ID:CDK7_HUMAN DESCRIPTION: RecName: Full=Cyclin-dependent kinase 7; EC=2.7.11.22; EC=2.7.11.23; AltName: Full=39 kDa protein kinase; Short=p39 Mo15; AltName: Full=CDK-activating kinase 1; AltName: Full=Cell division protein kinase 7; AltName: Full=Serine/threonine-protein kinase 1; AltName: Full=TFIIH basal transcription factor complex kinase subunit; FUNCTION: Serine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription. Cyclin- dependent kinases (CDKs) are activated by the binding to a cyclin and mediate the progression through the cell cycle. Each different complex controls a specific transition between 2 subsequent phases in the cell cycle. Required for both activation and complex formation of CDK1/cyclin-B during G2-M transition, and for activation of CDK2/cyclins during G1-S transition (but not complex formation). CDK7 is the catalytic subunit of the CDK-activating kinase (CAK) complex. Phosphorylates SPT5/SUPT5H, SF1/NR5A1, POLR2A, p53/TP53, CDK1, CDK2, CDK4, CDK6 and CDK11B/CDK11. CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation, thus regulating cell cycle progression. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminus domain (CTD) of its large subunit (POLR2A), allowing its escape from the promoter and elongation of the transcripts. Phosphorylation of POLR2A in complex with DNA promotes transcription initiation by triggering dissociation from DNA. Its expression and activity are constant throughout the cell cycle. Upon DNA damage, triggers p53/TP53 activation by phosphorylation, but is inactivated in turn by p53/TP53; this feedback loop may lead to an arrest of the cell cycle and of the transcription, helping in cell recovery, or to apoptosis. Required for DNA-bound peptides-mediated transcription and cellular growth inhibition. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CATALYTIC ACTIVITY: ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate. ENZYME REGULATION: Inactivated by phosphorylation. Repressed by roscovitine (seliciclib, CYC202), R547 (Ro-4584820) and SNS-032 (BMS-387032). The association of p53/TP53 to the CAK complex in response to DNA damage reduces kinase activity toward CDK2 and RNA polymerase II repetitive C-terminus domain (CTD), thus stopping cell cycle progression. The inactivation by roscovitine promotes caspase-mediated apoptosis in leukemic cells. SUBUNIT: Associates primarily with cyclin-H (CCNH) and MAT1 to form the CAK complex. CAK can further associate with the core- TFIIH to form the TFIIH basal transcription factor; this complex is sensitive to UV light. The CAK complex binds to p53/TP53 in response to DNA damage. Interacts with CDK2, SF1/NR5A1, PUF60 and PRKCI. SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Cytoplasm, perinuclear region. Note=Colocalizes with PRKCI in the cytoplasm and nucleus. Translocates from the nucleus to cytoplasm and perinuclear region in response to DNA-bound peptides. TISSUE SPECIFICITY: Ubiquitous. INDUCTION: Repressed by DNA-bound peptides. PTM: Phosphorylation of Ser-164 during mitosis inactivates the enzyme. Phosphorylation of Thr-170 is required for activity. Phosphorylated at Ser-164 and Thr-170 by CDK2. SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily. SIMILARITY: Contains 1 protein kinase domain. WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/cdk7/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P50613
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
AK308493 - Homo sapiens cDNA, FLJ98534. Y13120 - H.sapiens mRNA for serine/threonine protein kinase MO15. L20320 - Human protein serine/threonine kinase stk1 mRNA, complete cds. BC005298 - Homo sapiens cyclin-dependent kinase 7, mRNA (cDNA clone MGC:12365 IMAGE:3997991), complete cds. X79193 - H.sapiens CAK mRNA for CDK-activating kinase. AK026509 - Homo sapiens cDNA: FLJ22856 fis, clone KAT01479, highly similar to HSCAKCDK Homo sapiens CAK mRNA for CDK-activating kinase. X77303 - H.sapiens CAK1 mRNA for Cdk-activating kinase. X77743 - H.sapiens CDK activating kinase mRNA. BC000834 - Homo sapiens cyclin-dependent kinase 7, mRNA (cDNA clone MGC:5090 IMAGE:3455907), complete cds. CU674418 - Synthetic construct Homo sapiens gateway clone IMAGE:100019039 5' read CDK7 mRNA. CU675099 - Synthetic construct Homo sapiens gateway clone IMAGE:100019044 5' read CDK7 mRNA. AB385525 - Synthetic construct DNA, clone: pF1KB3201, Homo sapiens CDK7 gene for cell division protein kinase 7, complete cds, without stop codon, in Flexi system. KU177970 - Homo sapiens cyclin-dependent kinase 7 isoform 1 (CDK7) mRNA, partial cds. KU177971 - Homo sapiens cyclin-dependent kinase 7 isoform 3 (CDK7) mRNA, complete cds, alternatively spliced. AM392563 - Synthetic construct Homo sapiens clone IMAGE:100002736 for hypothetical protein (CDK7 gene). AM392604 - Synthetic construct Homo sapiens clone IMAGE:100002986 for hypothetical protein (CDK7 gene). AM392628 - Synthetic construct Homo sapiens clone IMAGE:100002987 for hypothetical protein (CDK7 gene). AM393110 - Synthetic construct Homo sapiens clone IMAGE:100002737 for hypothetical protein (CDK7 gene). KJ905710 - Synthetic construct Homo sapiens clone ccsbBroadEn_15380 CDK7 gene, encodes complete protein. KJ890886 - Synthetic construct Homo sapiens clone ccsbBroadEn_00280 CDK7 gene, encodes complete protein. KJ905167 - Synthetic construct Homo sapiens clone ccsbBroadEn_14577 CDK7 gene, encodes complete protein. X76171 - H.sapiens mRNA for Cdk activating kinase.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_rarPathway - Degradation of the RAR and RXR by the proteasome h_EfpPathway - Estrogen-responsive protein Efp controls cell cycle and breast tumors growth h_cellcyclePathway - Cyclins and Cell Cycle Regulation h_ptc1Pathway - Sonic Hedgehog (SHH) Receptor Ptc1 Regulates cell cycle
Reactome (by CSHL, EBI, and GO)
Protein P50613 (Reactome details) participates in the following event(s):
R-HSA-6810234 General transcription factors bind SNAPc:POU2F1:ZNF143:snRNA gene R-HSA-5689861 Recruitment of XPA and release of CAK R-HSA-6810238 RNA polymerase II binds initiation factors at promoter of snRNA gene (U1, U2, U4, U4atac, U5, U11, U12) R-HSA-73758 Recruitment of Active RNA Polymerase I to SL1:phos.UBF-1:rDNA Promoter R-HSA-109639 Formation of the closed pre-initiation complex R-HSA-112379 Recruitment of elongation factors to form elongation complex R-HSA-112383 Hypophosphorylation of RNA Pol II CTD by FCP1P protein R-HSA-167072 Hypophosphorylation of RNA Pol II CTD by FCP1P protein R-HSA-167077 Recruitment of elongation factors to form HIV-1 elongation complex R-HSA-167196 Recruitment of elongation factors to form HIV-1 elongation complex R-HSA-5691000 TFIIH binds GG-NER site to form a verification complex R-HSA-73946 Abortive initiation R-HSA-75856 Abortive Initiation Before Second Transition R-HSA-75891 Abortive Initiation After Second Transition R-HSA-77090 Methylation of GMP-cap by RNA Methyltransferase R-HSA-112385 Addition of nucleotides leads to transcript elongation R-HSA-167181 Addition of nucleotides leads to HIV-1 transcript elongation R-HSA-167468 Abortive HIV-1 Initiation After Second Transition R-HSA-167474 Abortive HIV-1 Initiation Before Second Transition R-HSA-167477 Abortive HIV-1 initiation after formation of the first phosphodiester bond R-HSA-170076 CAK-mediated phosphorylation of Cyclin B1:Cdc2 complexes R-HSA-170087 CAK-mediated phosphorylation of Cyclin A:Cdc2 complexes R-HSA-187949 CAK-mediated phosphorylation of Cyclin A:Cdk2 R-HSA-188350 CAK-mediated phosphorylation of Cyclin E:Cdk2 R-HSA-8942836 CDK4/6:CCND complexes are activated by T-loop phosphorylation of CDK4/6 R-HSA-6810235 RPAP2 binds RNA polymerase II phosphorylated at serine-7 residues of heptad repeats in the C-terminal domain R-HSA-6810233 CDK7 phosphorylates serine-5 and serine-7 of heptad repeats in C-terminal domain of RNA polymerase II at snRNA promoter R-HSA-6814885 CBCAP complex binds 7-methylguanosine cap of snRNA R-HSA-73769 Loss of Rrn3 from RNA Polymerase I promoter escape complex R-HSA-74994 Polymerase I Transcription Complex/Nascent Pre rRNA Complex pauses at the TTF-I:Sal Box R-HSA-74992 Dissociation of PTRF:Polymerase I/Nascent Pre rRNA Complex:TTF-I:Sal Box R-HSA-75873 Addition of Nucleotides 5 through 9 on the growing Transcript R-HSA-76576 Addition of nucleotides 10 and 11 on the growing transcript: Third Transition R-HSA-111264 Addition of nucleotides between position +11 and +30 R-HSA-77068 Activation of GT R-HSA-77069 RNA Polymerase II CTD (phosphorylated) binds to CE R-HSA-77073 SPT5 subunit of Pol II binds the RNA triphosphatase (RTP) R-HSA-77077 Capping complex formation R-HSA-75864 Newly Formed Phosphodiester Bond Stabilized and PPi Released R-HSA-75866 Nucleophillic Attack by 3'-hydroxyl Oxygen of nascent transcript on the Alpha Phosphate of NTP R-HSA-75949 RNA Polymerase II Promoter Opening: First Transition R-HSA-75862 Fall Back to Closed Pre-initiation Complex R-HSA-75861 NTP Binds Active Site of RNA Polymerase II R-HSA-113430 Extrusion of 5'-end of 30 nt long transcript through the pore in Pol II complex R-HSA-77071 Phosphorylation (Ser5) of RNA pol II CTD R-HSA-167117 Addition of nucleotides 10 and 11 on the growing HIV-1 transcript: Third Transition R-HSA-167136 Addition of nucleotides 5 through 9 on the growing HIV-1 transcript R-HSA-167134 Newly formed phosphodiester bond stabilized and PPi released R-HSA-167098 Phosphorylation (Ser5) of RNA pol II CTD R-HSA-167111 Extrusion of 5'-end of 30 nt long HIV-1 transcript through the pore in Pol II complex R-HSA-167130 Nucleophillic attack by 3'-hydroxyl oxygen of nascent HIV-1 transcript on the Alpha phosphate of NTP R-HSA-167133 Activation of GT R-HSA-167128 RNA Polymerase II CTD (phosphorylated) binds to CE R-HSA-167115 Addition of nucleotides between position +11 and +30 on HIV-1 transcript R-HSA-167153 SPT5 subunit of Pol II binds the RNA triphosphatase (RTP) R-HSA-167097 HIV Promoter Opening: First Transition R-HSA-167484 Fall Back to Closed Pre-initiation Complex R-HSA-167118 NTP binds active site of RNA Polymerase II in HIV-1 open pre-initiation complex R-HSA-6781840 ERCC6 binds stalled RNA Pol II R-HSA-6782211 DNA polymerases delta, epsilon or kappa bind the TC-NER site R-HSA-6782204 5' incision of damaged DNA strand by ERCC1:ERCC4 in TC-NER R-HSA-6782224 3' incision by ERCC5 (XPG) in TC-NER R-HSA-6782227 Ligation of newly synthesized repair patch to incised DNA in TC-NER R-HSA-6782208 Repair DNA synthesis of ~27-30 bases long patch by POLD, POLE or POLK in TC-NER R-HSA-6797616 CCNK:CDK12 binds RNA Pol II at DNA repair genes R-HSA-74993 PTRF Binds the Polymerase I Transcription Complex/Nascent Pre rRNA Complex paused at the TTF-I:Sal Box R-HSA-74986 Elongation of pre-rRNA transcript R-HSA-427366 Transcription of intergenic spacer of the rRNA gene R-HSA-77078 Hydrolysis of the 5'-end of the nascent transcript by the capping enzyme R-HSA-77081 Formation of the CE:GMP intermediate complex R-HSA-77085 Dissociation of transcript with 5'-GMP from GT R-HSA-77083 Transfer of GMP from the capping enzyme GT site to 5'-end of mRNA R-HSA-6781833 ERCC8 (CSA) binds stalled RNA Pol II R-HSA-6797606 CDK12 phosphorylates RNA Pol II CTD at DNA repair genes R-HSA-6781867 ERCC8:DDB1:CUL4:RBX1 ubiquitinates ERCC6 and RNA Pol II R-HSA-6782004 Assembly of the pre-incision complex in TC-NER R-HSA-6782069 UVSSA:USP7 deubiquitinates ERCC6 R-HSA-6782131 RNA Pol II backtracking in TC-NER R-HSA-6782138 ERCC5 and RPA bind TC-NER site R-HSA-6782141 Binding of ERCC1:ERCC4 (ERCC1:XPF) to pre-incision complex in TC-NER R-HSA-6807505 RNA polymerase II transcribes snRNA genes R-HSA-5696395 Formation of Incision Complex in GG-NER R-HSA-73857 RNA Polymerase II Transcription R-HSA-73762 RNA Polymerase I Transcription Initiation R-HSA-73779 RNA Polymerase II Transcription Pre-Initiation And Promoter Opening R-HSA-112382 Formation of RNA Pol II elongation complex R-HSA-113418 Formation of the Early Elongation Complex R-HSA-167158 Formation of the HIV-1 Early Elongation Complex 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-6781823 Formation of TC-NER Pre-Incision Complex R-HSA-674695 RNA Polymerase II Pre-transcription Events R-HSA-72086 mRNA Capping R-HSA-75955 RNA Polymerase II Transcription Elongation R-HSA-167246 Tat-mediated elongation of the HIV-1 transcript R-HSA-167162 RNA Polymerase II HIV Promoter Escape R-HSA-167161 HIV Transcription Initiation R-HSA-6781827 Transcription-Coupled Nucleotide Excision Repair (TC-NER) R-HSA-5696399 Global Genome Nucleotide Excision Repair (GG-NER) R-HSA-69273 Cyclin A/B1/B2 associated events during G2/M transition R-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry R-HSA-69202 Cyclin E associated events during G1/S transition R-HSA-69231 Cyclin D associated events in G1 R-HSA-74160 Gene expression (Transcription) R-HSA-73772 RNA Polymerase I Promoter Escape R-HSA-73863 RNA Polymerase I Transcription Termination R-HSA-73776 RNA Polymerase II Promoter Escape R-HSA-77075 RNA Pol II CTD phosphorylation and interaction with CE R-HSA-75953 RNA Polymerase II Transcription Initiation R-HSA-76042 RNA Polymerase II Transcription Initiation And Promoter Clearance R-HSA-167160 RNA Pol II CTD phosphorylation and interaction with CE during HIV infection R-HSA-167172 Transcription of the HIV genome R-HSA-6782135 Dual incision in TC-NER R-HSA-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER R-HSA-6796648 TP53 Regulates Transcription of DNA Repair Genes R-HSA-73854 RNA Polymerase I Promoter Clearance R-HSA-167169 HIV Transcription Elongation R-HSA-8953854 Metabolism of RNA R-HSA-5696398 Nucleotide Excision Repair R-HSA-69275 G2/M Transition R-HSA-69242 S Phase R-HSA-69206 G1/S Transition R-HSA-69236 G1 Phase R-HSA-73864 RNA Polymerase I Transcription R-HSA-73777 RNA Polymerase I Chain Elongation R-HSA-427413 NoRC negatively regulates rRNA expression R-HSA-162599 Late Phase of HIV Life Cycle R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-73894 DNA Repair R-HSA-453274 Mitotic G2-G2/M phases R-HSA-69278 Cell Cycle (Mitotic) R-HSA-453279 Mitotic G1-G1/S phases R-HSA-5250941 Negative epigenetic regulation of rRNA expression R-HSA-162587 HIV Life Cycle R-HSA-212436 Generic Transcription Pathway R-HSA-1640170 Cell Cycle R-HSA-212165 Epigenetic regulation of gene expression R-HSA-162906 HIV Infection R-HSA-5663205 Infectious disease R-HSA-1643685 Disease
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
