Q63699 (CDK2_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified May 14, 2014. Version 118. History...
Names and origin
|Protein names||Recommended name:|
Cyclin-dependent kinase 2
Cell division protein kinase 2
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||298 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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 By similarity. Ref.3
ATP + a protein = ADP + a phosphoprotein.
Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-160 activates it. Stimulated by MYC. Inactivated by CDKN1A (p21) By similarity.
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 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 By similarity. Binds to RB1. Interacts with CACUL1 By similarity. May interact with CEP63 By similarity. Ref.3
Cytoplasm › cytoskeleton › microtubule organizing center › centrosome By similarity. Nucleus › Cajal body By similarity. Cytoplasm By similarity. Endosome By similarity. 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 By similarity.
Induced transiently by TGFB1 at an early phase of TGFB1-mediated apoptosis. Ref.3
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 By similarity.
Nitrosylated after treatment with nitric oxide (DETA-NO) By similarity.
Contains 1 protein kinase domain.
|This entry describes 2 isoforms produced by alternative splicing. [Select]|
|Isoform CDK2-alpha (identifier: Q63699-1) |
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 CDK2-beta (identifier: Q63699-2) |
The sequence of this isoform is not available.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 298||298||Cyclin-dependent kinase 2||PRO_0000085772|
|Domain||4 – 286||283||Protein kinase|
|Nucleotide binding||10 – 18||9||ATP By similarity|
|Nucleotide binding||81 – 83||3||ATP By similarity|
|Nucleotide binding||129 – 132||4||ATP By similarity|
|Active site||127||1||Proton acceptor By similarity|
|Metal binding||132||1||Magnesium; catalytic By similarity|
|Metal binding||145||1||Magnesium; catalytic By similarity|
|Binding site||33||1||ATP By similarity|
|Binding site||86||1||ATP By similarity|
|Binding site||145||1||ATP By similarity|
|Site||9||1||CDK7 binding By similarity|
|Site||88 – 89||2||CDK7 binding By similarity|
|Site||166||1||CDK7 binding By similarity|
Amino acid modifications
|Modified residue||1||1||N-acetylmethionine By similarity|
|Modified residue||6||1||N6-acetyllysine By similarity|
|Modified residue||14||1||Phosphothreonine By similarity|
|Modified residue||15||1||Phosphotyrosine; by WEE1 By similarity|
|Modified residue||19||1||Phosphotyrosine By similarity|
|Modified residue||160||1||Phosphothreonine; by CAK and CCRK By similarity|
|Sequence conflict||79||1||V → C in BAA09638. Ref.2|
|Sequence conflict||99||1||L → I in BAA09638. Ref.2|
|Sequence conflict||124||1||L → C in BAA09638. Ref.2|
|||"A variant form of cyclin-dependent kinase 2 (Cdk2) in a malignantly transformed rat thyroid (FRTL-Tc) cell line."|
Kotani S., Endo T., Kitagawa M., Higashi H., Onaya T.
Oncogene 10:663-669(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"Synergistic gene expressions of cyclin E, cdk2, cdk5 and E2F-1 during the prolactin-induced G1/S transition in rat Nb2 pre-T lymphoma cells."|
Hosokawa Y., Yang M., Kaneko S., Tanaka M., Nakashima K.
Biochem. Mol. Biol. Int. 37:393-399(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 19-124.
|||"Cdc2 and Cdk2 kinase activated by transforming growth factor-beta1 trigger apoptosis through the phosphorylation of retinoblastoma protein in FaO hepatoma cells."|
Choi K.S., Eom Y.W., Kang Y., Ha M.J., Rhee H., Yoon J.-W., Kim S.-J.
J. Biol. Chem. 274:31775-31783(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS RB1 KINASE, INDUCTION BY TGFB1, INTERACTION WITH RB1.
|+||Additional computationally mapped references.|
|D28753 mRNA. Translation: BAA05947.1.|
D63162 mRNA. Translation: BAA09638.1.
3D structure databases
|SMR||Q63699. Positions 1-298. |
Protein-protein interaction databases
|IntAct||Q63699. 1 interaction.|
Protocols and materials databases
Genome annotation databases
|UCSC||RGD:70486. rat. [Q63699-1]|
|RGD||70486. Cdk2. |
Enzyme and pathway databases
|BRENDA||220.127.116.11. 5301. |
Gene expression databases
Family and domain databases
|InterPro||IPR011009. Kinase-like_dom. |
|Pfam||PF00069. Pkinase. 1 hit. |
|SMART||SM00220. S_TKc. 1 hit. |
|SUPFAM||SSF56112. SSF56112. 1 hit. |
|PROSITE||PS00107. PROTEIN_KINASE_ATP. 1 hit. |
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
|Accession||Primary (citable) accession number: Q63699|
Secondary accession number(s): O09136
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families