CDK9_DANRE
ID CDK9_DANRE Reviewed; 374 AA.
AC Q7SXE8; A0A0R4II91; Q7T3L5;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Cyclin-dependent kinase 9;
DE EC=2.7.11.22 {ECO:0000250|UniProtKB:P50750};
DE EC=2.7.11.23 {ECO:0000250|UniProtKB:P50750};
DE AltName: Full=Cell division protein kinase 9;
GN Name=cdk9 {ECO:0000312|ZFIN:ZDB-GENE-030131-321};
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 [MRNA] (ISOFORM 2).
RA Bauer M.P., Goetz F.W.;
RT "The isolation and characterization of cdk9 from the zebrafish.";
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Chen J.-Y., Wu J.-L.;
RT "Molecular analysis of CDC-9 in zebrafish.";
RL Submitted (NOV-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=26542022; DOI=10.1242/jcs.175018;
RA Matrone G., Wilson K.S., Maqsood S., Mullins J.J., Tucker C.S.,
RA Denvir M.A.;
RT "CDK9 and its repressor LARP7 modulate cardiomyocyte proliferation and
RT response to injury in the zebrafish heart.";
RL J. Cell Sci. 128:4560-4571(2015).
CC -!- FUNCTION: Protein kinase involved in the regulation of transcription.
CC Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex,
CC also called positive transcription elongation factor b (P-TEFb), which
CC facilitates the transition from abortive to productive elongation by
CC phosphorylating the CTD (C-terminal domain) of the large subunit of RNA
CC polymerase II (RNAP II) polr2a, supt5h and rdbp. This complex is
CC inactive when in the 7SK snRNP complex form. Regulates cytokine
CC inducible transcription networks by facilitating promoter recognition
CC of target transcription factors. P-TEFb is also involved in
CC cotranscriptional histone modification, mRNA processing and mRNA
CC export. {ECO:0000250|UniProtKB:P50750}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.22;
CC Evidence={ECO:0000250|UniProtKB:P50750};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC Evidence={ECO:0000250|UniProtKB:P50750};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.22; Evidence={ECO:0000250|UniProtKB:P50750};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609;
CC Evidence={ECO:0000250|UniProtKB:P50750};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[DNA-directed RNA polymerase] + ATP = ADP + H(+) + phospho-
CC [DNA-directed RNA polymerase]; Xref=Rhea:RHEA:10216, Rhea:RHEA-
CC COMP:11321, Rhea:RHEA-COMP:11322, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43176, ChEBI:CHEBI:68546,
CC ChEBI:CHEBI:456216; EC=2.7.11.23;
CC Evidence={ECO:0000250|UniProtKB:P50750};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10217;
CC Evidence={ECO:0000250|UniProtKB:P50750};
CC -!- SUBUNIT: Component of the super elongation complex (SEC). Associates
CC with ccnt1/cyclin-T1, ccnt2/cyclin-T2 or ccnk/cyclin-K to form active
CC P-TEFb. {ECO:0000250|UniProtKB:P50750, ECO:0000250|UniProtKB:Q99J95}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P50750}. Cytoplasm
CC {ECO:0000250|UniProtKB:P50750}. Nucleus, PML body
CC {ECO:0000250|UniProtKB:P50750}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q7SXE8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7SXE8-2; Sequence=VSP_060578, VSP_060579;
CC -!- DEVELOPMENTAL STAGE: Expressed from 24 hours post-fertilization (hpf)
CC (PubMed:26542022). Expression increases between 24 and 72 hpf and then
CC decreases towards 120 hpf (PubMed:26542022). In embryonic hearts
CC expression peaks at 48 hpf and again at 96 hpf, decreasing at 120 hpf
CC to levels then detected in adult hearts (PubMed:26542022).
CC {ECO:0000269|PubMed:26542022}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown of the protein causes in
CC larvae causes high levels of lethality. {ECO:0000269|PubMed:26542022}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.
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DR EMBL; AF268046; AAP47016.1; -; mRNA.
DR EMBL; AY181980; AAO60241.1; -; mRNA.
DR EMBL; BX530036; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC055634; AAH55634.1; -; mRNA.
DR RefSeq; NP_997756.1; NM_212591.1. [Q7SXE8-2]
DR AlphaFoldDB; Q7SXE8; -.
DR SMR; Q7SXE8; -.
DR STRING; 7955.ENSDARP00000065858; -.
DR Ensembl; ENSDART00000065859; ENSDARP00000065858; ENSDARG00000044811. [Q7SXE8-2]
DR Ensembl; ENSDART00000166287; ENSDARP00000134607; ENSDARG00000044811. [Q7SXE8-1]
DR Ensembl; ENSDART00000183640; ENSDARP00000144830; ENSDARG00000111590. [Q7SXE8-2]
DR GeneID; 321602; -.
DR KEGG; dre:321602; -.
DR CTD; 1025; -.
DR ZFIN; ZDB-GENE-030131-321; cdk9.
DR eggNOG; KOG0669; Eukaryota.
DR GeneTree; ENSGT00940000155373; -.
DR HOGENOM; CLU_000288_181_1_1; -.
DR OrthoDB; 925637at2759; -.
DR TreeFam; TF101039; -.
DR Reactome; R-DRE-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
DR Reactome; R-DRE-674695; RNA Polymerase II Pre-transcription Events.
DR Reactome; R-DRE-6796648; TP53 Regulates Transcription of DNA Repair Genes.
DR Reactome; R-DRE-6807505; RNA polymerase II transcribes snRNA genes.
DR Reactome; R-DRE-75955; RNA Polymerase II Transcription Elongation.
DR Reactome; R-DRE-9018519; Estrogen-dependent gene expression.
DR PRO; PR:Q7SXE8; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 21.
DR Bgee; ENSDARG00000044811; Expressed in blastula and 29 other tissues.
DR ExpressionAtlas; Q7SXE8; baseline.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0008353; F:RNA polymerase II CTD heptapeptide repeat kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0061026; P:cardiac muscle tissue regeneration; IMP:ZFIN.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0090594; P:inflammatory response to wounding; IMP:ZFIN.
DR GO; GO:0120187; P:positive regulation of protein localization to chromatin; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0065003; P:protein-containing complex assembly; IPI:ZFIN.
DR GO; GO:0060043; P:regulation of cardiac muscle cell proliferation; IMP:ZFIN.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; ATP-binding; Cytoplasm; DNA damage; DNA repair;
KW Kinase; Nucleotide-binding; Nucleus; Reference proteome;
KW Serine/threonine-protein kinase; Transcription; Transcription regulation;
KW Transferase.
FT CHAIN 1..374
FT /note="Cyclin-dependent kinase 9"
FT /id="PRO_0000449917"
FT DOMAIN 19..318
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 345..374
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 352..374
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 151
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 25..33
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 48
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT VAR_SEQ 1
FT /note="M -> MQRDKTGSSGGGEKPDRETAIM (in isoform 2)"
FT /id="VSP_060578"
FT VAR_SEQ 89..90
FT /note="Missing (in isoform 2)"
FT /id="VSP_060579"
SQ SEQUENCE 374 AA; 43131 MW; 7E1F2503DF03406D CRC64;
MSKYYDGVEF PFCDEFSKYE KLAKIGQGTF GEVFKAKHRQ TGKKVALKKV LMENEKEGFP
ITALREIKIL QLLKHENVVN LIEICRTKGE ATQFNRYKGS IYLVFDFCEH DLAGLLSNAN
VKFTLAEIKR VMQMLLNGLY YIHRNKILHR DMKAANVLIT RDGVLKLADF GLARAFSLAK
NSQGNRYTNR VVTLWYRPPE LLLGERDYGP PIDLWGAGCI MAEMWTRSPI MQGNTEQHQL
TLISQLCGSI TPEVWPGVDK KYELYQKMEL PKGQKRKVKD RLKAYVKDPY ALDLIDKLLV
LDPAQRIDSD DALNHDFFWS DPMPSDLKNM LSTHNTSMFE YLAPPRRRGH MPQQPANQNR
NPATTSQSEF DRVF
