dbPTM

CDK7_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	CDK7_HUMAN
UniProt AC	P50613
Protein Name	Cyclin-dependent kinase 7
Gene Name	CDK7
Organism	Homo sapiens (Human).
Sequence Length	346
Subcellular Localization	Nucleus. Cytoplasm. Cytoplasm, perinuclear region. Colocalizes with PRKCI in the cytoplasm and nucleus. Translocates from the nucleus to cytoplasm and perinuclear region in response to DNA-bound peptides.
Protein Description	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-terminal 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	MALDVKSRAKRYEKLDFLGEGQFATVYKARDKNTNQIVAIKKIKLGHRSEAKDGINRTALREIKLLQELSHPNIIGLLDAFGHKSNISLVFDFMETDLEVIIKDNSLVLTPSHIKAYMLMTLQGLEYLHQHWILHRDLKPNNLLLDENGVLKLADFGLAKSFGSPNRAYTHQVVTRWYRAPELLFGARMYGVGVDMWAVGCILAELLLRVPFLPGDSDLDQLTRIFETLGTPTEEQWPDMCSLPDYVTFKSFPGIPLHHIFSAAGDDLLDLIQGLFLFNPCARITATQALKMKYFSNRPGPTPGCQLPRPNCPVETLKEQSNPALAIKRKRTEALEQGGLPKKLIF

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Acetylation	------MALDVKSRA ------CCCCHHHHH	16.69	22814378
6	Ubiquitination	--MALDVKSRAKRYE --CCCCHHHHHHHHH	33.61	-
7	Phosphorylation	-MALDVKSRAKRYEK -CCCCHHHHHHHHHH	37.00	17192257
25	Phosphorylation	LGEGQFATVYKARDK CCCCCEEEEEEEECC	26.17	18691976
32	Ubiquitination	TVYKARDKNTNQIVA EEEEEECCCCCEEEE	61.18	-
34	Phosphorylation	YKARDKNTNQIVAIK EEEECCCCCEEEEEE	33.95	29888752
41	Ubiquitination	TNQIVAIKKIKLGHR CCEEEEEEEEECCCC	38.41	-
42	Ubiquitination	NQIVAIKKIKLGHRS CEEEEEEEEECCCCH	38.67	-
106	Phosphorylation	EVIIKDNSLVLTPSH EEEECCCCEEECHHH	29.95	27251275
110	Phosphorylation	KDNSLVLTPSHIKAY CCCCEEECHHHHHHH	18.44	27251275
112	Phosphorylation	NSLVLTPSHIKAYML CCEEECHHHHHHHHH	32.39	27251275
139	Ubiquitination	WILHRDLKPNNLLLD HHHCCCCCCCCEEEC	50.41	21906983
160	Ubiquitination	LADFGLAKSFGSPNR EHHHHHHHHHCCCCC	51.89	21906983
161	Phosphorylation	ADFGLAKSFGSPNRA HHHHHHHHHCCCCCC	29.27	23401153
164	Phosphorylation	GLAKSFGSPNRAYTH HHHHHHCCCCCCCCH	19.59	22167270
169	Phosphorylation	FGSPNRAYTHQVVTR HCCCCCCCCHHHHHH	11.08	23927012
170	Phosphorylation	GSPNRAYTHQVVTRW CCCCCCCCHHHHHHH	12.59	23927012
175	Phosphorylation	AYTHQVVTRWYRAPE CCCHHHHHHHHCCHH	19.34	23927012
217	Phosphorylation	VPFLPGDSDLDQLTR CCCCCCCCCHHHHHH	46.09	-
231	Phosphorylation	RIFETLGTPTEEQWP HHHHHHCCCCHHHCC	30.10	26853621
287	Phosphorylation	PCARITATQALKMKY HHHEEEHHHHHHHHH	13.01	17192257
291	Ubiquitination	ITATQALKMKYFSNR EEHHHHHHHHHHCCC	36.04	21906983
293	Ubiquitination	ATQALKMKYFSNRPG HHHHHHHHHHCCCCC	41.37	-
316	Phosphorylation	RPNCPVETLKEQSNP CCCCCHHHHHHCCCH	43.28	18691976
318	Ubiquitination	NCPVETLKEQSNPAL CCCHHHHHHCCCHHH	62.21	-
321	Phosphorylation	VETLKEQSNPALAIK HHHHHHCCCHHHHHH	45.96	25159151
328	Acetylation	SNPALAIKRKRTEAL CCHHHHHHHHHHHHH	46.38	25953088
328	Ubiquitination	SNPALAIKRKRTEAL CCHHHHHHHHHHHHH	46.38	21906983
330	Ubiquitination	PALAIKRKRTEALEQ HHHHHHHHHHHHHHH	59.68	-
332	Phosphorylation	LAIKRKRTEALEQGG HHHHHHHHHHHHHCC	28.75	20873877

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
161	S	Phosphorylation	Kinase	NEK6	Q9HC98	PSP
164	S	Phosphorylation	Kinase	CDK1	P06493	Uniprot
164	S	Phosphorylation	Kinase	CDK2	P24941	Uniprot
164	S	Phosphorylation	Kinase	CDK7	P50613	PhosphoELM
170	T	Phosphorylation	Kinase	CDK1	P06493	PSP
170	T	Phosphorylation	Kinase	CDK2	P24941	Uniprot
170	T	Phosphorylation	Kinase	CDK7	P50613	PhosphoELM
170	T	Phosphorylation	Kinase	PRKCI	P41743	GPS

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
164	S	Phosphorylation	9832506
Phosphorylated at Ser-164 and Thr-170 by CDK2.
164	S	Phosphorylation	9832506
Phosphorylation of Ser-164 during mitosis inactivates the enzyme.
170	T	Phosphorylation	8069918
Phosphorylated at Ser-164 and Thr-170 by CDK2.
170	T	Phosphorylation	8069918
Phosphorylation of Thr-170 is required for activity.

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of CDK7_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
MTA1_HUMAN	MTA1	physical	12527756
MAT1_HUMAN	MNAT1	physical	12527756
HDAC2_HUMAN	HDAC2	physical	12527756
ESR1_HUMAN	ESR1	physical	10949034
TF2H1_HUMAN	GTF2H1	physical	9130708
ERCC3_HUMAN	ERCC3	physical	9130708
MCM7_HUMAN	MCM7	physical	11056214
CCNH_HUMAN	CCNH	physical	8078587
P53_HUMAN	TP53	physical	9372954
P53_HUMAN	TP53	physical	9840937
CCNH_HUMAN	CCNH	physical	8521393
TF2H1_HUMAN	GTF2H1	physical	8521393
ERCC3_HUMAN	ERCC3	physical	8521393
MAT1_HUMAN	MNAT1	physical	8521393
SPT5H_HUMAN	SUPT5H	physical	10958691
RUVB2_HUMAN	RUVBL2	physical	17643375
CCNH_HUMAN	CCNH	physical	17643375
ERCC3_HUMAN	ERCC3	physical	17643375
MAT1_HUMAN	MNAT1	physical	17643375
ERCC5_HUMAN	ERCC5	physical	17643375
HS90B_HUMAN	HSP90AB1	physical	17643375
TF2H3_HUMAN	GTF2H3	physical	17643375
TF2H4_HUMAN	GTF2H4	physical	17643375
TF2H2_HUMAN	GTF2H2	physical	17643375
HNRPU_HUMAN	HNRNPU	physical	17643375
CCAR2_HUMAN	CCAR2	physical	17643375
TCPB_HUMAN	CCT2	physical	17643375
CDK2_HUMAN	CDK2	physical	8692842
H11_HUMAN	HIST1H1A	physical	8692842
RPB1_HUMAN	POLR2A	physical	8692842
CCNH_HUMAN	CCNH	physical	8692841
ANXA2_HUMAN	ANXA2	physical	8692841
ERCC2_HUMAN	ERCC2	physical	8692841
ERCC3_HUMAN	ERCC3	physical	8692841
TF2H1_HUMAN	GTF2H1	physical	8692841
RPB1_HUMAN	POLR2A	physical	18391197
CDK9_HUMAN	CDK9	physical	11145967
ANDR_HUMAN	AR	physical	21157430
SMAD1_HUMAN	SMAD1	physical	19914168
CTDP1_HUMAN	CTDP1	physical	19914168
CDK2_HUMAN	CDK2	physical	16191191
SPB1_SCHPO	spb1	physical	22508988
CDK2_HUMAN	CDK2	physical	10393546
CCNH_HUMAN	CCNH	physical	9218599
MAT1_HUMAN	MNAT1	physical	10801852
TAT_HV1H2	tat	physical	9334327
CCNH_HUMAN	CCNH	physical	9334327
MAT1_HUMAN	MNAT1	physical	9334327
RPB2_HUMAN	POLR2B	physical	9334327
CCNH_HUMAN	CCNH	physical	15698475
CDK2_HUMAN	CDK2	physical	7629134
CDK6_HUMAN	CDK6	physical	7629134
MAT1_HUMAN	MNAT1	physical	8521818
CCNH_HUMAN	CCNH	physical	8521818
RPB1_HUMAN	POLR2A	physical	15282296
T2EA_HUMAN	GTF2E1	physical	15282296
CDK2_HUMAN	CDK2	physical	15282296
BRCA1_HUMAN	BRCA1	physical	15282296
ERCC3_HUMAN	ERCC3	physical	10082552
CDK7_HUMAN	CDK7	physical	10082552
MAT1_HUMAN	MNAT1	physical	10082552
CCNH_HUMAN	CCNH	physical	10082552
UB2D1_HUMAN	UBE2D1	physical	21157430
A4_HUMAN	APP	physical	21832049
RPB1_HUMAN	POLR2A	physical	15009212
MAT1_HUMAN	MNAT1	physical	22939629
ERCC2_HUMAN	ERCC2	physical	22939629
RPB1_HUMAN	POLR2A	physical	11278802
T2EB_HUMAN	GTF2E2	physical	23064645
T2EA_HUMAN	GTF2E1	physical	23064645
CDK2_HUMAN	CDK2	physical	23064645
CDK9_HUMAN	CDK9	physical	23064645
RPB1_HUMAN	POLR2A	physical	23064645
RPB1_HUMAN	POLR2A	physical	16327805
CDK2_HUMAN	CDK2	physical	16327805
SPT5H_HUMAN	SUPT5H	physical	16327805
CCNH_HUMAN	CCNH	physical	11713533
CDK7_HUMAN	CDK7	physical	11113184
CDK2_HUMAN	CDK2	physical	11113184
CDK2_HUMAN	CDK2	physical	15530371
MBP_HUMAN	MBP	physical	15328539
P53_HUMAN	TP53	physical	9315650
CDK7_HUMAN	CDK7	physical	9315650
CDK7_HUMAN	CDK7	physical	10993082
DQA1_HUMAN	HLA-DQA1	physical	21988832
DHB4_HUMAN	HSD17B4	physical	21988832
CDK7_HUMAN	CDK7	physical	23602568
CCNH_HUMAN	CCNH	physical	23602568
ERCC2_HUMAN	ERCC2	physical	23602568
MAT1_HUMAN	MNAT1	physical	23602568
ERCC3_HUMAN	ERCC3	physical	23602568
TF2H1_HUMAN	GTF2H1	physical	23602568
TF2H2_HUMAN	GTF2H2	physical	23602568
ERCC5_HUMAN	ERCC5	physical	23602568
TF2H3_HUMAN	GTF2H3	physical	23602568
TF2H5_HUMAN	GTF2H5	physical	23602568
TF2H4_HUMAN	GTF2H4	physical	23602568
AT2B4_HUMAN	ATP2B4	physical	23602568
A2MG_HUMAN	A2M	physical	23602568
CCNA2_HUMAN	CCNA2	physical	26186194
HS90A_HUMAN	HSP90AA1	physical	26186194
HS90B_HUMAN	HSP90AB1	physical	26186194
FKBP5_HUMAN	FKBP5	physical	26186194
CDK20_HUMAN	CDK20	physical	26186194
CDC37_HUMAN	CDC37	physical	26186194
ERCC2_HUMAN	ERCC2	physical	26186194
CCNB1_HUMAN	CCNB1	physical	26186194
CACO2_HUMAN	CALCOCO2	physical	26186194
EF1A2_HUMAN	EEF1A2	physical	26186194
BROMI_HUMAN	TBC1D32	physical	26186194
PRP16_HUMAN	DHX38	physical	26186194
PI4KB_HUMAN	PI4KB	physical	26186194
TCEA1_HUMAN	TCEA1	physical	26186194
MPLKI_HUMAN	MPLKIP	physical	26186194
CCNE1_HUMAN	CCNE1	physical	26186194
CCNH_HUMAN	CCNH	physical	26344197
HNRPF_HUMAN	HNRNPF	physical	26344197
RPB1_HUMAN	POLR2A	physical	15328539
RPB1_HUMAN	POLR2A	physical	22379099
RPB1_HUMAN	POLR2A	physical	15530371
PI4KB_HUMAN	PI4KB	physical	28514442
BROMI_HUMAN	TBC1D32	physical	28514442
CDK20_HUMAN	CDK20	physical	28514442
FKBP5_HUMAN	FKBP5	physical	28514442
HS90A_HUMAN	HSP90AA1	physical	28514442
HS90B_HUMAN	HSP90AB1	physical	28514442
CCNA2_HUMAN	CCNA2	physical	28514442
ERCC2_HUMAN	ERCC2	physical	28514442
CCNE1_HUMAN	CCNE1	physical	28514442
CCNB1_HUMAN	CCNB1	physical	28514442
CACO2_HUMAN	CALCOCO2	physical	28514442
CDN1B_HUMAN	CDKN1B	physical	28514442
CCND2_HUMAN	CCND2	physical	17873913
CCNH_HUMAN	CCNH	physical	26340423

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
There are no disease associations of PTM sites.
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of CDK7_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"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.	18669648 [Abstract]
"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.	18691976 [Abstract]
"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.	17192257 [Abstract]
"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.	11113184 [Abstract]
"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.	9832506 [Abstract]
"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.	15530371 [Abstract]
"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.	19690332 [Abstract]
"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.	19369195 [Abstract]
"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.	18220336 [Abstract]

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