CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-008327
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Cyclin-dependent kinase 9 
Protein Synonyms/Alias
 C-2K; Cell division cycle 2-like protein kinase 4; Cell division protein kinase 9; Serine/threonine-protein kinase PITALRE; Tat-associated kinase complex catalytic subunit 
Gene Name
 CDK9 
Gene Synonyms/Alias
 CDC2L4; TAK 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
120ALEAAMAKQYDSVECubiquitination[1, 2]
135PFCDEVSKYEKLAKIubiquitination[2]
141SKYEKLAKIGQGTFGubiquitination[2, 3]
152GTFGEVFKARHRKTGubiquitination[1, 2, 3]
173KVLMENEKEGFPITAubiquitination[2, 3]
185ITALREIKILQLLKHubiquitination[2, 4]
268KILHRDMKAANVLITubiquitination[2]
281ITRDGVLKLADFGLAubiquitination[1, 2, 3, 4]
295ARAFSLAKNSQPNRYubiquitination[1, 2, 3]
386YEKLELVKGQKRKVKubiquitination[2]
397RKVKDRLKAYVRDPYubiquitination[2]
411YALDLIDKLLVLDPAubiquitination[2, 3]
462YLAPPRRKGSQITQQubiquitination[2]
Reference
 [1] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [4] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789] 
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. 
Sequence Annotation
 DOMAIN 19 315 Protein kinase.
 NP_BIND 25 33 ATP (By similarity).
 NP_BIND 104 106 ATP.
 REGION 166 191 T-loop.
 ACT_SITE 149 149 Proton acceptor (By similarity).
 BINDING 48 48 ATP.
 BINDING 167 167 ATP.
 MOD_RES 29 29 Phosphothreonine.
 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.
 MOD_RES 186 186 Phosphothreonine; by CaMK1D.
 MOD_RES 347 347 Phosphoserine; by CDK9 and PKA.
 MOD_RES 350 350 Phosphothreonine; by CDK9.
 MOD_RES 353 353 Phosphoserine; by CDK9.
 MOD_RES 354 354 Phosphothreonine; by CDK9.
 MOD_RES 357 357 Phosphoserine; by CDK9.
 MOD_RES 362 362 Phosphothreonine; by CDK9.
 MOD_RES 363 363 Phosphothreonine; by CDK9.  
Keyword
 3D-structure; Acetylation; Alternative splicing; ATP-binding; Complete proteome; Cytoplasm; DNA damage; DNA repair; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; 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
MQRDAPPRAP APAPRLPAPP IGAAASSGGG GGGGSGGGGG GASAAPAPPG LSGTTSPRGP 60
GGGRRAEEAG SAPRGRKWPW RRKWRGRGGA WSAAAAGPGA GAAAAATGGG GGALEAAMAK 120
QYDSVECPFC DEVSKYEKLA KIGQGTFGEV FKARHRKTGQ KVALKKVLME NEKEGFPITA 180
LREIKILQLL KHENVVNLIE ICRTKASPYN RCKGSIYLVF DFCEHDLAGL LSNVLVKFTL 240
SEIKRVMQML LNGLYYIHRN KILHRDMKAA NVLITRDGVL KLADFGLARA FSLAKNSQPN 300
RYTNRVVTLW YRPPELLLGE RDYGPPIDLW GAGCIMAEMW TRSPIMQGNT EQHQLALISQ 360
LCGSITPEVW PNVDNYELYE KLELVKGQKR KVKDRLKAYV RDPYALDLID KLLVLDPAQR 420
IDSDDALNHD FFWSDPMPSD LKGMLSTHLT SMFEYLAPPR RKGSQITQQS TNQSRNPATT 480
NQTEFERVF 489 
Gene Ontology
 GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
 GO:0016605; C:PML body; IDA:UniProtKB.
 GO:0008024; C:positive transcription elongation factor complex b; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; TAS:ProtInc.
 GO:0003677; F:DNA binding; IDA:MGI.
 GO:0008353; F:RNA polymerase II carboxy-terminal domain kinase activity; IDA:UniProtKB.
 GO:0017069; F:snRNA binding; IEA:Compara.
 GO:0044212; F:transcription regulatory region DNA binding; IEA:Compara.
 GO:0008283; P:cell proliferation; TAS:ProtInc.
 GO:0071345; P:cellular response to cytokine stimulus; IDA:UniProtKB.
 GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
 GO:0071157; P:negative regulation of cell cycle arrest; IDA:UniProtKB.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; TAS:Reactome.
 GO:0050434; P:positive regulation of viral transcription; TAS:Reactome.
 GO:0006282; P:regulation of DNA repair; IDA:UniProtKB.
 GO:0031056; P:regulation of histone modification; IDA:UniProtKB.
 GO:0043111; P:replication fork arrest; IDA:UniProtKB.
 GO:0006368; P:transcription elongation from RNA polymerase II promoter; TAS:Reactome.
 GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome.
 GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:Reactome.
 GO:0022415; P:viral reproductive process; TAS:Reactome. 
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