COQ8B_DANRE
ID COQ8B_DANRE Reviewed; 624 AA.
AC A3QJU3;
DT 19-FEB-2014, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2013, sequence version 2.
DT 03-AUG-2022, entry version 89.
DE RecName: Full=Atypical kinase COQ8B, mitochondrial {ECO:0000305};
DE EC=2.7.-.- {ECO:0000250|UniProtKB:Q8NI60};
DE AltName: Full=AarF domain-containing protein kinase 4 {ECO:0000250|UniProtKB:Q96D53};
DE AltName: Full=Coenzyme Q protein 8B {ECO:0000250|UniProtKB:Q96D53};
GN Name=coq8b {ECO:0000250|UniProtKB:Q96D53};
GN Synonyms=adck4 {ECO:0000250|UniProtKB:Q96D53};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP DISRUPTION PHENOTYPE.
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).
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. Its substrate specificity is unclear:
CC does not show any protein kinase activity. Probably acts as a small
CC molecule kinase, possibly a lipid kinase that phosphorylates a prenyl
CC lipid in the ubiquinone biosynthesis pathway. Required for podocyte
CC migration. {ECO:0000250|UniProtKB:Q8NI60,
CC ECO:0000250|UniProtKB:Q96D53}.
CC -!- SUBUNIT: Homodimer; homodimerizes via its transmembrane region.
CC Interacts with the multi-subunit COQ enzyme complex.
CC {ECO:0000250|UniProtKB:Q96D53}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion membrane
CC {ECO:0000250|UniProtKB:Q96D53}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:Q96D53}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q96D53}. Cell membrane
CC {ECO:0000250|UniProtKB:Q96D53}.
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. The KxGQ motif completely occludes the typical substrate
CC binding pocket. Nucleotide-binding opens the substrate binding pocket
CC and flips the active site from inside the hydrophobic core into a
CC catalytically competent, solvent-exposed posture.
CC {ECO:0000250|UniProtKB:Q8NI60}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown of the protein causes
CC nephrosis phenotype of periorbital edema and total body edema in 54% of
CC embryos at 120 hpf. The glomerular structures are altered, with
CC podocyte foot process effacement and disorganization, rarefaction of
CC slit membranes, and disorganization of the glomerular basement
CC membranes. {ECO:0000269|PubMed:24270420}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. ADCK protein
CC kinase family. {ECO:0000305}.
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DR EMBL; CR318657; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_001336310.1; XM_001336274.7.
DR AlphaFoldDB; A3QJU3; -.
DR SMR; A3QJU3; -.
DR STRING; 7955.ENSDARP00000115887; -.
DR PaxDb; A3QJU3; -.
DR PeptideAtlas; A3QJU3; -.
DR Ensembl; ENSDART00000172195; ENSDARP00000132291; ENSDARG00000101130.
DR GeneID; 799071; -.
DR KEGG; dre:799071; -.
DR CTD; 79934; -.
DR ZFIN; ZDB-GENE-060503-803; coq8b.
DR eggNOG; KOG1234; Eukaryota.
DR GeneTree; ENSGT00940000158965; -.
DR HOGENOM; CLU_006533_9_0_1; -.
DR OMA; KFHQDGP; -.
DR OrthoDB; 525494at2759; -.
DR PhylomeDB; A3QJU3; -.
DR PRO; PR:A3QJU3; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 15.
DR Bgee; ENSDARG00000101130; Expressed in blastula and 22 other tissues.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
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:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016301; F:kinase activity; IBA:GO_Central.
DR GO; GO:0021692; P:cerebellar Purkinje cell layer morphogenesis; ISS:UniProtKB.
DR GO; GO:0032836; P:glomerular basement membrane development; IMP:ZFIN.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0072015; P:podocyte development; IMP:ZFIN.
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; IPR034638; COQ8B.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR PANTHER; PTHR43851:SF4; PTHR43851:SF4; 1.
DR Pfam; PF03109; ABC1; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
PE 3: Inferred from homology;
KW ATP-binding; Cell membrane; Cytoplasm; Kinase; Membrane; Mitochondrion;
KW Nucleotide-binding; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..624
FT /note="Atypical kinase COQ8B, mitochondrial"
FT /id="PRO_0000425572"
FT TRANSMEM 189..205
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 285..517
FT /note="Protein kinase"
FT REGION 90..117
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 249..252
FT /note="KxGQ motif"
FT /evidence="ECO:0000250|UniProtKB:Q8NI60"
FT MOTIF 310..313
FT /note="AAAS motif"
FT /evidence="ECO:0000250|UniProtKB:Q8NI60"
FT ACT_SITE 461
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q8NI60"
FT BINDING 313
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8NI60"
FT BINDING 331
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8NI60"
FT BINDING 418..421
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8NI60"
FT BINDING 466
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8NI60"
FT BINDING 480
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8NI60"
SQ SEQUENCE 624 AA; 69460 MW; 4E42F359888C155F CRC64;
MLLSEVLQVL RGAGKVGAAF TSTQGEQLRL MACNSTFGAG MKAAAEAVEG VMGTVMGGGD
MTSKTDEFAG IEKWEEMDLD EAAKWSVASE MPPDFSSKDG RGETSETPVG AATGTIKGAG
WPAQNTRFLH VSASQHHFRF VHDSIVARLS PEDIQRAREA KQNIARPVRQ KLNERAKERK
VPATRISRLA NFGGLAVGLG IGAIAEVAKQ SFGGKRSEVG ALLDSPLLSE ANAERIVNTL
CKVRGAALKI GQMLSIQDNS FINPQLQKIF ERVRQSADFM PAWQMHKVLE EELGSGWREK
LSSIEEKPFA AASIGQVHHG VLPGGKEIAM KIQYPGVAES IHSDINNLMS VLKMSVVLPD
GLFADSSLEV LQRELAWECD YEREAKCAKR FRNLLKGDPV FVVPEVFDEL SARRVITMEL
VNGVPLDRCV DLDQETRNEI CFNILQLCLR ELFEFRFMQT DPNWSNFFYN SEQNKIFLLD
FGACRDYPEL FTDHYIEVVH AASVGDRATV LKKSKDLKFL TGFEAKAFED AHVEAVMILG
EAFASAEAFD FGTQSTTQRI QSLIPVMLRH RLTPPPEESY SLHRKMAGSF LICSKLKARF
SCRNMFLDVY NAYKRQQQER RSQV
