P51952 (CDK7_RAT) 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 protein kinase
Short name=P39 Mo15
CDK-activating kinase 1
Cell division protein kinase 7
TFIIH basal transcription factor complex kinase subunit

Gene names

Name:	Cdk7
Synonyms:	Cak, Cak1, Mo15

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	329 AA.
Sequence status	Fragment.
Protein existence	Evidence at transcript 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 By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate.
Enzyme regulation	Phosphorylation at Thr-162 is required for enzymatic activity. 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 By similarity.
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 By similarity.
Subcellular location	Nucleus By similarity. Cytoplasm By similarity. Cytoplasm › perinuclear region By similarity. Note: Colocalizes with PRKCI in the cytoplasm and nucleus. Translocates from the nucleus to cytoplasm and perinuclear region in response to DNA-bound peptides By similarity.
Post-translational modification	Phosphorylation of Ser-156 during mitosis inactivates the enzyme. Phosphorylation of Thr-162 is required for activity. Phosphorylated at Ser-156 and Thr-162 by CDK2 By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily. Contains 1 protein kinase domain.
Sequence caution	The sequence CAA58562.1 differs from that shown. Reason: Erroneous termination at position 313. Translated as Ser.

Ontologies

Keywords
Biological process	Cell cycle Cell division DNA damage DNA repair Meiosis Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA repair Inferred from electronic annotation. Source: UniProtKB-KW cell division Inferred from electronic annotation. Source: UniProtKB-KW meiosis Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cyclin-dependent protein kinase holoenzyme complex Traceable author statement PubMed 8906616. Source: RGD cytoskeleton Inferred from direct assay PubMed 15886195. Source: RGD cytosol Inferred from direct assay PubMed 15886195. Source: RGD holo TFIIH complex Inferred from sequence or structural similarity. Source: UniProtKB membrane Inferred from direct assay PubMed 15886195. Source: RGD 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 sequence or structural similarity. Source: UniProtKB RNA polymerase II carboxy-terminal domain kinase activity Inferred from sequence or structural similarity. Source: UniProtKB cyclin-dependent protein serine/threonine kinase activity Inferred from direct assay PubMed 8906616. Source: RGD protein complex binding Inferred from direct assay PubMed 7885450PubMed 9891058. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	‹1 – ›329	›329	Cyclin-dependent kinase 7		PRO_0000085793
Regions
	Domain	4 – 287	284	Protein kinase
	Nucleotide binding	10 – 18	9	ATP By similarity
Sites
	Active site	129	1	Proton acceptor By similarity
	Binding site	33	1	ATP By similarity
Amino acid modifications
	Modified residue	156	1	Phosphoserine; by CDK1 and CDK2 By similarity
	Modified residue	162	1	Phosphothreonine; by CDK2 By similarity
	Modified residue	313	1	Phosphoserine By similarity
Experimental info
	Non-terminal residue	1	1
	Non-terminal residue	329	1

Sequences

	Sequence		Length	Mass (Da)
	P51952 [UniParc]. Last modified May 10, 2005. Version 2. Checksum: B7159FD074881B0F	FASTA	329	37,141
	10 20 30 40 50 60 ANRNEKLDFL GEGQFATVYK ARDKNTNQIV AIKKIKLGHR SEAKDGINRT ALREIKLLQE 70 80 90 100 110 120 LSHPNIIGLL DAFGHKSNIS LVFDFMETDL EVIIKDNSLV LTPSHIKAYM LMTLQGLEYL 130 140 150 160 170 180 HQHWILHRDL KPNNLLLDEN GVLKLADFGL AKSFGSPNWA YTHQVVTRWY RAPELLFGAR 190 200 210 220 230 240 MYGVGVDMWA VGCILAELLL RVPFLPGDSD LDQLTRIFET LGTPTEEQWP DMCSLPDYVT 250 260 270 280 290 300 FKSFPGIPLQ HIFIAAGDDL LELIQGLFLF NPCTRITASQ ALRTKYFSNR PGPTPGCQLP 310 320 RPNCPVEALK EQSNPAMATK RKRAEALEQ

References

[1]	Wu L., Hall F. Submitted (DEC-1994) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Testis.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X83579 mRNA. Translation: CAA58562.1. Sequence problems.
IPI	IPI00207330.
PIR	S51085.
UniGene	Rn.98896.
3D structure databases
ProteinModelPortal	P51952.
SMR	P51952. Positions 5-303.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000025026.
PTM databases
PhosphoSite	P51952.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
UCSC	RGD:621124. rat.
Organism-specific databases
RGD	621124. Cdk7.
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000233024.
HOVERGEN	HBG014652.
InParanoid	P51952.
OrthoDB	EOG4KSPK0.
Gene expression databases
ArrayExpress	P51952.
Genevestigator	P51952.
GermOnline	ENSRNOG00000018510. Rattus norvegicus.
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...

Entry information

Entry name

CDK7_RAT

Accession

Primary (citable) accession number: P51952

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	May 10, 2005
Last modified:	May 1, 2013
This is version 113 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program