P50613 (CDK7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cyclin-dependent kinase 7
EC=2.7.11.22
EC=2.7.11.23

Alternative name(s):
39 kDa protein kinase
Short name=p39 Mo15
CDK-activating kinase 1
Cell division protein kinase 7
Serine/threonine-protein kinase 1
TFIIH basal transcription factor complex kinase subunit

Gene names

Name:	CDK7
Synonyms:	CAK, CAK1, CDKN7, MO15, STK1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	346 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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. Ref.9 Ref.12 Ref.13 Ref.15 Ref.17 Ref.18 Ref.19 Ref.22 Ref.24 Ref.25 Ref.26 Ref.28 Ref.29 Ref.31
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. 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. Ref.12 Ref.32
Subunit structure	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. Ref.11 Ref.12 Ref.14 Ref.16 Ref.17 Ref.19 Ref.22
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. Ref.16 Ref.29
Tissue specificity	Ubiquitous.
Induction	Repressed by DNA-bound peptides. Ref.12 Ref.29 Ref.32
Post-translational modification	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. Ref.10 Ref.15 Ref.39
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Cell cycle Cell division DNA damage DNA repair Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	7-methylguanosine mRNA capping Traceable author statement. Source: Reactome G1 phase of mitotic cell cycle Traceable author statement. Source: Reactome G1/S transition of mitotic cell cycle Traceable author statement. Source: Reactome G2/M transition of mitotic cell cycle Traceable author statement. Source: Reactome S phase of mitotic cell cycle Traceable author statement. Source: Reactome androgen receptor signaling pathway Non-traceable author statement PubMed 15572661. Source: UniProtKB cell cycle arrest Traceable author statement Ref.33. Source: UniProtKB cell division Inferred from electronic annotation. Source: UniProtKB-KW cell proliferation Traceable author statement PubMed 7533895. Source: ProtInc nucleotide-excision repair, DNA damage removal Traceable author statement. Source: Reactome positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 8692841. Source: UniProtKB positive regulation of viral transcription Traceable author statement. Source: Reactome regulation of cyclin-dependent protein serine/threonine kinase activity Traceable author statement PubMed 7533895. Source: ProtInc termination of RNA polymerase I transcription Traceable author statement. Source: Reactome transcription elongation from RNA polymerase I promoter Traceable author statement. Source: Reactome transcription elongation from RNA polymerase II promoter Traceable author statement. Source: Reactome transcription initiation from RNA polymerase I promoter Traceable author statement. Source: Reactome transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome transcription-coupled nucleotide-excision repair Traceable author statement. Source: Reactome viral reproduction Traceable author statement. Source: Reactome
Cellular_component	holo TFIIH complex Inferred from direct assay Ref.11. Source: UniProtKB mitochondrion Inferred from direct assay. Source: HPA perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW DNA-dependent ATPase activity Inferred from direct assay Ref.11. Source: UniProtKB RNA polymerase II carboxy-terminal domain kinase activity Inferred from direct assay PubMed 12721286Ref.11. Source: UniProtKB androgen receptor binding Non-traceable author statement PubMed 15572661. Source: UniProtKB cyclin-dependent protein serine/threonine kinase activity Traceable author statement Ref.2. Source: ProtInc transcription coactivator activity Non-traceable author statement PubMed 15572661. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 346

346

Cyclin-dependent kinase 7

PRO_0000085791

Regions

Domain

12 – 295

284

Protein kinase

Nucleotide binding

18 – 26

9

ATP

Sites

Active site

137

1

Proton acceptor Ref.39

Binding site

41

1

ATP

Amino acid modifications

Modified residue

7

1

Phosphoserine Ref.21

Modified residue

164

1

Phosphoserine; by CDK1 and CDK2 Ref.10 Ref.15 Ref.21 Ref.23

Modified residue

170

1

Phosphothreonine; by CDK2 Ref.10 Ref.15 Ref.23 Ref.30 Ref.35 Ref.38 Ref.39

Modified residue

321

1

Phosphoserine Ref.21 Ref.35

Natural variations

Natural variant

163

1

G → A. Ref.6

VAR_023118

Natural variant

285

1

T → M. Ref.6 Ref.40
Corresponds to variant rs34584424 [ dbSNP | Ensembl ].

VAR_023119

Experimental info

Mutagenesis

41

1

K → A: Total loss of activity.

Mutagenesis

91

1

F → G: Enhanced capacitiy to bind ATP analogs. Ref.17

Mutagenesis

164

1

S → A: No mitotic repression of transcriptional activity of the reconstituted TFIIH complex. Ref.10

Mutagenesis

170

1

T → A: Total loss of activity. Total loss of transcriptional activity of the reconstituted TFIIH complex. Ref.8 Ref.10

Sequence conflict

130

1

Q → R in AAH05298. Ref.7

Sequence conflict

249

1

F → C in CAA73587. Ref.5

Sequence conflict

321

1

S → A in CAA73587. Ref.5

Secondary structure

1

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346

Helix Strand Turn

Details...

Beta strand

14 – 21

8

Beta strand

24 – 30

7

Beta strand

36 – 42

7

Helix

58 – 68

11

Beta strand

77 – 81

5

Beta strand

88 – 92

5

Beta strand

95 – 97

3

Helix

98 – 102

5

Helix

113 – 130

18

Helix

140 – 142

3

Beta strand

143 – 145

3

Beta strand

151 – 153

3

Helix

157 – 159

3

Turn

161 – 163

3

Helix

181 – 184

4

Helix

192 – 208

17

Helix

218 – 229

12

Turn

234 – 236

3

Beta strand

237 – 239

3

Helix

257 – 260

4

Helix

266 – 276

11

Turn

280 – 282

3

Helix

286 – 290

5

Helix

293 – 295

3

Beta strand

297 – 299

3

Beta strand

304 – 307

4

Sequences

	Sequence		Length	Mass (Da)
	P50613 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 0A94BFA7DD416CEB	FASTA	346	39,038
	10 20 30 40 50 60 MALDVKSRAK RYEKLDFLGE GQFATVYKAR DKNTNQIVAI KKIKLGHRSE AKDGINRTAL 70 80 90 100 110 120 REIKLLQELS HPNIIGLLDA FGHKSNISLV FDFMETDLEV IIKDNSLVLT PSHIKAYMLM 130 140 150 160 170 180 TLQGLEYLHQ HWILHRDLKP NNLLLDENGV LKLADFGLAK SFGSPNRAYT HQVVTRWYRA 190 200 210 220 230 240 PELLFGARMY GVGVDMWAVG CILAELLLRV PFLPGDSDLD QLTRIFETLG TPTEEQWPDM 250 260 270 280 290 300 CSLPDYVTFK SFPGIPLHHI FSAAGDDLLD LIQGLFLFNP CARITATQAL KMKYFSNRPG 310 320 330 340 PTPGCQLPRP NCPVETLKEQ SNPALAIKRK RTEALEQGGL PKKLIF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cell cycle analysis of the activity, subcellular localization, and subunit composition of human CAK (CDK-activating kinase)." Tassan J.-P., Schultz S.J., Bartek J., Nigg E.A. J. Cell Biol. 127:467-478(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[2]	"Two novel human serine/threonine kinases with homologies to the cell cycle regulating Xenopus MO15, and NIMA kinases: cloning and characterization of their expression pattern." Levedakou E.N., He M., Baptist E.W., Craven R.J., Cance W.G., Welcsh P.L., Simmons A., Naylor S.L., Leach R.J., Lewis T.B., Bowcock A., Liu E.T. Oncogene 9:1977-1988(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Mammary gland.
[3]	"Cloning, expression and subcellular localization of the human homolog of p40MO15 catalytic subunit of cdk-activating kinase." Darbon J.-M., Devault A., Taviaux S., Fesquet D., Martinez A.-M., Galas S., Cavadore J.-C., Doree M., Blanchard J.-M. Oncogene 9:3127-3138(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Molecular cloning of the human CAK1 gene encoding a cyclin-dependent kinase-activating kinase." Wu L., Yee A., Liu L., Carbonaro-Hall D., Venkatesan N., Tolo T., Hall F.L. Oncogene 9:2089-2096(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fibroblast.
[5]	"Human and Xenopus MO15 mRNA are highly conserved but show different patterns of expression in adult tissues." Kobelt D., Karn T., Hock B., Holtrich U., Braeuninger A., Wolf G., Strebhardt K., Ruebsamen-Waigmann H. Oncol. Rep. 1:1269-1275(1994) Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lung and Thymus.
[6]	NIEHS SNPs program Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ALA-163 AND MET-285.
[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]. Tissue: Cervix and Urinary bladder.
[8]	"A novel cyclin associates with MO15/CDK7 to form the CDK-activating kinase." Fisher R.P., Morgan D.O. Cell 78:713-724(1994) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF THR-170.
[9]	"p53 is phosphorylated by CDK7-cyclin H in a p36MAT1-dependent manner." Ko L.J., Shieh S.-Y., Chen X., Jayaraman L., Tamai K., Taya Y., Prives C., Pan Z.-Q. Mol. Cell. Biol. 17:7220-7229(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS TP53 KINASE.
[10]	"The molecular mechanism of mitotic inhibition of TFIIH is mediated by phosphorylation of CDK7." Akoulitchev S., Reinberg D. Genes Dev. 12:3541-3550(1998) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-164 AND THR-170, MUTAGENESIS OF SER-164 AND THR-170.
[11]	"Immunoaffinity purification and functional characterization of human transcription factor IIH and RNA polymerase II from clonal cell lines that conditionally express epitope-tagged subunits of the multiprotein complexes." Kershnar E., Wu S.-Y., Chiang C.-M. J. Biol. Chem. 273:34444-34453(1998) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE TFIIH BASAL TRANSCRIPTION FACTOR.
[12]	"Regulation of CAK kinase activity by p53." Schneider E., Montenarh M., Wagner P. Oncogene 17:2733-2741(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS CDK2 KINASE, IDENTIFICATION IN COMPLEX WITH TP53, ENZYME REGULATION.
[13]	"Reconstitution of the transcription factor TFIIH: assignment of functions for the three enzymatic subunits, XPB, XPD, and cdk7." Tirode F., Busso D., Coin F., Egly J.-M. Mol. Cell 3:87-95(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[14]	"The FBP interacting repressor targets TFIIH to inhibit activated transcription." Liu J., He L., Collins I., Ge H., Libutti D., Li J., Egly J.-M., Levens D. Mol. Cell 5:331-341(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PUF60.
[15]	"Reciprocal activation by cyclin-dependent kinases 2 and 7 is directed by substrate specificity determinants outside the T loop." Garrett S., Barton W.A., Knights R., Jin P., Morgan D.O., Fisher R.P. Mol. Cell. Biol. 21:88-99(2001) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-164 AND THR-170 BY CDK2, FUNCTION AS CDK2 KINASE.
[16]	"Cyclin-dependent kinase activating kinase/Cdk7 co-localizes with PKC-iota in human glioma cells." Bicaku E., Patel R., Acevedo-Duncan M. Tissue Cell 37:53-58(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PRKCI, SUBCELLULAR LOCATION.
[17]	"Dichotomous but stringent substrate selection by the dual-function Cdk7 complex revealed by chemical genetics." Larochelle S., Batliner J., Gamble M.J., Barboza N.M., Kraybill B.C., Blethrow J.D., Shokat K.M., Fisher R.P. Nat. Struct. Mol. Biol. 13:55-62(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS SPT5/SUPT5H AND CDK KINASE, MUTAGENESIS OF PHE-91, IDENTIFICATION IN CAK COMPLEX.
[18]	"Requirements for Cdk7 in the assembly of Cdk1/cyclin B and activation of Cdk2 revealed by chemical genetics in human cells." Larochelle S., Merrick K.A., Terret M.-E., Wohlbold L., Barboza N.M., Zhang C., Shokat K.M., Jallepalli P.V., Fisher R.P. Mol. Cell 25:839-850(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CELL CYCLE REGULATION.
[19]	"Recognition of Cdk2 by Cdk7." Lolli G., Johnson L.N. Proteins 67:1048-1059(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS CDK2 KINASE, INTERACTION WITH CDK2.
[20]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[21]	"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-7; SER-164 AND SER-321, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[22]	"Phosphorylation of steroidogenic factor 1 is mediated by cyclin-dependent kinase 7." Lewis A.E., Rusten M., Hoivik E.A., Vikse E.L., Hansson M.L., Wallberg A.E., Bakke M. Mol. Endocrinol. 22:91-104(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS SF1/NR5A1 KINASE, INTERACTION WITH SF1/NR5A1.
[23]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-164 AND THR-170, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[24]	"TFIIH kinase places bivalent marks on the carboxy-terminal domain of RNA polymerase II." Akhtar M.S., Heidemann M., Tietjen J.R., Zhang D.W., Chapman R.D., Eick D., Ansari A.Z. Mol. Cell 34:387-393(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS POLR2A CTD KINASE.
[25]	"SUMOylation inhibits SF-1 activity by reducing CDK7-mediated serine 203 phosphorylation." Yang W.-H., Heaton J.H., Brevig H., Mukherjee S., Iniguez-Lluhi J.A., Hammer G.D. Mol. Cell. Biol. 29:613-625(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS SF1/NR5A1 KINASE.
[26]	"TFIIH-associated Cdk7 kinase functions in phosphorylation of C-terminal domain Ser7 residues, promoter-proximal pausing, and termination by RNA polymerase II." Glover-Cutter K., Larochelle S., Erickson B., Zhang C., Shokat K., Fisher R.P., Bentley D.L. Mol. Cell. Biol. 29:5455-5464(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS POLR2A CTD KINASE.
[27]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[28]	"Binding to DNA of the RNA-polymerase II C-terminal domain allows discrimination between Cdk7 and Cdk9 phosphorylation." Lolli G. Nucleic Acids Res. 37:1260-1268(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS POLR2A CTD KINASE.
[29]	"DNA-Bound peptides control the mRNA transcription through CDK7." Lv X., Wang J., Dong Z., Lv F., Qin Y. Peptides 30:681-688(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DNA-BOUND PEPTIDES TRANSCRIPTION INHIBITION, SUBCELLULAR LOCATION, INDUCTION.
[30]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-170, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[31]	"Cdc25 phosphatases are required for timely assembly of CDK1-cyclin B at the G2/M transition." Timofeev O., Cizmecioglu O., Settele F., Kempf T., Hoffmann I. J. Biol. Chem. 285:16978-16990(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS CDK1 AND CDK2 KINASE.
[32]	"R-roscovitine (Seliciclib) affects CLL cells more strongly than combinations of fludarabine or cladribine with cyclophosphamide: Inhibition of CDK7 sensitizes leukemic cells to caspase-dependent apoptosis." Rogalinska M., Blonski J.Z., Komina O., Goralski P., Zolnierczyk J.D., Piekarski H., Robak T., Kilianska Z.M., Wesierska-Gadek J. J. Cell. Biochem. 109:217-235(2010) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION.
[33]	"CAK-Cyclin-dependent Activating Kinase: a key kinase in cell cycle control and a target for drugs?" Lolli G., Johnson L.N. Cell Cycle 4:572-577(2005) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON CELL CYCLE REGULATION.
[34]	"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: REVIEW ON INHIBITORS, GENE FAMILY.
[35]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-170 AND SER-321, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[36]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[37]	"A history of TFIIH: Two decades of molecular biology on a pivotal transcription/repair factor." Egly J.M., Coin F. DNA Repair 10:714-721(2011) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON TRANSCRIPTION REGULATION.
[38]	"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-170, MASS SPECTROMETRY.
[39]	"The crystal structure of human CDK7 and its protein recognition properties." Lolli G., Lowe E.D., Brown N.R., Johnson L.N. Structure 12:2067-2079(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.02 ANGSTROMS) IN COMPLEX WITH ATP, ACTIVE SITE, PHOSPHORYLATION AT THR-170.
[40]	"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] MET-285.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X79193 mRNA. Translation: CAA55785.1.
L20320 mRNA. Translation: AAA36657.1.
X77743 mRNA. Translation: CAA54793.1.
X77303 mRNA. Translation: CAA54508.1.
Y13120 mRNA. Translation: CAA73587.1.
AY130859 Genomic DNA. Translation: AAM77799.1.
BC000834 mRNA. Translation: AAH00834.1.
BC005298 mRNA. Translation: AAH05298.1.

IPI

IPI00000685.

PIR

A54820.
I37215.

RefSeq

NP_001790.1. NM_001799.3.

UniGene

Hs.184298.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LG3	model	-	A	1-307	[»]
1PA8	model	-	A	181-346	[»]
1UA2	X-ray	3.02	A/B/C/D	1-346	[»]
2HIC	model	-	B	13-311	[»]

ProteinModelPortal

P50613.

ModBase

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Protein-protein interaction databases

DIP

DIP-5995N.

IntAct

P50613. 8 interactions.

STRING

9606.ENSP00000256443.

PTM databases

PhosphoSite

P50613.

Polymorphism databases

DMDM

1705722.

Proteomic databases

PaxDb

P50613.

PeptideAtlas

P50613.

PRIDE

P50613.

Protocols and materials databases

DNASU

1022.

StructuralBiologyKnowledgebase

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Genome annotation databases

Ensembl

ENST00000256443; ENSP00000256443; ENSG00000134058.
ENST00000571640; ENSP00000460075; ENSG00000262841.

GeneID

1022.

KEGG

hsa:1022.

UCSC

uc003jvs.4. human.

Organism-specific databases

CTD

1022.

GeneCards

GC05P068530.

HGNC

HGNC:1778. CDK7.

HPA

CAB004364.
HPA007932.

MIM

601955. gene.

neXtProt

NX_P50613.

PharmGKB

PA26314.

GenAtlas

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Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000233024.

HOVERGEN

HBG014652.

InParanoid

P50613.

KO

K02202.

OMA

PRPNCPA.

OrthoDB

EOG4KSPK0.

PhylomeDB

P50613.

Enzyme and pathway databases

BRENDA

2.7.11.22. 2681.

Pathway_Interaction_DB

retinoic_acid_pathway. Retinoic acid receptors-mediated signaling.

Reactome

REACT_115566. Cell Cycle.
REACT_116125. Disease.
REACT_1675. mRNA Processing.
REACT_1788. Transcription.
REACT_216. DNA Repair.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

P50613.

Bgee

P50613.

CleanEx

HS_CDK7.

Genevestigator

P50613.

GermOnline

ENSG00000134058. Homo sapiens.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P50613.

ChEMBL

CHEMBL3055.

EvolutionaryTrace

P50613.

GenomeRNAi

1022.

NextBio

4295.

SOURCE

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Entry information

Entry name

CDK7_HUMAN

Accession

Primary (citable) accession number: P50613
Secondary accession number(s): Q9BS60, Q9UE19

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 153 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.