ID COX18_HUMAN Reviewed; 333 AA.
AC Q8N8Q8; Q2PB66; Q2PB67; Q2PB68; Q49B97; Q6IPP9;
DT 14-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 27-MAR-2024, entry version 144.
DE RecName: Full=Cytochrome c oxidase assembly protein COX18, mitochondrial;
DE Short=COX18Hs;
DE AltName: Full=Cytochrome c oxidase assembly protein 18;
DE Flags: Precursor;
GN Name=COX18; Synonyms=OXA1L2;
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] (ISOFORM 1), SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=16212937; DOI=10.1016/j.bbrc.2005.09.127;
RA Sacconi S., Trevisson E., Pistollato F., Baldoin M.C., Rezzonico R.,
RA Bourget I., Desnuelle C., Tenconi R., Basso G., DiMauro S., Salviati L.;
RT "hCOX18 and hCOX19: two human genes involved in cytochrome c oxidase
RT assembly.";
RL Biochem. Biophys. Res. Commun. 337:832-839(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Teratocarcinoma;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4).
RC TISSUE=Cerebellum;
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 81-333 (ISOFORMS 1; 2 AND 3), AND FUNCTION.
RC TISSUE=Skeletal muscle;
RX PubMed=16911509; DOI=10.1111/j.1567-1364.2006.00083.x;
RA Gaisne M., Bonnefoy N.;
RT "The COX18 gene, involved in mitochondrial biogenesis, is functionally
RT conserved and tightly regulated in humans and fission yeast.";
RL FEMS Yeast Res. 6:869-882(2006).
RN [5]
RP IDENTIFICATION IN A COMPLEX WITH TMEM177; COA6; MT-CO2; COX20; SCO1 AND
RP SCO2.
RX PubMed=29154948; DOI=10.1016/j.bbamcr.2017.11.010;
RA Lorenzi I., Oeljeklaus S., Aich A., Ronsoer C., Callegari S., Dudek J.,
RA Warscheid B., Dennerlein S., Rehling P.;
RT "The mitochondrial TMEM177 associates with COX20 during COX2 biogenesis.";
RL Biochim. Biophys. Acta 1865:323-333(2017).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH MT-CO2 AND COX20.
RX PubMed=28330871; DOI=10.1074/jbc.m117.778514;
RA Bourens M., Barrientos A.;
RT "Human mitochondrial cytochrome c oxidase assembly factor COX18 acts
RT transiently as a membrane insertase within the subunit 2 maturation
RT module.";
RL J. Biol. Chem. 292:7774-7783(2017).
CC -!- FUNCTION: Mitochondrial membrane insertase required for the
CC translocation of the C-terminus of cytochrome c oxidase subunit II (MT-
CC CO2/COX2) across the mitochondrial inner membrane. Plays a role in MT-
CC CO2/COX2 maturation following the COX20-mediated stabilization of newly
CC synthesized MT-CO2/COX2 protein and before the action of the
CC metallochaperones SCO1/2. Essential for the assembly and stability of
CC the mitochondrial respiratory chain complex IV (also known as
CC cytochrome c oxidase). {ECO:0000269|PubMed:16911509,
CC ECO:0000269|PubMed:28330871}.
CC -!- SUBUNIT: Found in a complex with TMEM177, COA6, MT-CO2/COX2, COX20,
CC SCO1 and SCO2 (PubMed:29154948). Interacts transiently with MT-CO2/COX2
CC during its maturation (PubMed:28330871). Interacts with COX20 in a MT-
CC CO2/COX2-dependent manner (PubMed:28330871).
CC {ECO:0000269|PubMed:28330871, ECO:0000269|PubMed:29154948}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:16212937, ECO:0000269|PubMed:28330871}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:16212937}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Hs1;
CC IsoId=Q8N8Q8-1; Sequence=Displayed;
CC Name=2; Synonyms=Hs2;
CC IsoId=Q8N8Q8-2; Sequence=VSP_022312, VSP_022314;
CC Name=3; Synonyms=Hs3;
CC IsoId=Q8N8Q8-3; Sequence=VSP_022311, VSP_022315;
CC Name=4;
CC IsoId=Q8N8Q8-4; Sequence=VSP_022313, VSP_022316;
CC -!- SIMILARITY: Belongs to the OXA1/ALB3/YidC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH71812.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
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DR EMBL; AY957564; AAY35060.1; -; mRNA.
DR EMBL; AY957565; AAY35061.1; -; mRNA.
DR EMBL; AK096310; BAC04758.1; -; mRNA.
DR EMBL; BC071812; AAH71812.1; ALT_SEQ; mRNA.
DR EMBL; BC101684; AAI01685.1; -; mRNA.
DR EMBL; AM055750; CAJ20055.1; -; mRNA.
DR EMBL; AM055751; CAJ20056.1; -; mRNA.
DR EMBL; AM055752; CAJ20057.1; -; mRNA.
DR CCDS; CCDS3554.1; -. [Q8N8Q8-1]
DR RefSeq; NP_001284662.1; NM_001297733.1.
DR RefSeq; NP_001287658.1; NM_001300729.1.
DR RefSeq; NP_776188.1; NM_173827.3. [Q8N8Q8-1]
DR AlphaFoldDB; Q8N8Q8; -.
DR BioGRID; 130132; 9.
DR IntAct; Q8N8Q8; 2.
DR MINT; Q8N8Q8; -.
DR STRING; 9606.ENSP00000425261; -.
DR TCDB; 2.A.9.1.3; the membrane protein insertase (yidc/alb3/oxa1) family.
DR iPTMnet; Q8N8Q8; -.
DR PhosphoSitePlus; Q8N8Q8; -.
DR BioMuta; COX18; -.
DR DMDM; 38372495; -.
DR EPD; Q8N8Q8; -.
DR jPOST; Q8N8Q8; -.
DR MassIVE; Q8N8Q8; -.
DR MaxQB; Q8N8Q8; -.
DR PaxDb; 9606-ENSP00000425261; -.
DR PeptideAtlas; Q8N8Q8; -.
DR ProteomicsDB; 72449; -. [Q8N8Q8-1]
DR ProteomicsDB; 72450; -. [Q8N8Q8-2]
DR ProteomicsDB; 72451; -. [Q8N8Q8-3]
DR ProteomicsDB; 72452; -. [Q8N8Q8-4]
DR Pumba; Q8N8Q8; -.
DR Antibodypedia; 44370; 108 antibodies from 21 providers.
DR DNASU; 285521; -.
DR Ensembl; ENST00000295890.8; ENSP00000295890.4; ENSG00000163626.17. [Q8N8Q8-1]
DR Ensembl; ENST00000449739.6; ENSP00000394583.2; ENSG00000163626.17. [Q8N8Q8-3]
DR Ensembl; ENST00000510031.1; ENSP00000424978.1; ENSG00000163626.17. [Q8N8Q8-2]
DR GeneID; 285521; -.
DR KEGG; hsa:285521; -.
DR UCSC; uc003hgm.2; human. [Q8N8Q8-1]
DR AGR; HGNC:26801; -.
DR CTD; 285521; -.
DR DisGeNET; 285521; -.
DR GeneCards; COX18; -.
DR HGNC; HGNC:26801; COX18.
DR HPA; ENSG00000163626; Low tissue specificity.
DR MIM; 610428; gene.
DR neXtProt; NX_Q8N8Q8; -.
DR OpenTargets; ENSG00000163626; -.
DR PharmGKB; PA145008543; -.
DR VEuPathDB; HostDB:ENSG00000163626; -.
DR eggNOG; KOG1239; Eukaryota.
DR GeneTree; ENSGT00530000063506; -.
DR HOGENOM; CLU_2003161_0_0_1; -.
DR InParanoid; Q8N8Q8; -.
DR OrthoDB; 5395681at2759; -.
DR PhylomeDB; Q8N8Q8; -.
DR TreeFam; TF323948; -.
DR PathwayCommons; Q8N8Q8; -.
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; Q8N8Q8; -.
DR BioGRID-ORCS; 285521; 117 hits in 1158 CRISPR screens.
DR ChiTaRS; COX18; human.
DR GenomeRNAi; 285521; -.
DR Pharos; Q8N8Q8; Tbio.
DR PRO; PR:Q8N8Q8; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q8N8Q8; Protein.
DR Bgee; ENSG00000163626; Expressed in tibia and 188 other cell types or tissues.
DR ExpressionAtlas; Q8N8Q8; baseline and differential.
DR Genevisible; Q8N8Q8; HS.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0032977; F:membrane insertase activity; IDA:UniProtKB.
DR GO; GO:0033617; P:mitochondrial cytochrome c oxidase assembly; IMP:UniProtKB.
DR GO; GO:0032979; P:protein insertion into mitochondrial inner membrane from matrix; IDA:UniProtKB.
DR GO; GO:0051204; P:protein insertion into mitochondrial membrane; IGI:UniProtKB.
DR GO; GO:0008535; P:respiratory chain complex IV assembly; IGI:UniProtKB.
DR CDD; cd20069; 5TM_Oxa1-like; 1.
DR InterPro; IPR001708; YidC/ALB3/OXA1/COX18.
DR InterPro; IPR028055; YidC/Oxa/ALB_C.
DR PANTHER; PTHR12428:SF34; CYTOCHROME C OXIDASE ASSEMBLY PROTEIN COX18, MITOCHONDRIAL; 1.
DR PANTHER; PTHR12428; OXA1; 1.
DR Pfam; PF02096; 60KD_IMP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Reference proteome; Transit peptide;
KW Transmembrane; Transmembrane helix.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..333
FT /note="Cytochrome c oxidase assembly protein COX18,
FT mitochondrial"
FT /id="PRO_0000020354"
FT TOPO_DOM ?..167
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305|PubMed:16212937"
FT TRANSMEM 168..188
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 189..223
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305|PubMed:16212937"
FT TRANSMEM 224..244
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 245..262
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305|PubMed:16212937"
FT TRANSMEM 263..283
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 284..333
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305|PubMed:16212937"
FT VAR_SEQ 112..129
FT /note="VENLQPEIKTIARHLNQE -> AHLSKEYEEANFRAICAR (in isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:16911509"
FT /id="VSP_022311"
FT VAR_SEQ 112..127
FT /note="VENLQPEIKTIARHLN -> LGGKFAARNKNYCQAS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16911509"
FT /id="VSP_022312"
FT VAR_SEQ 113..147
FT /note="ENLQPEIKTIARHLNQEVAVRANQLGWSKRDARLT -> VSMGKKNRKQNRN
FT GISSNIKAVSHFTGRMSTGQEQ (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_022313"
FT VAR_SEQ 128..333
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16911509"
FT /id="VSP_022314"
FT VAR_SEQ 130..333
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16911509"
FT /id="VSP_022315"
FT VAR_SEQ 148..333
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_022316"
FT CONFLICT 311
FT /note="K -> R (in Ref. 4; CAJ20055)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 333 AA; 37063 MW; 4F2C18C7E78C08EE CRC64;
MLCRLGGRWL RPLPALQLWA RDLPLAPVPT SGAKRPTLPV WAVAPVSAVH ANGWYEALAA
SSPVRVAEEV LLGVHAATGL PWWGSILLST VALRGAVTLP LAAYQHYILA KVENLQPEIK
TIARHLNQEV AVRANQLGWS KRDARLTYLK NMRRLISELY VRDNCHPFKA TVLVWIQLPM
WIFMSFALRN LSTGAAHSEG FSVQEQLATG GILWFPDLTA PDSTWILPIS VGVINLLIVE
ICALQKIGMS RFQTYITYFV RAMSVLMIPI AATVPSSIVL YWLCSSFVGL SQNLLLRSPG
FRQLCRIPST KSDSETPYKD IFAAFNTKFI SRK
//
