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   27-MAR-2024, entry version 161.
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; 42.
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; 9606-ENSP00000300452; -.
DR   PeptideAtlas; Q9Y3A0; -.
DR   ProteomicsDB; 85990; -. [Q9Y3A0-1]
DR   ProteomicsDB; 85991; -. [Q9Y3A0-2]
DR   Pumba; Q9Y3A0; -.
DR   Antibodypedia; 31095; 53 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   AGR; HGNC:19693; -.
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; TVYWEER; -.
DR   OrthoDB; 535611at2759; -.
DR   PhylomeDB; Q9Y3A0; -.
DR   TreeFam; TF314625; -.
DR   PathwayCommons; Q9Y3A0; -.
DR   SignaLink; Q9Y3A0; -.
DR   UniPathway; UPA00232; -.
DR   BioGRID-ORCS; 51117; 463 hits in 1069 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 165 other cell types or tissues.
DR   ExpressionAtlas; Q9Y3A0; 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: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; NAS:ComplexPortal.
DR   HAMAP; MF_03111; Coq4; 1.
DR   InterPro; IPR007715; Coq4.
DR   InterPro; IPR027540; Coq4_euk.
DR   PANTHER; PTHR12922; UBIQUINONE BIOSYNTHESIS PROTEIN; 1.
DR   PANTHER; PTHR12922:SF7; UBIQUINONE BIOSYNTHESIS PROTEIN COQ4 HOMOLOG, MITOCHONDRIAL; 1.
DR   Pfam; PF05019; Coq4; 1.
DR   Genevisible; Q9Y3A0; HS.
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
//