Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  Cyclin-dependent kinase 7  

UniProtKB / Swiss-Prot ID :  CDK7_HUMAN

Gene Name (Synonyms) : 
CDK7, CAK, CAK1, CDKN7, MO15, STK1  

Species :  Homo sapiens (Human). 

Subcellular Localization :  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. 

Protein 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. 

Protein Sequence MALDVKSRAKRYEKLDFLGEGQFATVYKARDKNTNQIVAIKKIKLGHRSEAKDGINRTALREIKLLQELS...
Predicted Secondary Structure CCCCCCCCHHHEEEEEEEEECCCEEEEEEEECCCCCEEEEEEECCHHHHHHHHHHHHHHHHHHHHHHHCC...
Protein Variant
LocationDescription
163G -> A. VAR_023118
285T -> M (in dbSNP:rs34584424). VAR_023119
- top -

Overview of Protein Modification Sites with Functional and Structural Information
Accessible Surface Area (ASA)
Pred. Secondary
Real Secondary
Disorder Prediction
Protein Domain
&
Experimental PTM Sites
Predicted PTM Sites
Protein Variant
- top -

Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
7PhosphoserineLDVKSRAKR
CCCCCCHHH
37.00HPRD
Link-
7PhosphoserineLDVKSRAKR
CCCCCCHHH
37.00Phosphositeplus
Link-
7PhosphoserineLDVKSRAKR
CCCCCCHHH
37.00SysPTM
Link-
7Phosphoserine.LDVKSRAKR
CCCCCCHHH
37.00UniProtKB
Link-
25PhosphothreonineGQFATVYKA
CCCEEEEEE
26.17HPRD
Link
139Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)HRDLKPNNL
EEECCHHHE
50.41Phosphositeplus
Link
160Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)FGLAKSFGS
HHHHHHHCC
51.89Phosphositeplus
Link
161PhosphoserineGLAKSFGSP
HHHHHHCCC
29.27HPRD
Link
161PhosphoserineGLAKSFGSP
HHHHHHCCC
29.27PhosphoELM
Link
161PhosphoserineGLAKSFGSP
HHHHHHCCC
29.27Phosphositeplus
Link
164PhosphoserineKSFGSPNRA
HHHCCCCCE
19.59Phosphositeplus
Link
164PhosphoserineKSFGSPNRA
HHHCCCCCE
19.59SysPTM
Link
164Phosphoserine (CDK1)KSFGSPNRA
HHHCCCCCE
19.59HPRD
Link
164Phosphoserine (CDK2)KSFGSPNRA
HHHCCCCCE
19.59HPRD
Link
164Phosphoserine (CDK2;CDK7)KSFGSPNRA
HHHCCCCCE
19.59PhosphoELM
Link
164Phosphoserine; by CDK1 and CDK2.KSFGSPNRA
HHHCCCCCE
19.59UniProtKB
Link
169PhosphotyrosinePNRAYTHQV
CCCEEEEEE
11.08HPRD
Link
169Phosphotyrosine.PNRAYTHQV
CCCEEEEEE
11.08UniProtKB
Link
170PhosphothreonineNRAYTHQVV
CCEEEEEEE
12.59HPRD
Link
170PhosphothreonineNRAYTHQVV
CCEEEEEEE
12.59Phosphositeplus
Link
170PhosphothreonineNRAYTHQVV
CCEEEEEEE
12.59SysPTM
Link
170Phosphothreonine (CDK1)NRAYTHQVV
CCEEEEEEE
12.59HPRD
Link
170Phosphothreonine (CDK2)NRAYTHQVV
CCEEEEEEE
12.59HPRD
Link
170Phosphothreonine (CDK2;CDK7)NRAYTHQVV
CCEEEEEEE
12.59PhosphoELM
Link
170Phosphothreonine; by CDK2.NRAYTHQVV
CCEEEEEEE
12.59UniProtKB
Link
287PhosphothreonineRITATQALK
CCCHHHHHC
13.01HPRD
Link
287PhosphothreonineRITATQALK
CCCHHHHHC
13.01Phosphositeplus
Link
287PhosphothreonineRITATQALK
CCCHHHHHC
13.01SysPTM
Link
287Phosphothreonine.RITATQALK
CCCHHHHHC
13.01UniProtKB
Link
291Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)TQALKMKYF
HHHHCCCCC
36.04Phosphositeplus
Link
316PhosphothreonineCPVETLKEQ
CCCCCCCHH
43.28HPRD
Link-
321PhosphoserineLKEQSNPAL
CCHHHHHHH
45.96HPRD
Link-
321PhosphoserineLKEQSNPAL
CCHHHHHHH
45.96Phosphositeplus
Link-
321PhosphoserineLKEQSNPAL
CCHHHHHHH
45.96SysPTM
Link-
321Phosphoserine.LKEQSNPAL
CCHHHHHHH
45.96UniProtKB
Link-
328Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)ALAIKRKRT
HHHHHCCCC
46.38Phosphositeplus
Link-
- top -

Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
RPB1_HUMANdirect interactionDIP:57011EDIP16327805
CDC2_HUMANdirect interactionDIP:57012EDIP16327805
Q6IAW3_HUMANdirect interactionDIP:57015EDIP16327805
SPT5H_HUMANdirect interaction
direct interaction
direct interaction
DIP:57017EDIP16327805
16327805
16327805
MAT1_HUMANphysical interaction
physical interaction
physical interaction
physical interaction
EBI-1246014
EBI-1246050
EBI-1
intact8521818
8521818
8521818
8521818
CDK2_HUMANin vitroHPRD:15993HPRD11113184
CDC2_HUMANin vitroHPRD:15993HPRD7944411
11113184
ERCC2_HUMANin vitroHPRD:15993HPRD11445587
ESR1_HUMANin vivoHPRD:15993HPRD15461668
ERCC3_HUMANin vivoHPRD:15993HPRD9130708
E2F1_HUMANin vitroHPRD:15993HPRD10428966
TF2H1_HUMANin vivoHPRD:15993HPRD9130708
TF2H2_HUMANin vivoHPRD:15993HPRD9130708
LASP1_HUMANin vitro
in vivo
HPRD:15993HPRD12571245
MAT1_HUMANin vivoHPRD:15993HPRD9130708
8521393
PCGF6_HUMANin vitro
in vivo
HPRD:15993HPRD12167161
CCNH_HUMANin vivo
yeast 2-hybrid
HPRD:15993HPRD8078587
9056480
CDK7_HUMANyeast 2-hybridHPRD:15993HPRD9056480
MCM7_HUMANin vivoHPRD:15993HPRD11056214
THA_HUMANyeast 2-hybridHPRD:15993HPRD15249124
RRN3_HUMANENSP00000256443STRING
RPAB1_HUMANENSP00000256443STRING
RPAB2_HUMANENSP00000256443STRING
TAF9_HUMANENSP00000256443STRING
RPB3_HUMANENSP00000256443STRING
ERCC2_HUMANENSP00000256443STRING
RPB9_HUMANENSP00000256443STRING
RFA3_HUMANENSP00000256443STRING
CCND1_HUMANENSP00000256443STRING
CDN1B_HUMANENSP00000256443STRING
TF2H3_HUMANENSP00000256443STRING
TBP_HUMANENSP00000256443STRING
CDN1A_HUMANENSP00000256443STRING
T2FA_HUMANENSP00000256443STRING
TAF4_HUMANENSP00000256443STRING
RARA_HUMANENSP00000256443STRING
RFA1_HUMANENSP00000256443STRING
CCNB1_HUMANENSP00000256443STRING
CCNH_HUMANENSP00000256443STRING
DDB2_HUMANENSP00000256443STRING
CDK4_HUMANENSP00000256443STRING
TF2H4_HUMANENSP00000256443STRING
MAT1_HUMANENSP00000256443STRING
CCNT1_HUMANENSP00000256443STRING
MCES_HUMANENSP00000256443STRING
ELOB_HUMANENSP00000256443STRING
CCNE1_HUMANENSP00000256443STRING
ELL_HUMANENSP00000256443STRING
RPA2_HUMANENSP00000256443STRING
RPA1_HUMANENSP00000256443STRING
TAF12_HUMANENSP00000256443STRING
CCNT2_HUMANENSP00000256443STRING
ERCC8_HUMANENSP00000256443STRING
TF2H1_HUMANENSP00000256443STRING
CDK2_HUMANENSP00000256443STRING
T2AG_HUMANENSP00000256443STRING
TAF4B_HUMANENSP00000256443STRING
P53_HUMANENSP00000256443STRING
RPB4_HUMANENSP00000256443STRING
CCNA2_HUMANENSP00000256443STRING
TF2H2_HUMANENSP00000256443STRING
TAF1_HUMANENSP00000256443STRING
SSRP1_HUMANENSP00000256443STRING
T2EA_HUMANENSP00000256443STRING
ELOC_HUMANENSP00000256443STRING
XPC_HUMANENSP00000256443STRING
ERCC3_HUMANENSP00000256443STRING
RPAB3_HUMANENSP00000256443STRING
TF2AA_HUMANENSP00000256443STRING
TAF10_HUMANENSP00000256443STRING
CTDP1_HUMANENSP00000256443STRING
DDB1_HUMANENSP00000256443STRING
RPB7_HUMANENSP00000256443STRING
RPAC2_HUMANENSP00000256443STRING
UBF1_HUMANENSP00000256443STRING
CDC2_HUMANENSP00000256443STRING
CCNE2_HUMANENSP00000256443STRING
ERCC4_HUMANENSP00000256443STRING
TAF7_HUMANENSP00000256443STRING
RPB2_HUMANENSP00000256443STRING
RPB1_HUMANENSP00000256443STRING
RPAB5_HUMANENSP00000256443STRING
NCBP2_HUMANENSP00000256443STRING
NELFA_HUMANENSP00000256443STRING
TTF1_HUMANENSP00000256443STRING
NELFB_HUMANENSP00000256443STRING
NELFD_HUMANENSP00000256443STRING
RPAB4_HUMANENSP00000256443STRING
ERCC5_HUMANENSP00000256443STRING
T2EB_HUMANENSP00000256443STRING
PTRF_HUMANENSP00000256443STRING
RD23B_HUMANENSP00000256443STRING
XAB2_HUMANENSP00000256443STRING
T2FB_HUMANENSP00000256443STRING
TCEA1_HUMANENSP00000256443STRING
- top -

Disease Reference
Kegg disease
There are no disease associations of PTM sites.
Drug Reference
There are no disease associations of PTM sites.
- top -
Related Literatures of Post-Translational Modification
Phosphorylation
ReferencePubMed
"The molecular mechanism of mitotic inhibition of TFIIH is mediated byphosphorylation of CDK7.";
Akoulitchev S., Reinberg D.;
Genes Dev. 12:3541-3550(1998).
Cited for: PHOSPHORYLATION AT SER-164 AND THR-170, AND MUTAGENESIS OF SER-164 ANDTHR-170.
"Reciprocal activation by cyclin-dependent kinases 2 and 7 is directedby 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).
Cited for: PHOSPHORYLATION AT SER-164 AND THR-170 BY CDK2, AND FUNCTION AS CDK2KINASE.
"Proteomics analysis of protein kinases by target class-selectiveprefractionation 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).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-164 AND THR-170, ANDMASS SPECTROMETRY.
"Combining protein-based IMAC, peptide-based IMAC, and MudPIT forefficient 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).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-170, AND MASSSPECTROMETRY.
"Kinase-selective enrichment enables quantitative phosphoproteomics ofthe 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).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7; SER-164; THR-170;THR-287 AND SER-321, AND MASS SPECTROMETRY.
"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).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-164 AND THR-170, ANDMASS SPECTROMETRY.
"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).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-169 AND THR-170, ANDMASS SPECTROMETRY.
"Quantitative phosphoproteomic analysis of T cell receptor signalingreveals 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).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-170, AND MASSSPECTROMETRY.
"The crystal structure of human CDK7 and its protein recognitionproperties.";
Lolli G., Lowe E.D., Brown N.R., Johnson L.N.;
Structure 12:2067-2079(2004).
Cited for: X-RAY CRYSTALLOGRAPHY (3.02 ANGSTROMS) IN COMPLEX WITH ATP, ACTIVESITE, AND PHOSPHORYLATION AT THR-170.
- top -
Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures