COQ4_HUMAN
ID COQ4_HUMAN Reviewed; 265 AA.
AC Q9Y3A0; A8WBK8; B2R958; Q5T4B8; Q96EW4;
DT 19-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 14-APR-2009, sequence version 3.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Ubiquinone biosynthesis protein COQ4 homolog, mitochondrial {ECO:0000255|HAMAP-Rule:MF_03111};
DE AltName: Full=Coenzyme Q biosynthesis protein 4 homolog {ECO:0000255|HAMAP-Rule:MF_03111};
DE Flags: Precursor;
GN Name=COQ4 {ECO:0000255|HAMAP-Rule:MF_03111}; ORFNames=CGI-92;
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] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND FUNCTION.
RX PubMed=18474229; DOI=10.1016/j.bbrc.2008.04.172;
RA Casarin A., Jimenez-Ortega J.C., Trevisson E., Pertegato V., Doimo M.,
RA Ferrero-Gomez M.L., Abbadi S., Artuch R., Quinzii C., Hirano M., Basso G.,
RA Ocana C.S., Navas P., Salviati L.;
RT "Functional characterization of human COQ4, a gene required for coenzyme
RT Q10 biosynthesis.";
RL Biochem. Biophys. Res. Commun. 372:35-39(2008).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ALA-50.
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ALA-50.
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ALA-50.
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] (ISOFORM 1), AND VARIANT ALA-50.
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-108, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [8]
RP INVOLVEMENT IN COQ10D7, AND VARIANTS COQ10D7 SER-52; SER-64; GLY-145;
RP THR-174 DEL AND CYS-240.
RX PubMed=25658047; DOI=10.1016/j.ajhg.2014.12.023;
RA Brea-Calvo G., Haack T.B., Karall D., Ohtake A., Invernizzi F.,
RA Carrozzo R., Kremer L., Dusi S., Fauth C., Scholl-Burgi S., Graf E.,
RA Ahting U., Resta N., Laforgia N., Verrigni D., Okazaki Y., Kohda M.,
RA Martinelli D., Freisinger P., Strom T.M., Meitinger T., Lamperti C.,
RA Lacson A., Navas P., Mayr J.A., Bertini E., Murayama K., Zeviani M.,
RA Prokisch H., Ghezzi D.;
RT "COQ4 mutations cause a broad spectrum of mitochondrial disorders
RT associated with CoQ10 deficiency.";
RL Am. J. Hum. Genet. 96:309-317(2015).
RN [9]
RP VARIANT COQ10D7 CYS-240.
RX PubMed=26741492; DOI=10.1371/journal.pgen.1005679;
RA Kohda M., Tokuzawa Y., Kishita Y., Nyuzuki H., Moriyama Y., Mizuno Y.,
RA Hirata T., Yatsuka Y., Yamashita-Sugahara Y., Nakachi Y., Kato H.,
RA Okuda A., Tamaru S., Borna N.N., Banshoya K., Aigaki T., Sato-Miyata Y.,
RA Ohnuma K., Suzuki T., Nagao A., Maehata H., Matsuda F., Higasa K.,
RA Nagasaki M., Yasuda J., Yamamoto M., Fushimi T., Shimura M.,
RA Kaiho-Ichimoto K., Harashima H., Yamazaki T., Mori M., Murayama K.,
RA Ohtake A., Okazaki Y.;
RT "A comprehensive genomic analysis reveals the genetic landscape of
RT mitochondrial respiratory chain complex deficiencies.";
RL PLoS Genet. 12:E1005679-E1005679(2016).
CC -!- FUNCTION: Component of the coenzyme Q biosynthetic pathway. May play a
CC role in organizing a multi-subunit COQ enzyme complex required for
CC coenzyme Q biosynthesis. Required for steady-state levels of other COQ
CC polypeptides. {ECO:0000255|HAMAP-Rule:MF_03111,
CC ECO:0000269|PubMed:18474229}.
CC -!- PATHWAY: Cofactor biosynthesis; ubiquinone biosynthesis.
CC {ECO:0000255|HAMAP-Rule:MF_03111}.
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_03111}.
CC -!- INTERACTION:
CC Q9Y3A0; Q9NZJ6: COQ3; NbExp=4; IntAct=EBI-12284865, EBI-10897372;
CC Q9Y3A0; Q5HYK3: COQ5; NbExp=6; IntAct=EBI-12284865, EBI-12577722;
CC Q9Y3A0; Q9Y2Z9: COQ6; NbExp=3; IntAct=EBI-12284865, EBI-718148;
CC Q9Y3A0; Q99807: COQ7; NbExp=5; IntAct=EBI-12284865, EBI-11017131;
CC Q9Y3A0; P43356: MAGEA2B; NbExp=3; IntAct=EBI-12284865, EBI-5650739;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Mitochondrion inner membrane;
CC Peripheral membrane protein; Matrix side.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y3A0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y3A0-2; Sequence=VSP_036866;
CC -!- TISSUE SPECIFICITY: Expressed ubiquitously, but at high levels in
CC liver, lung and pancreas. {ECO:0000269|PubMed:18474229}.
CC -!- DISEASE: Coenzyme Q10 deficiency, primary, 7 (COQ10D7) [MIM:616276]: An
CC autosomal recessive disorder resulting from mitochondrial dysfunction
CC and characterized by decreased levels of coenzyme Q10, and severe
CC cardiac or neurologic symptoms soon after birth, usually resulting in
CC death. Rarely, symptoms may have later onset.
CC {ECO:0000269|PubMed:25658047, ECO:0000269|PubMed:26741492}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the COQ4 family. {ECO:0000255|HAMAP-
CC Rule:MF_03111}.
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DR EMBL; EU216419; ABW91141.1; -; mRNA.
DR EMBL; EU216420; ABW91142.1; -; mRNA.
DR EMBL; EU216421; ABW91143.1; -; mRNA.
DR EMBL; EU216422; ABW91144.1; -; mRNA.
DR EMBL; EU216423; ABW91145.1; -; mRNA.
DR EMBL; AF151850; AAD34087.1; -; mRNA.
DR EMBL; AK313650; BAG36405.1; -; mRNA.
DR EMBL; AL359091; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471090; EAW87776.1; -; Genomic_DNA.
DR EMBL; BC011895; AAH11895.1; -; mRNA.
DR CCDS; CCDS6898.1; -. [Q9Y3A0-1]
DR RefSeq; NP_057119.2; NM_016035.4. [Q9Y3A0-1]
DR AlphaFoldDB; Q9Y3A0; -.
DR SMR; Q9Y3A0; -.
DR BioGRID; 119305; 41.
DR ComplexPortal; CPX-3642; CoQ biosynthetic complex.
DR IntAct; Q9Y3A0; 13.
DR STRING; 9606.ENSP00000300452; -.
DR iPTMnet; Q9Y3A0; -.
DR PhosphoSitePlus; Q9Y3A0; -.
DR BioMuta; COQ4; -.
DR DMDM; 226694194; -.
DR EPD; Q9Y3A0; -.
DR jPOST; Q9Y3A0; -.
DR MassIVE; Q9Y3A0; -.
DR MaxQB; Q9Y3A0; -.
DR PaxDb; Q9Y3A0; -.
DR PeptideAtlas; Q9Y3A0; -.
DR PRIDE; Q9Y3A0; -.
DR ProteomicsDB; 85990; -. [Q9Y3A0-1]
DR ProteomicsDB; 85991; -. [Q9Y3A0-2]
DR Antibodypedia; 31095; 52 antibodies from 14 providers.
DR DNASU; 51117; -.
DR Ensembl; ENST00000300452.8; ENSP00000300452.3; ENSG00000167113.11. [Q9Y3A0-1]
DR GeneID; 51117; -.
DR KEGG; hsa:51117; -.
DR MANE-Select; ENST00000300452.8; ENSP00000300452.3; NM_016035.5; NP_057119.3.
DR UCSC; uc004bur.5; human. [Q9Y3A0-1]
DR CTD; 51117; -.
DR DisGeNET; 51117; -.
DR GeneCards; COQ4; -.
DR GeneReviews; COQ4; -.
DR HGNC; HGNC:19693; COQ4.
DR HPA; ENSG00000167113; Low tissue specificity.
DR MalaCards; COQ4; -.
DR MIM; 612898; gene.
DR MIM; 616276; phenotype.
DR neXtProt; NX_Q9Y3A0; -.
DR OpenTargets; ENSG00000167113; -.
DR Orphanet; 457185; Neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome.
DR PharmGKB; PA134957951; -.
DR VEuPathDB; HostDB:ENSG00000167113; -.
DR eggNOG; KOG3244; Eukaryota.
DR GeneTree; ENSGT00390000003828; -.
DR HOGENOM; CLU_061241_1_1_1; -.
DR InParanoid; Q9Y3A0; -.
DR OMA; KFFEFAN; -.
DR OrthoDB; 1264469at2759; -.
DR PhylomeDB; Q9Y3A0; -.
DR TreeFam; TF314625; -.
DR PathwayCommons; Q9Y3A0; -.
DR SignaLink; Q9Y3A0; -.
DR UniPathway; UPA00232; -.
DR BioGRID-ORCS; 51117; 441 hits in 1021 CRISPR screens.
DR ChiTaRS; COQ4; human.
DR GeneWiki; COQ4; -.
DR GenomeRNAi; 51117; -.
DR Pharos; Q9Y3A0; Tbio.
DR PRO; PR:Q9Y3A0; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q9Y3A0; protein.
DR Bgee; ENSG00000167113; Expressed in right uterine tube and 163 other tissues.
DR ExpressionAtlas; Q9Y3A0; baseline and differential.
DR Genevisible; Q9Y3A0; 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:0005739; C:mitochondrion; IDA:LIFEdb.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0110142; C:ubiquinone biosynthesis complex; IPI:ComplexPortal.
DR GO; GO:0006744; P:ubiquinone biosynthetic process; IC:ComplexPortal.
DR HAMAP; MF_03111; Coq4; 1.
DR InterPro; IPR007715; Coq4.
DR InterPro; IPR027540; Coq4_euk.
DR PANTHER; PTHR12922; PTHR12922; 1.
DR Pfam; PF05019; Coq4; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Phosphoprotein;
KW Primary mitochondrial disease; Reference proteome; Transit peptide;
KW Ubiquinone biosynthesis.
FT TRANSIT 1..30
FT /note="Mitochondrion"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03111"
FT CHAIN 31..265
FT /note="Ubiquinone biosynthesis protein COQ4 homolog,
FT mitochondrial"
FT /id="PRO_0000115240"
FT MOD_RES 108
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..24
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:18474229"
FT /id="VSP_036866"
FT VARIANT 20
FT /note="R -> Q (in dbSNP:rs9697215)"
FT /id="VAR_048829"
FT VARIANT 50
FT /note="G -> A (in dbSNP:rs3003601)"
FT /evidence="ECO:0000269|PubMed:10810093,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|Ref.5"
FT /id="VAR_054861"
FT VARIANT 52
FT /note="L -> S (in COQ10D7; dbSNP:rs786204770)"
FT /evidence="ECO:0000269|PubMed:25658047"
FT /id="VAR_073356"
FT VARIANT 64
FT /note="P -> S (in COQ10D7; dbSNP:rs766317663)"
FT /evidence="ECO:0000269|PubMed:25658047"
FT /id="VAR_073357"
FT VARIANT 145
FT /note="R -> G (in COQ10D7; dbSNP:rs774395996)"
FT /evidence="ECO:0000269|PubMed:25658047"
FT /id="VAR_073358"
FT VARIANT 174
FT /note="Missing (in COQ10D7)"
FT /evidence="ECO:0000269|PubMed:25658047"
FT /id="VAR_073359"
FT VARIANT 240
FT /note="R -> C (in COQ10D7; dbSNP:rs143441644)"
FT /evidence="ECO:0000269|PubMed:25658047,
FT ECO:0000269|PubMed:26741492"
FT /id="VAR_073360"
FT CONFLICT 230
FT /note="P -> H (in Ref. 2; AAD34087)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 265 AA; 29657 MW; BFD161918B2924E2 CRC64;
MATLLRPVLR RLCGLPGLQR PAAEMPLRAR SDGAGPLYSH HLPTSPLQKG LLAAGSAAMA
LYNPYRHDMV AVLGETTGHR TLKVLRDQMR RDPEGAQILQ ERPRISTSTL DLGKLQSLPE
GSLGREYLRF LDVNRVSPDT RAPTRFVDDE ELAYVIQRYR EVHDMLHTLL GMPTNILGEI
VVKWFEAVQT GLPMCILGAF FGPIRLGAQS LQVLVSELIP WAVQNGRRAP CVLNLYYERR
WEQSLRALRE ELGITAPPMH VQGLA
