COX6C_HUMAN
ID COX6C_HUMAN Reviewed; 75 AA.
AC P09669; B2R4D7;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 2.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Cytochrome c oxidase subunit 6C;
DE AltName: Full=Cytochrome c oxidase polypeptide VIc;
GN Name=COX6C;
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].
RX PubMed=2849755; DOI=10.1093/nar/16.22.10916;
RA Otsuka M., Mizuno Y., Yoshida M., Kagawa Y., Ohta S.;
RT "Nucleotide sequence of cDNA encoding human cytochrome c oxidase subunit
RT VIc.";
RL Nucleic Acids Res. 16:10916-10916(1988).
RN [2]
RP SEQUENCE REVISION TO 52.
RA Ohta S.;
RL Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10072584; DOI=10.1159/000015185;
RA Hofmann S., Lichtner P., Schuffenhauer S., Gerbitz K.D., Meitinger T.;
RT "Assignment of the human genes coding for cytochrome c oxidase subunits Va
RT (COX5A), VIc (COX6C) and VIIc (COX7C) to chromosome bands 15q25, 8q22-->q23
RT and 5q14 and of three pseudogenes (COX5AP1, COX6CP1, COX7CP1) to 14q22,
RT 16p12 and 13q14-->q21 by FISH and radiation hybrid mapping.";
RL Cytogenet. Cell Genet. 83:226-227(1998).
RN [4]
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 (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [6]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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 [8]
RP PROTEIN SEQUENCE [LARGE SCALE ANALYSIS] OF 2-11.
RC TISSUE=Leukemic T-cell;
RX PubMed=19892738; DOI=10.1073/pnas.0908958106;
RA Xu G., Shin S.B., Jaffrey S.R.;
RT "Global profiling of protease cleavage sites by chemoselective labeling of
RT protein N-termini.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:19310-19315(2009).
RN [9]
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 [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [11]
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 [12]
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 [13]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS) OF 3-75.
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:P04038}.
CC -!- PATHWAY: Energy metabolism; oxidative phosphorylation.
CC {ECO:0000250|UniProtKB:P04038}.
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 {ECO:0000269|PubMed:28844695, ECO:0000269|PubMed:30030519}.
CC -!- INTERACTION:
CC P09669; P42858: HTT; NbExp=4; IntAct=EBI-715040, EBI-466029;
CC P09669; P21673: SAT1; NbExp=3; IntAct=EBI-715040, EBI-711613;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:30030519}; Single-pass membrane protein
CC {ECO:0000269|PubMed:30030519}.
CC -!- SIMILARITY: Belongs to the cytochrome c oxidase subunit 6c family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/COX6CID251.html";
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DR EMBL; X13238; CAA31624.1; -; mRNA.
DR EMBL; AF067637; AAC73061.1; -; Genomic_DNA.
DR EMBL; AF067636; AAC73061.1; JOINED; Genomic_DNA.
DR EMBL; BT007007; AAP35653.1; -; mRNA.
DR EMBL; AK311791; BAG34734.1; -; mRNA.
DR EMBL; CH471060; EAW91791.1; -; Genomic_DNA.
DR EMBL; BC000187; AAH00187.1; -; mRNA.
DR CCDS; CCDS6284.1; -.
DR PIR; S01960; OGHU6C.
DR RefSeq; NP_004365.1; NM_004374.3.
DR RefSeq; XP_016868509.1; XM_017013020.1.
DR PDB; 5Z62; EM; 3.60 A; I=3-75.
DR PDBsum; 5Z62; -.
DR AlphaFoldDB; P09669; -.
DR SMR; P09669; -.
DR BioGRID; 107738; 120.
DR ComplexPortal; CPX-6123; Mitochondrial respiratory chain complex IV.
DR CORUM; P09669; -.
DR IntAct; P09669; 50.
DR MINT; P09669; -.
DR STRING; 9606.ENSP00000428895; -.
DR DrugBank; DB02659; Cholic Acid.
DR DrugBank; DB04464; N-Formylmethionine.
DR iPTMnet; P09669; -.
DR PhosphoSitePlus; P09669; -.
DR BioMuta; COX6C; -.
DR EPD; P09669; -.
DR jPOST; P09669; -.
DR MassIVE; P09669; -.
DR MaxQB; P09669; -.
DR PaxDb; P09669; -.
DR PeptideAtlas; P09669; -.
DR PRIDE; P09669; -.
DR ProteomicsDB; 52263; -.
DR TopDownProteomics; P09669; -.
DR Antibodypedia; 4263; 246 antibodies from 30 providers.
DR DNASU; 1345; -.
DR Ensembl; ENST00000297564.6; ENSP00000297564.2; ENSG00000164919.11.
DR Ensembl; ENST00000517682.6; ENSP00000429714.1; ENSG00000164919.11.
DR Ensembl; ENST00000518171.5; ENSP00000429755.1; ENSG00000164919.11.
DR Ensembl; ENST00000520271.5; ENSP00000428150.1; ENSG00000164919.11.
DR Ensembl; ENST00000520468.7; ENSP00000428895.1; ENSG00000164919.11.
DR Ensembl; ENST00000520517.5; ENSP00000429991.1; ENSG00000164919.11.
DR Ensembl; ENST00000522934.5; ENSP00000428702.1; ENSG00000164919.11.
DR Ensembl; ENST00000522940.5; ENSP00000428965.1; ENSG00000164919.11.
DR Ensembl; ENST00000523016.1; ENSP00000429707.1; ENSG00000164919.11.
DR Ensembl; ENST00000524245.5; ENSP00000429410.1; ENSG00000164919.11.
DR GeneID; 1345; -.
DR KEGG; hsa:1345; -.
DR MANE-Select; ENST00000520468.7; ENSP00000428895.1; NM_004374.4; NP_004365.1.
DR UCSC; uc003yiy.3; human.
DR CTD; 1345; -.
DR DisGeNET; 1345; -.
DR GeneCards; COX6C; -.
DR HGNC; HGNC:2285; COX6C.
DR HPA; ENSG00000164919; Low tissue specificity.
DR MIM; 124090; gene.
DR neXtProt; NX_P09669; -.
DR OpenTargets; ENSG00000164919; -.
DR PharmGKB; PA26802; -.
DR VEuPathDB; HostDB:ENSG00000164919; -.
DR eggNOG; ENOG502SEI2; Eukaryota.
DR GeneTree; ENSGT00940000162275; -.
DR HOGENOM; CLU_196254_0_0_1; -.
DR InParanoid; P09669; -.
DR OMA; YKNYDPM; -.
DR OrthoDB; 1618740at2759; -.
DR PhylomeDB; P09669; -.
DR TreeFam; TF353619; -.
DR BioCyc; MetaCyc:HS09158-MON; -.
DR PathwayCommons; P09669; -.
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; P09669; -.
DR SIGNOR; P09669; -.
DR UniPathway; UPA00705; -.
DR BioGRID-ORCS; 1345; 342 hits in 1049 CRISPR screens.
DR ChiTaRS; COX6C; human.
DR GeneWiki; COX6C; -.
DR GenomeRNAi; 1345; -.
DR Pharos; P09669; Tbio.
DR PRO; PR:P09669; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; P09669; protein.
DR Bgee; ENSG00000164919; Expressed in pons and 213 other tissues.
DR ExpressionAtlas; P09669; baseline and differential.
DR Genevisible; P09669; 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:0031966; C:mitochondrial membrane; IDA:ComplexPortal.
DR GO; GO:0005751; C:mitochondrial respiratory chain complex IV; IPI:ComplexPortal.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
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; IC:ComplexPortal.
DR CDD; cd00927; Cyt_c_Oxidase_VIc; 1.
DR Gene3D; 4.10.93.10; -; 1.
DR InterPro; IPR004204; COX6C.
DR InterPro; IPR034884; Cytochrome_c_oxidase_VIc/VIIs.
DR InterPro; IPR037169; Cytochrome_c_oxidase_VIc_sf.
DR Pfam; PF02937; COX6C; 1.
DR SUPFAM; SSF81415; SSF81415; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..75
FT /note="Cytochrome c oxidase subunit 6C"
FT /id="PRO_0000006131"
FT TOPO_DOM 1..13
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000269|PubMed:30030519"
FT TRANSMEM 14..54
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P04038"
FT TOPO_DOM 55..75
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000269|PubMed:30030519"
SQ SEQUENCE 75 AA; 8781 MW; D09FEE0C0AA7A798 CRC64;
MAPEVLPKPR MRGLLARRLR NHMAVAFVLS LGVAALYKFR VADQRKKAYA DFYRNYDVMK
DFEEMRKAGI FQSVK
