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cyclin-dependent kinase-2 (CDK2)

Function: - role in the control of the cell cycle - interacts with cyclins A, B1, B3, D, or E - expressed constitutively throughout the cell cycle - activity of CDK2 is maximal during S phase & G2 - CDK2/cyclin-E is maximally activated a few hours before onset of DNA synthesis - found in a complex with CABLES1, CCNA1 & CCNE1 - interacts with CABLES1 (putative) - interacts with UHRF2 - part of a complex consisting of UHRF2, CDK2 & CCNE1 - interacts with the speedy/Ringo proteins SPDYA & SPDYC - found in a complex with both SPDYA & CDKN1B/KIP1 - phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme - phosphorylation at Thr-160 activates enzyme - association of CDK2 with cyclins A or E with subsequent dephosphorylation of Tyr-15 & Thr-14 on CDK2 by cdc25 phosphatase & an independently regulated phosphorylation of Thr-160 activates CDK2 - CDK2 activity is required for DNA synthesis & is responsible for the phosphorylation of Rb protein & the modulation of DNA-bound replication protein A - CDK2 is the G1 kinase of fibroblasts Structure: - belongs to the protein kinase superfamily, CMGC Ser/Thr protein kinase family - CDC2/CDKX subfamily contains 1 protein kinase domain

Interactions

molecular events

General

cyclin-dependent kinase (CDK)

Properties

SIZE: entity length = 298 aa MW = 34 kD STATE: active state MOTIF: kinase domain SITE: 4-286 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 10-18 Thr phosphorylation site {T14} Tyr phosphorylation site {Y15} Tyr phosphorylation site {Y19} ATP-binding site NAME: ATP-binding site SITE: 33-33 ATP-binding site NAME: ATP-binding site SITE: 81-83 ATP-binding site NAME: ATP-binding site SITE: 86-86 aspartate residue {D127} ATP-binding site NAME: ATP-binding site SITE: 129-132 ATP-binding site NAME: ATP-binding site SITE: 145-145 Thr-phosphate {T160}

Database Correlations

OMIM 116953 UniProt P24941 Pfam PF00069 Entrez Gene 1017 Kegg hsa:1017 ENZYME 2.7.11.22

References

  1. Dulie V, Lees E, Reed SI. Association of human cyclin E with a periodic G1-S phase protein kinase. Science. 1992 Sep 25;257(5078):1958-61. PMID: 1329201
  2. De Bondt HL, Rosenblatt J, Jancarik J, Jones HD, Morgan DO, Kim SH. Crystal structure of cyclin-dependent kinase 2. Nature. 1993 Jun 17;363(6430):595-602. PMID: 8510751 {crystal}
  3. Morgan DO. Principles of CDK regulation. Nature. 1995 Mar 9;374(6518):131-4. Review. PMID: 7877684
  4. UniProt :accession P24941

Component-of

molecular complex