COX41_HUMAN
ID COX41_HUMAN Reviewed; 169 AA.
AC P13073; B2R4J2; D3DUM7; Q6P666;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 03-AUG-2022, entry version 213.
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;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=2444497; DOI=10.1016/0378-1119(87)90281-2;
RA Zeviani M., Nakagawa M., Herbert J., Lomax M.I., Grossman L.I.,
RA Sherbany A.A., Miranda A.F., Dimauro S., Schon E.A.;
RT "Isolation of a cDNA clone encoding subunit IV of human cytochrome c
RT oxidase.";
RL Gene 55:205-217(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2157630; DOI=10.1016/0378-1119(90)90281-u;
RA Lomax M.I., Welch M.D., Darras B.T., Francke U., Grossman L.I.;
RT "Novel use of a chimpanzee pseudogene for chromosomal mapping of human
RT cytochrome c oxidase subunit IV.";
RL Gene 86:209-216(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Skeletal muscle;
RA Park S.J., Modica-Napolitano J., Gross A., Ernst S.G., Aprille J.R.;
RL Submitted (OCT-1990) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Yu W., Andersson B., Worley K.C., Muzny D.M., Ding Y., Liu W.,
RA Ricafrente J.Y., Wentland M.A., Lennon G., Gibbs R.A.;
RL Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Placenta;
RA Bachman N.J., Wu W., Grossman L.I., Lomax M.I.;
RT "The COX4 gene and a linked gene, COX4AL, are controlled by a bidirectional
RT promoter.";
RL Submitted (MAY-1997) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Poyau A., Godinot C.;
RT "COX4, the human cytochrome c oxidase subunit IV gene.";
RL Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-3.
RC TISSUE=B-cell, and Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 26-169.
RX PubMed=10337626; DOI=10.1007/s003359901031;
RA Bachman N.J., Wu W., Schmidt T.R., Grossman L.I., Lomax M.I.;
RT "The 5-prime region of the COX4 gene contains a novel overlapping gene,
RT NOC4.";
RL Mamm. Genome 10:506-512(1999).
RN [12]
RP PROTEIN SEQUENCE OF 23-72.
RC TISSUE=Heart, and Muscle;
RX PubMed=1311608; DOI=10.1016/0167-4838(92)90395-t;
RA van Kuilenburg A.B.P., van Beeumen J.J., Demol H., van den Bogert C.,
RA Schouten I., Muijsers A.O.;
RT "Subunit IV of human cytochrome c oxidase, polymorphism and a putative
RT isoform.";
RL Biochim. Biophys. Acta 1119:218-224(1992).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-53 AND LYS-60, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [16]
RP CLEAVAGE OF TRANSIT PEPTIDE [LARGE SCALE ANALYSIS] AFTER ARG-22, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [17]
RP INTERACTION WITH AFG1L.
RX PubMed=26759378; DOI=10.1042/bj20151029;
RA Cesnekova J., Rodinova M., Hansikova H., Houstek J., Zeman J., Stiburek L.;
RT "The mammalian homologue of yeast Afg1 ATPase (lactation elevated 1)
RT mediates degradation of nuclear-encoded complex IV subunits.";
RL Biochem. J. 473:797-804(2016).
RN [18]
RP INVOLVEMENT IN MC4DN16, VARIANT MC4DN16 101-LYS-THR-102 DELINS ASN-SER, AND
RP CHARACTERIZATION OF VARIANT MC4DN16 101-LYS-THR-102 DELINS ASN-SER.
RX PubMed=28766551; DOI=10.1038/ejhg.2017.112;
RA Abu-Libdeh B., Douiev L., Amro S., Shahrour M., Ta-Shma A., Miller C.,
RA Elpeleg O., Saada A.;
RT "Mutation in the COX4I1 gene is associated with short stature, poor weight
RT gain and increased chromosomal breaks, simulating Fanconi anemia.";
RL Eur. J. Hum. Genet. 25:1142-1146(2017).
RN [19]
RP INVOLVEMENT IN MC4DN16, AND VARIANT MC4DN16 THR-152.
RX PubMed=31290619; DOI=10.1002/ajmg.a.61288;
RA Pillai N.R., AlDhaheri N.S., Ghosh R., Lim J., Streff H., Nayak A.,
RA Graham B.H., Hanchard N.A., Elsea S.H., Scaglia F.;
RT "Biallelic variants in COX4I1 associated with a novel phenotype resembling
RT Leigh syndrome with developmental regression, intellectual disability, and
RT seizures.";
RL Am. J. Med. Genet. A 179:2138-2143(2019).
RN [20]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.90 ANGSTROMS), AND SUBUNIT.
RX PubMed=28844695; DOI=10.1016/j.cell.2017.07.050;
RA Guo R., Zong S., Wu M., Gu J., Yang M.;
RT "Architecture of human mitochondrial respiratory megacomplex I2III2IV2.";
RL Cell 170:1247-1257(2017).
RN [21]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS) OF 26-169.
RX PubMed=30030519; DOI=10.1038/s41422-018-0071-1;
RA Zong S., Wu M., Gu J., Liu T., Guo R., Yang M.;
RT "Structure of the intact 14-subunit human cytochrome c oxidase.";
RL Cell Res. 28:1026-1034(2018).
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 COX4I1 (or
CC COX4I2), COX5A, COX5B, COX6A1 (or COX6A2), COX6B1 (or COX6B2), COX6C,
CC COX7A2 (or COX7A1), COX7B, COX7C, COX8A and NDUFA4, which are encoded
CC in the nuclear genome (PubMed:30030519). The complex exists as a
CC monomer or a dimer and forms supercomplexes (SCs) in the inner
CC mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I,
CC CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex,
CC complex III, CIII), resulting in different assemblies (supercomplex
CC SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)) (PubMed:28844695).
CC Interacts with AFG1L (PubMed:26759378). Interacts with PHB2; the
CC interaction decreases in absence of SPHK2 (By similarity). Interacts
CC with 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:P10888,
CC ECO:0000250|UniProtKB:P19783, ECO:0000269|PubMed:26759378,
CC ECO:0000269|PubMed:28844695, ECO:0000269|PubMed:30030519}.
CC -!- INTERACTION:
CC P13073; O14901: KLF11; NbExp=3; IntAct=EBI-1056574, EBI-948266;
CC P13073; P00395: MT-CO1; NbExp=2; IntAct=EBI-1056574, EBI-2117234;
CC P13073; O00560: SDCBP; NbExp=4; IntAct=EBI-1056574, EBI-727004;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:30030519}; Single-pass membrane protein
CC {ECO:0000269|PubMed:30030519}.
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- DISEASE: Mitochondrial complex IV deficiency, nuclear type 16 (MC4DN16)
CC [MIM:619060]: An autosomal recessive mitochondrial disorder with onset
CC in infancy and variable manifestations. MC4DN16 features include
CC feeding difficulties, poor overall growth, short stature, microcephaly,
CC developmental regression, severe hypotonia, and seizures. Cerebral and
CC cerebellar atrophy, and abnormal lesions in the basal ganglia can be
CC observed on brain imaging. Patient tissues show decreased levels and
CC activity of mitochondrial respiratory complex IV.
CC {ECO:0000269|PubMed:28766551, ECO:0000269|PubMed:31290619}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the cytochrome c oxidase IV family.
CC {ECO:0000305}.
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DR EMBL; M21575; AAA99312.1; -; mRNA.
DR EMBL; M34600; AAA52059.1; -; mRNA.
DR EMBL; X54802; CAA38573.1; -; mRNA.
DR EMBL; U90915; AAB51058.1; -; mRNA.
DR EMBL; AF005889; AAB94819.1; -; Genomic_DNA.
DR EMBL; AF017115; AAC99578.1; -; Genomic_DNA.
DR EMBL; AH005828; AAB97750.1; -; Genomic_DNA.
DR EMBL; BT019825; AAV38628.1; -; mRNA.
DR EMBL; AK311847; BAG34789.1; -; mRNA.
DR EMBL; CH471114; EAW95437.1; -; Genomic_DNA.
DR EMBL; CH471114; EAW95438.1; -; Genomic_DNA.
DR EMBL; BC008704; AAH08704.1; -; mRNA.
DR EMBL; BC021236; AAH21236.1; -; mRNA.
DR EMBL; BC062437; AAH62437.1; -; mRNA.
DR CCDS; CCDS10955.1; -.
DR PIR; S47012; OLHU4.
DR RefSeq; NP_001305715.1; NM_001318786.1.
DR RefSeq; NP_001305717.1; NM_001318788.1.
DR RefSeq; NP_001305723.1; NM_001318794.1.
DR RefSeq; NP_001305726.1; NM_001318797.1.
DR RefSeq; NP_001305731.1; NM_001318802.1.
DR RefSeq; NP_001852.1; NM_001861.4.
DR PDB; 5Z62; EM; 3.60 A; D=26-169.
DR PDBsum; 5Z62; -.
DR AlphaFoldDB; P13073; -.
DR SMR; P13073; -.
DR BioGRID; 107720; 398.
DR ComplexPortal; CPX-6123; Mitochondrial respiratory chain complex IV.
DR CORUM; P13073; -.
DR IntAct; P13073; 152.
DR MINT; P13073; -.
DR STRING; 9606.ENSP00000457513; -.
DR DrugBank; DB02659; Cholic Acid.
DR DrugBank; DB04464; N-Formylmethionine.
DR TCDB; 3.D.4.11.1; the proton-translocating cytochrome oxidase (cox) superfamily.
DR CarbonylDB; P13073; -.
DR GlyGen; P13073; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P13073; -.
DR MetOSite; P13073; -.
DR PhosphoSitePlus; P13073; -.
DR SwissPalm; P13073; -.
DR BioMuta; COX4I1; -.
DR EPD; P13073; -.
DR jPOST; P13073; -.
DR MassIVE; P13073; -.
DR MaxQB; P13073; -.
DR PaxDb; P13073; -.
DR PeptideAtlas; P13073; -.
DR PRIDE; P13073; -.
DR ProteomicsDB; 52896; -.
DR TopDownProteomics; P13073; -.
DR Antibodypedia; 1266; 958 antibodies from 45 providers.
DR DNASU; 1327; -.
DR Ensembl; ENST00000253452.8; ENSP00000253452.2; ENSG00000131143.10.
DR Ensembl; ENST00000561569.5; ENSP00000457015.1; ENSG00000131143.10.
DR Ensembl; ENST00000562336.5; ENSP00000457513.1; ENSG00000131143.10.
DR GeneID; 1327; -.
DR KEGG; hsa:1327; -.
DR MANE-Select; ENST00000253452.8; ENSP00000253452.2; NM_001861.6; NP_001852.1.
DR UCSC; uc002fje.4; human.
DR CTD; 1327; -.
DR DisGeNET; 1327; -.
DR GeneCards; COX4I1; -.
DR HGNC; HGNC:2265; COX4I1.
DR HPA; ENSG00000131143; Low tissue specificity.
DR MalaCards; COX4I1; -.
DR MIM; 123864; gene.
DR MIM; 619060; phenotype.
DR neXtProt; NX_P13073; -.
DR OpenTargets; ENSG00000131143; -.
DR Orphanet; 254905; Isolated cytochrome C oxidase deficiency.
DR PharmGKB; PA26781; -.
DR VEuPathDB; HostDB:ENSG00000131143; -.
DR eggNOG; KOG4075; Eukaryota.
DR GeneTree; ENSGT00390000002407; -.
DR HOGENOM; CLU_117340_1_0_1; -.
DR InParanoid; P13073; -.
DR OMA; PIRAKEQ; -.
DR OrthoDB; 1591226at2759; -.
DR PhylomeDB; P13073; -.
DR TreeFam; TF105061; -.
DR BioCyc; MetaCyc:HS05494-MON; -.
DR PathwayCommons; P13073; -.
DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-HSA-611105; Respiratory electron transport.
DR Reactome; R-HSA-9707564; Cytoprotection by HMOX1.
DR SignaLink; P13073; -.
DR SIGNOR; P13073; -.
DR UniPathway; UPA00705; -.
DR BioGRID-ORCS; 1327; 247 hits in 1096 CRISPR screens.
DR ChiTaRS; COX4I1; human.
DR GeneWiki; COX4I1; -.
DR GenomeRNAi; 1327; -.
DR Pharos; P13073; Tbio.
DR PRO; PR:P13073; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P13073; protein.
DR Bgee; ENSG00000131143; Expressed in apex of heart and 216 other tissues.
DR ExpressionAtlas; P13073; baseline and differential.
DR Genevisible; P13073; HS.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0031966; C:mitochondrial membrane; IDA:ComplexPortal.
DR GO; GO:0005751; C:mitochondrial respiratory chain complex IV; IMP:CAFA.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0004129; F:cytochrome-c oxidase activity; TAS:ProtInc.
DR GO; GO:0045333; P:cellular respiration; IC:ComplexPortal.
DR GO; GO:0006091; P:generation of precursor metabolites and energy; TAS:ProtInc.
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; Disease variant;
KW Membrane; Mitochondrion; Mitochondrion inner membrane; Phosphoprotein;
KW Primary mitochondrial disease; Reference proteome; Transit peptide;
KW Transmembrane; Transmembrane helix.
FT TRANSIT 1..22
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:1311608,
FT ECO:0007744|PubMed:25944712"
FT CHAIN 23..169
FT /note="Cytochrome c oxidase subunit 4 isoform 1,
FT mitochondrial"
FT /id="PRO_0000006084"
FT TOPO_DOM 23..98
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000269|PubMed:30030519"
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:0000269|PubMed:30030519"
FT MOD_RES 29
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P19783"
FT MOD_RES 29
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P19783"
FT MOD_RES 53
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
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:19608861"
FT MOD_RES 60
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P19783"
FT MOD_RES 67
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P19783"
FT VARIANT 3
FT /note="A -> T (in dbSNP:rs11557187)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_061127"
FT VARIANT 38
FT /note="Y -> F"
FT /id="VAR_002170"
FT VARIANT 101..102
FT /note="KT -> NS (in MC4DN16; decreased COX4I1 protein
FT levels)"
FT /evidence="ECO:0000269|PubMed:28766551"
FT /id="VAR_084181"
FT VARIANT 152
FT /note="P -> T (in MC4DN16)"
FT /evidence="ECO:0000269|PubMed:31290619"
FT /id="VAR_084182"
SQ SEQUENCE 169 AA; 19577 MW; F6382FFDCF3BE4ED CRC64;
MLATRVFSLV GKRAISTSVC VRAHESVVKS EDFSLPAYMD RRDHPLPEVA HVKHLSASQK
ALKEKEKASW SSLSMDEKVE LYRIKFKESF AEMNRGSNEW KTVVGGAMFF IGFTALVIMW
QKHYVYGPLP QSFDKEWVAK QTKRMLDMKV NPIQGLASKW DYEKNEWKK
