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 27-MAR-2024, entry version 180. 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}, CABC1 GN {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 SUBCELLULAR LOCATION. RX PubMed=33988507; DOI=10.7554/elife.64943; RA Zhang H., Cao X., Tang M., Zhong G., Si Y., Li H., Zhu F., Liao Q., Li L., RA Zhao J., Feng J., Li S., Wang C., Kaulich M., Wang F., Chen L., Li L., RA Xia Z., Liang T., Lu H., Feng X.H., Zhao B.; RT "A subcellular map of the human kinome."; RL Elife 10:0-0(2021). RN [20] 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 [21] 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 [22] 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 [23] 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 [24] 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 [25] 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 [26] 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: AKR1C8; 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, ECO:0000269|PubMed:33988507}. Membrane CC {ECO:0000255}; Single-pass membrane protein {ECO:0000255, CC 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}. 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; 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. DR RefSeq; XP_016857341.1; XM_017001852.1. DR PDB; 4PED; X-ray; 1.64 A; A=256-647. DR PDB; 5I35; X-ray; 2.30 A; A=256-647. DR PDB; 7UDP; X-ray; 2.01 A; A=256-647. DR PDB; 7UDQ; X-ray; 1.90 A; A/B=256-647. DR PDBsum; 4PED; -. DR PDBsum; 5I35; -. DR PDBsum; 7UDP; -. DR PDBsum; 7UDQ; -. DR AlphaFoldDB; Q8NI60; -. DR SMR; Q8NI60; -. DR BioGRID; 121312; 222. DR IntAct; Q8NI60; 213. 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 SwissPalm; Q8NI60; -. DR BioMuta; COQ8A; -. DR DMDM; 27923741; -. DR CPTAC; non-CPTAC-3019; -. DR CPTAC; non-CPTAC-3020; -. DR EPD; Q8NI60; -. DR jPOST; Q8NI60; -. DR MassIVE; Q8NI60; -. DR MaxQB; Q8NI60; -. DR PaxDb; 9606-ENSP00000355741; -. DR PeptideAtlas; Q8NI60; -. DR ProteomicsDB; 73833; -. [Q8NI60-1] DR ProteomicsDB; 73834; -. [Q8NI60-2] DR ProteomicsDB; 73835; -. [Q8NI60-3] DR ProteomicsDB; 73836; -. [Q8NI60-4] DR Pumba; Q8NI60; -. DR Antibodypedia; 20768; 366 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 AGR; HGNC:16812; -. 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; PLDKCFD; -. DR OrthoDB; 668390at2759; -. DR PhylomeDB; Q8NI60; -. DR TreeFam; TF300630; -. DR PathwayCommons; Q8NI60; -. DR SignaLink; Q8NI60; -. DR UniPathway; UPA00232; -. DR BioGRID-ORCS; 56997; 9 hits in 1192 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 101 other cell types or tissues. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. 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; IPR011009; Kinase-like_dom_sf. DR PANTHER; PTHR43851; -; 1. DR PANTHER; PTHR43851:SF1; ATYPICAL KINASE COQ8A, MITOCHONDRIAL; 1. DR Pfam; PF03109; ABC1; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR Genevisible; Q8NI60; HS. 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; uncertain 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 //