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 27-MAR-2024, entry version 162. 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, GN 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 SUBCELLULAR LOCATION, AND INTERACTION WITH PYURF. RX PubMed=35614220; DOI=10.1038/s41586-022-04765-3; RA Rensvold J.W., Shishkova E., Sverchkov Y., Miller I.J., Cetinkaya A., RA Pyle A., Manicki M., Brademan D.R., Alanay Y., Raiman J., Jochem A., RA Hutchins P.D., Peters S.R., Linke V., Overmyer K.A., Salome A.Z., RA Hebert A.S., Vincent C.E., Kwiecien N.W., Rush M.J.P., Westphall M.S., RA Craven M., Akarsu N.A., Taylor R.W., Coon J.J., Pagliarini D.J.; RT "Defining mitochondrial protein functions through deep multiomic RT profiling."; RL Nature 606:382-388(2022). RN [11] 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. Interacts with PYURF; CC the interaction is direct, stabilizes COQ5 protein and associates PYURF CC with COQ enzyme complex (PubMed:35614220). {ECO:0000255|HAMAP- CC Rule:MF_03191, ECO:0000269|PubMed:25152161, CC ECO:0000269|PubMed:35614220}. 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, CC ECO:0000269|PubMed:35614220}; Peripheral membrane protein CC {ECO:0000255|HAMAP-Rule:MF_03191, ECO:0000269|PubMed:25152161}; Matrix CC side {ECO:0000255|HAMAP-Rule:MF_03191, 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 107. DR ComplexPortal; CPX-3642; CoQ biosynthetic complex. DR IntAct; Q5HYK3; 28. 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; 9606-ENSP00000288532; -. DR PeptideAtlas; Q5HYK3; -. DR Pumba; Q5HYK3; -. DR Antibodypedia; 45543; 126 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 AGR; HGNC:28722; -. DR CTD; 84274; -. DR DisGeNET; 84274; -. DR GeneCards; COQ5; -. DR GeneReviews; 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; MNDVMSM; -. DR OrthoDB; 5487921at2759; -. DR PhylomeDB; Q5HYK3; -. DR TreeFam; TF106217; -. DR BioCyc; MetaCyc:ENSG00000110871-MONOMER; -. 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; 180 hits in 1157 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 102 other cell types or tissues. DR ExpressionAtlas; Q5HYK3; baseline and differential. 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 CDD; cd02440; AdoMet_MTases; 1. DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 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 NCBIfam; TIGR01934; MenG_MenH_UbiE; 1. DR PANTHER; PTHR43591:SF24; 2-METHOXY-6-POLYPRENYL-1,4-BENZOQUINOL METHYLASE, MITOCHONDRIAL; 1. DR PANTHER; PTHR43591; METHYLTRANSFERASE; 1. DR Pfam; PF01209; Ubie_methyltran; 1. DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1. DR PROSITE; PS51608; SAM_MT_UBIE; 1. DR PROSITE; PS01183; UBIE_1; 1. DR PROSITE; PS01184; UBIE_2; 1. DR Genevisible; Q5HYK3; HS. 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 //