General Information of the Protein
Protein ID
PT00874
Protein Name
Cyclin-dependent kinase 2
Secondarily
Protein Name
Cell division protein kinase 2
p33 protein kinase
Gene Name
CDK2
Secondarily
Gene Name
CDKN2
Sequence
MENFQKVEKIGEGTYGVVYKARNKLTGEVVALKKIRLDTETEGVPSTAIREISLLKELNHPNIVKLLDVIHTENKLYLVFEFLHQDLKKFMDASALTGIPLPLIKSYLFQLLQGLAFCHSHRVLHRDLKPQNLLINTEGAIKLADFGLARAFGVPVRTYTHEVVTLWYRAPEILLGCKYYSTAVDIWSLGCIFAEMVTRRALFPGDSEIDQLFRIFRTLGTPDEVVWPGVTSMPDYKPSFPKWARQDFSKVVPPLDEDGRSLLSQMLHYDPNKRISAKAALAHPFFQDVTKPVPHLRL
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Organism
Homo sapiens, Human
Protein Classification
Enzyme
>
Kinase
>
Protein Kinase
>
CMGC protein kinase group
>
CMGC protein kinase CDK family
>
CMGC protein kinase CDC2 subfamily
Function
Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2. Triggers duplication of centrosomes and DNA. Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. Phosphorylates CABLES1 (By similarity). Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation. Phosphorylation of RB1 disturbs its interaction with E2F1. NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. Required for vitamin D-mediated growth inhibition by being itself inactivated. Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner. USP37 is activated by phosphorylation and thus triggers G1-S transition. CTNNB1 phosphorylation regulates insulin internalization. Phosphorylates FOXP3 and negatively regulates its transcriptional activity and protein stability (By similarity). Phosphorylates CDK2AP2 (PubMed:12944431). Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks (PubMed:29203878).
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Uniprot ID
Primary ID:
P24941

Secondarily ID:
A8K7C6
O75100
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Ensembl ID
ENSG00000123374
HGNC ID
HGNC:1771
Subcellular Location
Cytoplasm
Cytoskeleton
Microtubule organizing center
Centrosome
Nucleus
Cajal body
Cytoplasm
Endosome
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL001040 , 293-NB2
Compound ID Compound Name Compound Formula
CP0638626
(1R,4S)-4-(3-(2-(3-methylisoxazol-5-yl)acetamido)-1H-pyrazol-5-yl)cycloheptyl(1-methylcyclopropyl)carbamate
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C21H29N5O4
 1
1
IC50 = 100 nM
   TI
   LI
   LO
   TS
CP0639170
(1R,3S)-3-(3-(2-(2-methoxypyridin-4-yl)acetamido)-1H-pyrazol-5-yl)cyclopentyl isopropylcarbamate
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C20H27N5O4
 1
1
IC50 = 100 nM
   TI
   LI
   LO
   TS
CP0639211
(1R,3S)-3-(3-(2-(2-methylthiazol-5-yl)acetamido)-1H-pyrazol-5-yl)cyclopentyl isopropylcarbamate
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C18H25N5O3S
 1
1
IC50 = 100 nM
   TI
   LI
   LO
   TS
CP0639212
(1R,3S)-3-(3-(2-(2-(methylsulfonyl)phenyl)acetamido)-1H-pyrazol-5-yl)cyclopentyl isopropylcarbamate
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C21H28N4O5S
 1
1
IC50 = 100 nM
   TI
   LI
   LO
   TS
CP0639227
(1R,3S)-3-(3-(thiazolo[4,5-b]pyridine-7-carboxamido)-1H-pyrazol-5-yl)cyclopentyl isopropylcarbamate
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C19H22N6O3S
 1
1
IC50 <= 100 nM
   TI
   LI
   LO
   TS
CP0639270
(1R,3S)-3-(3-(2-phenylacetamido)-1H-pyrazol-5-yl)cyclopentyl(1-methylcyclopropyl)carbamate
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C21H26N4O3
 1
1
IC50 <= 100 nM
   TI
   LI
   LO
   TS
CP0639271
(1R,3S)-3-(3-(2-phenylacetamido)-1H-pyrazol-5-yl)cyclopentyl isopropylcarbamate
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C20H26N4O3
 1
1
IC50 = 100 nM
   TI
   LI
   LO
   TS
CP0639459
(1R,3S)-3-(3-(2-(3-methylisoxazol-5-yl)acetamido)-1H-pyrazol-5-yl)cyclopentyl 2,2-dimethylazetidine-1-carboxylate
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C20H27N5O4
 1
1
IC50 <= 100 nM
   TI
   LI
   LO
   TS
CP0639484
(1R,3S)-3-(3-(1-methyl-1H-pyrazole-5-carboxamido)-1H-pyrazol-5-yl)cyclopentyl isopropylcarbamate
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C17H24N6O3
 1
1
IC50 <= 100 nM
   TI
   LI
   LO
   TS
CP0639485
(1S,3R)-3-(3-(2-phenylacetamido)-1H-pyrazol-5-yl)cyclopentyl(1-methylcyclopropyl)carbamate
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C21H26N4O3
 1
1
IC50 <= 100 nM
   TI
   LI
   LO
   TS
CP0639519
(1S,3R)-3-(3-(1-methyl-1H-pyrazole-5-carboxamido)-1H-pyrazol-5-yl)cyclopentyl isopropylcarbamate
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C17H24N6O3
 1
1
IC50 = 100 nM
   TI
   LI
   LO
   TS
CP0639562
(1R,3S)-3-(3-(3-(methoxymethyl)-1-methyl-1H-pyrazole-5-carboxamido)-1H-pyrazol-5-yl)cyclopentyl isopropyl(methyl)carbamate
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C20H30N6O4
 1
1
IC50 = 100 nM
   TI
   LI
   LO
   TS
Biochemical Assays
Compound ID Compound Name Compound Formula
CP0006340
Dinaciclib
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C21H28N6O2
 3
1 IC50 = 1 nM
2 IC50 < 3 nM
3 Kd = 18.4 nM
CP0001250
(16E)-14-methyl-20-oxa-5,7,14,27-tetrazatetracyclo[19.3.1.12,6.18,12]heptacosa-1(25),2(27),3,5,8,10,12(26),16,21,23-decaene
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C23H24N4O
 2
1 IC50 = 3 nM
2 IC50 = 5 nM
CP0015673
(2S,3S)-3-[[7-(benzylamino)-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-5-yl]amino]butane-1,2,4-triol
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C20H27N5O3
 1
1 IC50 = 3 nM
CP0001372
(2R,3R)-3-[2-[4-(cyclopropylsulfonimidoyl)anilino]-5-(trifluoromethyl)pyrimidin-4-yl]oxybutan-2-ol
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C18H21F3N4O3S
 1
1 IC50 = 9 nM
CP0004539
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]-4H-chromen-4-one
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C21H20ClNO5
 8
1 IC50 = 10 nM
2 IC50 = 40 nM
3 IC50 = 70 nM
4 IC50 = 170 nM
5 Kd = 200 nM
6 Kd = 550 nM
7 Ki = 40 nM
8 Ki = 190 nM
CP0001111
(2R)-2-[[6-(benzylamino)-9-isopropyl-purin-2-yl]amino]butan-1-ol
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C19H26N6O
 9
1 IC50 = 90 nM
2 IC50 = 100 nM
3 IC50 = 220 nM
4 IC50 = 370 nM
5 IC50 = 400 nM
6 IC50 = 600 nM
7 IC50 = 700 nM
8 Kd = 2900 nM
9 Kd = 3400 nM
CP0001206
2,6,9-Trisubstituted purine deriv. 26
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C15H18N6O
 2
1 IC50 = 1200 nM
2 IC50 = 7000 nM
Clinical Information about the Protein
Target 1 ( Cyclin-dependent kinase 2 (CDK2) )
Target Type Clinical trial Target
Disease 10 Target-related Diseases  10
1 Thymic cancer [ICD-11: 2C27]
2 Non-small-cell lung cancer [ICD-11: 2C25.Y]
3 Solid tumour/cancer [ICD-11: 2A00-2F9Z]
4 Lymphoma [ICD-11: 2A80-2A86]
5 Anaplastic astrocytoma [ICD-11: 2A00.0]
6 Acute lymphoblastic leukaemia [ICD-11: 2A85]
7 Small-cell lung cancer [ICD-11: 2C25.Y]
8 Advanced solid tumour [ICD-11: 2A00-2F9Z]
9 Obesity [ICD-11: 5B81]
10 Retinoblastoma [ICD-11: 2D02.2]
Clinical Trial Drug(s) 11 Clinical Trial Drugs  11
1 PHA848125 Phase 2
Thymic cancer
2 R-roscovitine Phase 2
Non-small-cell lung cancer
3 Ro 31-7453 Phase 2
Solid tumour/cancer
4 AG-024322 Phase 1
Solid tumour/cancer
5 AT7519 Phase 1
Solid tumour/cancer
6 AZD-5438 Phase 1
Solid tumour/cancer
7 CYC065 Phase 1
Lymphoma
8 FN-1501 Phase 1
Solid tumour/cancer
9 PHA-793887 Phase 1
Solid tumour/cancer
10 SNS-032 Phase 1
Solid tumour/cancer
11 TG02 Phase 1/2
Anaplastic astrocytoma
Discontinued Drug(s) 4 Discontinued Drugs  4
1 SCH 727965 Discontinued in Phase 3
Acute lymphoblastic leukaemia
2 BAY 10-00394 Discontinued in Phase 2
Small-cell lung cancer
3 R547 Discontinued in Phase 1
Advanced solid tumour
4 PD-0183812 Terminated
Retinoblastoma
Investigative Drug(s) 1 Investigative Drug  1
1 SCH-546909 Investigative
Solid tumour/cancer
Preclinical Drug(s) 1 Preclinical Drug  1
1 L-751250 Preclinical
Obesity