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Protein

Cyclin-dependent kinase 9

Gene

CDK9

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.24 Publications

Catalytic activityi

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

Enzyme regulationi

Inhibited by CDKI-71, CR8, GPC-286199, AG-024322, flavopiridol (alvocidib), RBG-286147, anilinopyrimidine 32, arylazopyrazole 31b, indirubin 3'-monoxime, meriolin 3,P276-00, olomoucine II, pyrazolotriazine, meriolin, variolin, thiazolyl-pyrimidine, thiazolyl-pyrimidine, indirubin-30-monoxime, ZK 304709, AG-012986, AT7519, R547, RGB-286638, imidazole pyrimidine, EXEL-3700, EXEL-8647, 5,6-dichloro-1-b-ribofur-anosyl-benzimidazole (DRB), P276-00, roscovitine (seliciclib, CYC202) and SNS-032 (BMS-387032). 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-48.6 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei48ATPPROSITE-ProRule annotation1 Publication1
Active sitei149Proton acceptorPROSITE-ProRule annotation1
Binding sitei167ATPPROSITE-ProRule annotation1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi25 – 33ATPPROSITE-ProRule annotation9
Nucleotide bindingi104 – 106ATPPROSITE-ProRule annotation1 Publication3

GO - Molecular functioni

  • 7SK snRNA binding Source: UniProtKB
  • ATP binding Source: UniProtKB-KW
  • chromatin binding Source: UniProtKB
  • cyclin-dependent protein serine/threonine kinase activity Source: UniProtKB
  • DNA binding Source: MGI
  • kinase activity Source: Reactome
  • protein kinase activity Source: ProtInc
  • protein serine/threonine kinase activity Source: Reactome
  • RNA polymerase II carboxy-terminal domain kinase activity Source: UniProtKB
  • RNA polymerase II core promoter sequence-specific DNA binding Source: Ensembl
  • transcription coactivator binding Source: UniProtKB

GO - Biological processi

  • cell proliferation Source: ProtInc
  • cellular response to cytokine stimulus Source: UniProtKB
  • DNA repair Source: UniProtKB-KW
  • negative regulation of cell cycle arrest Source: UniProtKB
  • negative regulation of mRNA polyadenylation Source: UniProtKB
  • positive regulation of cardiac muscle hypertrophy Source: Ensembl
  • positive regulation of histone H2B ubiquitination Source: UniProtKB
  • positive regulation of histone phosphorylation Source: UniProtKB
  • positive regulation of mRNA 3'-UTR binding Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • positive regulation of viral transcription Source: Reactome
  • protein phosphorylation Source: MGI
  • regulation of DNA repair Source: UniProtKB
  • regulation of histone modification Source: UniProtKB
  • regulation of muscle cell differentiation Source: UniProtKB
  • replication fork processing Source: UniProtKB
  • response to drug Source: Ensembl
  • snRNA transcription from RNA polymerase II promoter Source: Reactome
  • transcription elongation from RNA polymerase II promoter Source: Reactome
  • transcription from RNA polymerase II promoter Source: Reactome
  • transcription initiation from RNA polymerase II promoter Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

DNA damage, DNA repair, Transcription, Transcription regulation

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS06213-MONOMER.
BRENDAi2.7.11.22. 2681.
2.7.11.23. 2681.
ReactomeiR-HSA-112382. Formation of RNA Pol II elongation complex.
R-HSA-112387. Elongation arrest and recovery.
R-HSA-167152. Formation of HIV elongation complex in the absence of HIV Tat.
R-HSA-167200. Formation of HIV-1 elongation complex containing HIV-1 Tat.
R-HSA-167238. Pausing and recovery of Tat-mediated HIV elongation.
R-HSA-167243. Tat-mediated HIV elongation arrest and recovery.
R-HSA-167246. Tat-mediated elongation of the HIV-1 transcript.
R-HSA-167287. HIV elongation arrest and recovery.
R-HSA-167290. Pausing and recovery of HIV elongation.
R-HSA-176034. Interactions of Tat with host cellular proteins.
R-HSA-2173796. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
R-HSA-674695. RNA Polymerase II Pre-transcription Events.
R-HSA-6796648. TP53 Regulates Transcription of DNA Repair Genes.
R-HSA-6807505. RNA polymerase II transcribes snRNA genes.
R-HSA-75955. RNA Polymerase II Transcription Elongation.
SignaLinkiP50750.
SIGNORiP50750.

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclin-dependent kinase 9 (EC:2.7.11.22, EC:2.7.11.23)
Alternative name(s):
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 namesi
Name:CDK9
Synonyms:CDC2L4, TAK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:1780. CDK9.

Subcellular locationi

  • Nucleus
  • Cytoplasm
  • NucleusPML body

  • 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.

GO - Cellular componenti

  • cyclin/CDK positive transcription elongation factor complex Source: UniProtKB
  • cytoplasm Source: UniProtKB-SubCell
  • intracellular membrane-bounded organelle Source: HPA
  • membrane Source: UniProtKB
  • nucleoplasm Source: HPA
  • PML body Source: UniProtKB
  • transcription elongation factor complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Chronic activation of CDK9 causes cardiac myocyte enlargement leading to cardiac hypertrophy, and confers predisposition to heart failure.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi44K → R: Impaired kinase and transcriptional elongation activities, but normal cyclin T1 and HEXIM1 binding. 1 Publication1
Mutagenesisi167D → N: Abrogates kinase activity. 2 Publications1
Mutagenesisi175S → A: Constitutive kinase activity. 1 Publication1
Mutagenesisi175S → D: Mimics phosphorylation, constitutive loss of kinase activity. 1 Publication1
Mutagenesisi186T → A: Abrogates autophosphorylation; no effect on kinase activity, but impaired CTD phosphorylation. 3 Publications1
Mutagenesisi186T → D: Mimics autophosphorylation; constitutive kinase activity, independently of calcium signaling. 3 Publications1
Mutagenesisi347 – 357SQITQQSTNQS → AQIAQQAANQA: Loss of autophosphorylation and impaired interaction with HIV TAT. 1 PublicationAdd BLAST11
Mutagenesisi347 – 357SQITQQSTNQS → EQIEQQEENQE: Mimics autophosphorylation and promotes interaction with HIV TAT. 1 PublicationAdd BLAST11

Organism-specific databases

DisGeNETi1025.
OpenTargetsiENSG00000136807.
PharmGKBiPA26316.

Chemistry databases

ChEMBLiCHEMBL3116.
GuidetoPHARMACOLOGYi1981.

Polymorphism and mutation databases

BioMutaiCDK9.
DMDMi68067660.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000858001 – 372Cyclin-dependent kinase 9Add BLAST372

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei29Phosphothreonine1 Publication1
Modified residuei44N6-acetyllysine; by P300/CBP, PCAF/KAT2B and GCN5/KAT2A2 Publications1
Modified residuei48N6-acetyllysine; by PCAF/KAT2B and GCN5/KAT2A1 Publication1
Modified residuei175Phosphoserine1 Publication1
Modified residuei186Phosphothreonine; by CaMK1DCombined sources8 Publications1
Modified residuei347Phosphoserine; by CDK9 and PKACombined sources2 Publications1
Modified residuei350Phosphothreonine; by CDK9Combined sources1 Publication1
Modified residuei353Phosphoserine; by CDK91 Publication1
Modified residuei354Phosphothreonine; by CDK91 Publication1
Modified residuei357Phosphoserine; by CDK91 Publication1
Modified residuei362Phosphothreonine; by CDK91 Publication1
Modified residuei363Phosphothreonine; by CDK91 Publication1
Isoform 2 (identifier: P50750-2)
Modified residuei35PhosphoserineCombined sources1
Modified residuei54PhosphothreonineCombined sources1

Post-translational modificationi

Autophosphorylation at Thr-186, Ser-347, Thr-350, Ser-353, Thr-354 and Ser-357 triggers kinase activity by promoting cyclin and substrate binding (e.g. HIV TAT) upon conformational changes. Thr-186 phosphorylation requires the calcium Ca2+ signaling pathway, including CaMK1D and calmodulin. This inhibition is relieved by Thr-29 dephosphorylation. However, phosphorylation at Thr-29 is inhibitory within the HIV transcription initiation complex. Phosphorylation at Ser-175 inhibits kinase activity. Can be phosphorylated on either Thr-362 or Thr-363 but not on both simultaneously (PubMed:18566585).10 Publications
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, contributing to the activation of HIV-1 transcription.
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 and with the transcriptionally silent HIV-1 genome; deacetylated upon transcription stimulation.2 Publications
Polyubiquitinated and thus activated by UBR5. This ubiquitination is promoted by TFIIS/TCEA1 and favors 'Ser-2' phosphorylation of RPB1/POLR2A CTD.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP50750.
MaxQBiP50750.
PaxDbiP50750.
PeptideAtlasiP50750.
PRIDEiP50750.

PTM databases

iPTMnetiP50750.
PhosphoSitePlusiP50750.

Expressioni

Tissue specificityi

Ubiquitous.

Inductioni

By replication stress, in chromatin. Probably degraded by the proteasome upon Thr-186 dephosphorylation.

Gene expression databases

BgeeiENSG00000136807.
CleanExiHS_CDK9.
ExpressionAtlasiP50750. baseline and differential.
GenevisibleiP50750. HS.

Organism-specific databases

HPAiCAB004216.
HPA006738.

Interactioni

Subunit structurei

Component of the super elongation complex (SEC), at least composed of EAF1, EAF2, CDK9, MLLT3/AF9, AFF (AFF1 or AFF4), the P-TEFb complex and ELL (ELL, ELL2 or ELL3). Associates with CCNT1/cyclin-T1, CCNT2/cyclin-T2 (isoform A and 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 pre-initiation 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 the acidic/proline-rich region of HIV-1 and HIV-2 Tat via T-loop region, and is thus required for HIV to hijack host transcription machinery during its replication through cooperative binding to viral TAR RNA. 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. The large PER complex involved in the repression of transcriptional termination is composed of at least PER2, CDK9, DDX5, DHX9, NCBP1 and POLR2A. Isoform 3 binds to KU70/XRCC6. Interacts with herpes simplex virus 1 protein ICP22; this interaction inhibits the positive transcription elongation factor b (P-TEFb).30 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ATRQ135353EBI-1383449,EBI-968983
ATRIPQ8WXE13EBI-1383449,EBI-747353
CCNT1O6056313EBI-1383449,EBI-2479671
CDC37Q165433EBI-1383449,EBI-295634
CLSPNQ9HAW43EBI-1383449,EBI-1369377
DHX30Q7L2E35EBI-1383449,EBI-1211456
FKBP5Q134514EBI-1383449,EBI-306914
HEXIM1O949927EBI-1383449,EBI-2832510
HSP90AA1P079002EBI-1383449,EBI-296047
HSP90AB1P082382EBI-1383449,EBI-352572
JMJD6Q6NYC15EBI-1383449,EBI-8464037
LARP7Q4G0J37EBI-1383449,EBI-2371923
NR2E3Q9Y5X44EBI-1383449,EBI-7216962
tatP046085EBI-1383449,EBI-6164389From a different organism.

GO - Molecular functioni

  • transcription coactivator binding Source: UniProtKB

Protein-protein interaction databases

BioGridi107459. 189 interactors.
DIPiDIP-29016N.
IntActiP50750. 70 interactors.
MINTiMINT-1532814.
STRINGi9606.ENSP00000362361.

Chemistry databases

BindingDBiP50750.

Structurei

Secondary structure

1372
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi13 – 15Combined sources3
Helixi16 – 18Combined sources3
Beta strandi19 – 24Combined sources6
Beta strandi28 – 30Combined sources3
Beta strandi32 – 38Combined sources7
Turni39 – 41Combined sources3
Beta strandi44 – 49Combined sources6
Beta strandi56 – 59Combined sources4
Helixi61 – 72Combined sources12
Beta strandi81 – 87Combined sources7
Beta strandi98 – 104Combined sources7
Beta strandi107 – 109Combined sources3
Helixi110 – 115Combined sources6
Beta strandi116 – 118Combined sources3
Helixi123 – 142Combined sources20
Helixi152 – 154Combined sources3
Beta strandi155 – 157Combined sources3
Beta strandi163 – 165Combined sources3
Helixi168 – 170Combined sources3
Beta strandi178 – 181Combined sources4
Helixi192 – 194Combined sources3
Helixi197 – 200Combined sources4
Helixi209 – 224Combined sources16
Helixi234 – 245Combined sources12
Turni250 – 252Combined sources3
Helixi256 – 258Combined sources3
Helixi260 – 262Combined sources3
Helixi263 – 265Combined sources3
Helixi275 – 283Combined sources9
Helixi286 – 295Combined sources10
Helixi300 – 302Combined sources3
Helixi306 – 310Combined sources5
Helixi313 – 316Combined sources4
Beta strandi317 – 319Combined sources3
Helixi325 – 329Combined sources5
Helixi335 – 339Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1PF6model-A1-372[»]
3BLHX-ray2.48A2-330[»]
3BLQX-ray2.90A2-330[»]
3BLRX-ray2.80A2-330[»]
3LQ5X-ray3.00A2-330[»]
3MI9X-ray2.10A1-345[»]
3MIAX-ray3.00A1-345[»]
3MY1X-ray2.80A2-330[»]
3TN8X-ray2.95A2-330[»]
3TNHX-ray3.20A2-330[»]
3TNIX-ray3.23A2-330[»]
4BCFX-ray3.01A2-330[»]
4BCGX-ray3.08A2-330[»]
4BCHX-ray2.96A2-330[»]
4BCIX-ray3.10A2-330[»]
4BCJX-ray3.16A2-330[»]
4EC8X-ray3.60A2-372[»]
4EC9X-ray3.21A2-372[»]
4IMYX-ray2.94A/C/E1-330[»]
4OGRX-ray3.00A/E/I1-330[»]
4OR5X-ray2.90A/F7-332[»]
ProteinModelPortaliP50750.
SMRiP50750.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP50750.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini19 – 315Protein kinasePROSITE-ProRule annotationAdd BLAST297

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni166 – 191T-loopAdd BLAST26

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0600. Eukaryota.
ENOG410XPIR. LUCA.
GeneTreeiENSGT00860000133755.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiP50750.
KOiK02211.
OMAiSITTEVW.
OrthoDBiEOG091G08Z8.
PhylomeDBiP50750.
TreeFamiTF101039.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P50750-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAKQYDSVEC PFCDEVSKYE KLAKIGQGTF GEVFKARHRK TGQKVALKKV
60 70 80 90 100
LMENEKEGFP ITALREIKIL QLLKHENVVN LIEICRTKAS PYNRCKGSIY
110 120 130 140 150
LVFDFCEHDL AGLLSNVLVK FTLSEIKRVM QMLLNGLYYI HRNKILHRDM
160 170 180 190 200
KAANVLITRD GVLKLADFGL ARAFSLAKNS QPNRYTNRVV TLWYRPPELL
210 220 230 240 250
LGERDYGPPI DLWGAGCIMA EMWTRSPIMQ GNTEQHQLAL ISQLCGSITP
260 270 280 290 300
EVWPNVDNYE LYEKLELVKG QKRKVKDRLK AYVRDPYALD LIDKLLVLDP
310 320 330 340 350
AQRIDSDDAL NHDFFWSDPM PSDLKGMLST HLTSMFEYLA PPRRKGSQIT
360 370
QQSTNQSRNP ATTNQTEFER VF
Length:372
Mass (Da):42,778
Last modified:June 21, 2005 - v3
Checksum:i69E851CC6F7A0388
GO
Isoform 2 (identifier: P50750-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MQRDAPPRAP...GGGGALEAAM

Show »
Length:489
Mass (Da):53,365
Checksum:iA0437DC909235A20
GO

Sequence cautioni

The sequence CAI39767 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti163L → P in AAV38706 (Ref. 4) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04198259F → L.1 PublicationCorresponds to variant rs55640715dbSNPEnsembl.1
Natural variantiVAR_013456231G → A.2 Publications1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0162881M → MQRDAPPRAPAPAPRLPAPP IGAAASSGGGGGGGSGGGGG GASAAPAPPGLSGTTSPRGP GGGRRAEEAGSAPRGRKWPW RRKWRGRGGAWSAAAAGPGA GAAAAATGGGGGALEAAM in isoform 2. Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L25676 mRNA. Translation: AAA35668.1.
X80230 mRNA. Translation: CAA56516.1.
AF255306 Genomic DNA. Translation: AAF72183.1.
BT019903 mRNA. Translation: AAV38706.1.
AF517840 Genomic DNA. Translation: AAM54039.1.
AL162586 Genomic DNA. Translation: CAI39767.1. Sequence problems.
AL162586 Genomic DNA. Translation: CAI39768.1.
BC001968 mRNA. Translation: AAH01968.1.
CCDSiCCDS6879.1. [P50750-1]
PIRiA55262.
RefSeqiNP_001252.1. NM_001261.3. [P50750-1]
UniGeneiHs.150423.
Hs.706809.

Genome annotation databases

EnsembliENST00000373264; ENSP00000362361; ENSG00000136807. [P50750-1]
GeneIDi1025.
KEGGihsa:1025.
UCSCiuc004bse.3. human. [P50750-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L25676 mRNA. Translation: AAA35668.1.
X80230 mRNA. Translation: CAA56516.1.
AF255306 Genomic DNA. Translation: AAF72183.1.
BT019903 mRNA. Translation: AAV38706.1.
AF517840 Genomic DNA. Translation: AAM54039.1.
AL162586 Genomic DNA. Translation: CAI39767.1. Sequence problems.
AL162586 Genomic DNA. Translation: CAI39768.1.
BC001968 mRNA. Translation: AAH01968.1.
CCDSiCCDS6879.1. [P50750-1]
PIRiA55262.
RefSeqiNP_001252.1. NM_001261.3. [P50750-1]
UniGeneiHs.150423.
Hs.706809.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1PF6model-A1-372[»]
3BLHX-ray2.48A2-330[»]
3BLQX-ray2.90A2-330[»]
3BLRX-ray2.80A2-330[»]
3LQ5X-ray3.00A2-330[»]
3MI9X-ray2.10A1-345[»]
3MIAX-ray3.00A1-345[»]
3MY1X-ray2.80A2-330[»]
3TN8X-ray2.95A2-330[»]
3TNHX-ray3.20A2-330[»]
3TNIX-ray3.23A2-330[»]
4BCFX-ray3.01A2-330[»]
4BCGX-ray3.08A2-330[»]
4BCHX-ray2.96A2-330[»]
4BCIX-ray3.10A2-330[»]
4BCJX-ray3.16A2-330[»]
4EC8X-ray3.60A2-372[»]
4EC9X-ray3.21A2-372[»]
4IMYX-ray2.94A/C/E1-330[»]
4OGRX-ray3.00A/E/I1-330[»]
4OR5X-ray2.90A/F7-332[»]
ProteinModelPortaliP50750.
SMRiP50750.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107459. 189 interactors.
DIPiDIP-29016N.
IntActiP50750. 70 interactors.
MINTiMINT-1532814.
STRINGi9606.ENSP00000362361.

Chemistry databases

BindingDBiP50750.
ChEMBLiCHEMBL3116.
GuidetoPHARMACOLOGYi1981.

PTM databases

iPTMnetiP50750.
PhosphoSitePlusiP50750.

Polymorphism and mutation databases

BioMutaiCDK9.
DMDMi68067660.

Proteomic databases

EPDiP50750.
MaxQBiP50750.
PaxDbiP50750.
PeptideAtlasiP50750.
PRIDEiP50750.

Protocols and materials databases

DNASUi1025.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000373264; ENSP00000362361; ENSG00000136807. [P50750-1]
GeneIDi1025.
KEGGihsa:1025.
UCSCiuc004bse.3. human. [P50750-1]

Organism-specific databases

CTDi1025.
DisGeNETi1025.
GeneCardsiCDK9.
HGNCiHGNC:1780. CDK9.
HPAiCAB004216.
HPA006738.
MIMi603251. gene.
neXtProtiNX_P50750.
OpenTargetsiENSG00000136807.
PharmGKBiPA26316.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0600. Eukaryota.
ENOG410XPIR. LUCA.
GeneTreeiENSGT00860000133755.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiP50750.
KOiK02211.
OMAiSITTEVW.
OrthoDBiEOG091G08Z8.
PhylomeDBiP50750.
TreeFamiTF101039.

Enzyme and pathway databases

BioCyciZFISH:HS06213-MONOMER.
BRENDAi2.7.11.22. 2681.
2.7.11.23. 2681.
ReactomeiR-HSA-112382. Formation of RNA Pol II elongation complex.
R-HSA-112387. Elongation arrest and recovery.
R-HSA-167152. Formation of HIV elongation complex in the absence of HIV Tat.
R-HSA-167200. Formation of HIV-1 elongation complex containing HIV-1 Tat.
R-HSA-167238. Pausing and recovery of Tat-mediated HIV elongation.
R-HSA-167243. Tat-mediated HIV elongation arrest and recovery.
R-HSA-167246. Tat-mediated elongation of the HIV-1 transcript.
R-HSA-167287. HIV elongation arrest and recovery.
R-HSA-167290. Pausing and recovery of HIV elongation.
R-HSA-176034. Interactions of Tat with host cellular proteins.
R-HSA-2173796. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
R-HSA-674695. RNA Polymerase II Pre-transcription Events.
R-HSA-6796648. TP53 Regulates Transcription of DNA Repair Genes.
R-HSA-6807505. RNA polymerase II transcribes snRNA genes.
R-HSA-75955. RNA Polymerase II Transcription Elongation.
SignaLinkiP50750.
SIGNORiP50750.

Miscellaneous databases

ChiTaRSiCDK9. human.
EvolutionaryTraceiP50750.
GeneWikiiCDK9.
Cyclin-dependent_kinase_9.
GenomeRNAii1025.
PROiP50750.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000136807.
CleanExiHS_CDK9.
ExpressionAtlasiP50750. baseline and differential.
GenevisibleiP50750. HS.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCDK9_HUMAN
AccessioniPrimary (citable) accession number: P50750
Secondary accession number(s): Q5JU24
, Q5JU25, Q5U006, Q96TF1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: June 21, 2005
Last modified: November 30, 2016
This is version 191 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

CDK9 inhibition contributes to the anticancer activity of most CDK inhibitors under clinical investigation (PubMed:18423896 and PubMed:21779453). As a retroviruses target during the hijack of host transcription (e.g. HIV), CDK9 inhibitors might become specific antiretroviral agents (PubMed:18423896). May be a target for cardiac hypertrophy future treatments (PubMed:19757441 and PubMed:18423896). May also be a target in anti-inflammatory therapy in innate immunity and systemic inflammation (PubMed:18728388).2 Publications

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.