KinaseNET

Nomenclature

Short Name:

CDK9

Full Name:

Cyclin-dependent kinase 9

Alias:

C-2K
CDC2L4
Kinase Cdk9
PITALRE
TAK
Cell division cycle 2-like protein kinase 4
Cyclin-dependent kinase 9
EC 2.7.11.22
EC 2.7.11.23

Classification

Type:

Protein-serine/threonine kinase

Group:

CMGC

Family:

CDK

SubFamily:

CDK9

Specific Links

Entrez-Gene Entry:	1025
Entrez-Protein Entry:	NP_001252
GeneCards Entry:	CDC2L4
KinBASE Entry:	CDK9
OMIM Entry:	603251
Pfam Entry:	P50750
PhosphoNET Entry:	P50750
Phosphosite Plus Entry:	681
Protein Data Bank Entry:	1PF6
ScanSite Entry:	P50750
Source Entry:	CDK9
UCSD-Nature Entry:	A003128
UniProt Entry:	P50750
Kinexus Products:	CDK9 Cyclin-dependent protein-serine kinase 9 S347 phosphosite-specific antibody AB-PK574 Cyclin-dependent protein-serine kinase 9 T186 phosphosite-specific antibody AB-PK575 RNA polymerase II-CT KinSub - heptapeptide repeat from C-terminus peptide; CDKtide protein kinase substrate peptide - Powder PE-01ADN95 CDK7/9Subtide - CDK7 protein kinase substrate peptide - Powder PE-01BGR99 Cyclin-dependent protein-serine kinase 9 (R188-Y194, human) pT191 phosphopeptide - Powder PE-04ABE85 Cyclin-dependent protein-serine kinase 9 (N183-V189, human) pT186 phosphopeptide - Powder PE-04AJS99 Cyclin-dependent protein-serine kinase 9 (R344-T350, human) pS347 phosphopeptide - Powder PE-04AJT99 Cyclin-dependent protein-serine kinase 9 (R188-R195, human) pT191+pY194 phosphopeptide - Powder PE-04ASP99 Cyclin-dependent protein-serine kinase 9 (R188-R195, human) pT191+pY194 phosphopeptide - Powder PE-04ASQ01 Cyclin-dependent protein-serine kinase 9 (R172-V189, human) pS175+pS180+pY185+pT186 phosphopeptide - Powder PE-04ASR99

General Links

Structure

Mol. Mass (Da):

42,778

# Amino Acids:

372

# mRNA Isoforms:

mRNA Isoforms:

53,365 Da (489 AA; P50750-2); 42,778 Da (372 AA; P50750)

4D Structure:

Associates with CCNT1/cyclin-T1 to form P-TEFb. P-TEFb forms a complex with AFF4/AF5Q31. Also associates with CCNK/cyclin-K. Component of a complex which is at least composed of HTATSF1/Tat-SF1, P-TEFb complex, RNA pol II, SUPT5H, and NCL/nucleolin. Component of the 7SK snRNP complex at least composed of P-TEFb (composed of CDK9 and CCNT1/cyclin-T1), HEXIM1, HEXIM2, BCDIN3, SART3 proteins and 7SK and U6 snRNAs.

1D Structure:

Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence

3D Image (rendered using PV Viewer):

PDB ID

4EC9

Subfamily Alignment

Domain Distribution:

Start	End	Domain
19	315	Pkinase

Kinexus Products

Click on entries below for direct links to relevant products from Kinexus for this protein kinase.

hiddentext

○	Cyclin-dependent protein-serine kinase 9 S347 phosphosite-specific antibody AB-PK574
○	Cyclin-dependent protein-serine kinase 9 T186 phosphosite-specific antibody AB-PK575
○	RNA polymerase II-CT KinSub - heptapeptide repeat from C-terminus peptide; CDKtide protein kinase substrate peptide - Powder PE-01ADN95
○	CDK7/9Subtide - CDK7 protein kinase substrate peptide - Powder PE-01BGR99
○	Cyclin-dependent protein-serine kinase 9 (R188-Y194, human) pT191 phosphopeptide - Powder PE-04ABE85
○	Cyclin-dependent protein-serine kinase 9 (N183-V189, human) pT186 phosphopeptide - Powder PE-04AJS99
○	Cyclin-dependent protein-serine kinase 9 (R344-T350, human) pS347 phosphopeptide - Powder PE-04AJT99
○	Cyclin-dependent protein-serine kinase 9 (R188-R195, human) pT191+pY194 phosphopeptide - Powder PE-04ASP99
○	Cyclin-dependent protein-serine kinase 9 (R188-R195, human) pT191+pY194 phosphopeptide - Powder PE-04ASQ01
○	Cyclin-dependent protein-serine kinase 9 (R172-V189, human) pS175+pS180+pY185+pT186 phosphopeptide - Powder PE-04ASR99

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET

Acetylated:

K35, K44, K48, K49, K56, K68, K74, K127, K164, K178, K269, K274, K276, K345.

Methylated:

K21, K35, R86, K127, R370.

Serine phosphorylated:

S7, S175+, S180+, S317, S334, S347+, S353+, S357+.

Threonine phosphorylated:

T186+, T330, T333, T350+, T354+, T362, T363, T366.

Tyrosine phosphorylated:

Y185+, Y194-, Y338.

Ubiquitinated:

K24, K35, K56, K68, K88, K151, K164, K178, K269, K294, K345.

Distribution

Based on gene microarray analysis from the NCBI

Human Tissue Distribution

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

48

911

31

927
9

170

12

193
6

123

7

131
9

179

104

331
33

631

32

509
100

1895

67

5475
10

182

39

419
26

489

33

967
21

391

10

241
3

65

95

79
8

153

22

132
34

647

114

596
9

168

18

209
13

239

9

212
11

207

19

202
3

60

18

59
5

90

192

167
6

113

14

121
3

57

91

44
23

444

112

400
13

248

18

195
14

258

20

203
9

168

16

191
11

216

14

200
17

316

18

331
28

530

69

555
8

145

21

125
9

176

14

143
13

253

14

207
6

112

42

106
62

1167

18

796
38

717

30

1762
2

32

77

86
36

678

83

596
11

214

48

415

Evolution

Species Conservation

PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:

100

100

100
0

0

100
92.4

93.5

-
-

-

99
-

-

99
68.5

69.4

98
-

-

-
98.6

99.7

99
98.6

99.7

99
-

-

-
77.9

80.3

-
93

95.4

93
89.3

94.1

91
85.5

89.5

91
-

-

-
66

75.9

74
72.7

83.2

-
43.3

56.4

57
67.3

75.8

-
-

-

-
-

-

-
-

-

-
36

51

-
25.2

39.4

41
31.7

45.6

34

For a wider analysis go to PhosphoNET Evolution in PhosphoNET

Binding Proteins

Examples of known interacting proteins

hiddentext

No.	Name – UniProt ID
1	CCNT1 - O60563
2	POLR2A - P24928
3	CCNT2 - O60583
4	SKP2 - Q13309
5	CUL1 - Q13616
6	TP53 - P04637
7	RB1 - P06400
8	NBN - O60934
9	NFKB1 - P19838
10	STK36 - Q9NRP7
11	MED21 - Q13503
12	HEXIM2 - Q96MH2
13	RELA - Q04206
14	CDC34 - P49427
15	SKP1 - P63208

Regulation

Activation:

Phosphorylation at Ser-175 increases phosphotransferase activity.

Inhibition:

Synthesis:

Degradation:

Kinections Map

Click here to download a PPT of the image below

Known Upstream Kinases

For further details on these substrates click on the Substrate Short Name or UniProt ID. Phosphosite Location is hyperlinked to PhosphoNET predictions.

Based on in vitro and/or in vivo phosphorylation data

Kinase Short Name	UniProt ID (Human)	Phosphosite Location	Phosphosite Sequence	Effect of Phosphorylation

CDK9	P50750	T186	NSQPNRYTNRVVTLW	+
CDK9	P50750	S347	APPRRKGSQITQQST	+
CDK9	P50750	T362	NQSRNPATTNQTEFE
CDK9	P50750	T363	QSRNPATTNQTEFER

Known Downstream Substrates

For further details on these substrates click on the Substrate Short Name or UniProt ID. Phosphosite Location is hyperlinked to PhosphoNET predictions.

Based on in vitro and/or in vivo phosphorylation data

Substrate Short Name	UniProt ID (Human)	Phosphosite Location	Phosphosite Sequence	Effect of Phosphorylation

CDK9	P50750	S347	APPRRKGSQITQQST	+
CDK9	P50750	T186	NSQPNRYTNRVVTLW	+
CDK9	P50750	T362	NQSRNPATTNQTEFE
CDK9	P50750	T363	QSRNPATTNQTEFER
MBP	P02686	S299	GRDSRSGSPMARR__
MBP	P02686	T232	KNIVTPRTPPPSQGK
MyoD	P15172	S200	SGDSDASSPRSNCSD
p53	P04637	S315	LPNNTSSSPQPKKKP	+
p53	P04637	S33	LPENNVLSPLPSQAM	+
p53	P04637	S392	FKTEGPDSD______	+
POLR2A (RPB1)	P24928	S1616	TPQSPSYSPTSPSYS	+
POLR2A (RPB1)	P24928	S1619	SPSYSPTSPSYSPTS	+
POLR2A (RPB1)	P24928	S1896	SPTSPTYSPTSPVYT
POLR2A (RPB1)	P24928	S1931	SPTSPTYSPTSPKGS
PPARg-1	P37231	S112	AIKVEPASPPYYSEK	-
Rb	P06400	S795	SPYKFPSSPLRIPGG	-
Rb	P06400	S807	PGGNIYISPLKSPYK	-
Rb	P06400	S811	IYISPLKSPYKISEG	-
SPT5	O00267	T768	MTSTYGRTPMYGSQT
SPT5	O00267	T775	TPMYGSQTPMYGSGS
SPT5	O00267	T784	MYGSGSRTPMYGSQT
SPT5	O00267	T791	TPMYGSQTPLQDGSR
SPT5	O00267	T799	PLQDGSRTPHYGSQT
SPT5	O00267	T806	TPHYGSQTPLHDGSR
SPT5	O00267	T814	PLHDGSRTPAQSGAW

Protein Kinase Specificity

Matrix of observed frequency (%) of amino acids in aligned protein substrate phosphosites

Matrix Type:

Experimentally derived from alignment of 33 known protein substrate phosphosites.

Domain #:

Inhibitors

For further details on these inhibitors click on the Compound Name and enter it into DrugKiNET or click on the ID's

Based on in vitro and/or in vivo phosphorylation data

Compound Name	KD, Ki or IC50 (nM)	PubChem ID	ChEMBL ID	PubMed ID

CHEMBL424696	IC50 = 2.5 nM	44413509	424696	16682184
Staurosporine	IC50 = 3.3 nM	5279		19338355
CK7	Ki = 4 nM	447961		15027857
Dinaciclib	IC50 = 4 nM	46926350		20663931
SNS032	IC50 = 4 nM	3025986	296468	18926699
AT7519	Kd = 5.8 nM	11338033		22037378
CHEMBL1083152	Ki = 6 nM	11718021	1083152	20462263
Alvocidib	Kd = 6.4 nM	9910986	428690	18183025
CHEMBL1084715	Ki = 9 nM	11646645	1084715	20462263
RGB-286147	IC50 = 9 nM	9549301	258721	18077363
CHEMBL1083151	Ki = 11 nM	11632150	1083151	20462263
R547	Kd = 15 nM	6918852		22037378
AZD5438	IC50 = 20 nM	16747683
P276-00	IC50 = 20 nM	10406644		17363486
P1446A-05	IC50 = 22 nM
BAY1000394	IC50 < 25 nM			22821149
PHA-767491	IC50 = 34 nM	11715767	225519	18469809
TTT-3002	IC50 < 40 nM
Cdk1/2 Inhibitor III	IC50 > 50 nM	5330812	261720	22037377
SB218078	IC50 > 50 nM	447446	289422	22037377
Kenpaullone	IC50 = 64 nM	3820	296586	20621478
AC1NS7CD	Kd = 76 nM	5329665	295136	22037378
AT9283	IC50 > 100 nM	24905142		19143567
Alsterpaullone	IC50 > 150 nM	5005498	50894	22037377
Alsterpaullone; 2-Cyanoethyl	IC50 > 150 nM	16760286	260138	22037377
AS601245	IC50 > 150 nM	11422035	191384	22037377
K-252a; Nocardiopsis sp.	IC50 > 150 nM	3813	281948	22037377
PKR Inhibitor	IC50 > 150 nM	6490494	235641	22037377
A674563	Kd = 180 nM	11314340	379218	22037378
AST-487	Kd = 190 nM	11409972	574738	18183025
Roscovitine	IC50 = 230 nM	160355	14762	19128055
BML-275	IC50 > 250 nM	11524144	478629	22037377
Flt-3 Inhibitor III	IC50 > 250 nM	11772958		22037377
GSK-3 Inhibitor IX	IC50 > 250 nM	5287844	409450	22037377
IDR E804	IC50 > 250 nM	6419764	1802727	22037377
JAK3 Inhibitor VI	IC50 > 250 nM	16760524		22037377
Ro-32-0432	IC50 > 250 nM	127757	26501	22037377
SU11652	IC50 > 250 nM	24906267	13485	22037377
CHEMBL1084969	Ki = 264 nM	46830768	1084969	20462263
CHEMBL1084454	Ki = 337 nM	46830767	1084454	20462263
CHEMBL1083150	Ki = 348 nM	46830766	1083150	20462263
CHEMBL1082152	Kd = 410 nM	11560568	1082152	20138512
Kinome_756	Ki = 448 nM	10320107		20462263
JNJ-7706621	Kd = 470 nM	5330790	191003	18183025
CHEMBL482967	Ki = 480 nM	6420138	482967	20462263
Aloisine A	IC50 = 500 nM	5326843	75680	22037377
Aloisine; RP106	IC50 = 500 nM	44350092	126343	22037377
CGP74514A	IC50 = 500 nM	2794188	367625	22037377
Flt-3 Inhibitor II	IC50 = 500 nM	11601743	377193	22037377
Gö6976	IC50 = 500 nM	3501	302449	22037377
Gö6983	IC50 = 500 nM	3499	261491	22037377
PKCb Inhibitor	IC50 = 500 nM	6419755	366266	22037377
Lestaurtinib	Kd = 530 nM	126565		22037378
CHEMBL1086088	Ki = 564 nM	11647020	1086088	20462263
CK8	Ki = 575 nM	447962		20462263
Paullone	IC50 = 810 nM	369401	430574	20621478
Bisindolylmaleimide I	IC50 > 1 µM	2396	7463	22037377
CVT-313	IC50 > 1 µM	6918386	80713	22037377
GSK-3 Inhibitor X	IC50 > 1 µM	6538818	430226	22037377
Indirubin-3′-monoxime	IC50 > 1 µM	5326739		22037377
IRAK-1-4 Inhibitor I	IC50 > 1 µM	11983295	379787	22037377
JNKIN7	IC50 = 1 µM	57340685
MK5108	IC50 > 1 µM	24748204		20053775
N-Benzoylstaurosporine	IC50 > 1 µM	56603681	608533	22037377
Purvalanol A	IC50 > 1 µM	456214	23327	22037377
Silmitasertib	IC50 > 1 µM	24748573		21174434
SNS314	IC50 > 1 µM	16047143	514582	18678489
SU9516	IC50 > 1 µM	5289419	258805	22037377
Syk Inhibitor	IC50 > 1 µM	6419747	104279	22037377
Syk Inhibitor III	IC50 > 1 µM	672296	596380	22037377
TBCA	IC50 > 1 µM	1095828		22037377
TWS119	IC50 > 1 µM	9549289	405759	22037377
WZ3146	Kd > 1 µM	44607360		20033049
WZ4002	Kd > 1 µM	44607530		20033049
CHEMBL1083786	Ki = 1.153 µM	10024433	1083786	20462263
CHEMBL489833	IC50 = 1.22 µM	44582745	489833	19338355
Enzastaurin	Kd = 1.3 µM	176167	300138	22037378
Foretinib	Kd = 1.6 µM	42642645	1230609	22037378
CHEMBL248757	Ki > 1.644 µM	44444843	248757	17935989
PHA-665752	Kd = 1.8 µM	10461815	450786	22037378
CHEMBL210540	IC50 = 2.5 µM	16037675	210540	16682184
CHEMBL1084629	Ki = 2.605 µM	10430000	1084629	20462263
Linifanib	Kd = 3 µM	11485656	223360	18183025
SureCN4875304	IC50 > 3.5 µM	46871765		20472445
JNJ-28871063	IC50 > 4 µM	17747413		17975007
SureCN2579964	IC50 < 4 µM	290221	233000	22934575
BS181	IC50 = 4.2 µM	49867928		19638587
GSK461364A	IC50 > 4.5 µM	15983966	1908394
JNKIN8	IC50 > 4.5 µM	57340686

Disease Linkage

General Disease Association:

Infectious disease

Specific Diseases (Non-cancerous):

Hiv-1

Comments:

Chronic activation of CDK9 enlarges cardiac myocyte, which may result in cardiac hypertrophy, and predisposition to heart failure. Mutations on 347-357 positions lead to loss of autophosphorylation and can either impair or promote interaction with HIV TAT.

Gene Expression in Cancers:

TranscriptoNET (www.transcriptonet.ca) analysis with mRNA expression data retrieved from the National Center for Biotechnology Information's Gene Expression Omnibus (GEO) database, which was normalized against 60 abundantly and commonly found proteins, indicated altered expression for this protein kinase as shown here as the percent change from normal tissue controls (%CFC) as supported with the Student T-test in the following types of human cancers: Malignant pleural mesotheliomas (MPM) tumours (%CFC= +126, p<0.004); Prostate cancer - primary (%CFC= -46, p<0.0001); Skin melanomas - malignant (%CFC= +428, p<0.0001); and Uterine leiomyomas (%CFC= +61, p<0.084).

Mutagenesis Experiments:

Insertional mutagenesis studies in mice have not yet revealed a role for this protein kinase in mouse cancer oncogenesis.

Mutation Rate in All Cancers:

Percent mutation rates per 100 amino acids length in human cancers: 0.06 % in 24433 diverse cancer specimens. This rate is only -22 % lower than the average rate of 0.075 % calculated for human protein kinases in general.

Mutation Rate in Specific Cancers:

Highest percent mutation rates per 100 amino acids length in human cancers: 0.32 % in 1270 large intestine cancers tested; 0.31 % in 864 skin cancers tested.

Frequency of Mutated Sites:

None > 1 in 20,197 cancer specimens

Comments:

Only 3 insertions (I210fs*2 insertions frameshift), and no deletions or complex mutations are noted on the COSMIC website.

COSMIC Entry:

CDK9_ENST00000373264

OMIM Entry:

603251

Nomenclature

Short Name:

Full Name:

Alias:

Classification

Type:

Group:

Family:

SubFamily:

Specific Links

General Links

Structure

Mol. Mass (Da):

# Amino Acids:

# mRNA Isoforms:

mRNA Isoforms:

4D Structure:

1D Structure:

3D Image (rendered using PV Viewer):

PDB ID

Subfamily Alignment

Domain Distribution:

Kinexus Products

hiddentext

Post-translation Modifications

Acetylated:

Methylated:

Serine phosphorylated:

Threonine phosphorylated:

Tyrosine phosphorylated:

Ubiquitinated:

Distribution

Human Tissue Distribution

% Max Expression: Mean Expression: Number of Samples: Standard Deviation:

% Max Expression: Mean Expression: Number of Samples: Standard Deviation:

Evolution

Species Conservation

PhosphoNET % Identity: PhosphoNET % Similarity: Homologene %Identity:

PhosphoNET % Identity: PhosphoNET % Similarity: Homologene %Identity:

Binding Proteins

hiddentext

Regulation

Activation:

Inhibition:

Synthesis:

Degradation:

Kinections Map

Known Upstream Kinases

Based on in vitro and/or in vivo phosphorylation data

Known Downstream Substrates

Based on in vitro and/or in vivo phosphorylation data

Protein Kinase Specificity

Matrix Type:

Domain #:

Inhibitors

Based on in vitro and/or in vivo phosphorylation data

Disease Linkage

General Disease Association:

Specific Diseases (Non-cancerous):

Comments:

Gene Expression in Cancers:

Mutagenesis Experiments:

Mutation Rate in All Cancers:

Mutation Rate in Specific Cancers:

Frequency of Mutated Sites:

Comments:

COSMIC Entry:

OMIM Entry:

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:

PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity: