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Q5EAB2 (CDK9_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 91. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cyclin-dependent kinase 9

EC=2.7.11.22
EC=2.7.11.23
Alternative name(s):
Cell division protein kinase 9
Gene names
Name:CDK9
OrganismBos taurus (Bovine) [Reference proteome]
Taxonomic identifier9913 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos

Protein attributes

Sequence length372 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

Protein kinase involved in the regulation of transcription. Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A, SUPT5H and RDBP. This complex is inactive when in the 7SK snRNP complex form. Phosphorylates EP300, MYOD1, RPB1/POLR2A and AR, and the negative elongation factors DSIF and NELF. Regulates cytokine inducible transcription networks by facilitating promoter recognition of target transcription factors (e.g. TNF-inducible RELA/p65 activation and IL-6-inducible STAT3 signaling). Promotes RNA synthesis in genetic programs for cell growth, differentiation and viral pathogenesis. P-TEFb is also involved in cotranscriptional histone modification, mRNA processing and mRNA export. Modulates a complex network of chromatin modifications including histone H2B monoubiquitination (H2Bub1), H3 lysine 4 trimethylation (H3K4me3) and H3K36me3; integrates phosphorylation during transcription with chromatin modifications to control co-transcriptional histone mRNA processing. The CDK9/cyclin-K complex has also a kinase activity towards CTD of RNAP II and can substitute for CDK9/cyclin-T P-TEFb in vitro. Replication stress response protein; the CDK9/cyclin-K complex is required for genome integrity maintenance, by promoting cell cycle recovery from replication arrest and limiting single-stranded DNA amount in response to replication stress, thus reducing the breakdown of stalled replication forks and avoiding DNA damage. In addition, probable function in DNA repair of isoform 2via interaction with KU70/XRCC6. Promotes cardiac myocyte enlargement. RPB1/POLR2A phosphorylation on 'Ser-2' in CTD activates transcription. AR phosphorylation modulates AR transcription factor promoter selectivity and cell growth. DSIF and NELF phosphorylation promotes transcription by inhibiting their negative effect. The phosphorylation of MYOD1 enhances its transcriptional activity and thus promotes muscle differentiation By similarity.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate.

Enzyme regulation

Activation by Thr-186 phosphorylation is calcium Ca2+ signaling pathway-dependent; actively inactivated by dephosphorylation mediated by PPP1CA, PPM1A and PPM1B. Reversibly repressed by acetylation at Lys-44 and Lys-48 By similarity.

Subunit structure

Associates with CCNT1/cyclin-T1, CCNT2/cyclin-T2 (isoform Aand isoform B)or CCNK/cyclin-K to form active P-TEFb. P-TEFb forms a complex with AFF4/AF5Q31 and is part of the super elongation complex (SEC). Component of a complex which is composed of at least 5 members: HTATSF1/Tat-SF1, P-TEFb complex, RNA pol II, SUPT5H, and NCL/nucleolin. Associates with UBR5 and forms a transcription regulatory complex composed of CDK9, RNAP II, UBR5 and TFIIS/TCEA1 that can stimulate target gene transcription (e.g. gamma fibrinogen/FGG) by recruiting their promoters. Component of the 7SK snRNP inactive complex which is composed of at least 8 members: P-TEFb (composed of CDK9 and CCNT1/cyclin-T1), HEXIM1, HEXIM2, LARP7, BCDIN3, SART3 proteins and 7SK and U6 snRNAs. This inactive 7SK snRNP complex can also interact with NCOR1 and HDAC3, probably to regulate CDK9 acetylation. Release of P-TEFb from P-TEFb/7SK snRNP complex requires both PP2B to transduce calcium Ca2+ signaling in response to stimuli (e.g. UV or hexamethylene bisacetamide (HMBA)), and PPP1CA to dephosphorylate Thr-186. This released P-TEFb remains inactive in the preinitiation complex with BRD4 until new Thr-186 phosphorylation occurs after the synthesis of a short RNA. Interacts with BRD4, probably to target chromatin binding. Interacts with activated nuclear STAT3 and RELA/p65. Binds to AR and MYOD1. Forms a complex composed of CDK9, CCNT1/cyclin-T1, EP300 and GATA4 that stimulates hypertrophy in cardiomyocytes.

Subcellular location

Nucleus By similarity. Cytoplasm By similarity. NucleusPML body By similarity. Note: Accumulates on chromatin in response to replication stress. Complexed with CCNT1 in nuclear speckles, but uncomplexed form in the cytoplasm. The translocation from nucleus to cytoplasm is XPO1/CRM1-dependent. Associates with PML body when acetylated By similarity.

Post-translational modification

Autophosphorylation at Thr-186, Ser-347, Thr-350, Ser-353, Thr-354 and Ser-357 triggers kinase activity by promoting cyclin and substrate binding upon conformational changes. Thr-186 phosphorylation requires the calcium Ca2+ signaling pathway, including CaMK1D and calmodulin. This inhibition is relieved by Thr-29 dephosphorylation. Phosphorylation at Ser-175 inhibits kinase activity. Can be phosphorylated on either Thr-362 or Thr-363 but not on both simultaneously By similarity.

Dephosphorylation of Thr-186 by PPM1A and PPM1B blocks CDK9 activity and may lead to CDK9 proteasomal degradation. However, PPP1CA-mediated Thr-186 dephosphorylation is required to release P-TEFb from its inactive P-TEFb/7SK snRNP complex. Dephosphorylation of C-terminus Thr and Ser residues by protein phosphatase-1 (PP1) triggers CDK9 activity By similarity.

N6-acetylation of Lys-44 by CBP/p300 promotes kinase activity, whereas acetylation of both Lys-44 and Lys-48 mediated by PCAF/KAT2B and GCN5/KAT2A reduces kinase activity. The acetylated form associates with PML bodies in the nuclear matrix; deacetylated upon transcription stimulation By similarity.

Polyubiquitinated and thus activated by UBR5. This ubiquitination is promoted by TFIIS/TCEA1 and favors 'Ser-2' phosphorylation of RPB1/POLR2A CTD By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.

Contains 1 protein kinase domain.

Sequence caution

The sequence AAX46729.1 differs from that shown. Reason: Frameshift at position 231.

Ontologies

Keywords
   Biological processDNA damage
DNA repair
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA repair

Inferred from electronic annotation. Source: UniProtKB-KW

cellular response to cytokine stimulus

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell cycle arrest

Inferred from electronic annotation. Source: Ensembl

regulation of DNA repair

Inferred from electronic annotation. Source: Ensembl

regulation of histone modification

Inferred from electronic annotation. Source: Ensembl

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

replication fork arrest

Inferred from electronic annotation. Source: Ensembl

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentPML body

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

positive transcription elongation factor complex b

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

RNA polymerase II carboxy-terminal domain kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

chromatin binding

Inferred from electronic annotation. Source: Ensembl

cyclin-dependent protein serine/threonine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

snRNA binding

Inferred from electronic annotation. Source: Ensembl

transcription regulatory region DNA binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 372372Cyclin-dependent kinase 9
PRO_0000085799

Regions

Domain19 – 315297Protein kinase
Nucleotide binding25 – 339ATP By similarity
Nucleotide binding104 – 1063ATP By similarity
Region166 – 19126T-loop By similarity

Sites

Active site1491Proton acceptor By similarity
Binding site481ATP By similarity
Binding site1671ATP By similarity

Amino acid modifications

Modified residue291Phosphothreonine By similarity
Modified residue441N6-acetyllysine; by P300/CBP, PCAF/KAT2B and GCN5/KAT2A By similarity
Modified residue481N6-acetyllysine; by PCAF/KAT2B and GCN5/KAT2A By similarity
Modified residue1751Phosphoserine By similarity
Modified residue1861Phosphothreonine; by CaMK1D By similarity
Modified residue3471Phosphoserine; by CDK9 and PKA By similarity
Modified residue3501Phosphothreonine; by CDK9 By similarity
Modified residue3531Phosphoserine; by CDK9 By similarity
Modified residue3541Phosphothreonine; by CDK9 By similarity
Modified residue3571Phosphoserine; by CDK9 By similarity
Modified residue3621Phosphothreonine; by CDK9 By similarity
Modified residue3631Phosphothreonine; by CDK9 By similarity

Sequences

Sequence LengthMass (Da)Tools
Q5EAB2 [UniParc].

Last modified March 15, 2005. Version 1.
Checksum: 50A26ECAC9A36CAD

FASTA37242,748
        10         20         30         40         50         60 
MAKQYDSVEC PFCDEVTKYE KLAKIGQGTF GEVFKAKHRK TGQKVALKKV LMENEKEGFP 

        70         80         90        100        110        120 
ITALREIKIL QLLKHENVVN LIEICRTKAS PYNRCKGSIY LVFDFCEHDL AGLLSNVLVK 

       130        140        150        160        170        180 
FTLSEIKRVM QMLLNGLYYI HRNKILHRDM KAANVLITRD GVLKLADFGL ARAFSLAKNS 

       190        200        210        220        230        240 
QPNRYTNRVV TLWYRPPELL LGERDYGPPI DLWGAGCIMA EMWTRSPIMQ GNTEQHQLAL 

       250        260        270        280        290        300 
ISQLCGSITP EVWPNVDKYE LFEKVELVKG QKRKVKDRLK AYVRDPYALD LIDKLLVLDP 

       310        320        330        340        350        360 
AQRIDSDDAL NHDFFWSDPM PSDLKGMLST HLTSMFEYLA PPRRKGSQIT QQSTNQSRNP 

       370 
ATTNQTEFER VF 

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References

[1]"Characterization of 954 bovine full-CDS cDNA sequences."
Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L., Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.
BMC Genomics 6:166-166(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[2]NIH - Mammalian Gene Collection (MGC) project
Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: Hereford.
Tissue: Thalamus.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
BT020657 mRNA. Translation: AAX08674.1.
BT021882 mRNA. Translation: AAX46729.1. Frameshift.
BC118194 mRNA. Translation: AAI18195.1.
RefSeqNP_001014935.2. NM_001014935.2.
UniGeneBt.1465.

3D structure databases

ProteinModelPortalQ5EAB2.
SMRQ5EAB2. Positions 7-326.
ModBaseSearch...
MobiDBSearch...

Proteomic databases

PRIDEQ5EAB2.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSBTAT00000006162; ENSBTAP00000006162; ENSBTAG00000004695.
GeneID520580.
KEGGbta:520580.

Organism-specific databases

CTD1025.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00740000114964.
HOGENOMHOG000233024.
HOVERGENHBG014652.
InParanoidQ5EAB2.
KOK02211.
OMALMDNEKE.
OrthoDBEOG76DTSM.
TreeFamTF101039.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio20873133.

Entry information

Entry nameCDK9_BOVIN
AccessionPrimary (citable) accession number: Q5EAB2
Secondary accession number(s): Q148K6, Q58CR5
Entry history
Integrated into UniProtKB/Swiss-Prot: November 22, 2005
Last sequence update: March 15, 2005
Last modified: April 16, 2014
This is version 91 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families