COQ5_HUMAN
ID COQ5_HUMAN Reviewed; 327 AA.
AC Q5HYK3; B2RDU9; B3GK62; B4DEJ4; Q32Q28; Q53HH0; Q96LV1; Q9BSP8;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 2.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=2-methoxy-6-polyprenyl-1,4-benzoquinol methylase, mitochondrial {ECO:0000255|HAMAP-Rule:MF_03191};
DE EC=2.1.1.201 {ECO:0000255|HAMAP-Rule:MF_03191};
DE AltName: Full=Ubiquinone biosynthesis methyltransferase COQ5 {ECO:0000255|HAMAP-Rule:MF_03191};
DE Flags: Precursor;
GN Name=COQ5 {ECO:0000255|HAMAP-Rule:MF_03191, ECO:0000312|HGNC:HGNC:28722};
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], VARIANT THR-152, PATHWAY, INTERACTION WITH
RP COQ4, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Skin fibroblast;
RX PubMed=25152161; DOI=10.1016/j.bbalip.2014.08.007;
RA Nguyen T.P., Casarin A., Desbats M.A., Doimo M., Trevisson E.,
RA Santos-Ocana C., Navas P., Clarke C.F., Salviati L.;
RT "Molecular characterization of the human COQ5 C-methyltransferase in
RT coenzyme Q10 biosynthesis.";
RL Biochim. Biophys. Acta 1841:1628-1638(2014).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum, and Testis;
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], AND VARIANT THR-152.
RC TISSUE=Coronary artery;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Adipose tissue;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-152.
RC TISSUE=Lung;
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 [7]
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 [8]
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 [9]
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 [10]
RP INVOLVEMENT IN COQ10D9.
RX PubMed=29044765; DOI=10.1002/humu.23345;
RA Malicdan M.C.V., Vilboux T., Ben-Zeev B., Guo J., Eliyahu A.,
RA Pode-Shakked B., Dori A., Kakani S., Chandrasekharappa S.C., Ferreira C.R.,
RA Shelestovich N., Marek-Yagel D., Pri-Chen H., Blatt I., Niederhuber J.E.,
RA He L., Toro C., Taylor R.W., Deeken J., Yardeni T., Wallace D.C.,
RA Gahl W.A., Anikster Y.;
RT "A novel inborn error of the coenzyme Q10 biosynthesis pathway: cerebellar
RT ataxia and static encephalomyopathy due to COQ5 C-methyltransferase
RT deficiency.";
RL Hum. Mutat. 39:69-79(2018).
CC -!- FUNCTION: Methyltransferase required for the conversion of 2-
CC polyprenyl-6-methoxy-1,4-benzoquinol (DDMQH2) to 2-polyprenyl-3-methyl-
CC 6-methoxy-1,4-benzoquinol (DMQH2). {ECO:0000255|HAMAP-Rule:MF_03191}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2-methoxy-6-all-trans-polyprenyl-1,4-benzoquinol + S-
CC adenosyl-L-methionine = a 6-methoxy-3-methyl-2-all-trans-polyprenyl-
CC 1,4-benzoquinol + H(+) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:28286, Rhea:RHEA-COMP:10858, Rhea:RHEA-COMP:10859,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:84166, ChEBI:CHEBI:84167; EC=2.1.1.201;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03191};
CC -!- PATHWAY: Cofactor biosynthesis; ubiquinone biosynthesis.
CC {ECO:0000255|HAMAP-Rule:MF_03191, ECO:0000269|PubMed:25152161}.
CC -!- SUBUNIT: Component of a multi-subunit COQ enzyme complex, composed of
CC at least COQ3, COQ4, COQ5, COQ6, COQ7 and COQ9. {ECO:0000255|HAMAP-
CC Rule:MF_03191, ECO:0000269|PubMed:25152161}.
CC -!- INTERACTION:
CC Q5HYK3; Q9NZJ6: COQ3; NbExp=7; IntAct=EBI-12577722, EBI-10897372;
CC Q5HYK3; Q9Y3A0: COQ4; NbExp=6; IntAct=EBI-12577722, EBI-12284865;
CC Q5HYK3; Q9Y2Z9: COQ6; NbExp=9; IntAct=EBI-12577722, EBI-718148;
CC Q5HYK3; Q99807: COQ7; NbExp=7; IntAct=EBI-12577722, EBI-11017131;
CC Q5HYK3; O75208: COQ9; NbExp=11; IntAct=EBI-12577722, EBI-724524;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000255|HAMAP-
CC Rule:MF_03191, ECO:0000269|PubMed:25152161}; Peripheral membrane
CC protein {ECO:0000255|HAMAP-Rule:MF_03191, ECO:0000269|PubMed:25152161};
CC Matrix side {ECO:0000255|HAMAP-Rule:MF_03191,
CC ECO:0000269|PubMed:25152161}.
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest levels in liver,
CC lung, placenta and skeletal muscle. {ECO:0000269|PubMed:25152161}.
CC -!- DISEASE: Coenzyme Q10 deficiency, primary, 9 (COQ10D9) [MIM:619028]: A
CC form of coenzyme Q10 deficiency, an autosomal recessive disorder with
CC variable manifestations consistent with 5 major phenotypes. The
CC phenotypes include an encephalomyopathic form with seizures and ataxia;
CC a multisystem infantile form with encephalopathy, cardiomyopathy and
CC renal failure; a predominantly cerebellar form with ataxia and
CC cerebellar atrophy; Leigh syndrome with growth retardation; and an
CC isolated myopathic form. COQ10D9 patients show cerebellar ataxia with
CC cerebellar atrophy. Additional features include generalized tonic-
CC clonic seizures, and cognitive disability. Disease onset is in the
CC first decade of life. {ECO:0000269|PubMed:29044765}. Note=The disease
CC may be caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. MenG/UbiE family. {ECO:0000255|HAMAP-Rule:MF_03191}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB71567.1; Type=Miscellaneous discrepancy; Note=Non-canonical splice intron-exon junction.; Evidence={ECO:0000305};
CC Sequence=BAG38046.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; EU700459; ACD75052.1; -; mRNA.
DR EMBL; AK057777; BAB71567.1; ALT_SEQ; mRNA.
DR EMBL; AK222610; BAD96330.1; -; mRNA.
DR EMBL; AK293656; BAG57105.1; -; mRNA.
DR EMBL; AK315681; BAG38046.1; ALT_INIT; mRNA.
DR EMBL; BX647562; CAI46073.1; -; mRNA.
DR EMBL; CH471054; EAW98198.1; -; Genomic_DNA.
DR EMBL; BC004916; AAH04916.2; -; mRNA.
DR EMBL; BC107874; AAI07875.1; -; mRNA.
DR CCDS; CCDS31912.1; -.
DR RefSeq; NP_115690.3; NM_032314.3.
DR AlphaFoldDB; Q5HYK3; -.
DR SMR; Q5HYK3; -.
DR BioGRID; 124001; 104.
DR ComplexPortal; CPX-3642; CoQ biosynthetic complex.
DR IntAct; Q5HYK3; 27.
DR MINT; Q5HYK3; -.
DR STRING; 9606.ENSP00000288532; -.
DR iPTMnet; Q5HYK3; -.
DR PhosphoSitePlus; Q5HYK3; -.
DR BioMuta; COQ5; -.
DR DMDM; 90111987; -.
DR EPD; Q5HYK3; -.
DR jPOST; Q5HYK3; -.
DR MassIVE; Q5HYK3; -.
DR MaxQB; Q5HYK3; -.
DR PaxDb; Q5HYK3; -.
DR PeptideAtlas; Q5HYK3; -.
DR PRIDE; Q5HYK3; -.
DR Antibodypedia; 45543; 110 antibodies from 21 providers.
DR DNASU; 84274; -.
DR Ensembl; ENST00000288532.11; ENSP00000288532.6; ENSG00000110871.15.
DR GeneID; 84274; -.
DR KEGG; hsa:84274; -.
DR MANE-Select; ENST00000288532.11; ENSP00000288532.6; NM_032314.4; NP_115690.3.
DR UCSC; uc001tyn.4; human.
DR CTD; 84274; -.
DR DisGeNET; 84274; -.
DR GeneCards; COQ5; -.
DR HGNC; HGNC:28722; COQ5.
DR HPA; ENSG00000110871; Low tissue specificity.
DR MalaCards; COQ5; -.
DR MIM; 616359; gene.
DR MIM; 619028; phenotype.
DR neXtProt; NX_Q5HYK3; -.
DR OpenTargets; ENSG00000110871; -.
DR PharmGKB; PA143485438; -.
DR VEuPathDB; HostDB:ENSG00000110871; -.
DR eggNOG; KOG1540; Eukaryota.
DR GeneTree; ENSGT00390000001654; -.
DR InParanoid; Q5HYK3; -.
DR OMA; VRNFENL; -.
DR OrthoDB; 1125002at2759; -.
DR PhylomeDB; Q5HYK3; -.
DR TreeFam; TF106217; -.
DR BioCyc; MetaCyc:ENSG00000110871-MON; -.
DR BRENDA; 2.1.1.201; 2681.
DR PathwayCommons; Q5HYK3; -.
DR Reactome; R-HSA-2142789; Ubiquinol biosynthesis.
DR SignaLink; Q5HYK3; -.
DR UniPathway; UPA00232; -.
DR BioGRID-ORCS; 84274; 164 hits in 1078 CRISPR screens.
DR ChiTaRS; COQ5; human.
DR GenomeRNAi; 84274; -.
DR Pharos; Q5HYK3; Tbio.
DR PRO; PR:Q5HYK3; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q5HYK3; protein.
DR Bgee; ENSG00000110871; Expressed in hindlimb stylopod muscle and 100 other tissues.
DR ExpressionAtlas; Q5HYK3; baseline and differential.
DR Genevisible; Q5HYK3; HS.
DR GO; GO:0031314; C:extrinsic component of mitochondrial inner membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0110142; C:ubiquinone biosynthesis complex; IPI:ComplexPortal.
DR GO; GO:0043430; F:2-decaprenyl-6-methoxy-1,4-benzoquinone methyltransferase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0043333; F:2-octaprenyl-6-methoxy-1,4-benzoquinone methylase activity; IDA:UniProtKB.
DR GO; GO:0008168; F:methyltransferase activity; IBA:GO_Central.
DR GO; GO:0032259; P:methylation; IDA:UniProtKB.
DR GO; GO:0006744; P:ubiquinone biosynthetic process; IGI:UniProtKB.
DR Gene3D; 3.40.50.150; -; 1.
DR HAMAP; MF_01813; MenG_UbiE_methyltr; 1.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR004033; UbiE/COQ5_MeTrFase.
DR InterPro; IPR023576; UbiE/COQ5_MeTrFase_CS.
DR Pfam; PF01209; Ubie_methyltran; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR TIGRFAMs; TIGR01934; MenG_MenH_UbiE; 1.
DR PROSITE; PS51608; SAM_MT_UBIE; 1.
DR PROSITE; PS01183; UBIE_1; 1.
DR PROSITE; PS01184; UBIE_2; 1.
PE 1: Evidence at protein level;
KW Membrane; Methyltransferase; Mitochondrion; Mitochondrion inner membrane;
KW Primary mitochondrial disease; Reference proteome; S-adenosyl-L-methionine;
KW Transferase; Transit peptide; Ubiquinone biosynthesis.
FT TRANSIT 1..42
FT /note="Mitochondrion"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03191"
FT CHAIN 43..327
FT /note="2-methoxy-6-polyprenyl-1,4-benzoquinol methylase,
FT mitochondrial"
FT /id="PRO_0000228628"
FT BINDING 117
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03191"
FT BINDING 171
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03191"
FT BINDING 199..200
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03191"
FT VARIANT 152
FT /note="A -> T (in dbSNP:rs3742049)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:25152161, ECO:0000269|Ref.3"
FT /id="VAR_025702"
FT CONFLICT 78
FT /note="K -> R (in Ref. 4; CAI46073)"
FT /evidence="ECO:0000305"
FT CONFLICT 171
FT /note="D -> G (in Ref. 2; BAG38046)"
FT /evidence="ECO:0000305"
FT CONFLICT 291
FT /note="F -> S (in Ref. 6; AAH04916)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 327 AA; 37140 MW; 7D601DF6E74FFCC4 CRC64;
MAAPGSCALW SYCGRGWSRA MRGCQLLGLR SSWPGDLLSA RLLSQEKRAA ETHFGFETVS
EEEKGGKVYQ VFESVAKKYD VMNDMMSLGI HRVWKDLLLW KMHPLPGTQL LDVAGGTGDI
AFRFLNYVQS QHQRKQKRQL RAQQNLSWEE IAKEYQNEED SLGGSRVVVC DINKEMLKVG
KQKALAQGYR AGLAWVLGDA EELPFDDDKF DIYTIAFGIR NVTHIDQALQ EAHRVLKPGG
RFLCLEFSQV NNPLISRLYD LYSFQVIPVL GEVIAGDWKS YQYLVESIRR FPSQEEFKDM
IEDAGFHKVT YESLTSGIVA IHSGFKL
