Reviewed, UniProtKB/Swiss-Prot P50613 (CDK7_HUMAN)

Names and origin

Protein names

Recommended name:
    Cell division protein kinase 7
    EC=2.7.11.22
    EC=2.7.11.23
Alternative name(s):
    CDK-activating kinase
      Short name=CAK
    CAK1
    TFIIH basal transcription factor complex kinase subunit
    39 kDa protein kinase
    p39 Mo15
    STK1

Gene names

Name:	CDK7
Synonyms:	MO15

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

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

General annotation (Comments)

Function	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 two subsequent phases in the cell cycle. CDK7 is the catalytic subunit of the CDK-activating kinase (CAK) complex, a serine-threonine kinase. CAK activates the cyclin-associated kinases CDC2/CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation. 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. Involved in cell cycle control and in RNA transcription by RNA polymerase II. Its expression and activity are constant throughout the cell cycle. Ref.11
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate.
Enzyme regulation	Inactivated by phosphorylation.
Subunit structure	Associates primarily with cyclin H and MAT1 to form the CAK complex. CAK can further associate with the core-TFIIH to form the TFIIH basal transcription factor. Interacts with PUF60. Ref.12
Subcellular location	Nucleus.
Tissue specificity	Ubiquitous.
Post-translational modification	Phosphorylation of Ser-164 during mitosis inactivates the enzyme. Phosphorylation of Thr-170 is required for activity.
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	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
Gene Ontology (GO)
Biological process	RNA elongation from RNA polymerase II promoter Inferred from Experiment. Source: Reactome androgen receptor signaling pathway Non-traceable author statement. Source: UniProtKB cell cycle Inferred from electronic annotation. Source: UniProtKB-KW cell division Inferred from electronic annotation. Source: UniProtKB-KW cell proliferation Traceable author statement. Source: ProtInc nucleotide-excision repair, DNA damage removal Inferred from Experiment. Source: Reactome positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay. Source: UniProtKB protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro regulation of cyclin-dependent protein kinase activity Traceable author statement. Source: ProtInc transcription initiation from RNA polymerase II promoter Inferred from Experiment. Source: Reactome
Cellular component	holo TFIIH complex Ref.10 Inferred from direct assay. Source: UniProtKB mitochondrion Inferred from direct assay. Source: HPA
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW DNA-dependent ATPase activity Ref.10 Inferred from direct assay. Source: UniProtKB RNA polymerase II carboxy-terminal domain kinase activity Ref.10 Inferred from direct assay. Source: UniProtKB androgen receptor binding Non-traceable author statement. Source: UniProtKB cyclin-dependent protein kinase activity Ref.2 Traceable author statement. Source: ProtInc protein C-terminus binding Inferred from physical interaction. Source: UniProtKB transcription coactivator activity Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 346

346

Cell division protein 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.20

Binding site

41

1

ATP

Amino acid modifications

Modified residue

7

1

Phosphoserine Ref.15

Modified residue

164

1

Phosphoserine Ref.15 Ref.9 Ref.13 Ref.16

Modified residue

169

1

Phosphotyrosine

Modified residue

170

1

Phosphothreonine Ref.20 Ref.15 Ref.9 Ref.13 Ref.16 Ref.14 Ref.19

Modified residue

287

1

Phosphothreonine Ref.15

Modified residue

321

1

Phosphoserine Ref.15

Natural variations

Natural variant

163

1

G → A

VAR_023118

Natural variant

285

1

T → M: dbSNP rs34584424. Ref.6 Ref.21

VAR_023119

Experimental info

Mutagenesis

41

1

K → A: Total loss of activity.

Mutagenesis

164

1

S → A: No mitotic repression of transcriptional activity of the reconstituted TFIIH complex. Ref.9

Mutagenesis

170

1

T → A: Total loss of activity. Total loss of transcriptional activity of the reconstituted TFIIH complex. Ref.9 Ref.8

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)
	P50613-1 [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: 7929589] [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: 8208544] [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: 7936635] [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: 8208556] [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: 15489334] [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: 8069918] [Abstract] Cited for: MUTAGENESIS OF THR-170.
[9]	"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: 9832506] [Abstract] Cited for: PHOSPHORYLATION AT SER-164 AND THR-170, MUTAGENESIS OF SER-164 AND THR-170.
[10]	"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: 9852112] [Abstract] Cited for: IDENTIFICATION IN THE TFIIH BASAL TRANSCRIPTION FACTOR.
[11]	"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: 10024882] [Abstract] Cited for: FUNCTION.
[12]	"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: 10882074] [Abstract] Cited for: INTERACTION WITH PUF60.
[13]	"Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry." Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., Keri G., Wehland J., Daub H. Mol. Cell. Proteomics 6:537-547(2007) [PubMed: 17192257] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-164 AND THR-170, MASS SPECTROMETRY.
[14]	"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: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-170, MASS SPECTROMETRY.
[15]	"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: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7; SER-164; THR-170; THR-287 AND SER-321, MASS SPECTROMETRY.
[16]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-164 AND THR-170, MASS SPECTROMETRY.
[17]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[18]	"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: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-169 AND THR-170, MASS SPECTROMETRY.
[19]	"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: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-170, MASS SPECTROMETRY. Tissue: T-cell.
[20]	"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: 15530371] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.02 ANGSTROMS) IN COMPLEX WITH ATP, ACTIVE SITE, PHOSPHORYLATION AT THR-170.
[21]	"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: 17344846] [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.

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	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5995N.

STRING

P50613.

PTM databases

PhosphoSite

P50613.

Proteomic databases

PeptideAtlas

P50613.

PRIDE

P50613.

Genome annotation databases

Ensembl

ENST00000256443; ENSP00000256443; ENSG00000134058; Homo sapiens. [Genome view]

GeneID

1022.

KEGG

hsa:1022.

NMPDR

fig|9606.3.peg.25336.

UCSC

uc003jvs.2. human.

Organism-specific databases

CTD

1022.

GeneCards

GC05P068566.

H-InvDB

HIX0004919.
HIX0057667.

HGNC

HGNC:1778. CDK7.

HPA

CAB004364.
HPA007932.

MIM

601955. gene.

PharmGKB

PA26314.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG09228.

HOGENOM

HBG755340.

HOVERGEN

P50613.

InParanoid

P50613.

OMA

FMDTDLE.

OrthoDB

EOG980MGK.

PhylomeDB

P50613.

Enzyme and pathway databases

BRENDA

2.7.11.22. 247.
2.7.11.23. 247.

Pathway_Interaction_DB

retinoic_acid_pathway. Retinoic acid receptors-mediated signaling.

Reactome

REACT_152. Cell Cycle, Mitotic.
REACT_1675. mRNA Processing.
REACT_1788. Transcription.
REACT_216. DNA Repair.
REACT_6185. HIV Infection.
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.
IPR017442. Se/Thr_prot_kinase-like_dom.
IPR008271. Ser/Thr_prot_kinase_AS.
IPR002290. Ser/Thr_prot_kinase_dom.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

PROSITE

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

ProtoNet

Search...

Other Resources

BindingDB

P50613.

NextBio

4295.

SOURCE

Search...

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:	February 9, 2010
This is version 122 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.