Structural highlights
Disease
[CDKN3_HUMAN] Defects in CDKN3 are found in patients with hepatocellular carcinoma (HCC) [MIM:114550].[1]
Function
[CDKN3_HUMAN] May play a role in cell cycle regulation. Dual specificity phosphatase active toward substrates containing either phosphotyrosine or phosphoserine residues. Dephosphorylates CDK2 at 'Thr-160' in a cyclin-dependent manner.[2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The CDK-interacting protein phosphatase KAP dephosphorylates phosphoThr-160 (pThr-160) of the CDK2 activation segment, the site of regulatory phosphorylation that is essential for kinase activity. Here we describe the crystal structure of KAP in association with pThr-160-CDK2, representing an example of a protein phosphatase in complex with its intact protein substrate. The major protein interface between the two molecules is formed by the C-terminal lobe of CDK2 and the C-terminal helix of KAP, regions remote from the kinase-activation segment and the KAP catalytic site. The kinase-activation segment interacts with the catalytic site of KAP almost entirely via the phosphate group of pThr-160. This interaction requires that the activation segment is unfolded and drawn away from the kinase molecule, inducing a conformation of CDK2 similar to the activated state observed in the CDK2/cyclin A complex.
Phosphoprotein-protein interactions revealed by the crystal structure of kinase-associated phosphatase in complex with phosphoCDK2.,Song H, Hanlon N, Brown NR, Noble ME, Johnson LN, Barford D Mol Cell. 2001 Mar;7(3):615-26. PMID:11463386[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yeh CT, Lu SC, Chen TC, Peng CY, Liaw YF. Aberrant transcripts of the cyclin-dependent kinase-associated protein phosphatase in hepatocellular carcinoma. Cancer Res. 2000 Sep 1;60(17):4697-700. PMID:10987270
- ↑ Gyuris J, Golemis E, Chertkov H, Brent R. Cdi1, a human G1 and S phase protein phosphatase that associates with Cdk2. Cell. 1993 Nov 19;75(4):791-803. PMID:8242750
- ↑ Hannon GJ, Casso D, Beach D. KAP: a dual specificity phosphatase that interacts with cyclin-dependent kinases. Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1731-5. PMID:8127873
- ↑ Poon RY, Hunter T. Dephosphorylation of Cdk2 Thr160 by the cyclin-dependent kinase-interacting phosphatase KAP in the absence of cyclin. Science. 1995 Oct 6;270(5233):90-3. PMID:7569954
- ↑ Song H, Hanlon N, Brown NR, Noble ME, Johnson LN, Barford D. Phosphoprotein-protein interactions revealed by the crystal structure of kinase-associated phosphatase in complex with phosphoCDK2. Mol Cell. 2001 Mar;7(3):615-26. PMID:11463386
