Entry euk:COX3_HUMAN

ID   COX3_HUMAN              Reviewed;         261 AA.
AC   P00414; Q14Y83;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   30-MAY-2000, sequence version 2.
DT   15-MAR-2017, entry version 170.
DE   RecName: Full=Cytochrome c oxidase subunit 3;
DE   AltName: Full=Cytochrome c oxidase polypeptide III;
GN   Name=MT-CO3; Synonyms=COIII, COXIII, MTCO3;
OS   Homo sapiens (Human).
OG   Mitochondrion.
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=7219534; DOI=10.1038/290457a0;
RA   Anderson S., Bankier A.T., Barrell B.G., de Bruijn M.H.L.,
RA   Coulson A.R., Drouin J., Eperon I.C., Nierlich D.P., Roe B.A.,
RA   Sanger F., Schreier P.H., Smith A.J.H., Staden R., Young I.G.;
RT   "Sequence and organization of the human mitochondrial genome.";
RL   Nature 290:457-465(1981).
RN   [2]
RP   SEQUENCE REVISION TO 118.
RA   Kogelnik A., Brown M.;
RL   Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-31.
RX   PubMed=16776823; DOI=10.1186/1471-2164-7-151;
RA   Thangaraj K., Chaubey G., Singh V.K., Vanniarajan A., Thanseem I.,
RA   Reddy A.G., Singh L.;
RT   "In situ origin of deep rooting lineages of mitochondrial
RT   Macrohaplogroup 'M' in India.";
RL   BMC Genomics 7:151-151(2006).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 167-261.
RC   TISSUE=Endometrial adenocarcinoma;
RA   Swanson K.V., Griffiss J.;
RL   Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   INVOLVEMENT IN MELAS, AND VARIANT MELAS LEU-251.
RX   PubMed=18587274; DOI=10.3858/emm.2008.40.3.354;
RA   Choi B.O., Hwang J.H., Kim J., Cho E.M., Cho S.Y., Hwang S.J.,
RA   Lee H.W., Kim S.J., Chung K.W.;
RT   "A MELAS syndrome family harboring two mutations in mitochondrial
RT   genome.";
RL   Exp. Mol. Med. 40:354-360(2008).
RN   [6]
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.,
RA   Ayoub D., 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   [7]
RP   VARIANTS ILE-91; ARG-177 AND ILE-254.
RX   PubMed=1757091; DOI=10.1007/BF00206061;
RA   Marzuki S., Noer A.S., Lertrit P., Thyagarajan D., Kapsa R.,
RA   Utthanaphol P., Byrne E.;
RT   "Normal variants of human mitochondrial DNA and translation products:
RT   the building of a reference data base.";
RL   Hum. Genet. 88:139-145(1991).
RN   [8]
RP   VARIANTS LHON SER-78 AND THR-200.
RX   PubMed=8240356; DOI=10.1006/bbrc.1993.2321;
RA   Johns D.R., Neufeld M.J.;
RT   "Cytochrome c oxidase mutations in Leber hereditary optic
RT   neuropathy.";
RL   Biochem. Biophys. Res. Commun. 196:810-815(1993).
RN   [9]
RP   INVOLVEMENT IN MELAS, AND VARIANT MELAS LEU-251.
RX   PubMed=7496173; DOI=10.1016/0960-8966(94)00079-O;
RA   Manfredi G., Schon E.A., Moraes C.T., Bonilla E., Berry G.T.,
RA   Sladky J.T., Dimauro S.;
RT   "A new mutation associated with MELAS is located in a mitochondrial
RT   DNA polypeptide-coding gene.";
RL   Neuromuscul. Disord. 5:391-398(1995).
RN   [10]
RP   VARIANT MT-C4D 94-PHE--PHE-98 DEL, AND INVOLVEMENT IN RM-MT.
RX   PubMed=8630495; DOI=10.1038/ng0496-410;
RA   Keightley J.A., Hoffbuhr K.C., Burton M.D., Salas V.M.,
RA   Johnston W.S.W., Penn A.M.W., Buist N.R.M., Kennaway N.G.;
RT   "A microdeletion in cytochrome c oxidase (COX) subunit III associated
RT   with COX deficiency and recurrent myoglobinuria.";
RL   Nat. Genet. 12:410-416(1996).
RN   [11]
RP   VARIANTS ARG-3 AND SER-35.
RX   PubMed=9461455; DOI=10.1093/nar/26.4.967;
RA   Rieder M.J., Taylor S.L., Tobe V.O., Nickerson D.A.;
RT   "Automating the identification of DNA variations using quality-based
RT   fluorescence re-sequencing: analysis of the human mitochondrial
RT   genome.";
RL   Nucleic Acids Res. 26:967-973(1998).
CC   -!- FUNCTION: Subunits I, II and III form the functional core of the
CC       enzyme complex.
CC   -!- INTERACTION:
CC       P37840:SNCA; NbExp=3; IntAct=EBI-3932264, EBI-985879;
CC   -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000250};
CC       Multi-pass membrane protein {ECO:0000250}.
CC   -!- DISEASE: Leber hereditary optic neuropathy (LHON) [MIM:535000]: A
CC       maternally inherited disease resulting in acute or subacute loss
CC       of central vision, due to optic nerve dysfunction. Cardiac
CC       conduction defects and neurological defects have also been
CC       described in some patients. LHON results from primary
CC       mitochondrial DNA mutations affecting the respiratory chain
CC       complexes. {ECO:0000269|PubMed:8240356}. Note=The disease is
CC       caused by mutations affecting the gene represented in this entry.
CC   -!- DISEASE: Mitochondrial complex IV deficiency (MT-C4D)
CC       [MIM:220110]: A disorder of the mitochondrial respiratory chain
CC       with heterogeneous clinical manifestations, ranging from isolated
CC       myopathy to severe multisystem disease affecting several tissues
CC       and organs. Features include hypertrophic cardiomyopathy,
CC       hepatomegaly and liver dysfunction, hypotonia, muscle weakness,
CC       exercise intolerance, developmental delay, delayed motor
CC       development and mental retardation. Some affected individuals
CC       manifest a fatal hypertrophic cardiomyopathy resulting in neonatal
CC       death. A subset of patients manifest Leigh syndrome.
CC       {ECO:0000269|PubMed:8630495}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- DISEASE: Recurrent myoglobinuria mitochondrial (RM-MT)
CC       [MIM:550500]: Recurrent myoglobinuria is characterized by
CC       recurrent attacks of rhabdomyolysis (necrosis or disintegration of
CC       skeletal muscle) associated with muscle pain and weakness, and
CC       followed by excretion of myoglobin in the urine.
CC       {ECO:0000269|PubMed:8630495}. Note=The gene represented in this
CC       entry may be involved in disease pathogenesis.
CC   -!- DISEASE: Mitochondrial encephalomyopathy with lactic acidosis and
CC       stroke-like episodes syndrome (MELAS) [MIM:540000]: Genetically
CC       heterogeneous disorder, characterized by episodic vomiting,
CC       seizures, and recurrent cerebral insults resembling strokes and
CC       causing hemiparesis, hemianopsia, or cortical blindness.
CC       {ECO:0000269|PubMed:18587274, ECO:0000269|PubMed:7496173}.
CC       Note=The disease may be caused by mutations affecting the gene
CC       represented in this entry.
CC   -!- SIMILARITY: Belongs to the cytochrome c oxidase subunit 3 family.
CC       {ECO:0000305}.
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DR   EMBL; J01415; AAB58949.2; -; Genomic_DNA.
DR   EMBL; V00662; CAA24032.1; -; Genomic_DNA.
DR   EMBL; DQ654394; ABG27956.1; -; Genomic_DNA.
DR   EMBL; DQ654395; ABG27958.1; -; Genomic_DNA.
DR   EMBL; DQ654396; ABG27960.1; -; Genomic_DNA.
DR   EMBL; DQ654397; ABG27962.1; -; Genomic_DNA.
DR   EMBL; DQ654398; ABG27964.1; -; Genomic_DNA.
DR   EMBL; DQ654399; ABG27966.1; -; Genomic_DNA.
DR   EMBL; DQ654400; ABG27968.1; -; Genomic_DNA.
DR   EMBL; DQ654401; ABG27970.1; -; Genomic_DNA.
DR   EMBL; DQ654402; ABG27972.1; -; Genomic_DNA.
DR   EMBL; DQ654403; ABG27974.1; -; Genomic_DNA.
DR   EMBL; DQ654404; ABG27976.1; -; Genomic_DNA.
DR   EMBL; DQ654405; ABG27978.1; -; Genomic_DNA.
DR   EMBL; DQ654406; ABG27980.1; -; Genomic_DNA.
DR   EMBL; DQ654407; ABG27982.1; -; Genomic_DNA.
DR   EMBL; DQ654408; ABG27984.1; -; Genomic_DNA.
DR   EMBL; DQ654409; ABG27986.1; -; Genomic_DNA.
DR   EMBL; DQ654410; ABG27988.1; -; Genomic_DNA.
DR   EMBL; DQ654411; ABG27990.1; -; Genomic_DNA.
DR   EMBL; DQ654412; ABG27992.1; -; Genomic_DNA.
DR   EMBL; DQ654413; ABG27994.1; -; Genomic_DNA.
DR   EMBL; DQ654414; ABG27996.1; -; Genomic_DNA.
DR   EMBL; DQ654415; ABG27998.1; -; Genomic_DNA.
DR   EMBL; DQ654416; ABG28000.1; -; Genomic_DNA.
DR   EMBL; DQ654417; ABG28002.1; -; Genomic_DNA.
DR   EMBL; DQ654418; ABG28004.1; -; Genomic_DNA.
DR   EMBL; DQ654419; ABG28006.1; -; Genomic_DNA.
DR   EMBL; DQ654420; ABG28008.1; -; Genomic_DNA.
DR   EMBL; DQ654421; ABG28010.1; -; Genomic_DNA.
DR   EMBL; DQ654422; ABG28012.1; -; Genomic_DNA.
DR   EMBL; DQ654423; ABG28014.1; -; Genomic_DNA.
DR   EMBL; DQ654424; ABG28016.1; -; Genomic_DNA.
DR   EMBL; DQ654425; ABG28018.1; -; Genomic_DNA.
DR   EMBL; DQ654426; ABG28020.1; -; Genomic_DNA.
DR   EMBL; DQ654427; ABG28022.1; -; Genomic_DNA.
DR   EMBL; DQ654428; ABG28024.1; -; Genomic_DNA.
DR   EMBL; DQ654429; ABG28026.1; -; Genomic_DNA.
DR   EMBL; DQ654430; ABG28028.1; -; Genomic_DNA.
DR   EMBL; DQ654431; ABG28030.1; -; Genomic_DNA.
DR   EMBL; DQ654432; ABG28032.1; -; Genomic_DNA.
DR   EMBL; DQ654433; ABG28034.1; -; Genomic_DNA.
DR   EMBL; DQ654434; ABG28036.1; -; Genomic_DNA.
DR   EMBL; DQ654435; ABG28038.1; -; Genomic_DNA.
DR   EMBL; DQ654436; ABG28040.1; -; Genomic_DNA.
DR   EMBL; DQ654437; ABG28042.1; -; Genomic_DNA.
DR   EMBL; DQ654438; ABG28044.1; -; Genomic_DNA.
DR   EMBL; DQ654439; ABG28046.1; -; Genomic_DNA.
DR   EMBL; DQ654440; ABG28048.1; -; Genomic_DNA.
DR   EMBL; DQ654441; ABG28050.1; -; Genomic_DNA.
DR   EMBL; DQ654442; ABG28052.1; -; Genomic_DNA.
DR   EMBL; DQ654443; ABG28054.1; -; Genomic_DNA.
DR   EMBL; AF004341; AAB63452.1; -; Genomic_DNA.
DR   PIR; A00482; OTHU3.
DR   RefSeq; YP_003024032.1; NC_012920.1.
DR   ProteinModelPortal; P00414; -.
DR   SMR; P00414; -.
DR   BioGrid; 110617; 8.
DR   IntAct; P00414; 8.
DR   STRING; 9606.ENSP00000354982; -.
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   PhosphoSitePlus; P00414; -.
DR   DMDM; 6648058; -.
DR   EPD; P00414; -.
DR   PaxDb; P00414; -.
DR   PeptideAtlas; P00414; -.
DR   PRIDE; P00414; -.
DR   TopDownProteomics; P00414; -.
DR   Ensembl; ENST00000362079; ENSP00000354982; ENSG00000198938.
DR   GeneID; 4514; -.
DR   KEGG; hsa:4514; -.
DR   CTD; 4514; -.
DR   DisGeNET; 4514; -.
DR   GeneCards; MT-CO3; -.
DR   GeneReviews; MT-CO3; -.
DR   H-InvDB; HIX0060139; -.
DR   HGNC; HGNC:7422; MT-CO3.
DR   HPA; HPA042788; -.
DR   MalaCards; MT-CO3; -.
DR   MIM; 220110; phenotype.
DR   MIM; 516050; gene.
DR   MIM; 535000; phenotype.
DR   MIM; 540000; phenotype.
DR   MIM; 550500; phenotype.
DR   neXtProt; NX_P00414; -.
DR   OpenTargets; ENSG00000198938; -.
DR   Orphanet; 99845; Genetic recurrent myoglobinuria.
DR   Orphanet; 254905; Isolated cytochrome C oxidase deficiency.
DR   Orphanet; 104; Leber hereditary optic neuropathy.
DR   Orphanet; 255210; Maternally-inherited Leigh syndrome.
DR   Orphanet; 550; MELAS.
DR   eggNOG; KOG4664; Eukaryota.
DR   eggNOG; COG1845; LUCA.
DR   GeneTree; ENSGT00390000013064; -.
DR   HOGENOM; HOG000264954; -.
DR   HOVERGEN; HBG016686; -.
DR   InParanoid; P00414; -.
DR   KO; K02262; -.
DR   OMA; PWPLTGA; -.
DR   OrthoDB; EOG091G0GH8; -.
DR   PhylomeDB; P00414; -.
DR   TreeFam; TF343435; -.
DR   Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes.
DR   Reactome; R-HSA-611105; Respiratory electron transport.
DR   GeneWiki; MT-CO3; -.
DR   GenomeRNAi; 4514; -.
DR   PRO; PR:P00414; -.
DR   Proteomes; UP000005640; Mitochondrion.
DR   Bgee; ENSG00000198938; -.
DR   ExpressionAtlas; P00414; baseline and differential.
DR   Genevisible; P00414; HS.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
DR   GO; GO:0045277; C:respiratory chain complex IV; IDA:UniProtKB.
DR   GO; GO:0004129; F:cytochrome-c oxidase activity; IEA:InterPro.
DR   GO; GO:0019646; P:aerobic electron transport chain; IEA:InterPro.
DR   GO; GO:0006123; P:mitochondrial electron transport, cytochrome c to oxygen; TAS:Reactome.
DR   GO; GO:0008535; P:respiratory chain complex IV assembly; IMP:UniProtKB.
DR   CDD; cd01665; Cyt_c_Oxidase_III; 1.
DR   Gene3D; 1.20.120.80; -; 1.
DR   InterPro; IPR024791; Cyt_c/ubiquinol_Oxase_su3.
DR   InterPro; IPR033945; Cyt_c_oxase_su3_dom.
DR   InterPro; IPR000298; Cyt_c_oxidase-like_su3.
DR   InterPro; IPR013833; Cyt_c_oxidase_su3_a-hlx.
DR   PANTHER; PTHR11403; PTHR11403; 1.
DR   Pfam; PF00510; COX3; 1.
DR   SUPFAM; SSF81452; SSF81452; 1.
DR   PROSITE; PS50253; COX3; 1.
PE   1: Evidence at protein level;
KW   Complete proteome; Disease mutation;
KW   Leber hereditary optic neuropathy; MELAS syndrome; Membrane;
KW   Mitochondrion; Mitochondrion inner membrane; Polymorphism;
KW   Reference proteome; Transmembrane; Transmembrane helix.
FT   INIT_MET      1      1       Removed. {ECO:0000250|UniProtKB:P05505}.
FT   CHAIN         2    261       Cytochrome c oxidase subunit 3.
FT                                /FTId=PRO_0000183793.
FT   TRANSMEM     15     35       Helical. {ECO:0000255}.
FT   TRANSMEM     42     59       Helical. {ECO:0000255}.
FT   TRANSMEM     81    101       Helical. {ECO:0000255}.
FT   TRANSMEM    127    147       Helical. {ECO:0000255}.
FT   TRANSMEM    159    179       Helical. {ECO:0000255}.
FT   TRANSMEM    197    217       Helical. {ECO:0000255}.
FT   TRANSMEM    239    259       Helical. {ECO:0000255}.
FT   VARIANT       3      3       H -> R. {ECO:0000269|PubMed:9461455}.
FT                                /FTId=VAR_008573.
FT   VARIANT      35     35       F -> S. {ECO:0000269|PubMed:9461455}.
FT                                /FTId=VAR_008574.
FT   VARIANT      78     78       G -> S (in LHON; secondary mutation; does
FT                                not seem to directly cause the disease;
FT                                dbSNP:rs267606611).
FT                                {ECO:0000269|PubMed:8240356}.
FT                                /FTId=VAR_002167.
FT   VARIANT      91     91       V -> I (in dbSNP:rs2853825).
FT                                {ECO:0000269|PubMed:1757091}.
FT                                /FTId=VAR_008575.
FT   VARIANT      94     98       Missing (in MT-C4D; with RM-MT).
FT                                {ECO:0000269|PubMed:8630495}.
FT                                /FTId=VAR_033057.
FT   VARIANT     177    177       Q -> R. {ECO:0000269|PubMed:1757091}.
FT                                /FTId=VAR_008576.
FT   VARIANT     200    200       A -> T (in LHON; possible rare primary
FT                                mutation; dbSNP:rs200613617).
FT                                {ECO:0000269|PubMed:8240356}.
FT                                /FTId=VAR_002168.
FT   VARIANT     251    251       F -> L (in MELAS).
FT                                {ECO:0000269|PubMed:18587274,
FT                                ECO:0000269|PubMed:7496173}.
FT                                /FTId=VAR_002169.
FT   VARIANT     254    254       V -> I (in dbSNP:rs200809063).
FT                                {ECO:0000269|PubMed:1757091}.
FT                                /FTId=VAR_008577.
FT   CONFLICT    118    118       P -> R (in Ref. 1; CAA24032).
FT                                {ECO:0000305}.
CC   --------------------------------------------------------------------------
CC   The following FT lines are automated annotations from the MyHits database.
CC   --------------------------------------------------------------------------
FT   MYHIT         6    261       ipfam:COX3 [T]
FT   MYHIT         4    261       iprf:COX3 [T]
SQ   SEQUENCE   261 AA;  29951 MW;  A04385EF748B7C14 CRC64;
     MTHQSHAYHM VKPSPWPLTG ALSALLMTSG LAMWFHFHSM TLLMLGLLTN TLTMYQWWRD
     VTRESTYQGH HTPPVQKGLR YGMILFITSE VFFFAGFFWA FYHSSLAPTP QLGGHWPPTG
     ITPLNPLEVP LLNTSVLLAS GVSITWAHHS LMENNRNQMI QALLITILLG LYFTLLQASE
     YFESPFTISD GIYGSTFFVA TGFHGLHVII GSTFLTICFI RQLMFHFTSK HHFGFEAAAW
     YWHFVDVVWL FLYVSIYWWG S
//