UniProt Accession

 CDK9_RAT; Q641Z4 

Genbank Protein ID

 BC082037 

Genbank Nucleotide ID

 AAH82037.1 

Protein Name

 Cyclin-dependent kinase 9 

Protein Synonyms/Alias

 Cell division protein kinase 9 

Gene Name

 Cdk9 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Rattus norvegicus (Rat) 

NCBI Taxa ID

 10116 

Lysine Modification

Position	Peptide	Type	References
68	ITALREIKILQLLKH	ubiquitination	[1]
264	DKYELFEKLELVKGQ	ubiquitination	[1]

Reference

 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023] 

Functional Description

 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 2 via 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). 

Sequence Annotation

 DOMAIN 19 315 Protein kinase.
 NP_BIND 25 33 ATP (By similarity).
 NP_BIND 104 106 ATP (By similarity).
 REGION 166 191 T-loop (By similarity).
 ACT_SITE 149 149 Proton acceptor (By similarity).
 BINDING 48 48 ATP (By similarity).
 BINDING 167 167 ATP (By similarity).
 MOD_RES 29 29 Phosphothreonine (By similarity).
 MOD_RES 44 44 N6-acetyllysine; by P300/CBP, PCAF/KAT2B
 MOD_RES 48 48 N6-acetyllysine; by PCAF/KAT2B and
 MOD_RES 175 175 Phosphoserine (By similarity).
 MOD_RES 186 186 Phosphothreonine; by CaMK1D (By
 MOD_RES 347 347 Phosphoserine; by CDK9 and PKA (By
 MOD_RES 350 350 Phosphothreonine; by CDK9 (By
 MOD_RES 353 353 Phosphoserine; by CDK9 (By similarity).
 MOD_RES 354 354 Phosphothreonine; by CDK9 (By
 MOD_RES 357 357 Phosphoserine; by CDK9 (By similarity).
 MOD_RES 362 362 Phosphothreonine; by CDK9 (By
 MOD_RES 363 363 Phosphothreonine; by CDK9 (By  

Keyword

 Acetylation; ATP-binding; Complete proteome; Cytoplasm; DNA damage; DNA repair; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Transcription; Transcription regulation; Transferase; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 372 AA 

Protein Sequence

Gene Ontology

 GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
 GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
 GO:0008024; C:positive transcription elongation factor complex b; ISS:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IEA:EC.
 GO:0008353; F:RNA polymerase II carboxy-terminal domain kinase activity; IEA:EC.
 GO:0017069; F:snRNA binding; IEA:Compara.
 GO:0044212; F:transcription regulatory region DNA binding; IEA:Compara.
 GO:0071345; P:cellular response to cytokine stimulus; IEA:Compara.
 GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
 GO:0071157; P:negative regulation of cell cycle arrest; IEA:Compara.
 GO:0006282; P:regulation of DNA repair; IEA:Compara.
 GO:0031056; P:regulation of histone modification; IEA:Compara.
 GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
 GO:0043111; P:replication fork arrest; IEA:Compara.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. 

Interpro

 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 

Pfam

 PF00069; Pkinase 

SMART

 SM00220; S_TKc 

PROSITE

 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 

PRINTS