COQ8A_HUMAN
ID COQ8A_HUMAN Reviewed; 647 AA.
AC Q8NI60; Q5T7A5; Q63HK0; Q8NCJ6; Q9HBQ1; Q9NQ67;
DT 27-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Atypical kinase COQ8A, mitochondrial {ECO:0000305};
DE EC=2.7.-.- {ECO:0000269|PubMed:25498144};
DE AltName: Full=Chaperone activity of bc1 complex-like {ECO:0000303|PubMed:11888884};
DE Short=Chaperone-ABC1-like {ECO:0000303|PubMed:11888884};
DE AltName: Full=Coenzyme Q protein 8A {ECO:0000305};
DE AltName: Full=aarF domain-containing protein kinase 3 {ECO:0000312|HGNC:HGNC:16812};
DE Flags: Precursor;
GN Name=COQ8A {ECO:0000303|PubMed:27499294, ECO:0000312|HGNC:HGNC:16812};
GN Synonyms=ADCK3 {ECO:0000312|HGNC:HGNC:16812},
GN CABC1 {ECO:0000303|PubMed:11888884}; ORFNames=PP265;
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
RP INDUCTION.
RX PubMed=11888884;
RA Iiizumi M., Arakawa H., Mori T., Ando A., Nakamura Y.;
RT "Isolation of a novel gene, CABC1, encoding a mitochondrial protein that is
RT highly homologous to yeast activity of bc1 complex.";
RL Cancer Res. 62:1246-1250(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Skeletal muscle;
RA Ievolella C., Stanchi F., Bertocco E., Millino C., Faulkner G., Valle G.,
RA Lanfranchi G.;
RT "Full length sequencing of some human and murine muscular transcript
RT (Telethon Italy project B41).";
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X.,
RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X.,
RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Mammary gland;
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 MRNA] (ISOFORM 3).
RC TISSUE=Small intestine;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Uterus;
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 [8]
RP PROTEIN SEQUENCE OF N-TERMINUS, X-RAY CRYSTALLOGRAPHY (1.64 ANGSTROMS) OF
RP 256-647, FUNCTION, SUBCELLULAR LOCATION, PATHWAY, DOMAIN, ACTIVITY
RP REGULATION, MUTAGENESIS OF LYS-276; GLN-279; ALA-339; LYS-358; GLU-405;
RP GLU-411; ASP-488; ASN-493; ASP-507 AND ARG-611, AND CHARACTERIZATION OF
RP VARIANTS COQ10D4 TRP-299; CYS-429; SER-549 AND LYS-551.
RX PubMed=25498144; DOI=10.1016/j.molcel.2014.11.002;
RA Stefely J.A., Reidenbach A.G., Ulbrich A., Oruganty K., Floyd B.J.,
RA Jochem A., Saunders J.M., Johnson I.E., Minogue C.E., Wrobel R.L.,
RA Barber G.E., Lee D., Li S., Kannan N., Coon J.J., Bingman C.A.,
RA Pagliarini D.J.;
RT "Mitochondrial ADCK3 employs an atypical protein kinase-like fold to enable
RT coenzyme Q biosynthesis.";
RL Mol. Cell 57:83-94(2015).
RN [9]
RP INVOLVEMENT IN COQ10D4.
RX PubMed=20580948; DOI=10.1016/j.mito.2010.05.008;
RA Gerards M., van den Bosch B., Calis C., Schoonderwoerd K., van Engelen K.,
RA Tijssen M., de Coo R., van der Kooi A., Smeets H.;
RT "Nonsense mutations in CABC1/ADCK3 cause progressive cerebellar ataxia and
RT atrophy.";
RL Mitochondrion 10:510-515(2010).
RN [10]
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 [11]
RP FUNCTION.
RX PubMed=21296186; DOI=10.1016/j.bbalip.2011.01.009;
RA Xie L.X., Hsieh E.J., Watanabe S., Allan C.M., Chen J.Y., Tran U.C.,
RA Clarke C.F.;
RT "Expression of the human atypical kinase ADCK3 rescues coenzyme Q
RT biosynthesis and phosphorylation of Coq polypeptides in yeast coq8
RT mutants.";
RL Biochim. Biophys. Acta 1811:348-360(2011).
RN [12]
RP TISSUE SPECIFICITY.
RX PubMed=24270420; DOI=10.1172/jci69000;
RA Ashraf S., Gee H.Y., Woerner S., Xie L.X., Vega-Warner V., Lovric S.,
RA Fang H., Song X., Cattran D.C., Avila-Casado C., Paterson A.D.,
RA Nitschke P., Bole-Feysot C., Cochat P., Esteve-Rudd J., Haberberger B.,
RA Allen S.J., Zhou W., Airik R., Otto E.A., Barua M., Al-Hamed M.H.,
RA Kari J.A., Evans J., Bierzynska A., Saleem M.A., Bockenhauer D., Kleta R.,
RA El Desoky S., Hacihamdioglu D.O., Gok F., Washburn J., Wiggins R.C.,
RA Choi M., Lifton R.P., Levy S., Han Z., Salviati L., Prokisch H.,
RA Williams D.S., Pollak M., Clarke C.F., Pei Y., Antignac C., Hildebrandt F.;
RT "ADCK4 mutations promote steroid-resistant nephrotic syndrome through CoQ10
RT biosynthesis disruption.";
RL J. Clin. Invest. 123:5179-5189(2013).
RN [13]
RP SUBUNIT, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LEU-214; ALA-215;
RP ASN-216; PHE-217; GLY-218; GLY-219; LEU-220; ALA-221; VAL-222; GLY-223;
RP LEU-224; GLY-225; PHE-226; GLY-227; ALA-228; LEU-229 AND ALA-230.
RX PubMed=25216398; DOI=10.1021/ja505017f;
RA Khadria A.S., Mueller B.K., Stefely J.A., Tan C.H., Pagliarini D.J.,
RA Senes A.;
RT "A Gly-zipper motif mediates homodimerization of the transmembrane domain
RT of the mitochondrial kinase ADCK3.";
RL J. Am. Chem. Soc. 136:14068-14077(2014).
RN [14]
RP INVOLVEMENT IN COQ10D4.
RX PubMed=24218524; DOI=10.1136/jnnp-2013-306483;
RA Liu Y.T., Hersheson J., Plagnol V., Fawcett K., Duberley K.E., Preza E.,
RA Hargreaves I.P., Chalasani A., Laura M., Wood N.W., Reilly M.M.,
RA Houlden H.;
RT "Autosomal-recessive cerebellar ataxia caused by a novel ADCK3 mutation
RT that elongates the protein: clinical, genetic and biochemical
RT characterisation.";
RL J. Neurol. Neurosurg. Psych. 85:493-498(2014).
RN [15]
RP FUNCTION.
RX PubMed=25540914; DOI=10.1016/j.pep.2014.12.008;
RA Wheeler B., Jia Z.;
RT "Preparation and characterization of human ADCK3, a putative atypical
RT kinase.";
RL Protein Expr. Purif. 108:13-17(2015).
RN [16]
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 [17]
RP FUNCTION, INTERACTION WITH THE COQ ENZYME COMPLEX, DOMAIN, X-RAY
RP CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 256-647 IN COMPLEX WITH ANP NUCLEOTIDE,
RP ACTIVITY REGULATION, AND MUTAGENESIS OF LYS-276 AND ASP-507.
RX PubMed=27499294; DOI=10.1016/j.molcel.2016.06.030;
RA Stefely J.A., Licitra F., Laredj L., Reidenbach A.G., Kemmerer Z.A.,
RA Grangeray A., Jaeg-Ehret T., Minogue C.E., Ulbrich A., Hutchins P.D.,
RA Wilkerson E.M., Ruan Z., Aydin D., Hebert A.S., Guo X., Freiberger E.C.,
RA Reutenauer L., Jochem A., Chergova M., Johnson I.E., Lohman D.C.,
RA Rush M.J., Kwiecien N.W., Singh P.K., Schlagowski A.I., Floyd B.J.,
RA Forsman U., Sindelar P.J., Westphall M.S., Pierrel F., Zoll J.,
RA Dal Peraro M., Kannan N., Bingman C.A., Coon J.J., Isope P., Puccio H.,
RA Pagliarini D.J.;
RT "Cerebellar ataxia and coenzyme Q deficiency through loss of unorthodox
RT kinase activity.";
RL Mol. Cell 63:608-620(2016).
RN [18]
RP INTERACTION WITH THE COQ ENZYME COMPLEX.
RX PubMed=27499296; DOI=10.1016/j.molcel.2016.06.033;
RA Floyd B.J., Wilkerson E.M., Veling M.T., Minogue C.E., Xia C., Beebe E.T.,
RA Wrobel R.L., Cho H., Kremer L.S., Alston C.L., Gromek K.A., Dolan B.K.,
RA Ulbrich A., Stefely J.A., Bohl S.L., Werner K.M., Jochem A.,
RA Westphall M.S., Rensvold J.W., Taylor R.W., Prokisch H., Kim J.J.,
RA Coon J.J., Pagliarini D.J.;
RT "Mitochondrial protein interaction mapping identifies regulators of
RT respiratory chain function.";
RL Mol. Cell 63:621-632(2016).
RN [19]
RP VARIANT [LARGE SCALE ANALYSIS] THR-341.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [20]
RP VARIANTS COQ10D4 TRP-213; VAL-272; ASP-272 AND LYS-551.
RX PubMed=18319072; DOI=10.1016/j.ajhg.2007.12.022;
RA Mollet J., Delahodde A., Serre V., Chretien D., Schlemmer D., Lombes A.,
RA Boddaert N., Desguerre I., de Lonlay P., de Baulny H.O., Munnich A.,
RA Roetig A.;
RT "CABC1 gene mutations cause ubiquinone deficiency with cerebellar ataxia
RT and seizures.";
RL Am. J. Hum. Genet. 82:623-630(2008).
RN [21]
RP VARIANTS COQ10D4 CYS-514; SER-549 AND THR-584 DEL.
RX PubMed=18319074; DOI=10.1016/j.ajhg.2007.12.024;
RA Lagier-Tourenne C., Tazir M., Lopez L.C., Quinzii C.M., Assoum M.,
RA Drouot N., Busso C., Makri S., Ali-Pacha L., Benhassine T., Anheim M.,
RA Lynch D.R., Thibault C., Plewniak F., Bianchetti L., Tranchant C., Poch O.,
RA DiMauro S., Mandel J.-L., Barros M.H., Hirano M., Koenig M.;
RT "ADCK3, an ancestral kinase, is mutated in a form of recessive ataxia
RT associated with coenzyme Q10 deficiency.";
RL Am. J. Hum. Genet. 82:661-672(2008).
RN [22]
RP VARIANTS COQ10D4 TRP-213; CYS-271; ASP-272; VAL-272; TRP-299; THR-304;
RP VAL-304; CYS-429; SER-549 AND LYS-551.
RX PubMed=22036850; DOI=10.1136/jnnp-2011-301258;
RA Horvath R., Czermin B., Gulati S., Demuth S., Houge G., Pyle A.,
RA Dineiger C., Blakely E.L., Hassani A., Foley C., Brodhun M., Storm K.,
RA Kirschner J., Gorman G.S., Lochmuller H., Holinski-Feder E., Taylor R.W.,
RA Chinnery P.F.;
RT "Adult-onset cerebellar ataxia due to mutations in CABC1/ADCK3.";
RL J. Neurol. Neurosurg. Psych. 83:174-178(2012).
RN [23]
RP VARIANT COQ10D4 ARG-602.
RX PubMed=24048965; DOI=10.1007/8904_2013_251;
RA Blumkin L., Leshinsky-Silver E., Zerem A., Yosovich K., Lerman-Sagie T.,
RA Lev D.;
RT "Heterozygous mutations in the ADCK3 gene in siblings with cerebellar
RT atrophy and extreme phenotypic variability.";
RL JIMD Rep. 12:103-107(2014).
RN [24]
RP INVOLVEMENT IN COQ10D4.
RX PubMed=26818466; DOI=10.1111/cge.12742;
RA Barca E., Musumeci O., Montagnese F., Marino S., Granata F., Nunnari D.,
RA Peverelli L., DiMauro S., Quinzii C.M., Toscano A.;
RT "Cerebellar ataxia and severe muscle CoQ10 deficiency in a patient with a
RT novel mutation in ADCK3.";
RL Clin. Genet. 90:156-160(2016).
RN [25]
RP VARIANTS COQ10D4 TRP-299 AND VAL-578.
RX PubMed=27106809; DOI=10.1111/ene.13003;
RA Hikmat O., Tzoulis C., Knappskog P.M., Johansson S., Boman H.,
RA Sztromwasser P., Lien E., Brodtkorb E., Ghezzi D., Bindoff L.A.;
RT "ADCK3 mutations with epilepsy, stroke-like episodes and ataxia: a POLG
RT mimic?";
RL Eur. J. Neurol. 23:1188-1194(2016).
CC -!- FUNCTION: Atypical kinase involved in the biosynthesis of coenzyme Q,
CC also named ubiquinone, an essential lipid-soluble electron transporter
CC for aerobic cellular respiration (PubMed:25498144, PubMed:21296186,
CC PubMed:25540914, PubMed:27499294). Its substrate specificity is
CC unclear: does not show any protein kinase activity (PubMed:25498144,
CC PubMed:27499294). Probably acts as a small molecule kinase, possibly a
CC lipid kinase that phosphorylates a prenyl lipid in the ubiquinone
CC biosynthesis pathway, as suggested by its ability to bind coenzyme Q
CC lipid intermediates (PubMed:25498144, PubMed:27499294). Shows an
CC unusual selectivity for binding ADP over ATP (PubMed:25498144).
CC {ECO:0000269|PubMed:25498144, ECO:0000269|PubMed:27499294,
CC ECO:0000305|PubMed:21296186, ECO:0000305|PubMed:25540914}.
CC -!- ACTIVITY REGULATION: Autoinhibited by the N-terminal domain, containing
CC the KxGQ motif, that completely occludes the typical substrate binding
CC pocket. Nucleotide-binding relieves inhibition (PubMed:27499294).
CC {ECO:0000269|PubMed:25498144, ECO:0000269|PubMed:27499294}.
CC -!- PATHWAY: Cofactor biosynthesis; ubiquinone biosynthesis.
CC {ECO:0000269|PubMed:25498144}.
CC -!- SUBUNIT: Homodimer; homodimerizes via its transmembrane region
CC (PubMed:25216398). Interacts with the multi-subunit COQ enzyme complex,
CC composed of at least COQ3, COQ4, COQ5, COQ6, COQ7 and COQ9
CC (PubMed:27499294, PubMed:27499296). {ECO:0000269|PubMed:25216398,
CC ECO:0000269|PubMed:27499294, ECO:0000269|PubMed:27499296}.
CC -!- INTERACTION:
CC Q8NI60; Q8WTS1: ABHD5; NbExp=3; IntAct=EBI-745535, EBI-2813554;
CC Q8NI60; Q6RW13: AGTRAP; NbExp=4; IntAct=EBI-745535, EBI-741181;
CC Q8NI60; Q6RW13-2: AGTRAP; NbExp=6; IntAct=EBI-745535, EBI-11522760;
CC Q8NI60; Q5T2L2: AKR1C8P; NbExp=3; IntAct=EBI-745535, EBI-22006248;
CC Q8NI60; Q9NU02: ANKEF1; NbExp=3; IntAct=EBI-745535, EBI-8464238;
CC Q8NI60; Q9H0Y0: ATG10; NbExp=3; IntAct=EBI-745535, EBI-1048913;
CC Q8NI60; Q3SXR2: C3orf36; NbExp=3; IntAct=EBI-745535, EBI-18036948;
CC Q8NI60; Q96HJ3-2: CCDC34; NbExp=3; IntAct=EBI-745535, EBI-17641690;
CC Q8NI60; P09496-2: CLTA; NbExp=3; IntAct=EBI-745535, EBI-4401010;
CC Q8NI60; Q8IZR5-2: CMTM4; NbExp=3; IntAct=EBI-745535, EBI-17278014;
CC Q8NI60; Q96DZ9-2: CMTM5; NbExp=6; IntAct=EBI-745535, EBI-11522780;
CC Q8NI60; Q9NX76: CMTM6; NbExp=3; IntAct=EBI-745535, EBI-1054315;
CC Q8NI60; P02458-1: COL2A1; NbExp=3; IntAct=EBI-745535, EBI-12375799;
CC Q8NI60; O75208: COQ9; NbExp=11; IntAct=EBI-745535, EBI-724524;
CC Q8NI60; Q9BSY9: DESI2; NbExp=3; IntAct=EBI-745535, EBI-12878374;
CC Q8NI60; Q9BPU6: DPYSL5; NbExp=3; IntAct=EBI-745535, EBI-724653;
CC Q8NI60; Q86UW9: DTX2; NbExp=3; IntAct=EBI-745535, EBI-740376;
CC Q8NI60; Q96KS9: FAM167A; NbExp=3; IntAct=EBI-745535, EBI-10290462;
CC Q8NI60; Q6ZNL6: FGD5; NbExp=3; IntAct=EBI-745535, EBI-7962481;
CC Q8NI60; Q8TAC2: JOSD2; NbExp=3; IntAct=EBI-745535, EBI-12205593;
CC Q8NI60; P13473-2: LAMP2; NbExp=3; IntAct=EBI-745535, EBI-21591415;
CC Q8NI60; Q96B96: LDAF1; NbExp=8; IntAct=EBI-745535, EBI-7055862;
CC Q8NI60; Q9H2C1: LHX5; NbExp=3; IntAct=EBI-745535, EBI-25835523;
CC Q8NI60; Q99732: LITAF; NbExp=3; IntAct=EBI-745535, EBI-725647;
CC Q8NI60; P0DP58-2: LYNX1; NbExp=3; IntAct=EBI-745535, EBI-21916939;
CC Q8NI60; Q96M61: MAGEB18; NbExp=3; IntAct=EBI-745535, EBI-741835;
CC Q8NI60; Q969L2: MAL2; NbExp=5; IntAct=EBI-745535, EBI-944295;
CC Q8NI60; P27338: MAOB; NbExp=3; IntAct=EBI-745535, EBI-3911344;
CC Q8NI60; Q6IN84: MRM1; NbExp=3; IntAct=EBI-745535, EBI-5454865;
CC Q8NI60; Q9H2K0: MTIF3; NbExp=3; IntAct=EBI-745535, EBI-3923617;
CC Q8NI60; Q69YL0: NCBP2AS2; NbExp=3; IntAct=EBI-745535, EBI-10986258;
CC Q8NI60; Q6N063-2: OGFOD2; NbExp=3; IntAct=EBI-745535, EBI-22006224;
CC Q8NI60; Q8N138: ORMDL3; NbExp=3; IntAct=EBI-745535, EBI-721750;
CC Q8NI60; Q96AL5: PBX3; NbExp=3; IntAct=EBI-745535, EBI-741171;
CC Q8NI60; Q58EX7-2: PLEKHG4; NbExp=3; IntAct=EBI-745535, EBI-21503705;
CC Q8NI60; Q9UI14: RABAC1; NbExp=12; IntAct=EBI-745535, EBI-712367;
CC Q8NI60; Q96HR9: REEP6; NbExp=9; IntAct=EBI-745535, EBI-750345;
CC Q8NI60; Q96HR9-2: REEP6; NbExp=3; IntAct=EBI-745535, EBI-14065960;
CC Q8NI60; P47804-3: RGR; NbExp=3; IntAct=EBI-745535, EBI-25834767;
CC Q8NI60; Q8N5U6: RNF10; NbExp=3; IntAct=EBI-745535, EBI-714023;
CC Q8NI60; Q9NS64: RPRM; NbExp=3; IntAct=EBI-745535, EBI-1052363;
CC Q8NI60; Q9NTN9-3: SEMA4G; NbExp=3; IntAct=EBI-745535, EBI-9089805;
CC Q8NI60; Q9Y371: SH3GLB1; NbExp=11; IntAct=EBI-745535, EBI-2623095;
CC Q8NI60; O60902-3: SHOX2; NbExp=3; IntAct=EBI-745535, EBI-9092164;
CC Q8NI60; O60906: SMPD2; NbExp=3; IntAct=EBI-745535, EBI-12828299;
CC Q8NI60; Q9C004: SPRY4; NbExp=3; IntAct=EBI-745535, EBI-354861;
CC Q8NI60; O60499-2: STX10; NbExp=3; IntAct=EBI-745535, EBI-12094584;
CC Q8NI60; Q9UBB9: TFIP11; NbExp=13; IntAct=EBI-745535, EBI-1105213;
CC Q8NI60; Q7Z6W1: TMCO2; NbExp=3; IntAct=EBI-745535, EBI-12807858;
CC Q8NI60; Q8WW34: TMEM239; NbExp=5; IntAct=EBI-745535, EBI-9675724;
CC Q8NI60; Q8WW34-2: TMEM239; NbExp=3; IntAct=EBI-745535, EBI-11528917;
CC Q8NI60; O43399: TPD52L2; NbExp=3; IntAct=EBI-745535, EBI-782604;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:11888884,
CC ECO:0000269|PubMed:25498144}. Membrane {ECO:0000255}; Single-pass
CC membrane protein {ECO:0000255, ECO:0000305|PubMed:25216398}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q8NI60-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NI60-2; Sequence=VSP_022351;
CC Name=3;
CC IsoId=Q8NI60-3; Sequence=VSP_022353;
CC Name=4;
CC IsoId=Q8NI60-4; Sequence=VSP_022352;
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest levels in adrenal
CC gland, heart, pancreas, nasal mucosa, stomach, uterus and skeletal
CC muscle. {ECO:0000269|PubMed:24270420}.
CC -!- INDUCTION: By p53/TP53. {ECO:0000269|PubMed:11888884}.
CC -!- DOMAIN: Adopts an atypical protein kinase-like fold: while it adopts a
CC core fold similar to that of well-characterized protein kinase-like
CC domains, a number of features are positioned to inhibit the kinase
CC activity: (1) an atypical AAAS motif in an alanine-rich (A-rich) loop
CC that replaces the canonical glycine-rich (G-rich) nucleotide-binding
CC loop and limits ATP binding by establishing an unusual selectivity for
CC ADP and (2) an N-terminal domain, containing the KxGQ motif, that
CC completely occludes the typical substrate binding pocket
CC (PubMed:25498144). Nucleotide-binding opens the substrate binding
CC pocket and flips the active site from inside the hydrophobic core into
CC a catalytically competent, solvent-exposed posture (PubMed:27499294).
CC {ECO:0000269|PubMed:25498144, ECO:0000269|PubMed:27499294}.
CC -!- DISEASE: Coenzyme Q10 deficiency, primary, 4 (COQ10D4) [MIM:612016]: An
CC autosomal recessive disorder characterized by childhood-onset of
CC cerebellar ataxia and exercise intolerance. Patient manifest gait
CC ataxia and cerebellar atrophy with slow progression. Additional
CC features include brisk tendon reflexes and Hoffmann sign, variable
CC psychomotor retardation and variable seizures.
CC {ECO:0000269|PubMed:18319072, ECO:0000269|PubMed:18319074,
CC ECO:0000269|PubMed:20580948, ECO:0000269|PubMed:22036850,
CC ECO:0000269|PubMed:24048965, ECO:0000269|PubMed:24218524,
CC ECO:0000269|PubMed:25498144, ECO:0000269|PubMed:26818466,
CC ECO:0000269|PubMed:27106809}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. ADCK protein
CC kinase family. {ECO:0000305}.
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DR EMBL; AB073905; BAB91363.1; -; mRNA.
DR EMBL; AJ278126; CAC00482.1; -; mRNA.
DR EMBL; AF218003; AAG17245.1; -; mRNA.
DR EMBL; AK074693; BAC11143.1; -; mRNA.
DR EMBL; BX648860; CAH56132.1; -; mRNA.
DR EMBL; AL353689; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC005171; AAH05171.2; -; mRNA.
DR CCDS; CCDS1557.1; -. [Q8NI60-1]
DR RefSeq; NP_064632.2; NM_020247.4. [Q8NI60-1]
DR RefSeq; XP_005273258.1; XM_005273201.1. [Q8NI60-1]
DR RefSeq; XP_011542540.1; XM_011544238.1. [Q8NI60-1]
DR RefSeq; XP_011542541.1; XM_011544239.2. [Q8NI60-1]
DR RefSeq; XP_011542542.1; XM_011544240.2.
DR RefSeq; XP_011542543.1; XM_011544241.2. [Q8NI60-1]
DR RefSeq; XP_016857341.1; XM_017001852.1. [Q8NI60-1]
DR PDB; 4PED; X-ray; 1.64 A; A=256-647.
DR PDB; 5I35; X-ray; 2.30 A; A=256-647.
DR PDBsum; 4PED; -.
DR PDBsum; 5I35; -.
DR AlphaFoldDB; Q8NI60; -.
DR SMR; Q8NI60; -.
DR BioGRID; 121312; 110.
DR IntAct; Q8NI60; 206.
DR MINT; Q8NI60; -.
DR STRING; 9606.ENSP00000355741; -.
DR BindingDB; Q8NI60; -.
DR ChEMBL; CHEMBL5550; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q8NI60; -.
DR iPTMnet; Q8NI60; -.
DR PhosphoSitePlus; Q8NI60; -.
DR BioMuta; COQ8A; -.
DR DMDM; 27923741; -.
DR EPD; Q8NI60; -.
DR jPOST; Q8NI60; -.
DR MassIVE; Q8NI60; -.
DR MaxQB; Q8NI60; -.
DR PaxDb; Q8NI60; -.
DR PeptideAtlas; Q8NI60; -.
DR PRIDE; Q8NI60; -.
DR ProteomicsDB; 73833; -. [Q8NI60-1]
DR ProteomicsDB; 73834; -. [Q8NI60-2]
DR ProteomicsDB; 73835; -. [Q8NI60-3]
DR ProteomicsDB; 73836; -. [Q8NI60-4]
DR Antibodypedia; 20768; 334 antibodies from 30 providers.
DR DNASU; 56997; -.
DR Ensembl; ENST00000366777.4; ENSP00000355739.3; ENSG00000163050.18. [Q8NI60-1]
DR Ensembl; ENST00000366778.5; ENSP00000355740.1; ENSG00000163050.18. [Q8NI60-3]
DR GeneID; 56997; -.
DR KEGG; hsa:56997; -.
DR MANE-Select; ENST00000366777.4; ENSP00000355739.3; NM_020247.5; NP_064632.2.
DR UCSC; uc001hqm.2; human. [Q8NI60-1]
DR CTD; 56997; -.
DR DisGeNET; 56997; -.
DR GeneCards; COQ8A; -.
DR GeneReviews; COQ8A; -.
DR HGNC; HGNC:16812; COQ8A.
DR HPA; ENSG00000163050; Group enriched (skeletal muscle, tongue).
DR MalaCards; COQ8A; -.
DR MIM; 606980; gene.
DR MIM; 612016; phenotype.
DR neXtProt; NX_Q8NI60; -.
DR OpenTargets; ENSG00000163050; -.
DR Orphanet; 139485; Autosomal recessive ataxia due to ubiquinone deficiency.
DR PharmGKB; PA25999; -.
DR VEuPathDB; HostDB:ENSG00000163050; -.
DR VEuPathDB; HostDB:ENSG00000288674; -.
DR eggNOG; KOG1234; Eukaryota.
DR GeneTree; ENSGT00940000156810; -.
DR HOGENOM; CLU_006533_9_1_1; -.
DR InParanoid; Q8NI60; -.
DR OMA; QVERVMN; -.
DR PhylomeDB; Q8NI60; -.
DR TreeFam; TF300630; -.
DR PathwayCommons; Q8NI60; -.
DR SignaLink; Q8NI60; -.
DR UniPathway; UPA00232; -.
DR BioGRID-ORCS; 56997; 8 hits in 1110 CRISPR screens.
DR ChiTaRS; COQ8A; human.
DR GeneWiki; CABC1; -.
DR GenomeRNAi; 56997; -.
DR Pharos; Q8NI60; Tbio.
DR PRO; PR:Q8NI60; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q8NI60; protein.
DR Bgee; ENSG00000163050; Expressed in gastrocnemius and 100 other tissues.
DR Genevisible; Q8NI60; HS.
DR GO; GO:0031314; C:extrinsic component of mitochondrial inner membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0043531; F:ADP binding; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016301; F:kinase activity; IDA:UniProtKB.
DR GO; GO:0016310; P:phosphorylation; IDA:UniProtKB.
DR GO; GO:0006744; P:ubiquinone biosynthetic process; IMP:UniProtKB.
DR CDD; cd13970; ABC1_ADCK3; 1.
DR InterPro; IPR004147; ABC1_dom.
DR InterPro; IPR034646; ADCK3_dom.
DR InterPro; IPR034640; COQ8A.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR PANTHER; PTHR43851:SF1; PTHR43851:SF1; 1.
DR Pfam; PF03109; ABC1; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Direct protein sequencing;
KW Disease variant; Kinase; Membrane; Mitochondrion; Neurodegeneration;
KW Nucleotide-binding; Primary mitochondrial disease; Reference proteome;
KW Transferase; Transit peptide; Transmembrane; Transmembrane helix;
KW Ubiquinone biosynthesis.
FT TRANSIT 1..162
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:25498144"
FT CHAIN 163..647
FT /note="Atypical kinase COQ8A, mitochondrial"
FT /id="PRO_0000000262"
FT TRANSMEM 214..230
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25216398"
FT DOMAIN 329..518
FT /note="Protein kinase"
FT REGION 90..117
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 182..203
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 276..279
FT /note="KxGQ motif"
FT /evidence="ECO:0000269|PubMed:25498144"
FT MOTIF 337..340
FT /note="AAAS motif"
FT /evidence="ECO:0000269|PubMed:25498144"
FT ACT_SITE 488
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:27499294"
FT BINDING 340
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:27499294,
FT ECO:0000305|PubMed:25498144, ECO:0000312|PDB:5I35"
FT BINDING 358
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:27499294,
FT ECO:0000312|PDB:5I35"
FT BINDING 445..448
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:27499294,
FT ECO:0000312|PDB:5I35"
FT BINDING 493
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:27499294,
FT ECO:0000312|PDB:5I35"
FT BINDING 507
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:27499294,
FT ECO:0000312|PDB:5I35"
FT VAR_SEQ 1..484
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15498874"
FT /id="VSP_022351"
FT VAR_SEQ 1..279
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_022352"
FT VAR_SEQ 1..52
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_022353"
FT VARIANT 85
FT /note="H -> Q (in dbSNP:rs2297411)"
FT /id="VAR_020319"
FT VARIANT 213
FT /note="R -> W (in COQ10D4; dbSNP:rs119468005)"
FT /evidence="ECO:0000269|PubMed:18319072,
FT ECO:0000269|PubMed:22036850"
FT /id="VAR_044402"
FT VARIANT 271
FT /note="R -> C (in COQ10D4; dbSNP:rs145034527)"
FT /evidence="ECO:0000269|PubMed:22036850"
FT /id="VAR_072622"
FT VARIANT 272
FT /note="G -> D (in COQ10D4; dbSNP:rs119468006)"
FT /evidence="ECO:0000269|PubMed:18319072,
FT ECO:0000269|PubMed:22036850"
FT /id="VAR_044403"
FT VARIANT 272
FT /note="G -> V (in COQ10D4; dbSNP:rs119468006)"
FT /evidence="ECO:0000269|PubMed:18319072,
FT ECO:0000269|PubMed:22036850"
FT /id="VAR_044404"
FT VARIANT 299
FT /note="R -> W (in COQ10D4; decreased stability;
FT dbSNP:rs201908721)"
FT /evidence="ECO:0000269|PubMed:22036850,
FT ECO:0000269|PubMed:25498144, ECO:0000269|PubMed:27106809"
FT /id="VAR_072623"
FT VARIANT 304
FT /note="A -> T (in COQ10D4; dbSNP:rs778798354)"
FT /evidence="ECO:0000269|PubMed:22036850"
FT /id="VAR_072624"
FT VARIANT 304
FT /note="A -> V (in COQ10D4; dbSNP:rs748118737)"
FT /evidence="ECO:0000269|PubMed:22036850"
FT /id="VAR_072625"
FT VARIANT 341
FT /note="I -> T (in dbSNP:rs55798516)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_045576"
FT VARIANT 429
FT /note="Y -> C (in COQ10D4; decreased stability;
FT dbSNP:rs144147839)"
FT /evidence="ECO:0000269|PubMed:22036850,
FT ECO:0000269|PubMed:25498144"
FT /id="VAR_072626"
FT VARIANT 514
FT /note="Y -> C (in COQ10D4; dbSNP:rs119468008)"
FT /evidence="ECO:0000269|PubMed:18319074"
FT /id="VAR_044405"
FT VARIANT 549
FT /note="G -> S (in COQ10D4; decreased stability;
FT dbSNP:rs119468009)"
FT /evidence="ECO:0000269|PubMed:18319074,
FT ECO:0000269|PubMed:22036850, ECO:0000269|PubMed:25498144"
FT /id="VAR_044406"
FT VARIANT 551
FT /note="E -> K (in COQ10D4; decreased stability;
FT dbSNP:rs119468004)"
FT /evidence="ECO:0000269|PubMed:18319072,
FT ECO:0000269|PubMed:22036850, ECO:0000269|PubMed:25498144"
FT /id="VAR_044407"
FT VARIANT 578
FT /note="F -> V (in COQ10D4; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:27106809"
FT /id="VAR_076860"
FT VARIANT 584
FT /note="Missing (in COQ10D4; dbSNP:rs387906299)"
FT /evidence="ECO:0000269|PubMed:18319074"
FT /id="VAR_044408"
FT VARIANT 602
FT /note="P -> R (in COQ10D4; dbSNP:rs61995958)"
FT /evidence="ECO:0000269|PubMed:24048965"
FT /id="VAR_072627"
FT MUTAGEN 214
FT /note="L->A,I,L,F: Strongly impairs homodimerization."
FT /evidence="ECO:0000269|PubMed:25216398"
FT MUTAGEN 214
FT /note="L->I,F,G,V: Slightly impaired homodimerization."
FT /evidence="ECO:0000269|PubMed:25216398"
FT MUTAGEN 215
FT /note="A->I,L,G: Does not impair homodimerization."
FT /evidence="ECO:0000269|PubMed:25216398"
FT MUTAGEN 216
FT /note="N->A,L,F,M: Does not impair homodimerization."
FT /evidence="ECO:0000269|PubMed:25216398"
FT MUTAGEN 217
FT /note="F->A: Slightly impaired homodimerization."
FT /evidence="ECO:0000269|PubMed:25216398"
FT MUTAGEN 218
FT /note="G->I,L,F: Slightly impaired homodimerization."
FT /evidence="ECO:0000269|PubMed:25216398"
FT MUTAGEN 219
FT /note="G->A,F: Slightly impaired homodimerization."
FT /evidence="ECO:0000269|PubMed:25216398"
FT MUTAGEN 219
FT /note="G->I: Strongly impairs homodimerization."
FT /evidence="ECO:0000269|PubMed:25216398"
FT MUTAGEN 220
FT /note="L->G: Impaired homodimerization."
FT /evidence="ECO:0000269|PubMed:25216398"
FT MUTAGEN 221
FT /note="A->L: Slightly impaired homodimerization."
FT /evidence="ECO:0000269|PubMed:25216398"
FT MUTAGEN 222
FT /note="V->A: Slightly impaired homodimerization."
FT /evidence="ECO:0000269|PubMed:25216398"
FT MUTAGEN 223
FT /note="G->A,I,L,F: Strongly impairs homodimerization."
FT /evidence="ECO:0000269|PubMed:25216398"
FT MUTAGEN 224
FT /note="L->V: Impaired homodimerization."
FT /evidence="ECO:0000269|PubMed:25216398"
FT MUTAGEN 225
FT /note="G->L: Slightly impaired homodimerization."
FT /evidence="ECO:0000269|PubMed:25216398"
FT MUTAGEN 226
FT /note="F->A: Slightly impaired homodimerization."
FT /evidence="ECO:0000269|PubMed:25216398"
FT MUTAGEN 227
FT /note="G->V,F,L,I: Strongly impairs homodimerization."
FT /evidence="ECO:0000269|PubMed:25216398"
FT MUTAGEN 228
FT /note="A->I,L,F: Does not impair homodimerization."
FT /evidence="ECO:0000269|PubMed:25216398"
FT MUTAGEN 229
FT /note="L->A: Slightly impaired homodimerization."
FT /evidence="ECO:0000269|PubMed:25216398"
FT MUTAGEN 230
FT /note="A->I: Slightly impaired homodimerization."
FT /evidence="ECO:0000269|PubMed:25216398"
FT MUTAGEN 276
FT /note="K->R,H: Does not affect selectivity for binding ADP
FT or ATP. Impaired multi-subunit COQ enzyme complex."
FT /evidence="ECO:0000269|PubMed:25498144,
FT ECO:0000269|PubMed:27499294"
FT MUTAGEN 279
FT /note="Q->R,H: Does not affect selectivity for binding ADP
FT or ATP."
FT /evidence="ECO:0000269|PubMed:25498144"
FT MUTAGEN 339
FT /note="A->G: Enables autophosphorylation but inhibits
FT coenzyme Q biosynthesis in vivo."
FT /evidence="ECO:0000269|PubMed:25498144"
FT MUTAGEN 358
FT /note="K->R: Abolishes binding ADP or ATP."
FT /evidence="ECO:0000269|PubMed:25498144"
FT MUTAGEN 405
FT /note="E->A,Q: Slightly affects selectivity for binding ADP
FT or ATP."
FT /evidence="ECO:0000269|PubMed:25498144"
FT MUTAGEN 411
FT /note="E->Q: Impaired binding ADP or ATP."
FT /evidence="ECO:0000269|PubMed:25498144"
FT MUTAGEN 488
FT /note="D->N: Impaired binding ADP or ATP."
FT /evidence="ECO:0000269|PubMed:25498144"
FT MUTAGEN 493
FT /note="N->A: Impaired binding ADP or ATP."
FT /evidence="ECO:0000269|PubMed:25498144"
FT MUTAGEN 507
FT /note="D->N: Strongly impairs binding ADP or ATP. Impaired
FT multi-subunit COQ enzyme complex."
FT /evidence="ECO:0000269|PubMed:25498144,
FT ECO:0000269|PubMed:27499294"
FT MUTAGEN 611
FT /note="R->A,Q: Does not affect selectivity for binding ADP
FT or ATP."
FT /evidence="ECO:0000269|PubMed:25498144"
FT CONFLICT 283..284
FT /note="IQ -> VR (in Ref. 4; BAC11143)"
FT /evidence="ECO:0000305"
FT HELIX 260..269
FT /evidence="ECO:0007829|PDB:4PED"
FT HELIX 271..281
FT /evidence="ECO:0007829|PDB:4PED"
FT STRAND 284..289
FT /evidence="ECO:0007829|PDB:4PED"
FT HELIX 291..302
FT /evidence="ECO:0007829|PDB:4PED"
FT HELIX 303..306
FT /evidence="ECO:0007829|PDB:4PED"
FT HELIX 309..320
FT /evidence="ECO:0007829|PDB:4PED"
FT HELIX 325..327
FT /evidence="ECO:0007829|PDB:4PED"
FT STRAND 328..331
FT /evidence="ECO:0007829|PDB:4PED"
FT STRAND 336..339
FT /evidence="ECO:0007829|PDB:4PED"
FT STRAND 342..349
FT /evidence="ECO:0007829|PDB:4PED"
FT STRAND 354..360
FT /evidence="ECO:0007829|PDB:4PED"
FT TURN 362..364
FT /evidence="ECO:0007829|PDB:4PED"
FT HELIX 365..367
FT /evidence="ECO:0007829|PDB:4PED"
FT HELIX 368..382
FT /evidence="ECO:0007829|PDB:4PED"
FT STRAND 387..389
FT /evidence="ECO:0007829|PDB:5I35"
FT HELIX 391..393
FT /evidence="ECO:0007829|PDB:4PED"
FT HELIX 395..405
FT /evidence="ECO:0007829|PDB:4PED"
FT HELIX 408..421
FT /evidence="ECO:0007829|PDB:4PED"
FT TURN 422..424
FT /evidence="ECO:0007829|PDB:4PED"
FT STRAND 426..429
FT /evidence="ECO:0007829|PDB:4PED"
FT HELIX 435..437
FT /evidence="ECO:0007829|PDB:4PED"
FT STRAND 442..446
FT /evidence="ECO:0007829|PDB:4PED"
FT STRAND 450..452
FT /evidence="ECO:0007829|PDB:4PED"
FT HELIX 453..455
FT /evidence="ECO:0007829|PDB:4PED"
FT HELIX 461..480
FT /evidence="ECO:0007829|PDB:4PED"
FT STRAND 484..488
FT /evidence="ECO:0007829|PDB:4PED"
FT HELIX 491..493
FT /evidence="ECO:0007829|PDB:4PED"
FT STRAND 494..497
FT /evidence="ECO:0007829|PDB:4PED"
FT TURN 498..501
FT /evidence="ECO:0007829|PDB:4PED"
FT STRAND 502..505
FT /evidence="ECO:0007829|PDB:4PED"
FT HELIX 508..510
FT /evidence="ECO:0007829|PDB:5I35"
FT STRAND 511..513
FT /evidence="ECO:0007829|PDB:4PED"
FT HELIX 516..530
FT /evidence="ECO:0007829|PDB:4PED"
FT HELIX 534..543
FT /evidence="ECO:0007829|PDB:4PED"
FT HELIX 553..571
FT /evidence="ECO:0007829|PDB:4PED"
FT HELIX 581..588
FT /evidence="ECO:0007829|PDB:4PED"
FT HELIX 589..594
FT /evidence="ECO:0007829|PDB:4PED"
FT STRAND 596..600
FT /evidence="ECO:0007829|PDB:5I35"
FT HELIX 604..622
FT /evidence="ECO:0007829|PDB:4PED"
FT HELIX 630..643
FT /evidence="ECO:0007829|PDB:4PED"
SQ SEQUENCE 647 AA; 71950 MW; DEF8F022027BF6CC CRC64;
MAAILGDTIM VAKGLVKLTQ AAVETHLQHL GIGGELIMAA RALQSTAVEQ IGMFLGKVQG
QDKHEEYFAE NFGGPEGEFH FSVPHAAGAS TDFSSASAPD QSAPPSLGHA HSEGPAPAYV
ASGPFREAGF PGQASSPLGR ANGRLFANPR DSFSAMGFQR RFFHQDQSPV GGLTAEDIEK
ARQAKARPEN KQHKQTLSEH ARERKVPVTR IGRLANFGGL AVGLGFGALA EVAKKSLRSE
DPSGKKAVLG SSPFLSEANA ERIVRTLCKV RGAALKLGQM LSIQDDAFIN PHLAKIFERV
RQSADFMPLK QMMKTLNNDL GPNWRDKLEY FEERPFAAAS IGQVHLARMK GGREVAMKIQ
YPGVAQSINS DVNNLMAVLN MSNMLPEGLF PEHLIDVLRR ELALECDYQR EAACARKFRD
LLKGHPFFYV PEIVDELCSP HVLTTELVSG FPLDQAEGLS QEIRNEICYN ILVLCLRELF
EFHFMQTDPN WSNFFYDPQQ HKVALLDFGA TREYDRSFTD LYIQIIRAAA DRDRETVRAK
SIEMKFLTGY EVKVMEDAHL DAILILGEAF ASDEPFDFGT QSTTEKIHNL IPVMLRHRLV
PPPEETYSLH RKMGGSFLIC SKLKARFPCK AMFEEAYSNY CKRQAQQ
