COQ8A_MOUSE
ID COQ8A_MOUSE Reviewed; 645 AA.
AC Q60936; Q8K0M1; Q9D657; Q9DBR5; Q9JHR3;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 27-JAN-2003, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Atypical kinase COQ8A, mitochondrial {ECO:0000305};
DE EC=2.7.-.- {ECO:0000250|UniProtKB:Q8NI60};
DE AltName: Full=Chaperone activity of bc1 complex-like {ECO:0000250|UniProtKB:Q8NI60};
DE Short=Chaperone-ABC1-like {ECO:0000250|UniProtKB:Q8NI60};
DE AltName: Full=Coenzyme Q protein 8A {ECO:0000250|UniProtKB:Q8NI60};
DE AltName: Full=aarF domain-containing protein kinase 3 {ECO:0000312|MGI:MGI:1914676};
DE Flags: Precursor;
GN Name=Coq8a {ECO:0000250|UniProtKB:Q8NI60};
GN Synonyms=Adck3 {ECO:0000312|MGI:MGI:1914676}, Cabc1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Skeletal muscle;
RA Ievolella C., Millino C., Lanfranchi G.;
RT "Full length sequencing of some human and murine muscular transcript
RT (Telethon Italy project B41).";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Lung, and Skin;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Salivary gland;
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 250-547 (ISOFORM 1).
RC TISSUE=Heart;
RA Wilks J., Billadello J.J.;
RL Submitted (JUL-1995) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Pancreas, and
RC Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
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).
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:27499294). Its substrate
CC specificity is unclear: does not show any protein kinase activity
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 (By similarity). Shows an unusual selectivity for
CC binding ADP over ATP (By similarity). {ECO:0000250|UniProtKB:Q8NI60,
CC ECO:0000269|PubMed:27499294}.
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.
CC {ECO:0000250|UniProtKB:Q8NI60}.
CC -!- PATHWAY: Cofactor biosynthesis; ubiquinone biosynthesis.
CC {ECO:0000250|UniProtKB:Q8NI60}.
CC -!- SUBUNIT: Homodimer; homodimerizes via its transmembrane region.
CC Interacts with the multi-subunit COQ enzyme complex, composed of at
CC least COQ3, COQ4, COQ5, COQ6, COQ7 and COQ9.
CC {ECO:0000250|UniProtKB:Q8NI60}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q8NI60}.
CC Membrane {ECO:0000255}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:Q8NI60, ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q60936-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q60936-2; Sequence=VSP_022354;
CC -!- TISSUE SPECIFICITY: Present in various tissues (at protein level).
CC {ECO:0000269|PubMed:27499294}.
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. Nucleotide-
CC binding opens the substrate binding pocket and flips the active site
CC from inside the hydrophobic core into a catalytically competent,
CC solvent-exposed posture. {ECO:0000250|UniProtKB:Q8NI60}.
CC -!- DISRUPTION PHENOTYPE: Mice were born at the expected Mendelian
CC frequency and do not show overt phenotype under normal conditions. They
CC however develop a slowly progressive loss of coordination after birth
CC and develop ataxia and seizures. Defects are due to dysfunctional
CC cerebellar Purkinje cells and defective skeletal muscle. Mice display
CC tissue-specific coenzyme Q deficiency: coenzyme Q levels are normal in
CC younger mice but significantly and specifically reduced in skeletal
CC muscle. However, normal coenzyme Q levels are observed in whole
CC cerebella, suggesting that cerebellar Purkinje cells are specifically
CC affected. {ECO:0000269|PubMed:27499294}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. ADCK protein
CC kinase family. {ECO:0000305}.
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DR EMBL; AJ278735; CAC00538.1; -; mRNA.
DR EMBL; AK004791; BAB23567.2; -; mRNA.
DR EMBL; AK014605; BAB29459.2; -; mRNA.
DR EMBL; U31629; AAA86413.1; -; mRNA.
DR CCDS; CCDS15566.1; -. [Q60936-1]
DR RefSeq; NP_001156762.1; NM_001163290.1. [Q60936-1]
DR RefSeq; NP_075830.2; NM_023341.3. [Q60936-1]
DR RefSeq; XP_006497024.1; XM_006496961.2. [Q60936-1]
DR RefSeq; XP_006497025.1; XM_006496962.2. [Q60936-1]
DR AlphaFoldDB; Q60936; -.
DR SMR; Q60936; -.
DR BioGRID; 212178; 2.
DR IntAct; Q60936; 4.
DR MINT; Q60936; -.
DR STRING; 10090.ENSMUSP00000027766; -.
DR iPTMnet; Q60936; -.
DR PhosphoSitePlus; Q60936; -.
DR SwissPalm; Q60936; -.
DR EPD; Q60936; -.
DR jPOST; Q60936; -.
DR MaxQB; Q60936; -.
DR PaxDb; Q60936; -.
DR PeptideAtlas; Q60936; -.
DR PRIDE; Q60936; -.
DR ProteomicsDB; 283494; -. [Q60936-1]
DR ProteomicsDB; 283495; -. [Q60936-2]
DR Antibodypedia; 20768; 334 antibodies from 30 providers.
DR DNASU; 67426; -.
DR Ensembl; ENSMUST00000027766; ENSMUSP00000027766; ENSMUSG00000026489. [Q60936-1]
DR Ensembl; ENSMUST00000170472; ENSMUSP00000128290; ENSMUSG00000026489. [Q60936-1]
DR GeneID; 67426; -.
DR KEGG; mmu:67426; -.
DR UCSC; uc007dvx.2; mouse. [Q60936-1]
DR CTD; 56997; -.
DR MGI; MGI:1914676; Coq8a.
DR VEuPathDB; HostDB:ENSMUSG00000026489; -.
DR eggNOG; KOG1234; Eukaryota.
DR GeneTree; ENSGT00940000156810; -.
DR HOGENOM; CLU_006533_9_1_1; -.
DR InParanoid; Q60936; -.
DR OMA; QVERVMN; -.
DR OrthoDB; 525494at2759; -.
DR PhylomeDB; Q60936; -.
DR TreeFam; TF300630; -.
DR UniPathway; UPA00232; -.
DR BioGRID-ORCS; 67426; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Coq8a; mouse.
DR PRO; PR:Q60936; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q60936; protein.
DR Bgee; ENSMUSG00000026489; Expressed in extra-ocular muscle and 231 other tissues.
DR ExpressionAtlas; Q60936; baseline and differential.
DR Genevisible; Q60936; MM.
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; HDA:MGI.
DR GO; GO:0043531; F:ADP binding; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016301; F:kinase activity; ISS:UniProtKB.
DR GO; GO:0016310; P:phosphorylation; ISS:UniProtKB.
DR GO; GO:0006744; P:ubiquinone biosynthetic process; ISS: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 Alternative splicing; ATP-binding; Kinase; Membrane; Mitochondrion;
KW Nucleotide-binding; Reference proteome; Transferase; Transit peptide;
KW Transmembrane; Transmembrane helix; Ubiquinone biosynthesis.
FT TRANSIT 1..159
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:Q8NI60"
FT CHAIN 160..645
FT /note="Atypical kinase COQ8A, mitochondrial"
FT /id="PRO_0000000263"
FT TRANSMEM 211..227
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 326..515
FT /note="Protein kinase"
FT REGION 99..134
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 179..200
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 273..276
FT /note="KxGQ motif"
FT /evidence="ECO:0000250|UniProtKB:Q8NI60"
FT MOTIF 334..337
FT /note="AAAS motif"
FT /evidence="ECO:0000250|UniProtKB:Q8NI60"
FT COMPBIAS 99..114
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 485
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q8NI60"
FT BINDING 337
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8NI60"
FT BINDING 355
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8NI60"
FT BINDING 442..445
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8NI60"
FT BINDING 490
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8NI60"
FT BINDING 504
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8NI60"
FT VAR_SEQ 1..276
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_022354"
FT CONFLICT 213
FT /note="N -> D (in Ref. 2; BAB29459)"
FT /evidence="ECO:0000305"
FT CONFLICT 388
FT /note="P -> S (in Ref. 2; BAB29459)"
FT /evidence="ECO:0000305"
FT CONFLICT 546..547
FT /note="GY -> RP (in Ref. 4; AAA86413)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 645 AA; 71743 MW; C94854B41211F880 CRC64;
MAAMLGDAIM VAKGLAKLTQ AAVETHLQNL GLGGELLLAA RALQSTAVEQ FSMVFGKVQG
QDKHEDSYAT ENFEDLEAEV QFSTPQAAGT SLDFSAASSL DQSLSPSHSQ GPAPAYASSG
PFREAGLPGQ ATSPMGRVNG RLFVDHRDLF LANGIQRRSF HQDQSSVGGL TAEDIEKARQ
AKARPESKPH KQMLSERARE RKVPVTRIGR LANFGGLAVG LGIGALAEVA KKSLRSENST
GKKAVLDSSP FLSEANAERI VSTLCKVRGA ALKLGQMLSI QDDAFINPHL AKIFERVRQS
ADFMPLKQMT KTLNSDLGPH WRDKLEYFEE RPFAAASIGQ VHLARMKGGR EVAMKIQYPG
VAQSINSDVN NLMAVLNMSN MLPEGLFPEH LIDVLRRELT LECDYQREAA YAKKFRELLK
DHPFFYVPEI VDELCSPHVL TTELISGFPL DQAEGLSQEV RNEICYNILV LCLRELFEFH
VMQTDPNWSN FFYDPQQHKV ALLDFGATRE YDRSFTDLYI QVIRAAADQD REAVLKKSIE
MKFLTGYEVK AMEDAHLDAI LILGEAFASE EPFDFGTQST TEKIHNLIPV MLKHRLIPPP
EETYSLHRKM GGSFLICSKL KARFPCKAMF EEAYSNYCRM KSGLQ
