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P50750

- CDK9_HUMAN

UniProt

P50750 - CDK9_HUMAN

Protein

Cyclin-dependent kinase 9

Gene

CDK9

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 166 (01 Oct 2014)
      Sequence version 3 (21 Jun 2005)
      Previous versions | rss
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    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)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei48 – 481ATP1 PublicationPROSITE-ProRule annotation
    Active sitei149 – 1491Proton acceptorPROSITE-ProRule annotation
    Binding sitei167 – 1671ATP1 PublicationPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi25 – 339ATPPROSITE-ProRule annotation
    Nucleotide bindingi104 – 1063ATP1 PublicationPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. chromatin binding Source: Ensembl
    3. cyclin-dependent protein serine/threonine kinase activity Source: ProtInc
    4. DNA binding Source: MGI
    5. protein binding Source: UniProtKB
    6. protein kinase activity Source: ProtInc
    7. RNA polymerase II carboxy-terminal domain kinase activity Source: UniProtKB
    8. snRNA binding Source: Ensembl
    9. transcription regulatory region DNA binding Source: Ensembl

    GO - Biological processi

    1. cell proliferation Source: ProtInc
    2. cellular response to cytokine stimulus Source: UniProtKB
    3. DNA repair Source: UniProtKB-KW
    4. gene expression Source: Reactome
    5. negative regulation of cell cycle arrest Source: UniProtKB
    6. positive regulation of transcription from RNA polymerase II promoter Source: Reactome
    7. positive regulation of viral transcription Source: Reactome
    8. protein phosphorylation Source: MGI
    9. regulation of DNA repair Source: UniProtKB
    10. regulation of histone modification Source: UniProtKB
    11. replication fork arrest Source: UniProtKB
    12. transcription, DNA-templated Source: Reactome
    13. transcription elongation from RNA polymerase II promoter Source: Reactome
    14. transcription from RNA polymerase II promoter Source: Reactome
    15. transcription initiation from RNA polymerase II promoter Source: Reactome
    16. transforming growth factor beta receptor signaling pathway Source: Reactome
    17. viral process Source: Reactome

    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

    BRENDAi2.7.11.22. 2681.
    ReactomeiREACT_120734. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
    REACT_22107. RNA Polymerase II Pre-transcription Events.
    REACT_22201. Formation of HIV elongation complex in the absence of HIV Tat.
    REACT_6143. Pausing and recovery of Tat-mediated HIV elongation.
    REACT_6162. Tat-mediated elongation of the HIV-1 transcript.
    REACT_6244. Pausing and recovery of HIV elongation.
    REACT_6259. HIV elongation arrest and recovery.
    REACT_6344. Tat-mediated HIV elongation arrest and recovery.
    REACT_6346. Formation of HIV-1 elongation complex containing HIV-1 Tat.
    REACT_6905. Interactions of Tat with host cellular proteins.
    REACT_833. RNA Polymerase II Transcription Elongation.
    SignaLinkiP50750.

    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
    ProteomesiUP000005640: 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

    1. cytoplasm Source: UniProtKB-SubCell
    2. intracellular membrane-bounded organelle Source: HPA
    3. membrane Source: UniProtKB
    4. nucleoplasm Source: Reactome
    5. nucleus Source: HPA
    6. PML body Source: UniProtKB
    7. positive transcription elongation factor complex b Source: UniProtKB
    8. transcription elongation factor complex Source: ProtInc

    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)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi44 – 441K → R: Impaired kinase and transcriptional elongation activities, but normal cyclin T1 and HEXIM1 binding. 1 Publication
    Mutagenesisi167 – 1671D → N: Abrogates kinase activity. 2 Publications
    Mutagenesisi175 – 1751S → A: Constitutive kinase activity. 1 Publication
    Mutagenesisi175 – 1751S → D: Mimics phosphorylation, constitutive loss of kinase activity. 1 Publication
    Mutagenesisi186 – 1861T → A: Abrogates autophosphorylation; no effect on kinase activity, but impaired CTD phosphorylation. 3 Publications
    Mutagenesisi186 – 1861T → D: Mimics autophosphorylation; constitutive kinase activity, independently of calcium signaling. 3 Publications
    Mutagenesisi347 – 35711SQITQQSTNQS → AQIAQQAANQA: Loss of autophosphorylation and impaired interaction with HIV TAT. Add
    BLAST
    Mutagenesisi347 – 35711SQITQQSTNQS → EQIEQQEENQE: Mimics autophosphorylation and promotes interaction with HIV TAT. Add
    BLAST

    Organism-specific databases

    PharmGKBiPA26316.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 372372Cyclin-dependent kinase 9PRO_0000085800Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei29 – 291Phosphothreonine1 Publication
    Modified residuei44 – 441N6-acetyllysine; by P300/CBP, PCAF/KAT2B and GCN5/KAT2A2 Publications
    Modified residuei48 – 481N6-acetyllysine; by PCAF/KAT2B and GCN5/KAT2A1 Publication
    Modified residuei175 – 1751Phosphoserine2 Publications
    Modified residuei186 – 1861Phosphothreonine; by CaMK1D10 Publications
    Modified residuei347 – 3471Phosphoserine; by CDK9 and PKA4 Publications
    Modified residuei350 – 3501Phosphothreonine; by CDK92 Publications
    Modified residuei353 – 3531Phosphoserine; by CDK91 Publication
    Modified residuei354 – 3541Phosphothreonine; by CDK91 Publication
    Modified residuei357 – 3571Phosphoserine; by CDK91 Publication
    Modified residuei362 – 3621Phosphothreonine; by CDK92 Publications
    Modified residuei363 – 3631Phosphothreonine; by CDK92 Publications

    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).13 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

    MaxQBiP50750.
    PaxDbiP50750.
    PRIDEiP50750.

    PTM databases

    PhosphoSiteiP50750.

    Expressioni

    Tissue specificityi

    Ubiquitous.

    Inductioni

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

    Gene expression databases

    BgeeiP50750.
    CleanExiHS_CDK9.
    GenevestigatoriP50750.

    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/XRCC6.29 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.

    Protein-protein interaction databases

    BioGridi107459. 176 interactions.
    DIPiDIP-29016N.
    IntActiP50750. 61 interactions.
    MINTiMINT-1532814.
    STRINGi9606.ENSP00000362361.

    Structurei

    Secondary structure

    1
    372
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi13 – 153
    Helixi16 – 183
    Beta strandi19 – 246
    Beta strandi28 – 303
    Beta strandi32 – 387
    Turni39 – 413
    Beta strandi44 – 496
    Beta strandi56 – 594
    Helixi61 – 7212
    Beta strandi81 – 877
    Beta strandi98 – 1047
    Beta strandi107 – 1093
    Helixi110 – 1156
    Beta strandi116 – 1183
    Helixi123 – 14220
    Helixi152 – 1543
    Beta strandi155 – 1573
    Beta strandi163 – 1653
    Helixi168 – 1703
    Beta strandi178 – 1814
    Helixi192 – 1943
    Helixi197 – 2004
    Helixi209 – 22416
    Helixi234 – 24512
    Turni250 – 2523
    Helixi256 – 2583
    Helixi260 – 2623
    Helixi263 – 2653
    Helixi275 – 2839
    Helixi286 – 29510
    Helixi300 – 3023
    Helixi306 – 3105
    Helixi313 – 3164
    Beta strandi317 – 3193
    Helixi325 – 3295
    Helixi335 – 3395

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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. Positions 6-327.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP50750.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini19 – 315297Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni166 – 19126T-loopAdd
    BLAST

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000233024.
    HOVERGENiHBG014652.
    InParanoidiP50750.
    KOiK02211.
    OMAiMELPKGQ.
    OrthoDBiEOG76DTSM.
    PhylomeDBiP50750.
    TreeFamiTF101039.

    Family and domain databases

    InterProiIPR011009. 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]
    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. Align

    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

    MAKQYDSVEC PFCDEVSKYE KLAKIGQGTF GEVFKARHRK TGQKVALKKV    50
    LMENEKEGFP ITALREIKIL QLLKHENVVN LIEICRTKAS PYNRCKGSIY 100
    LVFDFCEHDL AGLLSNVLVK FTLSEIKRVM QMLLNGLYYI HRNKILHRDM 150
    KAANVLITRD GVLKLADFGL ARAFSLAKNS QPNRYTNRVV TLWYRPPELL 200
    LGERDYGPPI DLWGAGCIMA EMWTRSPIMQ GNTEQHQLAL ISQLCGSITP 250
    EVWPNVDNYE LYEKLELVKG QKRKVKDRLK AYVRDPYALD LIDKLLVLDP 300
    AQRIDSDDAL NHDFFWSDPM PSDLKGMLST HLTSMFEYLA PPRRKGSQIT 350
    QQSTNQSRNP ATTNQTEFER VF 372
    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

    Note: Contains a phosphoserine at position 35.

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

    Sequence cautioni

    The sequence CAI39767.1 differs from that shown. Reason: Erroneous gene model prediction.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti163 – 1631L → P in AAV38706. 1 PublicationCurated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti59 – 591F → L.1 Publication
    Corresponds to variant rs55640715 [ dbSNP | Ensembl ].
    VAR_041982
    Natural varianti231 – 2311G → A.2 Publications
    VAR_013456

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 11M → MQRDAPPRAPAPAPRLPAPP IGAAASSGGGGGGGSGGGGG GASAAPAPPGLSGTTSPRGP GGGRRAEEAGSAPRGRKWPW RRKWRGRGGAWSAAAAGPGA GAAAAATGGGGGALEAAM in isoform 2. CuratedVSP_016288

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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.2. human. [P50750-1]

    Polymorphism databases

    DMDMi68067660.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS6879.1. [P50750-1 ]
    PIRi A55262.
    RefSeqi NP_001252.1. NM_001261.3. [P50750-1 ]
    UniGenei Hs.150423.
    Hs.706809.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1PF6 model - A 1-372 [» ]
    3BLH X-ray 2.48 A 2-330 [» ]
    3BLQ X-ray 2.90 A 2-330 [» ]
    3BLR X-ray 2.80 A 2-330 [» ]
    3LQ5 X-ray 3.00 A 2-330 [» ]
    3MI9 X-ray 2.10 A 1-345 [» ]
    3MIA X-ray 3.00 A 1-345 [» ]
    3MY1 X-ray 2.80 A 2-330 [» ]
    3TN8 X-ray 2.95 A 2-330 [» ]
    3TNH X-ray 3.20 A 2-330 [» ]
    3TNI X-ray 3.23 A 2-330 [» ]
    4BCF X-ray 3.01 A 2-330 [» ]
    4BCG X-ray 3.08 A 2-330 [» ]
    4BCH X-ray 2.96 A 2-330 [» ]
    4BCI X-ray 3.10 A 2-330 [» ]
    4BCJ X-ray 3.16 A 2-330 [» ]
    4EC8 X-ray 3.60 A 2-372 [» ]
    4EC9 X-ray 3.21 A 2-372 [» ]
    4IMY X-ray 2.94 A/C/E 1-330 [» ]
    4OGR X-ray 3.00 A/E/I 1-330 [» ]
    4OR5 X-ray 2.90 A/F 7-332 [» ]
    ProteinModelPortali P50750.
    SMRi P50750. Positions 6-327.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107459. 176 interactions.
    DIPi DIP-29016N.
    IntActi P50750. 61 interactions.
    MINTi MINT-1532814.
    STRINGi 9606.ENSP00000362361.

    Chemistry

    BindingDBi P50750.
    ChEMBLi CHEMBL3038475.
    GuidetoPHARMACOLOGYi 1981.

    PTM databases

    PhosphoSitei P50750.

    Polymorphism databases

    DMDMi 68067660.

    Proteomic databases

    MaxQBi P50750.
    PaxDbi P50750.
    PRIDEi P50750.

    Protocols and materials databases

    DNASUi 1025.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000373264 ; ENSP00000362361 ; ENSG00000136807 . [P50750-1 ]
    GeneIDi 1025.
    KEGGi hsa:1025.
    UCSCi uc004bse.2. human. [P50750-1 ]

    Organism-specific databases

    CTDi 1025.
    GeneCardsi GC09P130547.
    HGNCi HGNC:1780. CDK9.
    HPAi CAB004216.
    HPA006738.
    MIMi 603251. gene.
    neXtProti NX_P50750.
    PharmGKBi PA26316.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000233024.
    HOVERGENi HBG014652.
    InParanoidi P50750.
    KOi K02211.
    OMAi MELPKGQ.
    OrthoDBi EOG76DTSM.
    PhylomeDBi P50750.
    TreeFami TF101039.

    Enzyme and pathway databases

    BRENDAi 2.7.11.22. 2681.
    Reactomei REACT_120734. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
    REACT_22107. RNA Polymerase II Pre-transcription Events.
    REACT_22201. Formation of HIV elongation complex in the absence of HIV Tat.
    REACT_6143. Pausing and recovery of Tat-mediated HIV elongation.
    REACT_6162. Tat-mediated elongation of the HIV-1 transcript.
    REACT_6244. Pausing and recovery of HIV elongation.
    REACT_6259. HIV elongation arrest and recovery.
    REACT_6344. Tat-mediated HIV elongation arrest and recovery.
    REACT_6346. Formation of HIV-1 elongation complex containing HIV-1 Tat.
    REACT_6905. Interactions of Tat with host cellular proteins.
    REACT_833. RNA Polymerase II Transcription Elongation.
    SignaLinki P50750.

    Miscellaneous databases

    ChiTaRSi CDK9. human.
    EvolutionaryTracei P50750.
    GeneWikii CDK9.
    Cyclin-dependent_kinase_9.
    GenomeRNAii 1025.
    NextBioi 4305.
    PROi P50750.
    SOURCEi Search...

    Gene expression databases

    Bgeei P50750.
    CleanExi HS_CDK9.
    Genevestigatori P50750.

    Family and domain databases

    InterProi IPR011009. 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 ]
    Pfami PF00069. Pkinase. 1 hit.
    [Graphical view ]
    SMARTi SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "PITALRE, a nuclear CDC2-related protein kinase that phosphorylates the retinoblastoma protein in vitro."
      Grana X., de Luca A., Sang N., Fu Y., Claudio P.P., Rosenblatt J., Morgan D.O., Giordano A.
      Proc. Natl. Acad. Sci. U.S.A. 91:3834-3838(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. "Cloning of a full-length cDNA sequence encoding a cdc2-related protein kinase from human endothelial cells."
      Best J.L., Presky D.H., Swerlick R.A., Burns D.K., Chu W.
      Biochem. Biophys. Res. Commun. 208:562-568(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ALA-231.
    3. "Genomic organization and characterization of promoter function of the human CDK9 gene."
      Liu H., Rice A.P.
      Gene 252:51-59(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ALA-231.
    4. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
      Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
      Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    5. NIEHS SNPs program
      Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    6. "DNA sequence and analysis of human chromosome 9."
      Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L.
      , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
      Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Cervix.
    8. "A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat and mediates its high-affinity, loop-specific binding to TAR RNA."
      Wei P., Garber M.E., Fang S.-M., Fischer W.H., Jones K.A.
      Cell 92:451-462(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HIV TAT.
    9. "Evidence that P-TEFb alleviates the negative effect of DSIF on RNA polymerase II-dependent transcription in vitro."
      Wada T., Takagi T., Yamaguchi Y., Watanabe D., Handa H.
      EMBO J. 17:7395-7403(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    10. "Identification of multiple cyclin subunits of human P-TEFb."
      Peng J.-M., Zhu Y., Milton J.T., Price D.H.
      Genes Dev. 12:755-762(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION IN A COMPLEX WITH CCNT1 AND CCNT2.
    11. "A novel RNA polymerase II-containing complex potentiates Tat-enhanced HIV-1 transcription."
      Parada C.A., Roeder R.G.
      EMBO J. 18:3688-3701(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH HTATSF1; CCNT1; RNA POL II; SUPT5H AND NCL.
    12. "Cyclin K functions as a CDK9 regulatory subunit and participates in RNA polymerase II transcription."
      Fu T.J., Peng J., Lee G., Price D.H., Flores O.
      J. Biol. Chem. 274:34527-34530(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH CCNK.
    13. "FACT relieves DSIF/NELF-mediated inhibition of transcriptional elongation and reveals functional differences between P-TEFb and TFIIH."
      Wada T., Orphanides G., Hasegawa J., Kim D.-K., Shima D., Yamaguchi Y., Fukuda A., Hisatake K., Oh S., Reinberg D., Handa H.
      Mol. Cell 5:1067-1072(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    14. "Domains in the SPT5 protein that modulate its transcriptional regulatory properties."
      Ivanov D., Kwak Y.T., Guo J., Gaynor R.B.
      Mol. Cell. Biol. 20:2970-2983(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    15. "CDK9 autophosphorylation regulates high-affinity binding of the human immunodeficiency virus type 1 tat-P-TEFb complex to TAR RNA."
      Garber M.E., Mayall T.P., Suess E.M., Meisenhelder J., Thompson N.E., Jones K.A.
      Mol. Cell. Biol. 20:6958-6969(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION BY PKA, AUTOPHOSPHORYLATION, PHOSPHORYLATION AT SER-347; THR-350; SER-353; THR-354 AND SER-357, INTERACTION WITH HIV TAT, MUTAGENESIS OF 347-SER--SER-357 AND ASP-167.
    16. "Positive transcription elongation factor B phosphorylates hSPT5 and RNA polymerase II carboxyl-terminal domain independently of cyclin-dependent kinase-activating kinase."
      Kim J.B., Sharp P.A.
      J. Biol. Chem. 276:12317-12323(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF ASP-167 AND THR-186.
    17. "DSIF and NELF interact with RNA polymerase II elongation complex and HIV-1 Tat stimulates P-TEFb-mediated phosphorylation of RNA polymerase II and DSIF during transcription elongation."
      Ping Y.-H., Rana T.M.
      J. Biol. Chem. 276:12951-12958(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    18. "The peptidyl-prolyl isomerase Pin1 interacts with hSpt5 phosphorylated by Cdk9."
      Lavoie S.B., Albert A.L., Handa H., Vincent M., Bensaude O.
      J. Mol. Biol. 312:675-685(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    19. "P-TEFb containing cyclin K and Cdk9 can activate transcription via RNA."
      Lin X., Taube R., Fujinaga K., Peterlin B.M.
      J. Biol. Chem. 277:16873-16878(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH CCNK/CYCLIN K.
    20. "MCEF, the newest member of the AF4 family of transcription factors involved in leukemia, is a positive transcription elongation factor-b-associated protein."
      Estable M.C., Naghavi M.H., Kato H., Xiao H., Qin J., Vahlne A., Roeder R.G.
      J. Biomed. Sci. 9:234-245(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH AFF4.
    21. "CDK9 has the intrinsic property to shuttle between nucleus and cytoplasm, and enhanced expression of cyclin T1 promotes its nuclear localization."
      Napolitano G., Licciardo P., Carbone R., Majello B., Lania L.
      J. Cell. Physiol. 192:209-215(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    22. "Spt5 cooperates with human immunodeficiency virus type 1 Tat by preventing premature RNA release at terminator sequences."
      Bourgeois C.F., Kim Y.K., Churcher M.J., West M.J., Karn J.
      Mol. Cell. Biol. 22:1079-1093(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    23. Cited for: FUNCTION AS MYOD1 KINASE, INTERACTION WITH MYOD1 AND CCNT2.
    24. "Methylation of SPT5 regulates its interaction with RNA polymerase II and transcriptional elongation properties."
      Kwak Y.T., Guo J., Prajapati S., Park K.-J., Surabhi R.M., Miller B., Gehrig P., Gaynor R.B.
      Mol. Cell 11:1055-1066(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SUPT5H.
    25. "Coordination of transcription factor phosphorylation and histone methylation by the P-TEFb kinase during human immunodeficiency virus type 1 transcription."
      Zhou M., Deng L., Lacoste V., Park H.U., Pumfery A., Kashanchi F., Brady J.N., Kumar A.
      J. Virol. 78:13522-13533(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    26. "Dynamics of human immunodeficiency virus transcription: P-TEFb phosphorylates RD and dissociates negative effectors from the transactivation response element."
      Fujinaga K., Irwin D., Huang Y., Taube R., Kurosu T., Peterlin B.M.
      Mol. Cell. Biol. 24:787-795(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    27. "Analysis of the large inactive P-TEFb complex indicates that it contains one 7SK molecule, a dimer of HEXIM1 or HEXIM2, and two P-TEFb molecules containing Cdk9 phosphorylated at threonine 186."
      Li Q., Price J.P., Byers S.A., Cheng D., Peng J., Price D.H.
      J. Biol. Chem. 280:28819-28826(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION IN INACTIVE 7SK SNRNP COMPLEX, PHOSPHORYLATION AT THR-186.
    28. "The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription."
      Jang M.K., Mochizuki K., Zhou M., Jeong H.S., Brady J.N., Ozato K.
      Mol. Cell 19:523-534(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH BRD4.
    29. "Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4."
      Yang Z., Yik J.H., Chen R., He N., Jang M.K., Ozato K., Zhou Q.
      Mol. Cell 19:535-545(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH BRD4.
    30. "The functional role of an interleukin 6-inducible CDK9.STAT3 complex in human gamma-fibrinogen gene expression."
      Hou T., Ray S., Brasier A.R.
      J. Biol. Chem. 282:37091-37102(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CYTOKINE SIGNALING, INTERACTION WITH STAT3.
    31. "Systematic analysis of the protein interaction network for the human transcription machinery reveals the identity of the 7SK capping enzyme."
      Jeronimo C., Forget D., Bouchard A., Li Q., Chua G., Poitras C., Therien C., Bergeron D., Bourassa S., Greenblatt J., Chabot B., Poirier G.G., Hughes T.R., Blanchette M., Price D.H., Coulombe B.
      Mol. Cell 27:262-274(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION IN THE 7SK SNRNP COMPLEX.
    32. "Regulation of P-TEFb elongation complex activity by CDK9 acetylation."
      Fu J., Yoon H.-G., Qin J., Wong J.
      Mol. Cell. Biol. 27:4641-4651(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION AT LYS-44 BY P300/CBP, IDENTIFICATION IN COMPLEX WITH NCOR1; HEXIM1 AND HDAC3, MUTAGENESIS OF LYS-44.
    33. "PP2B and PP1alpha cooperatively disrupt 7SK snRNP to release P-TEFb for transcription in response to Ca2+ signaling."
      Chen R., Liu M., Li H., Xue Y., Ramey W.N., He N., Ai N., Luo H., Zhu Y., Zhou N., Zhou Q.
      Genes Dev. 22:1356-1368(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-186, DEPHOSPHORYLATION BY PPP1CA, P-TEFB/7SK SNRNP COMPLEX, SUBUNIT, INTERACTION WITH BRD4, ENZYME REGULATION.
    34. "Phosphatase PPM1A regulates phosphorylation of Thr-186 in the Cdk9 T-loop."
      Wang Y., Dow E.C., Liang Y.Y., Ramakrishnan R., Liu H., Sung T.L., Lin X., Rice A.P.
      J. Biol. Chem. 283:33578-33584(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-186, DEPHOSPHORYLATION BY PPM1A AND PPM1B.
    35. "A La-related protein modulates 7SK snRNP integrity to suppress P-TEFb-dependent transcriptional elongation and tumorigenesis."
      He N., Jahchan N.S., Hong E., Li Q., Bayfield M.A., Maraia R.J., Luo K., Zhou Q.
      Mol. Cell 29:588-599(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION IN COMPLEX WITH LARP7 IN 7SK SNRNP COMPLEX.
    36. "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
      Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
      Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-347, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35 (ISOFORM 2), IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    37. "Acetylation of conserved lysines in the catalytic core of cyclin-dependent kinase 9 inhibits kinase activity and regulates transcription."
      Sabo A., Lusic M., Cereseto A., Giacca M.
      Mol. Cell. Biol. 28:2201-2212(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION AT LYS-44 AND LYS-48 BY PCAF/KAT2B AND GCN5/KAT2A, ENZYME REGULATION BY ACETYLATION, SUBCELLULAR LOCATION.
    38. "RelA Ser276 phosphorylation is required for activation of a subset of NF-kappaB-dependent genes by recruiting cyclin-dependent kinase 9/cyclin T1 complexes."
      Nowak D.E., Tian B., Jamaluddin M., Boldogh I., Vergara L.A., Choudhary S., Brasier A.R.
      Mol. Cell. Biol. 28:3623-3638(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CYTOKINE SIGNALING, INTERACTION WITH RELA/P65.
    39. "Insights into the function of the human P-TEFb component CDK9 in the regulation of chromatin modifications and co-transcriptional mRNA processing."
      Pirngruber J., Shchebet A., Johnsen S.A.
      Cell Cycle 8:3636-3642(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN HISTONE REGULATION.
    40. "CDK9 directs H2B monoubiquitination and controls replication-dependent histone mRNA 3'-end processing."
      Pirngruber J., Shchebet A., Schreiber L., Shema E., Minsky N., Chapman R.D., Eick D., Aylon Y., Oren M., Johnsen S.A.
      EMBO Rep. 10:894-900(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN HISTONE H2B UBIQUITINATION.
    41. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-347 AND THR-350, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35 (ISOFORM 2), IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    42. "55K isoform of CDK9 associates with Ku70 and is involved in DNA repair."
      Liu H., Herrmann C.H., Chiang K., Sung T.L., Moon S.H., Donehower L.A., Rice A.P.
      Biochem. Biophys. Res. Commun. 397:245-250(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN DNA REPAIR, INTERACTION WITH KU70/XRCC6.
    43. "Cyclin-dependent kinase 9-cyclin K functions in the replication stress response."
      Yu D.S., Zhao R., Hsu E.L., Cayer J., Ye F., Guo Y., Shyr Y., Cortez D.
      EMBO Rep. 11:876-882(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CDK9/CYCLIN K COMPLEX DURING REPLICATION STRESS.
    44. "Cyclin-dependent kinase-9 is a component of the p300/GATA4 complex required for phenylephrine-induced hypertrophy in cardiomyocytes."
      Sunagawa Y., Morimoto T., Takaya T., Kaichi S., Wada H., Kawamura T., Fujita M., Shimatsu A., Kita T., Hasegawa K.
      J. Biol. Chem. 285:9556-9568(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CARDIAC HYPERTROPHY, IDENTIFICATION IN COMPLEX WITH CCNT1/CYCLIN-T1; EP300 AND GATA4.
    45. "HIV-1 Tat and host AFF4 recruit two transcription elongation factors into a bifunctional complex for coordinated activation of HIV-1 transcription."
      He N., Liu M., Hsu J., Xue Y., Chou S., Burlingame A., Krogan N.J., Alber T., Zhou Q.
      Mol. Cell 38:428-438(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION IN THE SEC COMPLEX.
    46. "AFF4, a component of the ELL/P-TEFb elongation complex and a shared subunit of MLL chimeras, can link transcription elongation to leukemia."
      Lin C., Smith E.R., Takahashi H., Lai K.C., Martin-Brown S., Florens L., Washburn M.P., Conaway J.W., Conaway R.C., Shilatifard A.
      Mol. Cell 37:429-437(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION IN THE SEC COMPLEX.
    47. Cited for: FUNCTION IN AR KINASE, INTERACTION WITH AR.
    48. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    49. Cited for: IDENTIFICATION IN THE SEC COMPLEX.
    50. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
      Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
      Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-186, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    51. "CDKI-71, a novel CDK9 inhibitor, is preferentially cytotoxic to cancer cells compared to flavopiridol."
      Liu X., Shi S., Lam F., Pepper C., Fischer P.M., Wang S.
      Int. J. Cancer 130:1216-1226(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME REGULATION BY CDKI-71.
    52. "Transcription factor IIS cooperates with the E3 ligase UBR5 to ubiquitinate the CDK9 subunit of the positive transcription elongation factor B."
      Cojocaru M., Bouchard A., Cloutier P., Cooper J.J., Varzavand K., Price D.H., Coulombe B.
      J. Biol. Chem. 286:5012-5022(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS RPB1/POLR2A CTD KINASE, POLYUBIQUITINATION BY UBR5, INTERACTION WITH UBR5 AND TFIIS/TCEA1.
    53. "Cdk9 T-loop phosphorylation is regulated by the calcium signaling pathway."
      Ramakrishnan R., Rice A.P.
      J. Cell. Physiol. 227:609-617(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-186, ENZYME REGULATION, DEGRADATION BY THE PROTEASOME, MUTAGENESIS OF THR-186.
    54. Cited for: PHOSPHORYLATION AT SER-175, DEPHOSPHORYLATION AT SER-175 BY PP1, MUTAGENESIS OF SER-175.
    55. "Controlling the elongation phase of transcription with P-TEFb."
      Peterlin B.M., Price D.H.
      Mol. Cell 23:297-305(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON NELF AND DSIF KINASE ACTIVITY.
    56. "Expanding role of cyclin dependent kinases in cytokine inducible gene expression."
      Brasier A.R.
      Cell Cycle 7:2661-2666(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON CYTOKINE SIGNALING.
    57. "Role of the cyclin-dependent kinase 9-related pathway in mammalian gene expression and human diseases."
      Romano G., Giordano A.
      Cell Cycle 7:3664-3668(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON TRANSCRIPTION REGULATION, INHIBITORS.
    58. "Cyclin-dependent kinase 9: a key transcriptional regulator and potential drug target in oncology, virology and cardiology."
      Wang S., Fischer P.M.
      Trends Pharmacol. Sci. 29:302-313(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON TRANSCRIPTION REGULATION, INHIBITORS.
    59. "Cell cycle, CDKs and cancer: a changing paradigm."
      Malumbres M., Barbacid M.
      Nat. Rev. Cancer 9:153-166(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME REGULATION, GENE FAMILY.
    60. "Pharmacological targeting of CDK9 in cardiac hypertrophy."
      Krystof V., Chamrad I., Jorda R., Kohoutek J.
      Med. Res. Rev. 30:646-666(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON CARDIAC HYPERTROPHY, INHIBITORS.
    61. "A role for cdk9-cyclin k in maintaining genome integrity."
      Yu D.S., Cortez D.
      Cell Cycle 10:28-32(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON GENOME INTEGRITY MAINTENANCE.
    62. "Crystal structure of HIV-1 Tat complexed with human P-TEFb."
      Tahirov T.H., Babayeva N.D., Varzavand K., Cooper J.J., Sedore S.C., Price D.H.
      Nature 465:747-751(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 1-345 IN COMPLEX WITH HIV-1 TAT AND CCNT1, PHOSPHORYLATION AT THR-186.
    63. "The structure of P-TEFb (CDK9/cyclin T1), its complex with flavopiridol and regulation by phosphorylation."
      Baumli S., Lolli G., Lowe E.D., Troiani S., Rusconi L., Bullock A.N., Debreczeni J.E., Knapp S., Johnson L.N.
      EMBO J. 27:1907-1918(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.48 ANGSTROMS) OF 2-330 IN COMPLEX WITH INHIBITOR FLAVOPIRIDOL; ATP AND CCNT1, PHOSPHORYLATION AT THR-186 SER-347; THR-362 AND THR-363, AUTOPHOSPHORYLATION, MUTAGENESIS OF THR-186.
    64. "Halogen bonds form the basis for selective P-TEFb inhibition by DRB."
      Baumli S., Endicott J.A., Johnson L.N.
      Chem. Biol. 17:931-936(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 2-330 IN COMPLEX WITH INHIBITOR DRB, PHOSPHORYLATION AT THR-186.
    65. "CDK inhibitors roscovitine and CR8 trigger Mcl-1 down-regulation and apoptotic cell death in neuroblastoma cells."
      Bettayeb K., Baunbaek D., Delehouze C., Loaec N., Hole A.J., Baumli S., Endicott J.A., Douc-Rasy S., Benard J., Oumata N., Galons H., Meijer L.
      Genes Cancer 1:369-380(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 2-330 IN COMPLEX WITH CCNT1; INHIBITORS ROSCOVITINE AND CR8, PHOSPHORYLATION AT THR-186, ENZYME REGULATION.
    66. "Patterns of somatic mutation in human cancer genomes."
      Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
      , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
      Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-59.

    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: October 1, 2014
    This is version 166 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

    External Data

    Dasty 3