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CDK9/CDC2L4  Protein, Antibody, ELISA Kit, cDNA Clone

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    CDK9/CDC2L4 Related Protein, Antibody, cDNA Gene, and ELISA Kits

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    CDK9/CDC2L4 Summary & Protein Information

    CDK9/CDC2L4 Background

    Catalytic activity: ATP + a protein = ADP + a phosphoprotein.; ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate.
    Enzyme regulation: ENZYME REGULATION: 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 Ca(2+) signaling pathway-dependent; actively inactivated by dephosphorylation mediated by PPP1CA, PPM1A and PPM1B. Reversibly repressed by acetylation at Lys-44 and Lys-48. {ECO:0000269|PubMed:18250157, ECO:0000269|PubMed:18483222, ECO:0000269|PubMed:19238148, ECO:0000269|PubMed:21448926, ECO:0000269|PubMed:21484792, ECO:0000269|PubMed:21779453}.
    Subunit structure: 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 Ca(2+) 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). {ECO:0000269|PubMed:10393184, ECO:0000269|PubMed:10574912, ECO:0000269|PubMed:10958691, ECO:0000269|PubMed:11884399, ECO:0000269|PubMed:12037670, ECO:0000269|PubMed:12065898, ECO:0000269|PubMed:12718890, ECO:0000269|PubMed:15965233, ECO:0000269|PubMed:16109376, ECO:0000269|PubMed:16109377, ECO:0000269|PubMed:17452463, ECO:0000269|PubMed:17643375, ECO:0000269|PubMed:17956865, ECO:0000269|PubMed:18249148, ECO:0000269|PubMed:18362169, ECO:0000269|PubMed:18483222, ECO:0000269|PubMed:18566585, ECO:0000269|PubMed:20081228, ECO:0000269|PubMed:20159561, ECO:0000269|PubMed:20471948, ECO:0000269|PubMed:20493174, ECO:0000269|PubMed:20535204, ECO:0000269|PubMed:20851342, ECO:0000269|PubMed:20980437, ECO:0000269|PubMed:21127351, ECO:0000269|PubMed:21779453, ECO:0000269|PubMed:22195968, ECO:0000269|PubMed:23029222, ECO:0000269|PubMed:9491887, ECO:0000269|PubMed:9499409}.
    Subcellular location: Nucleus. Cytoplasm. Nucleus, PML 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.
    Tissue specificity: Ubiquitous.
    Induction: By replication stress, in chromatin. Probably degraded by the proteasome upon Thr-186 dephosphorylation.
    Post-translational: 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 Ca(2+) 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). {ECO:0000269|PubMed:10958691, ECO:0000269|PubMed:15965233, ECO:0000269|PubMed:18483222, ECO:0000269|PubMed:18566585, ECO:0000269|PubMed:18829461, ECO:0000269|PubMed:20535204, ECO:0000269|PubMed:20851342, ECO:0000269|PubMed:21448926, ECO:0000269|PubMed:21533037, ECO:0000269|PubMed:21779453}.; 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. {ECO:0000269|PubMed:17452463, ECO:0000269|PubMed:18250157}.; Polyubiquitinated and thus activated by UBR5. This ubiquitination is promoted by TFIIS/TCEA1 and favors 'Ser-2' phosphorylation of RPB1/POLR2A CTD. {ECO:0000269|PubMed:21127351}.
    Involvement in disease: DISEASE: Note=Chronic activation of CDK9 causes cardiac myocyte enlargement leading to cardiac hypertrophy, and confers predisposition to heart failure.
    Sequence similarity: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.; Contains 1 protein kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00159}.
    General information above from UniProt

    CDK9/CDC2L4 Alternative Name

    CDK9/CDC2L4 Related Studies