COX41_MOUSE
ID COX41_MOUSE Reviewed; 169 AA.
AC P19783; Q545A9;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Cytochrome c oxidase subunit 4 isoform 1, mitochondrial;
DE AltName: Full=Cytochrome c oxidase polypeptide IV;
DE AltName: Full=Cytochrome c oxidase subunit IV isoform 1;
DE Short=COX IV-1;
DE Flags: Precursor;
GN Name=Cox4i1; Synonyms=Cox4, Cox4a;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Heart;
RX PubMed=2173832; DOI=10.1093/nar/18.21.6454;
RA Grossman L.I., Akamatsu M.;
RT "Nucleotide sequence of a mouse cDNA for subunit IV of cytochrome c
RT oxidase.";
RL Nucleic Acids Res. 18:6454-6454(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=1654830; DOI=10.1016/0003-9861(91)90169-j;
RA Carter R.S., Avadhani N.G.;
RT "Cloning and characterization of the mouse cytochrome c oxidase subunit IV
RT gene.";
RL Arch. Biochem. Biophys. 288:97-106(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone marrow;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP PROTEIN SEQUENCE OF 30-41; 43-60; 68-75; 84-95; 136-143 AND 160-169, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP INTERACTION WITH PHB2, AND SUBCELLULAR LOCATION.
RX PubMed=20959514; DOI=10.1096/fj.10-167502;
RA Strub G.M., Paillard M., Liang J., Gomez L., Allegood J.C., Hait N.C.,
RA Maceyka M., Price M.M., Chen Q., Simpson D.C., Kordula T., Milstien S.,
RA Lesnefsky E.J., Spiegel S.;
RT "Sphingosine-1-phosphate produced by sphingosine kinase 2 in mitochondria
RT interacts with prohibitin 2 to regulate complex IV assembly and
RT respiration.";
RL FASEB J. 25:600-612(2011).
RN [7]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-29 AND LYS-60, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-29; LYS-60 AND LYS-67, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
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:P00424}.
CC -!- PATHWAY: Energy metabolism; oxidative phosphorylation.
CC {ECO:0000250|UniProtKB:P00424}.
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 Interacts with PHB2; the interaction decreases in absence of SPHK2
CC (PubMed:20959514). Interacts with AFG1L (By similarity). Interacts with
CC ABCB7; this interaction allows the regulation of cellular iron
CC homeostasis and cellular reactive oxygen species (ROS) levels in
CC cardiomyocytes (By similarity). {ECO:0000250|UniProtKB:P00423,
CC ECO:0000250|UniProtKB:P10888, ECO:0000250|UniProtKB:P13073,
CC ECO:0000269|PubMed:20959514}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:P00423}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:P00423}.
CC -!- SIMILARITY: Belongs to the cytochrome c oxidase IV family.
CC {ECO:0000305}.
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DR EMBL; X54691; CAA38507.1; -; mRNA.
DR EMBL; M37831; AAB02139.1; -; Genomic_DNA.
DR EMBL; M58034; AAB02139.1; JOINED; Genomic_DNA.
DR EMBL; M37829; AAB02140.1; -; mRNA.
DR EMBL; AK012583; BAB28333.1; -; mRNA.
DR EMBL; AK019276; BAB31643.1; -; mRNA.
DR EMBL; AK150447; BAE29569.1; -; mRNA.
DR CCDS; CCDS40498.1; -.
DR PIR; S12142; S12142.
DR RefSeq; NP_001280488.1; NM_001293559.1.
DR RefSeq; NP_034071.2; NM_009941.3.
DR PDB; 7O37; EM; 3.20 A; d=23-169.
DR PDB; 7O3C; EM; 3.30 A; d=23-169.
DR PDB; 7O3E; EM; 3.60 A; d=23-169.
DR PDBsum; 7O37; -.
DR PDBsum; 7O3C; -.
DR PDBsum; 7O3E; -.
DR AlphaFoldDB; P19783; -.
DR SMR; P19783; -.
DR BioGRID; 198840; 49.
DR CORUM; P19783; -.
DR IntAct; P19783; 11.
DR MINT; P19783; -.
DR STRING; 10090.ENSMUSP00000034276; -.
DR iPTMnet; P19783; -.
DR PhosphoSitePlus; P19783; -.
DR EPD; P19783; -.
DR jPOST; P19783; -.
DR MaxQB; P19783; -.
DR PaxDb; P19783; -.
DR PeptideAtlas; P19783; -.
DR PRIDE; P19783; -.
DR ProteomicsDB; 284102; -.
DR TopDownProteomics; P19783; -.
DR Antibodypedia; 1266; 958 antibodies from 45 providers.
DR DNASU; 12857; -.
DR Ensembl; ENSMUST00000034276; ENSMUSP00000034276; ENSMUSG00000031818.
DR Ensembl; ENSMUST00000181586; ENSMUSP00000138019; ENSMUSG00000031818.
DR GeneID; 12857; -.
DR KEGG; mmu:12857; -.
DR UCSC; uc009nrh.2; mouse.
DR CTD; 1327; -.
DR MGI; MGI:88473; Cox4i1.
DR VEuPathDB; HostDB:ENSMUSG00000031818; -.
DR eggNOG; KOG4075; Eukaryota.
DR GeneTree; ENSGT00390000002407; -.
DR HOGENOM; CLU_117340_1_0_1; -.
DR InParanoid; P19783; -.
DR OMA; ESYAEMN; -.
DR OrthoDB; 1591226at2759; -.
DR PhylomeDB; P19783; -.
DR TreeFam; TF105061; -.
DR Reactome; R-MMU-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-MMU-611105; Respiratory electron transport.
DR Reactome; R-MMU-9707564; Cytoprotection by HMOX1.
DR UniPathway; UPA00705; -.
DR BioGRID-ORCS; 12857; 18 hits in 71 CRISPR screens.
DR ChiTaRS; Cox4i1; mouse.
DR PRO; PR:P19783; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; P19783; protein.
DR Bgee; ENSMUSG00000031818; Expressed in right colon and 256 other tissues.
DR ExpressionAtlas; P19783; baseline and differential.
DR Genevisible; P19783; MM.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0031966; C:mitochondrial membrane; IDA:MGI.
DR GO; GO:0005751; C:mitochondrial respiratory chain complex IV; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0006123; P:mitochondrial electron transport, cytochrome c to oxygen; IBA:GO_Central.
DR CDD; cd00922; Cyt_c_Oxidase_IV; 1.
DR Gene3D; 1.10.442.10; -; 1.
DR InterPro; IPR013288; Cyt_c_oxidase_su4.
DR InterPro; IPR004203; Cyt_c_oxidase_su4_fam.
DR InterPro; IPR036639; Cyt_c_oxidase_su4_sf.
DR PANTHER; PTHR10707; PTHR10707; 1.
DR Pfam; PF02936; COX4; 1.
DR PRINTS; PR01873; CYTCOXIDASE4.
DR SUPFAM; SSF81406; SSF81406; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Direct protein sequencing; Membrane;
KW Mitochondrion; Mitochondrion inner membrane; Phosphoprotein;
KW Reference proteome; Transit peptide; Transmembrane; Transmembrane helix.
FT TRANSIT 1..22
FT /note="Mitochondrion"
FT CHAIN 23..169
FT /note="Cytochrome c oxidase subunit 4 isoform 1,
FT mitochondrial"
FT /id="PRO_0000006085"
FT TOPO_DOM 23..98
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000250|UniProtKB:P00423"
FT TRANSMEM 99..124
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P00423"
FT TOPO_DOM 125..169
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000250|UniProtKB:P00423"
FT MOD_RES 29
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 29
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 56
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10888"
FT MOD_RES 58
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10888"
FT MOD_RES 60
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 60
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 67
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT CONFLICT 140..141
FT /note="MQ -> IE (in Ref. 2; AAB02139/AAB02140)"
FT /evidence="ECO:0000305"
FT TURN 32..34
FT /evidence="ECO:0007829|PDB:7O37"
FT STRAND 44..46
FT /evidence="ECO:0007829|PDB:7O37"
FT HELIX 57..65
FT /evidence="ECO:0007829|PDB:7O37"
FT HELIX 75..85
FT /evidence="ECO:0007829|PDB:7O37"
FT HELIX 90..93
FT /evidence="ECO:0007829|PDB:7O37"
FT HELIX 99..124
FT /evidence="ECO:0007829|PDB:7O37"
FT HELIX 131..133
FT /evidence="ECO:0007829|PDB:7O37"
FT HELIX 135..147
FT /evidence="ECO:0007829|PDB:7O37"
FT TURN 152..155
FT /evidence="ECO:0007829|PDB:7O37"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:7O37"
FT TURN 162..165
FT /evidence="ECO:0007829|PDB:7O37"
SQ SEQUENCE 169 AA; 19530 MW; D30B1DBBE14FDBEA CRC64;
MLASRALSLI GKRAISTSVC LRAHGSVVKS EDYAFPTYAD RRDYPLPDVA HVTMLSASQK
ALKEKEKADW SSLSRDEKVQ LYRIQFNESF AEMNRGTNEW KTVVGMAMFF IGFTALVLIW
EKSYVYGPIP HTFDRDWVAM QTKRMLDMKA NPIQGFSAKW DYDKNEWKK
