CDK2_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: CDK2_MOUSE
• UniProt AC: P97377
• Protein Name: Cyclin-dependent kinase 2
• Gene Name: Cdk2
• Organism: Mus musculus (Mouse).
• Sequence Length: 346
• Subcellular Localization: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Nucleus, Cajal body. Cytoplasm. Endosome. Localized at the centrosomes in late G2 phase after separation of the centrosomes but before the start of prophase. Nuclear-cytoplasmic traf
• Protein Description: 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. [PubMed: 23853094 Phosphorylates CDK2AP2 (By similarity]
• Protein Sequence: MENFQKVEKIGEGTYGVVYKAKNKLTGEVVALKKIRLDTETEGVPSTAIREISLLKELNHPNIVKLLDVIHTENKLYLVFEFLHQDLKKFMDASALTGIPLPLIKSYLFQLLQGLAFCHSHRVLHRDLKPQNLLINAEGSIKLADFGLARAFGVPVRTYTHEVVTLWYRAPEILLGCKYYSTAVDIWSLGCIFAEMHLVCTQHHAKCCGEHRRNGRHSLCPLCSYLEVAASQGGGMTAVSAPHPVTRRALFPGDSEIDQLFRIFRTLGTPDEVVWPGVTSMPDYKPSFPKWARQDFSKVVPPLDEDGRSLLSQMLHYDPNKRISAKAALAHPFFQDVTKPVPHLRL

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
1	Acetylation	-------MENFQKVE -------CCCCCEEE	9.54	-
6	Acetylation	--MENFQKVEKIGEG --CCCCCEEEECCCC	48.50	-
9	Acetylation	ENFQKVEKIGEGTYG CCCCEEEECCCCCCE	60.02	23806337
14	Phosphorylation	VEKIGEGTYGVVYKA EEECCCCCCEEEEEE	16.89	22322096
15	Phosphorylation	EKIGEGTYGVVYKAK EECCCCCCEEEEEEE	20.84	22322096
19	Phosphorylation	EGTYGVVYKAKNKLT CCCCEEEEEEECCCC	11.65	21082442
39	Phosphorylation	LKKIRLDTETEGVPS EEEEECCCCCCCCCH	49.77	22817900
94	Phosphorylation	LKKFMDASALTGIPL HHHHHCHHHHHCCCH	21.39	26643407
97	Phosphorylation	FMDASALTGIPLPLI HHCHHHHHCCCHHHH	32.55	26643407
158	Phosphorylation	AFGVPVRTYTHEVVT HHCCCEEEEECEEEE	32.76	21082442
159	Phosphorylation	FGVPVRTYTHEVVTL HCCCEEEEECEEEEH	8.78	26745281
160	Phosphorylation	GVPVRTYTHEVVTLW CCCEEEEECEEEEHH	15.79	19688729
165	Phosphorylation	TYTHEVVTLWYRAPE EEECEEEEHHHCCHH	19.42	23984901
218	Phosphorylation	HRRNGRHSLCPLCSY CCCCCCCCCCHHHHH	30.24	11585773
224	Phosphorylation	HSLCPLCSYLEVAAS CCCCHHHHHHHHHHH	40.20	21183079
225	Phosphorylation	SLCPLCSYLEVAASQ CCCHHHHHHHHHHHC	13.09	21082442
309	Phosphorylation	PLDEDGRSLLSQMLH CCCCCHHHHHHHHHC	38.91	22817900
317	Phosphorylation	LLSQMLHYDPNKRIS HHHHHHCCCCCCCCC	29.18	22817900

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

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
15	Y	Phosphorylation	Kinase	WEE1	P47810	Uniprot
160	T	Phosphorylation	Kinase	CCRK	Q9JHU3	Uniprot
160	T	Phosphorylation	Kinase	CAK	Q03147	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
14	T	Phosphorylation	Phosphorylated on Thr-14 and Tyr-15 during S and G2 phases before being dephosphorylated by CDC25A.	-
160	T	Phosphorylation	Phosphorylated at Thr-160 by CDK7 in a CAK complex.	-
160	T	Phosphorylation	Phosphorylation at Thr-160 promotes kinase activity, whereas phosphorylation at Tyr-15 by WEE1 reduces slightly kinase activity.	-

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of CDK2_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
PURA_MOUSE	Pura	physical	15707957
CDN1A_MOUSE	Cdkn1a	physical	15707957
H11_HUMAN	HIST1H1A	physical	18667424
H12_BOVIN	HIST1H1C	physical	18635963
RB_MOUSE	Rb1	physical	18356301
CCNA1_MOUSE	Ccna1	physical	18356301
CCNE1_MOUSE	Ccne1	physical	18356301
CDN1A_MOUSE	Cdkn1a	physical	18356301
CDC6_MOUSE	Cdc6	physical	18356301
H15_HUMAN	HIST1H1B	physical	17699765
RB_MOUSE	Rb1	physical	16102793
CDN1B_MOUSE	Cdkn1b	physical	16102793
BCL2_MOUSE	Bcl2	physical	16102793
P53_MOUSE	Trp53	physical	16102793
CDN1A_MOUSE	Cdkn1a	physical	15155733
H10_MOUSE	H1f0	physical	14561402
H10_HUMAN	H1F0	physical	12466960
SMN_MOUSE	Smn1	physical	12420317
CCNA2_MOUSE	Ccna2	physical	10068472
CCND2_MOUSE	Ccnd2	physical	9584157
CDN1A_MOUSE	Cdkn1a	physical	9488036
TNFC_MOUSE	Ltb	physical	7604037
H11_MOUSE	Hist1h1a	physical	8226784
H15_HUMAN	HIST1H1B	physical	16120603
H10_HUMAN	H1F0	physical	11463824
H11_MOUSE	Hist1h1a	physical	15749021
CCNE1_MOUSE	Ccne1	physical	15749021
H11_MOUSE	Hist1h1a	physical	17371838
NPM_MOUSE	Npm1	physical	16376875
CDN1B_MOUSE	Cdkn1b	physical	8033213
H11_MOUSE	Hist1h1a	physical	12007403
PCNA_MOUSE	Pcna	physical	12970760
CDN1A_MOUSE	Cdkn1a	physical	12970760
CCNE1_MOUSE	Ccne1	physical	12970760
H12_MOUSE	Hist1h1c	physical	12970760
CDN1B_MOUSE	Cdkn1b	physical	11328857
H11_MOUSE	Hist1h1a	physical	14627988
RB_HUMAN	RB1	physical	16627785
H12_MOUSE	Hist1h1c	physical	9281369
H12_MOUSE	Hist1h1c	physical	22898779
H11_MOUSE	Hist1h1a	physical	15707957
H15_MOUSE	Hist1h1b	physical	16627785
H11_MOUSE	Hist1h1a	physical	8547220
BRCA2_MOUSE	Brca2	physical	25218637

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Phosphorylation

"Large scale localization of protein phosphorylation by use ofelectron capture dissociation mass spectrometry.";
Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
Mol. Cell. Proteomics 8:904-912(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-15, AND MASSSPECTROMETRY.
PubMed: 19131326

"Cables enhances cdk2 tyrosine 15 phosphorylation by Wee1, inhibitscell growth, and is lost in many human colon and squamous cancers.";
Wu C.-L., Kirley S.D., Xiao H., Chuang Y., Chung D.C., Zukerberg L.R.;
Cancer Res. 61:7325-7332(2001).
Cited for: PHOSPHORYLATION AT TYR-15, MUTAGENESIS OF TYR-15, IDENTIFICATION IN ACOMPLEX WITH CABLES1; CCNA1 AND CCNE1, AND INTERACTION WITH CABLES1.
PubMed: 11585773