KinaseNET

Nomenclature

Short Name:

CDK2

Full Name:

Cyclin-dependent kinase 2

Alias:

Cyclin-dependent kinase 2
EC 2.7.11.22
Kinase Cdk2
P33 protein kinase

Classification

Type:

Protein-serine/threonine kinase

Group:

CMGC

Family:

CDK

SubFamily:

CDC2

Specific Links

BioCarta Entry:	p53 pathway
Entrez-Gene Entry:	1017
Entrez-Protein Entry:	NP_001789
GeneCards Entry:	CDK2
KinBASE Entry:	CDK2
OMIM Entry:	116953
Pfam Entry:	P24941
PhosphoNET Entry:	P24941
Phosphosite Plus Entry:	583
Protein Data Bank Entry:	1AQ1
ScanSite Entry:	P24941
Source Entry:	CDK2
UCSD-Nature Entry:	A000606
UniProt Entry:	P24941
Kinexus Products:	CDK2 Cyclin-dependent protein-serine kinase 2 T160 phosphosite-specific antibody AB-PK568 RNA polymerase II-CT KinSub - heptapeptide repeat from C-terminus peptide; CDKtide protein kinase substrate peptide - Powder PE-01ADN95 CDK1-3 Selectide - CDK1 (CDC2) protein kinase substrate peptide - Powder PE-01BGO99 Cyclin-dependent protein-serine kinase 2 (R157-V163, human) pT160 phosphopeptide - Powder PE-04ADY95 Cyclin-dependent protein-serine kinase 2 (P155-V163, human) pT158+pY159+pT160 phosphopeptide - Powder PE-04ASK95 Cyclin-dependent protein-serine kinase 2 (E162-A170, human) pT165+pY168 phosphopeptide - Powder PE-04ASL01

General Links

Structure

Mol. Mass (Da):

33,930

# Amino Acids:

298

# mRNA Isoforms:

mRNA Isoforms:

33,930 Da (298 AA; P24941); 30,035 Da (264 AA; P24941-2)

4D Structure:

Found in a complex with CABLES1, CCNA1 and CCNE1. Interacts with CABLES1. Interacts with UHRF2. Part of a complex consisting of UHRF2, CDK2 and CCNE1. Interacts with the Speedy/Ringo proteins SPDYA and SPDYC. Found in a complex with both SPDYA and CDKN1B/KIP1.

3D Structure:

Download QuickTime Animation

1D Structure:

Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence

3D Image (rendered using PV Viewer):

PDB ID

1FIN

Subfamily Alignment

Domain Distribution:

Start	End	Domain
4	286	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 2 T160 phosphosite-specific antibody AB-PK568
○	RNA polymerase II-CT KinSub - heptapeptide repeat from C-terminus peptide; CDKtide protein kinase substrate peptide - Powder PE-01ADN95
○	CDK1-3 Selectide - CDK1 (CDC2) protein kinase substrate peptide - Powder PE-01BGO99
○	Cyclin-dependent protein-serine kinase 2 (R157-V163, human) pT160 phosphopeptide - Powder PE-04ADY95
○	Cyclin-dependent protein-serine kinase 2 (P155-V163, human) pT158+pY159+pT160 phosphopeptide - Powder PE-04ASK95
○	Cyclin-dependent protein-serine kinase 2 (E162-A170, human) pT165+pY168 phosphopeptide - Powder PE-04ASL01

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET

Acetylated:

K6.

Serine phosphorylated:

S46.

Sumoylated:

K33.

Threonine phosphorylated:

T14-, T39, T137, T158+, T160+, T165-.

Tyrosine phosphorylated:

Y15-, Y19+, Y159+, Y168-, Y179+, Y269.

Ubiquitinated:

K9, K20, K24, K33, K56, K129, K142, K237, K250, K273, K278, K291.

Distribution

Based on gene microarray analysis from the NCBI

Human Tissue Distribution

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

60

802

42

1010
4

57

20

52
7

90

8

65
59

794

122

3052
49

663

36

602
24

322

119

1181
21

278

47

575
100

1344

48

3005
25

336

24

263
8

102

113

138
6

77

35

92
50

668

236

605
4

59

41

60
5

71

18

86
8

104

26

115
3

38

22

35
11

146

207

130
5

67

19

62
4

59

125

69
32

436

162

498
6

80

23

85
8

113

30

154
6

85

19

54
6

87

19

72
17

234

23

293
83

1118

71

2448
6

77

44

75
7

98

19

86
7

92

20

83
8

101

42

103
43

575

30

657
38

510

51

498
88

1185

91

1875
48

651

83

586
4

55

57

61

Evolution

Species Conservation

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

100

100

100
69.8

79.7

100
99.7

99.7

100
-

-

99
-

-

98
99

99.7

99
-

-

-
85.3

85.8

99
98.7

99.7

99
-

-

-
-

-

-
65.3

77.9

93
88.9

95

90
90.3

95

90
-

-

-
62.7

74.8

66
69.9

82.3

-
56.9

69.9

-
75.9

88.6

-
66.4

83.2

-
66.8

82.2

-
-

-

66
67.1

81.5

69
62.4

79.2

65
-

-

65

For a wider analysis go to PhosphoNET Evolution in PhosphoNET

Binding Proteins

Examples of known interacting proteins

hiddentext

No.	Name – UniProt ID
1	CCNA2 - P20248
2	CCNA1 - P78396
3	CDKN3 - Q16667
4	CCNE1 - P24864
5	ORC2L - Q13416
6	CCNE2 - O96020
7	MCM3 - P25205
8	CDKN1B - P46527
9	CCNB2 - O95067
10	CCNB3 - Q8WWL7
11	CKS1B - P61024
12	SKP2 - Q13309
13	BRCA1 - P38398
14	RB1 - P06400
15	RBL1 - P28749

Regulation

Activation:

Phosphorylation at Thr-160 increases phosphotransferase activity. Phosphorylation at Tyr-179 increases phosphotransferase activity and interaction with CCNA2. Cyclin A2 stimulates the catalytic activity of CDK2.

Inhibition:

Phosphorylation at Thr-14 and Tyr-15 inhibits phosphotransferase activity.

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

LYN	P07948	Y15	EKIGEGTYGVVYKAR	-
WEE1	P30291	Y15	EKIGEGTYGVVYKAR	-
Akt1	P31749	T39	LKKIRLDTETEGVPS	?
CDK7	P50613	S46	TETEGVPSTAIREIS
CDK7	P50613	T160	GVPVRTYTHEVVTLW	+
ERK1	P27361	T160	GVPVRTYTHEVVTLW	+
CDK2	P24941	T160	GVPVRTYTHEVVTLW	+
ERK2	P28482	T160	GVPVRTYTHEVVTLW	+
CCRK	Q8IZL9	T160	GVPVRTYTHEVVTLW	+
CDK7	P50613	T165	TYTHEVVTLWYRAPE	-
CDK7	P50613	Y168	HEVVTLWYRAPEILL	-
CDK7	P50613	Y179	EILLGCKYYSTAVDI	+

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

AML1 (RUNX1)	Q01196	S266	QYLGSIASPSVHPAT
AML1 (RUNX1)	Q01196	S276	VHPATPISPGRASGM
AML1 (RUNX1)	Q01196	T273	SPSVHPATPISPGRA	+
ANKRD17	O75179	S2042	KEHYPVSSPSSPSPP
ANKRD17	O75179	S2045	YPVSSPSSPSPPAQP
ANKRD17	O75179	S2401	SSGVRAPSPAPSSVP
ATRIP	Q8WXE1	S224	APSVSHVSPRKNPSV
Axin	O15169	S486	LRTPGRQSPGPGHRS
Axin	O15169	S493	SPGPGHRSPDSGHVA
Axin	O15169	T481	HVQRVLRTPGRQSPG
B-Myb (MYBL2)	P10244	S282	KREDQEGSPPETSLP	+
B-Myb (MYBL2)	P10244	S393	RGELIPISPSTEVGG	+
B-Myb (MYBL2)	P10244	S452	PVKTLPFSPSQFLNF	+
B-Myb (MYBL2)	P10244	S577	RKPGLRRSPIKKVRK	+
B-Myb (MYBL2)	P10244	T266	TDLDAVRTPEPLEEF	+
B-Myb (MYBL2)	P10244	T405	VGGSGIGTPPSVLKR	+
B-Myb (MYBL2)	P10244	T444	NSLTPKSTPVKTLPF	+
B-Myb (MYBL2)	P10244	T487	SQKVVVTTPLHRDKT	+
B-Myb (MYBL2)	P10244	T494	TPLHRDKTPLHQKHA	+
B-Myb (MYBL2)	P10244	T515	QKYSMDNTPHTPTPF	+
B-Myb (MYBL2)	P10244	T518	SMDNTPHTPTPFKNA	+
B-Myb (MYBL2)	P10244	T520	DNTPHTPTPFKNALE	+
BARD1	Q99728	S148	NSIKMWFSPRSKKVR
BARD1	Q99728	S251	SQPSVISSPQINGEI
BARD1	Q99728	S288	PLAEQIESPDTKSRN
BARD1	Q99728	T299	KSRNEVVTPEKVCKN
BRCA1	P38398	S1497	EPGVERSSPSKCPSL
BTG1	P62324	S159	ELLLGRTSPSKNYNM
C-EBPb	P17676	T235	SSSSPPGTPSPADAK
Cdc25A	P30304	S116	PQKLLGCSPALKRSH	+
Cdc25A	P30304	S18	RRLLFACSPPPASQP	+
Cdc25C	P30307	T130	PAQLLCSTPNGLDRG	+
Cdc6	Q99741	S106	DNQLTIKSPSKRELA
Cdc6	Q99741	S54	RVKALPLSPRKRLGD
Cdc6	Q99741	S74	TPHLPPCSPPKQGKK
CDC7	O00311	T376	QVAPRAGTPGFRAPE	-
CDK2	P24941	T160	GVPVRTYTHEVVTLW	+
CDK7	P50613	S164	GLAKSFGSPNRAYTH	-
CDK7	P50613	T170	GSPNRAYTHQVVTRW	+
Cdt1	Q9H211	S31	KLACRTPSPARPALR
Cdt1	Q9H211	T29	PPKLACRTPSPARPA
CDX2	Q99626	S283	RSVPEPLSPVSSLQA
Chk1 (CHEK1)	O14757	S286	TSGGVSESPSGFSKH	+
Chk1 (CHEK1)	O14757	S301	IQSNLDFSPVNSASS	?
Cip1 (p21, CDKN1A)	P38936	S129	SGEQAEGSPGGPGDS	-
Coilin	P38432	S184	SVCSKRKSPKKKEKC
Ctip	Q99708	T847	FRYIPPNTPENFWEV
CTNNB1	P35222	S33	QQQSYLDSGIHSGAT	-
CTNNB1	P35222	S37	YLDSGIHSGATTTAP	?
CTNNB1	P35222	S45	GATTTAPSLSGKGNP	+
CTNNB1	P35222	T41	GIHSGATTTAPSLSG	?
CTTN (Cortactin)	Q14247	S405	KTQTPPVSPAPQPTE	-
Cyclin A2	P20248	S154	PMDGSFESPHTMDMS
Cyclin E1 (CCNE1)	P24864	S387	LSEQNRASPLPSGLL
Cyclin E1 (CCNE1)	P24864	S399	GLLTPPQSGKKQSSG
Cyclin E1 (CCNE1)	P24864	T395	PLPSGLLTPPQSGKK
DDX3	O00571	T203	LTRYTRPTPVQKHAI
DLG1 (SAP97)	Q12959	S158	FVSHSHISPIKPTEA
DLG1 (SAP97)	Q12959	S443	FLGQTPASPARYSPV
E2A	P15923	S139	LNSPGPLSPSGMKGT
E2A	P15923	S245	PMLGGGSSPLPLPPG
E2F5	Q15329	T261	SQSLTPVTPQKSSMA
eEF2	P13639	T435	RIMGPNYTPGKKEDL
ERa (ESR1)	P03372	S104	FPPLNSVSPSPLMLL	+
ERa (ESR1)	P03372	S106	PLNSVSPSPLMLLHP	+
ERa (ESR1)	P03372	S118	LHPPPQLSPFLQPHG	+
FOXM1	Q08050	T611	ETLPISSTPSKSVLP	+
FOXO1A	Q12778	S249	EGGKSGKSPRRRAAS	-
FOXO1A	Q12778	S298	QFSKWPASPGSHSND	-
GANP	O60318	S508	FWHRKKISPNKKPFS
GR	P04150	S203	DLEFSSGSPGKETNE
GR	P04150	S211	PGKETNESPWRSDLL	?
GRASP65	Q9BQQ3	S273	DPLPGPGSPSHSAPD
HIRA	P54198	T555	LSPSVLTTPSKIEPM
hnRNP K	P61978	S216	ILDLISESPIKGRAQ	+
HR6A	P49459	S120	LDEPNPNSPANSQAA
Id2	Q02363	S5	___MKAFSPVRSVRK
Id3	Q02535	S5	___MKALSPVRGCYE
IREB2	P48200	S157	LQKAGKLSPLKVQPK
LIG1	P18858	S51	GVVSESDSPVKRPGR
LIG1	P18858	S76	EEEDEALSPAKGQKP
LIG1	P18858	S91	ALDCSQVSPPRPATS
LIG3	P49916	S210	TTTGQVTSPVKGASF
LIG3	P49916	S913	EKLATKSSPVKVGEK
LIG3	P49916	T191	LSSKAAGTPKKKAVV
MAP2	P11137	S136	ETANLPPSPPPSPAS
MARCKS	P29966	S26	GEAAVASSPSKANGQ
MARCKS	P29966	S27	GEAAVASSPSKANGQ
MARCKS	P29966	T150	TPSPSNETPKKKKKR
MCL1	Q07820	S64	IGGSAGASPPSTLTP
MCM2	P49736	S108	DVEELTASQREAAER	+
MCM2	P49736	S13	ESFTMASSPAQRRRG	?
MCM2	P49736	S139	RRGLLYDSDEEDEER	+
MCM2	P49736	S17	RGNDPLTSSPGRSSR
MCM2	P49736	S18	GNDPLTSSPGRSSRR
MCM2	P49736	S26	RGNDPLTSSPGRSSR
MCM2	P49736	S27	GNDPLTSSPGRSSRR	?
MCM2	P49736	S32	RTDALTSSPGRDLPP
MCM2	P49736	S40	RRTDALTSSPGRDLP	+
MCM2	P49736	S41	RTDALTSSPGRDLPP	+
MCM2	P49736	S53	LPPFEDESEGLLGTE	+
MCM3	P25205	S611	SSDTARTSPVTARTL
MCM4	P33991	S3	_____MSSPASTPSR
MCM4	P33991	S32	RSEDARSSPSQRRRG
MCM4	P33991	S54	ELQPMPTSPGVDLQS
MCM4	P33991	T110	PRSGVRGTPVRQRPD
MCM4	P33991	T19	GSRRGRATPAQTPRS
MDM2	Q00987	T218	SSSESTGTPSNPDLD
MELF4 (MEF)	Q99607	S648	SPTPAPFSPFNPTSL	-
MELF4 (MEF)	Q99607	T643	SLLTRSPTPAPFSPF
MyoD	P15172	S200	SGDSDASSPRSNCSD
NF-YA	P23511	S320	GEGGRFFSPKEKDSP
NF-YA	P23511	S326	FSPKEKDSPHMQDPN
Nogo	Q9NQC3	S15	PLVSSSDSPPRPQPA
NPAT	Q14207	S1100	VSFPNLDSPNVSSTL	+
NPAT	Q14207	S775	LPTIILSSPTKSPTK	+
NPAT	Q14207	S779	ILSSPTKSPTKNAEL	+
NPAT	Q14207	T1270	SDLPVPRTPGSGAGE	+
NPAT	Q14207	T1350	ISRTTSATPLKDNTQ	+
NPM1	P06748	S70	EAMNYEGSPIKVTLA
NPM1	P06748	T199	VKKSIRDTPAKNAQK
NPM1	P06748	T234	SFKKQEKTPKTPKGP
NRIF3	Q13352	S33	KKSVITYSPTTGTCQ
NRIF3	Q13352	S46	CQMSLFASPTSSEEQ
NSBP1	P82970	T31	SAMLVPVTPEVKPKR
p27Kip1	P46527	T187	NAGSVEQTPKKPGLR	+
p53	P04637	S315	LPNNTSSSPQPKKKP	+
p63	Q9H3D4	T491	PQQRNALTPTTIPDG	-
p73	O15350	T86	AASASPYTPEHAASV
POLL	Q9UGP5	S167	ALLQTALSPPPPPTR
POLL	Q9UGP5	S177	PPPTRPVSPPQKAKE
POLL	Q9UGP5	S230	LEGDCEPSPAPAVLD
POLL	Q9UGP5	T553	GPGRVLPTPTEKDVF
PPP1CA	P62138	T320	NPGGRPITPPRNSAK	-
PR	P06401	S162	PATQRVLSPLMSRSG	?
PR	P06401	S190	KVLPRGLSPARQLLL	?
PR	P06401	S213	SGAPVKPSPQAAAVE
PR	P06401	S400	GAEASARSPRSYLVA	?
PR	P06401	S676	LSQRFTFSPGQDIQL	?
PRKAR1A	P10644	S83	DSREDEISPPPPNPV	-
PTPN2	P17706	S304	LSPAFDHSPNKIMTE
PTPN6 (SHP1)	P29350	S591	DKEKSKGSLKRK___
PXR (NR1I2)	O75469	S350	MQAISLFSPDRPGVL	+
Rad9	Q99638	S328	VLPSISLSPGPQPPK	?
RanGAP1	P46060	S442	STFLAFPSPEKLLRL
RanGAP1	P46060	T409	GQGEKSATPSRKILD
Rb	P06400	S249	AVIPINGSPRTPRRG
Rb	P06400	S608	TAADMYLSPVRSPKK	-
Rb	P06400	S612	MYLSPVRSPKKKGST	-
Rb	P06400	S807	PGGNIYISPLKSPYK	-
Rb	P06400	S811	IYISPLKSPYKISEG	-
Rb	P06400	T252	PINGSPRTPRRGQNR
Rb	P06400	T356	DSFETQRTPRKSNLD	-
Rb	P06400	T373	VNVIPPHTPVRTVMN	-
Rb	P06400	T821	KISEGLPTPTKMTPR	-
Rb	P06400	T826	LPTPTKMTPRSRILV	-
Rb-like 2	Q08999	S1044	YPFVRTGSPRRIQLS
Rb-like 2	Q08999	S1068	HKNETMLSPREKIFY
Rb-like 2	Q08999	S1080	IFYYFSNSPSKRLRE
Rb-like 2	Q08999	S1112	LLEDGSESPAKRICP
Rb-like 2	Q08999	S413	VRYIKENSPCVTPVS
Rb-like 2	Q08999	S639	DEICIAGSPLTPRRV
Rb-like 2	Q08999	S662	GLGRSITSPTTLYDR
Rb-like 2	Q08999	S688	RLFVENDSPSDGGTP
Rb-like 2	Q08999	S952	DSRSHQNSPTELNKD
Rb-like 2	Q08999	T1097	SMIRTGETPTKKRGI
Rb-like 2	Q08999	T417	KENSPCVTPVSTATH
Rb-like 2	Q08999	T642	CIAGSPLTPRRVTEV
Rb-like 2	Q08999	T694	DSPSDGGTPGRMPPQ
RPL12	P30050	S38	KIGPLGLSPKKVGDD
SF3B1	O75533	T244	GRAKGSETPGATPGS
SF3B1	O75533	T248	GSETPGATPGSKIWD
SF3B1	O75533	T313	HGSGWAETPRTDRGG
SIRT2	Q8IXJ6	S368	PNPSTSASPKKSPPP
SKP2	Q13309	S64	SNLGHPESPPRKRLK
Smad3	P84022	S213	NLSPNPMSPAHNNLD	-
Smad3	P84022	T179	PQSNIPETPPPGYLS	-
Smad3	P84022	T8	MSSILPFTPPIVKRL
SNRNP70	P08621	S226	YDERPGPSPLPHRDR
TIF-IA	Q9NYV6	S44	LENDFFNSPPRKTVR
TK1	P04183	S13	LPTVLPGSPSKTRGQ
UBF	P17480	S389	INKKQATSPASKKPA
UBF	P17480	S484	ERGKLPESPKRAEEI
ZBTB16	Q05516	S197	SFGLSAMSPTKAAVD
ZBTB16	Q05516	T282	RGKEGPGTPTRSSVI
ZC3HC1 (NIPA)	Q86WB0	S395	PGLEVPSSPLRKAKR	-

Protein Kinase Specificity

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

Matrix Type:

Experimentally derived from alignment of 543 known protein substrate phosphosites and 35 peptides phosphorylated by recombinant CDK2 in vitro tested in-house by Kinexus.

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

CHEMBL363607	IC50 = 300 pM	44398371	363607	15974571
Staurosporine	IC50 = 360 pM	5279		19397322
Cdk1/2 Inhibitor III	IC50 = 500 pM	5330812	261720	15974571
R547	Kd = 530 pM	6918852		22037378
Roscovitine	IC50 = 600 pM	160355	14762	10743948
Dinaciclib	IC50 = 1 nM	46926350		20663931
CHEMBL194721	IC50 = 2 nM	44401437	194721	16584130
CK7	Ki = 2 nM	447961		15027857
CHEMBL1684800	IC50 = 2.13 nM	52938983	1684800	21353571
Kinome_3681	IC50 = 2.8 nM	10029385	362558	15267232
CHEMBL306856	IC50 = 4 nM	5330769	306856	12824014
Purvalanol A	IC50 = 4 nM	456214	23327	12941335
TTT-3002	IC50 < 4 nM
AC1NS7CD	IC50 = 5 nM	5329665	295136	12190313
NU6102	IC50 = 5.4 nM	4566		12941338
AZD5438	IC50 = 6 nM	16747683		18815031
Purvalanol B	IC50 = 6 nM	448991	23254	9677190
CHEMBL1784637	IC50 = 6.4 nM	46864270	1784637	21561767
CHEMBL191336	IC50 = 7 nM	9863538	191336	15999992
Olomoucine	IC50 = 7 nM	4592	280074	10743948
BMS-265246	IC50 = 9 nM	5329775		12824044
7-hydroxystaurosporine	IC50 = 10 nM	72271	1236539
A 443654	IC50 < 10 nM	10172943	379300	17850214
BX795	IC50 = 10 nM	10077147	577784
CHEMBL424696	IC50 = 14 nM	44413509	424696	16682184
AC1NS8PD	IC50 = 15 nM	5330256		11101352
Alsterpaullone	IC50 = 15 nM	5005498	50894	16584130
CHEMBL195641	IC50 = 19 nM	44401410	195641	15808450
Lestaurtinib	Kd = 20 nM	126565		22037378
JNJ-7706621	Kd = 23 nM	5330790	191003	18183025
Alsterpaullone; 2-Cyanoethyl	IC50 < 25 nM	16760286	260138	22037377
BAY1000394	IC50 < 25 nM			22821149
JAK3 Inhibitor VI	IC50 < 25 nM	16760524		22037377
PKR Inhibitor	IC50 < 25 nM	6490494	235641	22037377
RGB-286147	IC50 < 25 nM	9549301	258721	22037377
PHA-533533	IC50 = 27 nM	5330949	191144	16616492
Aminopurvalanol A	IC50 = 28 nM	6604931		12678910
AT7519	Kd = 30 nM	11338033		22037378
CHEMBL1084715	Ki = 32 nM	11646645	1084715	20462263
CHEMBL383104	IC50 = 33 nM	11361885	383104	16290148
SU9516	IC50 = 35 nM	5289419	258805	16584130
CHEMBL1092754	IC50 = 35.5 nM	44541014	1092754	20188552
PNU-292137	IC50 = 37 nM	449087	115220	15189033
SNS032	IC50 = 38 nM	3025986	296468	18842409
Alvocidib	IC50 = 40 nM	9910986	428690	18469809
Gö6976	IC50 < 40 nM	3501	302449
Ro-31-8220	IC50 < 40 nM	5083	6291
Milciclib	IC50 = 45 nM	16718576	564829	19603809
A674563	Ki = 46 nM	11314340	379218	16678413
GSK-3 Inhibitor IX	IC50 > 50 nM	5287844	409450	22037377
CHEMBL1080569	IC50 = 53 nM	11568147	1080569	20137932
AC1NS8P1	IC50 = 58 nM	5330252		11101352
CHEMBL364935	IC50 = 73 nM	44401506	364935	15808450
1PU	IC50 = 78 nM	445840	141247	11741480
AC1NS9GN	IC50 = 78 nM	5330583		16584130
Amgen TBK 1 inhibitor (Compound II)	IC50 < 80 nM
Princeton's TrkA inhibitor compound 20h	IC50 < 80 nM
CHEMBL73718	IC50 = 89 nM	5330766	73718	12824014
CVT-313	IC50 = 95 nM	6918386	80713	9360999
CHEMBL1650545	IC50 > 100 nM	53316611	1650545	21128646
GSK650394A	IC50 < 100 nM	25022668	558642
Momelotinib	IC50 < 100 nM	25062766		19295546
R406	IC50 = 100 nM	11984591
Staurosporine aglycone	IC50 = 100 nM	3035817	281948
Syk Inhibitor IV	IC50 = 100 nM	10200390
SQ67563	IC50 = 110 nM	5329767	14619	12643928
SU11274	IC50 = 110 nM	9549297	261641	12824044
Aloisine A	IC50 = 120 nM	5326843	75680	12519061
CHEMBL388956	IC50 = 140 nM	10356352	388956	20097066
CHEMBL590109	IC50 = 140 nM	46224684	590109	19926477
AC1O6ZUA	Kd < 150 nM	6539569	408019	19035792
CGP74514A	IC50 > 150 nM	2794188	367625	22037377
CHEMBL1082152	Kd = 150 nM	11560568	1082152	20138512
GSK-3 Inhibitor X	IC50 > 150 nM	6538818	430226	22037377
IDR E804	IC50 > 150 nM	6419764	1802727	22037377
CHEMBL1084629	Ki = 156 nM	10430000	1084629	20462263
MK8776	IC50 = 160 nM	16224745		21094607
CHEMBL1084454	Ki = 168 nM	46830767	1084454	20462263
CHIR-124	IC50 = 191 nM	11502647		17255282
CK8	Ki = 220 nM	447962		15027857
P276-00	IC50 = 224 nM	10406644		17363486
AC1NS8RA	IC50 = 230 nM	5330279	365847	15801830
CHEMBL1083151	Ki = 239 nM	11632150	1083151	20462263
PHA-767491	IC50 = 240 nM	11715767	225519	18469809
Aloisine; RP106	IC50 > 250 nM	44350092	126343	22037377
Compound 52	IC50 > 250 nM	2856		22037377
Indirubin-3′-monoxime	IC50 > 250 nM	5326739		22037377
CHEMBL1083152	Ki = 256 nM	11718021	1083152	20462263
K-252a; Nocardiopsis sp.	IC50 = 260 nM	3813	281948	14552792
CHEMBL76326	IC50 = 265 nM	5330780	76326	12824014
SB216763	= 269 nM	176158
CHEMBL1083150	Ki = 286 nM	46830766	1083150	20462263
Kinome_756	Ki = 297 nM	10320107		20462263
CHEMBL489833	IC50 = 337 nM	44582745	489833	19338355
SB415286	IC50 = 380 nM	4210951	322970	12852764
CHEMBL482967	Ki = 390 nM	6420138	482967	20462263
BI-D1870	IC50 < 400 nM	25023738	573107
K00596a	IC50 < 400 nM	9549298	200027
Kenpaullone	IC50 < 400 nM	3820	296586
LKB1(AAK1 dual inhibitor)	Kd < 400 nM	44588117	516312	19035792
SureCN3470757	IC50 < 400 nM	11588244	375236
CHEMBL1083786	Ki = 432 nM	10024433	1083786	20462263
CHEMBL73781	IC50 = 432 nM	5330771	73781	12824014
AC1NS8R7	IC50 = 439 nM	5330278		15801830
AC1NS8R9	439 nM
AST-487	Kd = 450 nM	11409972	574738	22037378
CHEMBL73764	IC50 = 450 nM	5330783	73764	12824014
Danusertib	IC50 = 462 nM	21874004	402548	17125279
CHEMBL1086088	Ki = 463 nM	11647020	1086088	20462263
ALX-270-403-M001	IC50 = 500 nM			22037377
AZ960	IC50 < 500 nM	25099184		18775810
CHEMBL307152	IC50 < 500 nM	11655119	307152	12824014
AT9283	IC50 = 510 nM	24905142		19143567
CHEMBL1084969	Ki = 522 nM	46830768	1084969	20462263
Arcyriaflavin A	IC50 = 530 nM	5327723	268368	12747775
SB218078	IC50 = 540 nM	447446	289422	15149678
CHEMBL76337	IC50 = 567 nM	5330785	76337	12824014
Novartis 12a (PKD1)	IC50 < 600 nM
BX912	IC50 = 650 nM	11754511		15772071
CHEMBL308979	IC50 = 685 nM	5330778	308979	12824014
BMS-754807	IC50 = 795 nM	24785538		19996272
CHEMBL312292	IC50 = 796 nM	5330775	312292	12824014
BML-275	IC50 < 800 nM	11524144	478629
Bohemine	IC50 = 800 nM	2422	83980	10891109
IKK-2 Inhibitor IV	IC50 < 800 nM	9903786	257167
IKK-2 Inhibitor VIII	IC50 < 800 nM	66576999	368427
JNK Inhibitor VIII	Ki = 820 nM	11624601	210618	16759099
Pyrimidylpyrrole, 11e	Ki = 850 nM	11634725	583042	19827834
Debromohymenialdisine	IC50 = 856 nM	5288032		11784156
BS181	IC50 = 880 nM	49867928		19638587
BX517	IC50 > 900 nM	11161844	228654
CHEMBL311851	IC50 = 902 nM	5330767	311851	12824014
CHEMBL75952	IC50 = 942 nM	5330764	75952	12824014
CHEMBL72808	IC50 = 972 nM	5330774	72808	12824014
CHEMBL75368	IC50 = 978 nM	5330777	75368	12824014
1;9-Pyrazoloanthrone	IC50 = 1 µM	8515	7064
AG-E-60384	IC50 > 1 µM	6419741	413188	22037377
AT7867	IC50 > 1 µM	11175137	428462	20423992
Baricitinib	IC50 > 1 µM	44205240		20363976
BAY65-1942	IC50 = 1 µM	44572415	516203
Bisindolylmaleimide I	IC50 < 1 µM	2396	7463
BMS-536924	IC50 > 1 µM	10390396	401930	16134929
CHEMBL306501	IC50 = 1 µM	5330768	306501	12824014
CHEMBL311543	IC50 = 1 µM	10671412	311543	12824014
CHIR 99021 (CT 99021)	IC50 = 1 µM	9956119	412142
CP673451	IC50 > 1 µM	10158940		15705896
Flt-3 Inhibitor II	IC50 > 1 µM	11601743	377193	22037377
GSK429286	IC50 = 1 µM	11373846	375312
Icotinib	IC50 > 1 µM	22024915		22112293
K-252c	IC50 = 1 µM	3815	16958	14552792
MK5108	IC50 > 1 µM	24748204		20053775
MRT67307	IC50 = 1 µM	44464263
N-Benzoylstaurosporine	IC50 > 1 µM	56603681	608533	22037377
NU6140	IC50 > 1 µM	10202471	1802728	22037377
PF-228	IC50 = 1 µM	11612883		17395594
Ponatinib	IC50 > 1 µM	24826799		19878872
Regorafenib	IC50 > 1 µM	11167602		21170960
Ro-32-0432	IC50 > 1 µM	127757	26501	22037377
Ruboxistaurin	IC50 = 1 µM	153999	91829
Ruxolitinib	IC50 = 1 µM	25126798	1789941
SGI-1776	IC50 > 1 µM			19734450
Silmitasertib	IC50 > 1 µM	24748573		21174434
SNS314	IC50 > 1 µM	16047143	514582	18678489
SureCN4139760	IC50 > 1 µM	25065806		18691885
Syk Inhibitor	IC50 > 1 µM	6419747	104279	22037377
Syk Inhibitor II	IC50 = 1 µM	16760670
WZ3146	Kd > 1 µM	44607360		20033049
WZ4002	Kd > 1 µM	44607530		20033049
CHEMBL307630	IC50 = 1.06 µM	5330779	307630	12824014
NU2058	Ki = 1.2 µM	4564	269881	16913703
CHEMBL511337	Kd < 1.25 µM	44588220	511337	19035792
SureCN7685369	Kd < 1.25 µM	9925594	526901	19035792
CHEMBL306047	IC50 = 1.28 µM	5330781	306047	12824014
NU6027	Ki = 1.3 µM	398148		10956187
CHEMBL73772	IC50 = 1.33 µM	5330786	73772	12824014
CHEMBL1788116	IC50 = 1.4 µM	11422034	1788116	15999997
Nintedanib	Kd = 1.4 µM	9809715	502835	22037378
AC1NS7GH	IC50 = 1.5 µM	5329714	334881	11063609
BX320	IC50 = 1.5 µM	657138	573108	15772071
CHEMBL72076	IC50 = 1.5 µM	5330787	72076	12824014
CHEMBL73794	IC50 = 1.67 µM	5330784	73794	12824014
CHEMBL210540	IC50 = 1.7 µM	16037675	210540	16682184
CHEMBL310491	IC50 = 1.8 µM	5330782	310491	12824014
BMS-777607	IC50 > 2 µM	24794418		19260711
SB202190	IC50 = 2 µM	5353940	278041
CHEMBL430606	IC50 = 2.03 µM	5330776	430606	12824014
CHEMBL362814	IC50 = 2.1 µM	11316975	362814	15267232
AC1NS7GK	IC50 = 2.11 µM	5329715	133498	11063609
Sotrastaurin	IC50 = 2.3 µM	10296883	565612	19827831
2-dimethylamino-4;5;6;7-tetrabromo-1H-benzimidazole	IC50 = 2.38 µM	5326976	376505	15566294
Paullone	IC50 = 2.7 µM	369401	430574	20621478
GDC-0068	IC50 < 3 µM	24995523		22934575
H-1152; Glycyl	IC50 > 3 µM	16760635
KT5720	IC50 > 3 µM	3844	608532
Tofacitinib	IC50 > 3 µM	9926791	221959
CHEMBL248757	Ki = 3.088 µM	44444843	248757	17935989
CHEMBL494221	Ki > 3.1 µM	44219633	494221	19414255
BCP9000906	IC50 = 3.3 µM	5494425	21156	11934592
SureCN4875304	IC50 > 3.5 µM	46871765		20472445
CHEMBL489083	IC50 = 3.6 µM	25178539	489083	19053831
CHEMBL1288582	IC50 = 4 µM	49839480	1288582	20965724
CHEMBL493169	Ki > 4 µM	44219632	493169	19414255
JNJ-28871063	IC50 > 4 µM	17747413		17975007
Hypothemycin	IC50 > 4.5 µM	5477775	471474
JNKIN7	IC50 > 4.5 µM	57340685
SureCN12253834	IC50 = 4.7 µM	42625986	504547	19317452

Disease Linkage

General Disease Association:

Cancer, skin and mucosal lesions

Specific Diseases (Non-cancerous):

Pemphigus vulgaris

Comments:

In pemphigus vulgaris skin and mucosal membrane lesions will develop, and CDK2 plays an essential role.

Specific Cancer Types:

Tetraploidy; Male germ cell tumours

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: Colon mucosal cell adenomas (%CFC= +78, p<0.0001); Skin melanomas - malignant (%CFC= +512, p<0.0001); and Vulvar intraepithelial neoplasia (%CFC= +130, p<0.004). The COSMIC website notes an up-regulated expression score for CDK2 in diverse human cancers of 560, which is 1.2-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 42 for this protein kinase in human cancers was 0.7-fold of the average score of 60 for the human protein kinases.

Mutagenesis Experiments:

Insertional mutagenesis studies in mice have not yet revealed a role for this protein kinase in mouse cancer oncogenesis. Mutations resulting in reduced CAK phosphorylation at the T160 activating phosphosite include K9F, and K88E + K89V, while a L166R mutation can result in reduced CAK phosphorylation and lower protein-serine/threonine phosphotransferase activity. Phosphotransferase activity can be fully removed with a T160A mutation. Phosphotransferase activity can be increased 2-fold with either a T14A, or a Y15F mutation.

Mutation Rate in All Cancers:

Percent mutation rates per 100 amino acids length in human cancers: 0.06 % in 25535 diverse cancer specimens. This rate is only -21 % 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: 0.42 % in 1128 large intestine cancers tested.

Frequency of Mutated Sites:

Most frequent mutations with the number of reports indicated in brackets: P45L (3).

Comments:

Only 1 deletion, and no insertions or complex mutations are noted on the COSMIC website.

COSMIC Entry:

CDK2

OMIM Entry:

116953

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:

3D Structure:

1D Structure:

3D Image (rendered using PV Viewer):

PDB ID

Subfamily Alignment

Domain Distribution:

Kinexus Products

hiddentext

Post-translation Modifications

Acetylated:

Serine phosphorylated:

Sumoylated:

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:

Specific Cancer Types:

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: