P24941 (CDK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cyclin-dependent kinase 2
EC=2.7.11.22

Alternative name(s):
Cell division protein kinase 2
p33 protein kinase

Gene names

Name:	CDK2
Synonyms:	CDKN2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	298 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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. Interacts with cyclins A, B1, B3, D, or E. 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. Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.27 Ref.32 Ref.37 Ref.38 Ref.40 Ref.41 Ref.42 Ref.44 Ref.46 Ref.47 Ref.64
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-160 activates it. Inhibited by 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), AG-024322, N-(4-Piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide (AT7519), R547 (Ro-4584820), purine, pyrimidine and pyridine derivatives, 2-aminopyrimidines, paullones, thiazo derivatives, macrocyclic quinoxalin-2-one, pyrazolo[1,5-a]-1,3,5-triazine, pyrazolo[1,5-a]pyrimidine, 2-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine (roscovitine, seliciclib and CYC202), SNS-032 (BMS-387032), triazolo[1,5-a]pyrimidines, staurosporine and olomoucine. Stimulated by MYC. Inactivated by CDKN1A (p21). Ref.12 Ref.37 Ref.60
Subunit structure	Found in a complex with CABLES1, CCNA1 and CCNE1. Interacts with CABLES1 By similarity. 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. Binds to RB1 and CDK7. Binding to CDKN1A (p21) leads to CDK2/cyclin E inactivation at the G1-S phase DNA damage checkpoint, thereby arresting cells at the G1-S transition during DNA repair. Associated with PTPN6 and beta-catenin/CTNNB1. Ref.13 Ref.17 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.26 Ref.30 Ref.44 Ref.48
Subcellular location	Cytoplasm › cytoskeleton › centrosome. Nucleus › Cajal body. Cytoplasm. Endosome. Note: Localized at the centrosomes in late G2 phase after separation of the centrosomes but before the start of prophase. Nuclear-cytoplasmic trafficking is mediated during the inhibition by 1,25-(OH)2D3. Ref.16 Ref.32 Ref.37 Ref.44
Induction	Induced transiently by TGFB1 at an early phase of TGFB1-mediated apoptosis. Ref.12 Ref.32 Ref.37 Ref.47 Ref.60
Post-translational modification	Phosphorylated at Thr-160 by CDK7 in a CAK complex. Phosphorylation at Thr-160 promotes kinase activity, whereas phosphorylation at Tyr-15 by WEE1 reduces slightly kinase activity. Phosphorylated on Thr-14 and Tyr-15 during S and G2 phases before being dephosphorylated by CDC25A. Ref.11 Ref.18 Ref.24 Ref.25 Ref.28 Ref.29 Ref.30 Ref.31 Ref.33 Ref.34 Ref.35 Ref.37 Ref.39 Ref.62 Ref.63 Ref.65 Ref.68 Nitrosylated after treatment with nitric oxide (DETA-NO).
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Cell cycle Cell division DNA damage DNA repair Meiosis Mitosis
Cellular component	Cytoplasm Cytoskeleton Endosome Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Nitration Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest Traceable author statement. Source: Reactome DNA repair Inferred from electronic annotation. Source: UniProtKB-KW DNA replication Traceable author statement Ref.49. Source: UniProtKB G1/S transition of mitotic cell cycle Traceable author statement. Source: Reactome G2 phase of mitotic cell cycle Traceable author statement. Source: Reactome G2/M transition of mitotic cell cycle Traceable author statement. Source: ProtInc M/G1 transition of mitotic cell cycle Traceable author statement. Source: Reactome Ras protein signal transduction Inferred from expression pattern. Source: BHF-UCL S phase of mitotic cell cycle Traceable author statement. Source: Reactome anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process Traceable author statement. Source: Reactome blood coagulation Traceable author statement. Source: Reactome cell division Inferred from electronic annotation. Source: UniProtKB-KW cellular response to nitric oxide Traceable author statement Ref.38. Source: UniProtKB centrosome duplication Traceable author statement Ref.49. Source: UniProtKB histone phosphorylation Inferred from direct assay. Source: GOC meiosis Traceable author statement Ref.49. Source: UniProtKB mitosis Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of cell proliferation Traceable author statement. Source: ProtInc regulation of DNA replication Traceable author statement. Source: ProtInc regulation of gene silencing Inferred from direct assay Ref.40. Source: UniProtKB regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle Traceable author statement. Source: Reactome traversing start control point of mitotic cell cycle Traceable author statement. Source: ProtInc
Cellular component	Cajal body Inferred from direct assay Ref.16. Source: UniProtKB centrosome Traceable author statement Ref.49. Source: UniProtKB cyclin-dependent protein kinase holoenzyme complex Inferred from direct assay. Source: UniProtKB cytosol Traceable author statement. Source: Reactome endosome Inferred from direct assay Ref.44. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW cyclin-dependent protein kinase activity Inferred from direct assay Ref.46. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CCNA2	P20248	16	EBI-375096,EBI-457097
CCNE1	P24864	9	EBI-375096,EBI-519526
CCNE2	O96020	5	EBI-375096,EBI-375033
CCNH	P51946	2	EBI-375096,EBI-741406
CDKN1A	P38936	9	EBI-375096,EBI-375077
CDKN1B	P46527	12	EBI-375096,EBI-519280
CDKN3	Q16667	2	EBI-375096,EBI-1031527
RB1	P06400	3	EBI-375096,EBI-491274
UHRF2	Q96PU4	4	EBI-375096,EBI-625304

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P24941-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P24941-2)

Also known as: CDK2deltaT;

The sequence of this isoform differs from the canonical sequence as follows:
     163-196: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 298

298

Cyclin-dependent kinase 2

PRO_0000085769

Regions

Domain

4 – 286

283

Protein kinase

Nucleotide binding

10 – 18

9

ATP

Nucleotide binding

81 – 83

3

ATP

Nucleotide binding

129 – 132

4

ATP

Sites

Active site

127

1

Proton acceptor

Metal binding

132

1

Magnesium; catalytic

Metal binding

145

1

Magnesium; catalytic

Binding site

33

1

ATP

Binding site

86

1

ATP

Binding site

145

1

ATP

Site

9

1

CDK7 binding

Site

88 – 89

2

CDK7 binding

Site

166

1

CDK7 binding

Amino acid modifications

Modified residue

1

1

N-acetylmethionine Ref.36

Modified residue

6

1

N6-acetyllysine Ref.36

Modified residue

14

1

Phosphothreonine Ref.11 Ref.25 Ref.29 Ref.34 Ref.65

Modified residue

15

1

Phosphotyrosine; by WEE1 Ref.11 Ref.28 Ref.29 Ref.31 Ref.33 Ref.34 Ref.35 Ref.65

Modified residue

19

1

Phosphotyrosine Ref.28 Ref.29 Ref.34

Modified residue

46

1

Phosphoserine Ref.31 Ref.34

Modified residue

158

1

Phosphothreonine Ref.34

Modified residue

159

1

Phosphotyrosine Ref.34

Modified residue

160

1

Phosphothreonine; by CAK and CCRK Ref.11 Ref.24 Ref.29 Ref.35 Ref.37 Ref.39 Ref.62 Ref.63 Ref.65 Ref.68

Natural variations

Alternative sequence

163 – 196

34

Missing in isoform 2.

VSP_041998

Natural variant

15

1

Y → S.
Corresponds to variant rs3087335 [ dbSNP | Ensembl ].

VAR_016157

Natural variant

18

1

V → L.
Corresponds to variant rs11554376 [ dbSNP | Ensembl ].

VAR_053927

Natural variant

45

1

P → L in a glioblastoma multiforme sample; somatic mutation. Ref.69

VAR_041972

Natural variant

290

1

T → S. Ref.6 Ref.69
Corresponds to variant rs2069413 [ dbSNP | Ensembl ].

VAR_019988

Experimental info

Mutagenesis

9

1

K → F: Reduced phosphorylation by CAK. Ref.30

Mutagenesis

14

1

T → A: 2-fold increase in activity. Ref.11

Mutagenesis

15

1

Y → F: 2-fold increase in activity. Ref.11

Mutagenesis

88 – 89

2

KK → EV: Reduced phosphorylation by CAK.

Mutagenesis

160

1

T → A: Abolishes activity. Ref.11

Mutagenesis

166

1

L → R: Reduced phosphorylation by CAK and reduced kinase activity. Ref.30

Sequence conflict

8 – 12

5

EKIGE → AQIGQ in BAA32794. Ref.5

Sequence conflict

25 – 29

5

LTGEV → STGQM in BAA32794. Ref.5

Sequence conflict

272 – 277

6

NKRISA → YKRFST in BAA32794. Ref.5

Sequence conflict

286 – 287

2

FQ → LE in BAA32794. Ref.5

Secondary structure

1

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298

Helix Strand Turn

Details...

Beta strand

4 – 12

9

Beta strand

14 – 23

10

Turn

24 – 26

3

Beta strand

29 – 35

7

Helix

46 – 55

10

Beta strand

66 – 72

7

Beta strand

75 – 81

7

Beta strand

84 – 86

3

Helix

87 – 93

7

Turn

94 – 97

4

Helix

101 – 120

20

Helix

130 – 132

3

Beta strand

133 – 135

3

Beta strand

141 – 143

3

Helix

148 – 152

5

Helix

171 – 174

4

Helix

183 – 198

16

Helix

208 – 219

12

Turn

224 – 226

3

Helix

230 – 232

3

Helix

248 – 251

4

Helix

257 – 266

10

Turn

271 – 273

3

Helix

277 – 281

5

Helix

284 – 286

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 1, 1992. Version 2. Checksum: F90A0F4E70910B51	FASTA	298	33,930
	10 20 30 40 50 60 MENFQKVEKI GEGTYGVVYK ARNKLTGEVV ALKKIRLDTE TEGVPSTAIR EISLLKELNH 70 80 90 100 110 120 PNIVKLLDVI HTENKLYLVF EFLHQDLKKF MDASALTGIP LPLIKSYLFQ LLQGLAFCHS 130 140 150 160 170 180 HRVLHRDLKP QNLLINTEGA IKLADFGLAR AFGVPVRTYT HEVVTLWYRA PEILLGCKYY 190 200 210 220 230 240 STAVDIWSLG CIFAEMVTRR ALFPGDSEID QLFRIFRTLG TPDEVVWPGV TSMPDYKPSF 250 260 270 280 290 PKWARQDFSK VVPPLDEDGR SLLSQMLHYD PNKRISAKAA LAHPFFQDVT KPVPHLRL
	Isoform 2 (CDK2deltaT) [UniParc]. Checksum: 50CE890992AC71EE	FASTA	264	30,035
	10 20 30 40 50 60 MENFQKVEKI GEGTYGVVYK ARNKLTGEVV ALKKIRLDTE TEGVPSTAIR EISLLKELNH 70 80 90 100 110 120 PNIVKLLDVI HTENKLYLVF EFLHQDLKKF MDASALTGIP LPLIKSYLFQ LLQGLAFCHS 130 140 150 160 170 180 HRVLHRDLKP QNLLINTEGA IKLADFGLAR AFGVPVRTYT HEVTRRALFP GDSEIDQLFR 190 200 210 220 230 240 IFRTLGTPDE VVWPGVTSMP DYKPSFPKWA RQDFSKVVPP LDEDGRSLLS QMLHYDPNKR 250 260 ISAKAALAHP FFQDVTKPVP HLRL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A new human p34 protein kinase, CDK2, identified by complementation of a cdc28 mutation in Saccharomyces cerevisiae, is a homolog of Xenopus Eg1." Elledge S.J., Spottswood M.R. EMBO J. 10:2653-2659(1991) [PubMed: 1714386] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Isolation of the human cdk2 gene that encodes the cyclin A- and adenovirus E1A-associated p33 kinase." Tsai L.-H., Harlow E., Meyerson M. Nature 353:174-177(1991) [PubMed: 1653904] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Cloning of a human cDNA encoding a CDC2-related kinase by complementation of a budding yeast cdc28 mutation." Ninomiya-Tsuji J., Nomoto S., Yasuda H., Reed S.I., Matsumoto K. Proc. Natl. Acad. Sci. U.S.A. 88:9006-9010(1991) [PubMed: 1717994] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]	"Sequence of deletion type cdk2 variant in human breast cancer." Nishikawa T., Ohta T., Fukuda M., Ogata H., Okamoto K., Isohashi F., Arima K., Yamaguchi S. Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 2).
[5]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]	NIEHS SNPs program Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT SER-290.
[7]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[8]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed: 16541075] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Placenta.
[11]	"Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15." Gu Y., Rosenblatt J., O'Morgan D.O. EMBO J. 11:3995-4005(1992) [PubMed: 1396589] [Abstract] Cited for: PHOSPHORYLATION AT THR-14; TYR-15 AND THR-160, MUTAGENESIS OF THR-14; TYR-15 AND THR-160.
[12]	"Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5." Meijer L., Borgne A., Mulner O., Chong J.P.J., Blow J.J., Inagaki N., Inagaki M., Delcros J.-G., Moulinoux J.-P. Eur. J. Biochem. 243:527-536(1997) [PubMed: 9030781] [Abstract] Cited for: ENZYME REGULATION BY ROSCOVITINE AND OLOMOUCINE.
[13]	"Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1." Harbour J.W., Luo R.X., Dei Santi A., Postigo A.A., Dean D.C. Cell 98:859-869(1999) [PubMed: 10499802] [Abstract] Cited for: FUNCTION AS RB1 KINASE, INTERACTION WITH CYCLIN E.
[14]	"Nucleophosmin/B23 is a target of CDK2/cyclin E in centrosome duplication." Okuda M., Horn H.F., Tarapore P., Tokuyama Y., Smulian A.G., Chan P.K., Knudsen E.S., Hofmann I.A., Snyder J.D., Bove K.E., Fukasawa K. Cell 103:127-140(2000) [PubMed: 11051553] [Abstract] Cited for: FUNCTION AS NPM1 KINASE.
[15]	"NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription." Zhao J., Kennedy B.K., Lawrence B.D., Barbie D.A., Matera A.G., Fletcher J.A., Harlow E. Genes Dev. 14:2283-2297(2000) [PubMed: 10995386] [Abstract] Cited for: FUNCTION AS NPAT KINASE.
[16]	"Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription." Ma T., Van Tine B.A., Wei Y., Garrett M.D., Nelson D., Adams P.D., Wang J., Qin J., Chow L.T., Harper J.W. Genes Dev. 14:2298-2313(2000) [PubMed: 10995387] [Abstract] Cited for: FUNCTION AS NPAT KINASE, SUBCELLULAR LOCATION.
[17]	"The C-terminal regulatory domain of p53 contains a functional docking site for cyclin A." Luciani M.G., Hutchins J.R.A., Zheleva D., Hupp T.R. J. Mol. Biol. 300:503-518(2000) [PubMed: 10884347] [Abstract] Cited for: FUNCTION AS P53/TP53 KINASE, INTERACTION WITH CYCLIN A AND CYCLIN B1.
[18]	"Reciprocal activation by cyclin-dependent kinases 2 and 7 is directed by 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) [PubMed: 11113184] [Abstract] Cited for: FUNCTION AS CDK7 KINASE, PHOSPHORYLATION BY CDK7.
[19]	"Characterization and expression of mammalian cyclin b3, a prepachytene meiotic cyclin." Nguyen T.B., Manova K., Capodieci P., Lindon C., Bottega S., Wang X.-Y., Refik-Rogers J., Pines J., Wolgemuth D.J., Koff A. J. Biol. Chem. 277:41960-41969(2002) [PubMed: 12185076] [Abstract] Cited for: INTERACTION WITH CCNB3.
[20]	"Human Speedy: a novel cell cycle regulator that enhances proliferation through activation of Cdk2." Porter L.A., Dellinger R.W., Tynan J.A., Barnes E.A., Kong M., Lenormand J.-L., Donoghue D.J. J. Cell Biol. 157:357-366(2002) [PubMed: 11980914] [Abstract] Cited for: INTERACTION WITH SPDYA.
[21]	"Human Spy1 promotes survival of mammalian cells following DNA damage." Barnes E.A., Porter L.A., Lenormand J.-L., Dellinger R.W., Donoghue D.J. Cancer Res. 63:3701-3707(2003) [PubMed: 12839962] [Abstract] Cited for: INTERACTION WITH SPDYA.
[22]	"Spy1 interacts with p27Kip1 to allow G1/S progression." Porter L.A., Kong-Beltran M., Donoghue D.J. Mol. Biol. Cell 14:3664-3674(2003) [PubMed: 12972555] [Abstract] Cited for: INTERACTION WITH SPDYA, IDENTIFICATION IN A COMPLEX WITH CDKN1B AND SPDYA.
[23]	"NIRF induces G1 arrest and associates with Cdk2." Li Y., Mori T., Hata H., Homma Y., Kochi H. Biochem. Biophys. Res. Commun. 319:464-468(2004) [PubMed: 15178429] [Abstract] Cited for: INTERACTION WITH UHRF2, IDENTIFICATION IN A COMPLEX WITH UHRF2 AND CCNE1.
[24]	"p42, a novel cyclin-dependent kinase-activating kinase in mammalian cells." Liu Y., Wu C., Galaktionov K. J. Biol. Chem. 279:4507-4514(2004) [PubMed: 14597612] [Abstract] Cited for: PHOSPHORYLATION AT THR-160.
[25]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-14, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[26]	"Identification and comparative analysis of multiple mammalian Speedy/Ringo proteins." Cheng A., Xiong W., Ferrell J.E. Jr., Solomon M.J. Cell Cycle 4:155-165(2005) [PubMed: 15611625] [Abstract] Cited for: INTERACTION WITH SPDYA AND SPDYC.
[27]	"CDK-dependent phosphorylation of BRCA2 as a regulatory mechanism for recombinational repair." Esashi F., Christ N., Gannon J., Liu Y., Hunt T., Jasin M., West S.C. Nature 434:598-604(2005) [PubMed: 15800615] [Abstract] Cited for: FUNCTION AS BRCA2 KINASE.
[28]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-15 AND TYR-19, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[29]	"Proteomics analysis of protein kinases by target class-selective prefractionation 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) [PubMed: 17192257] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-14; TYR-15; TYR-19 AND THR-160, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[30]	"Recognition of Cdk2 by Cdk7." Lolli G., Johnson L.N. Proteins 67:1048-1059(2007) [PubMed: 17373709] [Abstract] Cited for: PHOSPHORYLATION BY CAK, MUTAGENESIS OF LYS-9; 88-LYS-LYS-89 AND LEU-166, INTERACTION WITH CDK7.
[31]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the 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) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-15 AND SER-46, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[32]	"Cyclin A/cdk2 coordinates centrosomal and nuclear mitotic events." De Boer L., Oakes V., Beamish H., Giles N., Stevens F., Somodevilla-Torres M., Desouza C., Gabrielli B. Oncogene 27:4261-4268(2008) [PubMed: 18372919] [Abstract] Cited for: FUNCTION IN MITOSE REGULATION, SUBCELLULAR LOCATION.
[33]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-15, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[34]	"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) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-14; TYR-15; TYR-19; SER-46; THR-158 AND TYR-159, MASS SPECTROMETRY.
[35]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals 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) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-15 AND THR-160, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[36]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND LYS-6, MASS SPECTROMETRY.
[37]	"Nuclear targeting of cyclin-dependent kinase 2 reveals essential roles of cyclin-dependent kinase 2 localization and cyclin E in vitamin D-mediated growth inhibition." Flores O., Wang Z., Knudsen K.E., Burnstein K.L. Endocrinology 151:896-908(2010) [PubMed: 20147522] [Abstract] Cited for: FUNCTION IN VITAMIN D-MEDIATED GROWTH INHIBITION, SUBCELLULAR LOCATION, ENZYME REGULATION, PHOSPHORYLATION AT THR-160.
[38]	"Cdk2 nitrosylation and loss of mitochondrial potential mediate NO-dependent biphasic effect on HL-60 cell cycle." Kumar S., Barthwal M.K., Dikshit M. Free Radic. Biol. Med. 48:851-861(2010) [PubMed: 20079829] [Abstract] Cited for: FUNCTION, NITROSYLATION.
[39]	"Cdc25 phosphatases are required for timely assembly of CDK1-cyclin B at the G2/M transition." Timofeev O., Cizmecioglu O., Settele F., Kempf T., Hoffmann I. J. Biol. Chem. 285:16978-16990(2010) [PubMed: 20360007] [Abstract] Cited for: PHOSPHORYLATION AT THR-160 BY CAK, DEPHOSPHORYLATION BY CDC25A.
[40]	"Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation of EZH2." Chen S., Bohrer L.R., Rai A.N., Pan Y., Gan L., Zhou X., Bagchi A., Simon J.A., Huang H. Nat. Cell Biol. 12:1108-1114(2010) [PubMed: 20935635] [Abstract] Cited for: FUNCTION AS EZH2 KINASE.
[41]	"Cdk2 is required for p53-independent G2/M checkpoint control." Chung J.H., Bunz F. PLoS Genet. 6:E1000863-E1000863(2010) [PubMed: 20195506] [Abstract] Cited for: FUNCTION IN DNA DAMAGE CHECKPOINT.
[42]	"Phosphorylation by Cdk2 is required for Myc to repress Ras-induced senescence in cotransformation." Hydbring P., Bahram F., Su Y., Tronnersjoe S., Hoegstrand K., von der Lehr N., Sharifi H.R., Lilischkis R., Hein N., Wu S., Vervoorts J., Henriksson M., Grandien A., Luescher B., Larsson L.-G. Proc. Natl. Acad. Sci. U.S.A. 107:58-63(2010) [PubMed: 19966300] [Abstract] Cited for: FUNCTION AS MYC KINASE.
[43]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[44]	"Compartmentalized CDK2 is connected with SHP-1 and beta-catenin and regulates insulin internalization." Fiset A., Xu E., Bergeron S., Marette A., Pelletier G., Siminovitch K.A., Olivier M., Beauchemin N., Faure R.L. Cell. Signal. 23:911-919(2011) [PubMed: 21262353] [Abstract] Cited for: FUNCTION AS CTNNB1 KINASE, SUBCELLULAR LOCATION, INTERACTION WITH PTPN6 AND CTNNB1.
[45]	"Discovery of a novel class of 2-aminopyrimidines as CDK1 and CDK2 inhibitors." Lee J., Kim K.H., Jeong S. Bioorg. Med. Chem. Lett. 21:4203-4205(2011) [PubMed: 21684737] [Abstract] Cited for: INHIBITORS.
[46]	"Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and promote S phase entry." Huang X., Summers M.K., Pham V., Lill J.R., Liu J., Lee G., Kirkpatrick D.S., Jackson P.K., Fang G., Dixit V.M. Mol. Cell 42:511-523(2011) [PubMed: 21596315] [Abstract] Cited for: FUNCTION AS USP37 KINASE.
[47]	"An important role for CDK2 in G1 to S checkpoint activation and DNA damage response in human embryonic stem cells." Neganova I., Vilella F., Atkinson S.P., Lloret M., Passos J.F., von Zglinicki T., O'Connor J.-E., Burks D., Jones R., Armstrong L., Lako M. Stem Cells 29:651-659(2011) [PubMed: 21319273] [Abstract] Cited for: FUNCTION IN CELL CYCLE REGULATION.
[48]	"A dual role of Cdk2 in DNA damage response." Satyanarayana A., Kaldis P. Cell Div. 4:9-9(2009) [PubMed: 19445729] [Abstract] Cited for: REVIEW ON DNA REPAIR, INTERACTION WITH CDKN1A/P21.
[49]	"Cell cycle, CDKs and cancer: a changing paradigm." Malumbres M., Barbacid M. Nat. Rev. Cancer 9:153-166(2009) [PubMed: 19238148] [Abstract] Cited for: REVIEW ON CELL CYCLE CONTROL, INHIBITORS, GENE FAMILY.
[50]	"Mammalian cell-cycle regulation: several Cdks, numerous cyclins and diverse compensatory mechanisms." Satyanarayana A., Kaldis P. Oncogene 28:2925-2939(2009) [PubMed: 19561645] [Abstract] Cited for: REVIEW, GENE FAMILY.
[51]	"Tipping the balance: Cdk2 enables Myc to suppress senescence." Hydbring P., Larsson L.-G. Cancer Res. 70:6687-6691(2010) [PubMed: 20713526] [Abstract] Cited for: REVIEW ON SENESCENCE.
[52]	"Cyclin dependent kinase 1 inhibitors: a review of recent progress." Wang Q., Su L., Liu N., Zhang L., Xu W., Fang H. Curr. Med. Chem. 18:2025-2043(2011) [PubMed: 21517772] [Abstract] Cited for: REVIEW ON INHIBITORS.
[53]	"Crystal structure of cyclin-dependent kinase 2." de Bondt H.L., Rosenblatt J., Jancarik J., Jones H.D., Morgan D.O., Kim S.-H. Nature 363:595-602(1993) [PubMed: 8510751] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
[54]	"Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex." Jeffrey P.D., Russo A.A., Polyak K., Gibbs E., Hurwitz J., Massague J., Pavletich N.P. Nature 376:313-320(1995) [PubMed: 7630397] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF COMPLEX WITH CYCLIN A.
[55]	"Crystal structure and mutational analysis of the human CDK2 kinase complex with cell cycle-regulatory protein CksHs1." Bourne Y., Watson M.H., Hickey M.J., Holmes W., Rocque W., Reed S.I., Tainer J.A. Cell 84:863-874(1996) [PubMed: 8601310] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF COMPLEX WITG CKS1.
[56]	"High-resolution crystal structures of human cyclin-dependent kinase 2 with and without ATP: bound waters and natural ligand as guides for inhibitor design." Schulze-Gahmen U., de Bondt H.L., Kim S.-H. J. Med. Chem. 39:4540-4546(1996) [PubMed: 8917641] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
[57]	"Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex." Russo A.A., Jeffrey P.D., Patten A.K., Massague J., Pavletich N.P. Nature 382:325-331(1996) [PubMed: 8684460] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF COMPLEX WITH CG2A AND KIP1.
[58]	"Structural basis of cyclin-dependent kinase activation by phosphorylation." Russo A.A., Jeffrey P.D., Pavletich N.P. Nat. Struct. Biol. 3:696-700(1996) [PubMed: 8756328] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF COMPLEX WITH CG2A.
[59]	"Structural basis for specificity and potency of a flavonoid inhibitor of human CDK2, a cell cycle kinase." de Azevedo W.F. Jr., Mueller-Dieckmann H.-J., Schulze-Gahmen U., Worland P.J., Sausville E., Kim S.-H. Proc. Natl. Acad. Sci. U.S.A. 93:2735-2740(1996) [PubMed: 8610110] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.33 ANGSTROMS) OF COMPLEX WITH L868276.
[60]	"Protein kinase inhibition by staurosporine revealed in details of the molecular interaction with CDK2." Lawrie A.M., Noble M.E.M., Tunnah P., Brown N.R., Johnson L.N., Endicott J.A. Nat. Struct. Biol. 4:796-801(1997) [PubMed: 9334743] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH STAUROSPORINE, ENZYME REGULATION.
[61]	"Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors." Gray N.S., Wodicka L., Thunnissen A.-M.W.H., Norman T.C., Kwon S., Espinoza F.H., Morgan D.O., Barnes G., Leclerc S., Meijer L., Kim S.H., Lockhart D.J., Schultz P.G. Science 281:533-538(1998) [PubMed: 9677190] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS).
[62]	"Triazolo[1,5-a]pyrimidines as novel CDK2 inhibitors: protein structure-guided design and SAR." Richardson C.M., Williamson D.S., Parratt M.J., Borgognoni J., Cansfield A.D., Dokurno P., Francis G.L., Howes R., Moore J.D., Murray J.B., Robertson A., Surgenor A.E., Torrance C.J. Bioorg. Med. Chem. Lett. 16:1353-1357(2006) [PubMed: 16325401] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH INHIBITORS, PHOSPHORYLATION AT THR-160.
[63]	"Discovery of a potent CDK2 inhibitor with a novel binding mode, using virtual screening and initial, structure-guided lead scoping." Richardson C.M., Nunns C.L., Williamson D.S., Parratt M.J., Dokurno P., Howes R., Borgognoni J., Drysdale M.J., Finch H., Hubbard R.E., Jackson P.S., Kierstan P., Lentzen G., Moore J.D., Murray J.B., Simmonite H., Surgenor A.E., Torrance C.J. Bioorg. Med. Chem. Lett. 17:3880-3885(2007) [PubMed: 17570665] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEX WITH INHIBITORS, PHOSPHORYLATION AT THR-160.
[64]	"Cyclin B and cyclin A confer different substrate recognition properties on CDK2." Brown N.R., Lowe E.D., Petri E., Skamnaki V., Antrobus R., Johnson L.N. Cell Cycle 6:1350-1359(2007) [PubMed: 17495531] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 1-288 IN COMPLEX WITH CCNB1, FUNCTION.
[65]	"How tyrosine 15 phosphorylation inhibits the activity of cyclin-dependent kinase 2-cyclin A." Welburn J.P.I., Tucker J.A., Johnson T., Lindert L., Morgan M., Willis A., Noble M.E.M., Endicott J.A. J. Biol. Chem. 282:3173-3181(2007) [PubMed: 17095507] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH ATP, PHOSPHORYLATION AT THR-14; TYR-15 AND THR-160.
[66]	"Structure-guided discovery of cyclin-dependent kinase inhibitors." Fischmann T.O., Hruza A., Duca J.S., Ramanathan L., Mayhood T., Windsor W.T., Le H.V., Guzi T.J., Dwyer M.P., Paruch K., Doll R.J., Lees E., Parry D., Seghezzi W., Madison V. Biopolymers 89:372-379(2008) [PubMed: 17937404] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.28 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
[67]	"Identification of N-(4-piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide (AT7519), a novel cyclin dependent kinase inhibitor using fragment-based X-ray crystallography and structure based drug design." Wyatt P.G., Woodhead A.J., Berdini V., Boulstridge J.A., Carr M.G., Cross D.M., Davis D.J., Devine L.A., Early T.R., Feltell R.E., Lewis E.J., McMenamin R.L., Navarro E.F., O'Brien M.A., O'Reilly M., Reule M., Saxty G., Seavers L.C. , Smith D.M., Squires M.S., Trewartha G., Walker M.T., Woolford A.J. J. Med. Chem. 51:4986-4999(2008) [PubMed: 18656911] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.68 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
[68]	"Briefly bound to activate: transient binding of a second catalytic magnesium activates the structure and dynamics of CDK2 kinase for catalysis." Bao Z.Q., Jacobsen D.M., Young M.A. Structure 19:675-690(2011) [PubMed: 21565702] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.91 ANGSTROMS) OF 1-296 IN COMPLEX WITH ATP AND MAGNESIUM, PHOSPHORYLATION AT THR-160.
[69]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-45 AND SER-290.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X61622 mRNA. Translation: CAA43807.1.
X62071 mRNA. Translation: CAA43985.1.
M68520 mRNA. Translation: AAA35667.1.
AB012305 mRNA. Translation: BAA32794.1.
BT006821 mRNA. Translation: AAP35467.1.
AF512553 Genomic DNA. Translation: AAM34794.1.
AK291941 mRNA. Translation: BAF84630.1.
AC025162 Genomic DNA. No translation available.
AC034102 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW96858.1.
BC003065 mRNA. Translation: AAH03065.1.

IPI

IPI00031681.

PIR

A41227.

RefSeq

NP_001789.2. NM_001798.3.
NP_439892.2. NM_052827.2.

UniGene

Hs.19192.
Hs.689624.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AQ1	X-ray	2.00	A	1-298	[»]
1B38	X-ray	2.00	A	1-298	[»]
1B39	X-ray	2.10	A	1-298	[»]
1BUH	X-ray	2.60	A	1-298	[»]
1CKP	X-ray	2.05	A	1-298	[»]
1DI8	X-ray	2.20	A	1-298	[»]
1DM2	X-ray	2.10	A	1-298	[»]
1E1V	X-ray	1.95	A	1-298	[»]
1E1X	X-ray	1.85	A	1-298	[»]
1E9H	X-ray	2.50	A/C	1-296	[»]
1F5Q	X-ray	2.50	A/C	1-298	[»]
1FIN	X-ray	2.30	A/C	1-298	[»]
1FQ1	X-ray	3.00	B	1-298	[»]
1FVT	X-ray	2.20	A	1-298	[»]
1FVV	X-ray	2.80	A/C	1-298	[»]
1G5S	X-ray	2.61	A	1-298	[»]
1GIH	X-ray	2.80	A	1-298	[»]
1GII	X-ray	2.00	A	1-298	[»]
1GIJ	X-ray	2.20	A	1-298	[»]
1GY3	X-ray	2.70	A/C	1-296	[»]
1GZ8	X-ray	1.30	A	1-298	[»]
1H00	X-ray	1.60	A	1-298	[»]
1H01	X-ray	1.79	A	1-298	[»]
1H07	X-ray	1.85	A	1-298	[»]
1H08	X-ray	1.80	A	1-298	[»]
1H0V	X-ray	1.90	A	1-298	[»]
1H0W	X-ray	2.10	A	1-298	[»]
1H1P	X-ray	2.10	A/C	1-298	[»]
1H1Q	X-ray	2.50	A/C	1-298	[»]
1H1R	X-ray	2.00	A/C	1-298	[»]
1H1S	X-ray	2.00	A/C	1-298	[»]
1H24	X-ray	2.50	A/C	1-298	[»]
1H25	X-ray	2.50	A/C	1-298	[»]
1H26	X-ray	2.24	A/C	1-298	[»]
1H27	X-ray	2.20	A/C	1-298	[»]
1H28	X-ray	2.80	A/C	1-298	[»]
1HCK	X-ray	1.90	A	1-298	[»]
1HCL	X-ray	1.80	A	1-298	[»]
1JST	X-ray	2.60	A/C	1-298	[»]
1JSU	X-ray	2.30	A	1-298	[»]
1JSV	X-ray	1.96	A	1-298	[»]
1JVP	X-ray	1.53	P	1-298	[»]
1KE5	X-ray	2.20	A	1-298	[»]
1KE6	X-ray	2.00	A	1-298	[»]
1KE7	X-ray	2.00	A	1-298	[»]
1KE8	X-ray	2.00	A	1-298	[»]
1KE9	X-ray	2.00	A	1-298	[»]
1OGU	X-ray	2.60	A/C	1-298	[»]
1OI9	X-ray	2.10	A/C	1-298	[»]
1OIQ	X-ray	2.31	A	1-298	[»]
1OIR	X-ray	1.91	A	1-298	[»]
1OIT	X-ray	1.60	A	1-298	[»]
1OIU	X-ray	2.00	A/C	1-298	[»]
1OIY	X-ray	2.40	A/C	1-298	[»]
1OKV	X-ray	2.40	A/C	1-298	[»]
1OKW	X-ray	2.50	A/C	1-298	[»]
1OL1	X-ray	2.90	A/C	1-298	[»]
1OL2	X-ray	2.60	A/C	1-298	[»]
1P2A	X-ray	2.50	A	1-298	[»]
1P5E	X-ray	2.22	A/C	1-298	[»]
1PF8	X-ray	2.51	A	1-298	[»]
1PKD	X-ray	2.30	A/C	1-296	[»]
1PW2	X-ray	1.95	A	1-298	[»]
1PXI	X-ray	1.95	A	1-298	[»]
1PXJ	X-ray	2.30	A	1-298	[»]
1PXK	X-ray	2.80	A	1-298	[»]
1PXL	X-ray	2.50	A	1-298	[»]
1PXM	X-ray	2.53	A	1-298	[»]
1PXN	X-ray	2.50	A	1-298	[»]
1PXO	X-ray	1.96	A	1-298	[»]
1PXP	X-ray	2.30	A	1-298	[»]
1PYE	X-ray	2.00	A	1-298	[»]
1QMZ	X-ray	2.20	A/C	1-298	[»]
1R78	X-ray	2.00	A	1-298	[»]
1URC	X-ray	2.60	A/C	1-298	[»]
1URW	X-ray	1.60	A	1-298	[»]
1V1K	X-ray	2.31	A	1-298	[»]
1VYW	X-ray	2.30	A/C	1-298	[»]
1VYZ	X-ray	2.21	A	1-298	[»]
1W0X	X-ray	2.20	C	1-298	[»]
1W8C	X-ray	2.05	A	1-298	[»]
1W98	X-ray	2.15	A	1-297	[»]
1WCC	X-ray	2.20	A	1-298	[»]
1Y8Y	X-ray	2.00	A	1-298	[»]
1Y91	X-ray	2.15	A	1-298	[»]
1YKR	X-ray	1.80	A	1-298	[»]
2A0C	X-ray	1.95	X	1-298	[»]
2A4L	X-ray	2.40	A	1-298	[»]
2B52	X-ray	1.88	A	1-298	[»]
2B53	X-ray	2.00	A	1-298	[»]
2B54	X-ray	1.85	A	1-298	[»]
2B55	X-ray	1.85	A	1-298	[»]
2BHE	X-ray	1.90	A	1-298	[»]
2BHH	X-ray	2.60	A	1-298	[»]
2BKZ	X-ray	2.60	A/C	1-298	[»]
2BPM	X-ray	2.40	A/C	1-298	[»]
2BTR	X-ray	1.85	A	1-298	[»]
2BTS	X-ray	1.99	A	1-298	[»]
2C4G	X-ray	2.70	A/C	1-298	[»]
2C5N	X-ray	2.10	A/C	1-298	[»]
2C5O	X-ray	2.10	A/C	1-298	[»]
2C5V	X-ray	2.90	A/C	1-298	[»]
2C5X	X-ray	2.90	A/C	1-298	[»]
2C5Y	X-ray	2.25	A	1-298	[»]
2C68	X-ray	1.95	A	1-298	[»]
2C69	X-ray	2.10	A	1-298	[»]
2C6I	X-ray	1.80	A	1-298	[»]
2C6K	X-ray	1.90	A	1-298	[»]
2C6L	X-ray	2.30	A	1-298	[»]
2C6M	X-ray	1.90	A	1-298	[»]
2C6O	X-ray	2.10	A	1-298	[»]
2C6T	X-ray	2.61	A/C	1-298	[»]
2CCH	X-ray	1.70	A/C	1-298	[»]
2CCI	X-ray	2.70	A/C	1-298	[»]
2CJM	X-ray	2.30	A/C	1-298	[»]
2CLX	X-ray	1.80	A	1-298	[»]
2DS1	X-ray	2.00	A	1-298	[»]
2DUV	X-ray	2.20	A	1-298	[»]
2EXM	X-ray	1.80	A	1-298	[»]
2FVD	X-ray	1.85	A	1-298	[»]
2G9X	X-ray	2.50	A/C	1-298	[»]
2HIC	model	-	A	1-298	[»]
2I40	X-ray	2.80	A/C	1-298	[»]
2IW6	X-ray	2.30	A/C	1-298	[»]
2IW8	X-ray	2.30	A/C	1-298	[»]
2IW9	X-ray	2.00	A/C	1-298	[»]
2J9M	X-ray	2.50	A	1-298	[»]
2JGZ	X-ray	2.90	A	1-288	[»]
2R3F	X-ray	1.50	A	1-298	[»]
2R3G	X-ray	1.55	A	1-298	[»]
2R3H	X-ray	1.50	A	1-298	[»]
2R3I	X-ray	1.28	A	1-298	[»]
2R3J	X-ray	1.65	A	1-298	[»]
2R3K	X-ray	1.70	A	1-298	[»]
2R3L	X-ray	1.65	A	1-298	[»]
2R3M	X-ray	1.70	A	1-298	[»]
2R3N	X-ray	1.63	A	1-298	[»]
2R3O	X-ray	1.80	A	1-298	[»]
2R3P	X-ray	1.66	A	1-298	[»]
2R3Q	X-ray	1.35	A	1-298	[»]
2R3R	X-ray	1.47	A	1-298	[»]
2R64	X-ray	2.30	A	1-298	[»]
2UUE	X-ray	2.06	A/C	1-298	[»]
2UZB	X-ray	2.70	A/C	1-298	[»]
2UZD	X-ray	2.72	A/C	1-298	[»]
2UZE	X-ray	2.40	A/C	1-298	[»]
2UZL	X-ray	2.40	A/C	1-298	[»]
2UZN	X-ray	2.30	A	1-298	[»]
2UZO	X-ray	2.30	A	1-298	[»]
2V0D	X-ray	2.20	A	1-298	[»]
2V22	X-ray	2.60	A/C	1-298	[»]
2VTA	X-ray	2.00	A	1-298	[»]
2VTH	X-ray	1.90	A	1-298	[»]
2VTI	X-ray	2.00	A	1-298	[»]
2VTJ	X-ray	2.20	A	1-298	[»]
2VTL	X-ray	2.00	A	1-298	[»]
2VTM	X-ray	2.25	A	1-298	[»]
2VTN	X-ray	2.20	A	1-298	[»]
2VTO	X-ray	2.19	A	1-298	[»]
2VTP	X-ray	2.15	A	1-298	[»]
2VTQ	X-ray	1.90	A	1-298	[»]
2VTR	X-ray	1.90	A	1-298	[»]
2VTS	X-ray	1.90	A	1-298	[»]
2VTT	X-ray	1.68	A	1-298	[»]
2VU3	X-ray	1.85	A	1-298	[»]
2VV9	X-ray	1.90	A	1-298	[»]
2W05	X-ray	1.90	A	1-298	[»]
2W06	X-ray	2.04	A	1-298	[»]
2W17	X-ray	2.15	A	1-298	[»]
2W1H	X-ray	2.15	A	1-298	[»]
2WEV	X-ray	2.30	A/C	1-298	[»]
2WFY	X-ray	2.53	A/C	1-298	[»]
2WHB	X-ray	2.90	A/C	1-298	[»]
2WIH	X-ray	2.50	A/C	1-298	[»]
2WIP	X-ray	2.80	A/C	1-298	[»]
2WMA	X-ray	2.80	A/C	1-298	[»]
2WMB	X-ray	2.60	A/C	1-298	[»]
2WPA	X-ray	2.51	A/C	1-298	[»]
2WXV	X-ray	2.60	A/C	1-298	[»]
2X1N	X-ray	2.75	A/C	1-298	[»]
2XMY	X-ray	1.90	A	1-298	[»]
2XNB	X-ray	1.85	A	1-298	[»]
3BHT	X-ray	2.00	A/C	1-298	[»]
3BHU	X-ray	2.30	A/C	1-298	[»]
3BHV	X-ray	2.10	A/C	1-298	[»]
3DDP	X-ray	2.70	A/C	1-298	[»]
3DDQ	X-ray	1.80	A/C	1-298	[»]
3DOG	X-ray	2.70	A/C	1-298	[»]
3EID	X-ray	3.15	A/C	1-298	[»]
3EJ1	X-ray	3.22	A/C	1-298	[»]
3EOC	X-ray	3.20	A/C	1-298	[»]
3EZR	X-ray	1.90	A	1-298	[»]
3EZV	X-ray	1.99	A	1-298	[»]
3F5X	X-ray	2.40	A/C	1-298	[»]
3FZ1	X-ray	1.90	A	1-298	[»]
3IG7	X-ray	1.80	A	1-298	[»]
3IGG	X-ray	1.80	A	1-298	[»]
3LE6	X-ray	2.00	A	1-298	[»]
3LFN	X-ray	2.28	A	1-298	[»]
3LFQ	X-ray	2.03	A	1-298	[»]
3LFS	X-ray	2.40	A	1-298	[»]
3MY5	X-ray	2.10	A/C	1-298	[»]
3NS9	X-ray	1.78	A	1-298	[»]
3PJ8	X-ray	1.96	A	1-298	[»]
3PXF	X-ray	1.80	A	1-298	[»]
3PXQ	X-ray	1.90	A	1-298	[»]
3PXR	X-ray	2.00	A	1-298	[»]
3PXY	X-ray	1.80	A	1-298	[»]
3PXZ	X-ray	1.70	A	1-298	[»]
3PY0	X-ray	1.75	A	1-298	[»]
3PY1	X-ray	2.05	A	1-298	[»]
3QHR	X-ray	2.17	A/C	1-296	[»]
3QHW	X-ray	1.91	A/C	1-296	[»]
3S2P	X-ray	2.30	A	1-298	[»]

ProteinModelPortal

P24941.

SMR

P24941. Positions 1-298.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-161N.

IntAct

P24941. 30 interactions.

MINT

MINT-96328.

STRING

P24941.

PTM databases

PhosphoSite

P24941.

Polymorphism databases

DMDM

116051.

Proteomic databases

PRIDE

P24941.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000266970; ENSP00000266970; ENSG00000123374.

GeneID

1017.

KEGG

hsa:1017.

UCSC

uc001sit.2. human.

Organism-specific databases

CTD

1017.

GeneCards

GC12P056360.

H-InvDB

HIX0010710.

HGNC

HGNC:1771. CDK2.

HPA

CAB013115.

MIM

116953. gene.

neXtProt

NX_P24941.

PharmGKB

PA101.

GenAtlas

Search...

Phylogenomic databases

GeneTree

ENSGT00600000083998.

HOGENOM

HBG755340.

HOVERGEN

HBG014652.

InParanoid

P24941.

OMA

IFAEMCN.

OrthoDB

EOG4C5CJV.

PhylomeDB

P24941.

Enzyme and pathway databases

BRENDA

2.7.11.22. 2681.

Pathway_Interaction_DB

bard1pathway. BARD1 signaling events.
foxm1pathway. FOXM1 transcription factor network.
foxopathway. FoxO family signaling.
il2_1pathway. IL2-mediated signaling events.
smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling.
prlsignalingeventspathway. Signaling events mediated by PRL.

Reactome

REACT_111183. Meiosis.
REACT_152. Cell Cycle, Mitotic.
REACT_1538. Cell Cycle Checkpoints.
REACT_383. DNA Replication.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

P24941.

Bgee

P24941.

CleanEx

HS_CDK2.

Genevestigator

P24941.

GermOnline

ENSG00000123374. Homo sapiens.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_kinase-like_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR002290. Ser/Thr_kinase_dom.
[Graphical view]

KO

K02206.

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P24941.

NextBio

4273.

SOURCE

Search...

Entry information

Entry name

CDK2_HUMAN

Accession

Primary (citable) accession number: P24941
Secondary accession number(s): A8K7C6, O75100

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 1992
Last sequence update:	August 1, 1992
Last modified:	January 25, 2012
This is version 160 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.