro; IPR008972; Cupredoxin.
DR InterPro; IPR014222; Cyt_c_oxidase_su2.
DR InterPro; IPR011759; Cyt_c_oxidase_su2_TM_dom.
DR InterPro; IPR036257; Cyt_c_oxidase_su2_TM_sf.
DR PANTHER; PTHR22888; PTHR22888; 1.
DR Pfam; PF00116; COX2; 1.
DR Pfam; PF02790; COX2_TM; 1.
DR SUPFAM; SSF49503; SSF49503; 1.
DR SUPFAM; SSF81464; SSF81464; 1.
DR TIGRFAMs; TIGR02866; CoxB; 1.
DR PROSITE; PS00078; COX2; 1.
DR PROSITE; PS50857; COX2_CUA; 1.
DR PROSITE; PS50999; COX2_TM; 1.
PE 1: Evidence at protein level;
KW Copper; Electron transport; Magnesium; Membrane; Metal-binding;
KW Mitochondrion; Mitochondrion inner membrane; Phosphoprotein;
KW Reference proteome; Respiratory chain; Translocase; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..227
FT /note="Cytochrome c oxidase subunit 2"
FT /id="PRO_0000183677"
FT TOPO_DOM 1..14
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000250|UniProtKB:P68530"
FT TRANSMEM 15..45
FT /note="Helical; Name=I"
FT /evidence="ECO:0000250|UniProtKB:P68530"
FT TOPO_DOM 46..59
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000250|UniProtKB:P68530"
FT TRANSMEM 60..87
FT /note="Helical; Name=II"
FT /evidence="ECO:0000250|UniProtKB:P68530"
FT TOPO_DOM 88..227
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000250|UniProtKB:P68530"
FT BINDING 161
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="A1"
FT /evidence="ECO:0000250|UniProtKB:P68530"
FT BINDING 196
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="A1"
FT /evidence="ECO:0000250|UniProtKB:P68530"
FT BINDING 196
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="A2"
FT /evidence="ECO:0000250|UniProtKB:P68530"
FT BINDING 198
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="A2"
FT /evidence="ECO:0000250|UniProtKB:P68530"
FT BINDING 198
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="ligand shared with MT-CO1"
FT /evidence="ECO:0000250|UniProtKB:P68530"
FT BINDING 200
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="A1"
FT /evidence="ECO:0000250|UniProtKB:P68530"
FT BINDING 200
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="A2"
FT /evidence="ECO:0000250|UniProtKB:P68530"
FT BINDING 204
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="A2"
FT /evidence="ECO:0000250|UniProtKB:P68530"
FT BINDING 207
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="A1"
FT /evidence="ECO:0000250|UniProtKB:P68530"
FT MOD_RES 218
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CONFLICT 17
FT /note="M -> I (in Ref. 7; AAP31514)"
FT /evidence="ECO:0000305"
FT CONFLICT 21
FT /note="T -> M (in Ref. 1; AAA67374)"
FT /evidence="ECO:0000305"
FT CONFLICT 29
FT /note="M -> I (in Ref. 7; AAP31514)"
FT /evidence="ECO:0000305"
FT CONFLICT 45
FT /note="M -> I (in Ref. 7; AAP31514)"
FT /evidence="ECO:0000305"
FT CONFLICT 56
FT /note="M -> I (in Ref. 7; AAP31514)"
FT /evidence="ECO:0000305"
FT CONFLICT 59
FT /note="Q -> H (in Ref. 5; AAA67314)"
FT /evidence="ECO:0000305"
FT CONFLICT 130
FT /note="P -> L (in Ref. 4; no nucleotide entry and 5;
FT AAA67314)"
FT /evidence="ECO:0000305"
FT CONFLICT 164
FT /note="A -> P (in Ref. 4; no nucleotide entry and 5;
FT AAA67314)"
FT /evidence="ECO:0000305"
FT CONFLICT 165
FT /note="V -> I (in Ref. 2; AAB00992, 3; CAA32957 and 5;
FT AAA67314)"
FT /evidence="ECO:0000305"
FT CONFLICT 179
FT /note="L -> P (in Ref. 5; AAA67314)"
FT /evidence="ECO:0000305"
FT CONFLICT 189
FT /note="P -> L (in Ref. 4; no nucleotide entry and 5;
FT AAA67314)"
FT /evidence="ECO:0000305"
FT CONFLICT 208
FT /note="P -> L (in Ref. 4; no nucleotide entry and 5;
FT AAA67314)"
FT /evidence="ECO:0000305"
FT CONFLICT 218
FT /note="Y -> H (in Ref. 1; AAA67374)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 227 AA; 25928 MW; 9EA986B08B629664 CRC64;
MAYPFQLGLQ DATSPIMEEL TNFHDHTLMI VFLISSLVLY IISLMLTTKL THTSTMDAQE
VETIWTILPA VILILIALPS LRILYMMDEI NNPVLTVKTM GHQWYWSYEY TDYEDLCFDS
YMIPTNDLKP GELRLLEVDN RVVLPMELPI RMLISSEDVL HSWAVPSLGL KTDAIPGRLN
QATVTSNRPG LFYGQCSEIC GSNHSFMPIV LEMVPLKYFE NWSASMI
