CDKN3

Cyclin-dependent kinase inhibitor 3
PDB rendering based on 1fpz.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1FPZ​, 1FQ1​
Identifiers
Symbols	CDKN3 ; CDI1; CIP2; KAP; KAP1
External IDs	OMIM: 123832 MGI: 1919641 HomoloGene: 3805 GeneCards: CDKN3 Gene
EC number	3.1.3.16, 3.1.3.48
Gene ontology Molecular function • protein serine/threonine phosphatase activity • protein tyrosine phosphatase activity • protein binding • protein tyrosine/serine/threonine phosphatase activity Cellular component • cytoplasm • perinuclear region of cytoplasm Biological process • regulation of cyclin-dependent protein serine/threonine kinase activity • G1/S transition of mitotic cell cycle • protein dephosphorylation • cell cycle arrest • negative regulation of cell proliferation • peptidyl-tyrosine dephosphorylation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1033	72391
Ensembl	ENSG00000100526	ENSMUSG00000037628
UniProt	Q16667	Q810P3
RefSeq (mRNA)	NM_001130851	NM_028222
RefSeq (protein)	NP_001124323	NP_082498
Location (UCSC)	Chr 14: 54.4 – 54.42 Mb	Chr 14: 46.76 – 46.77 Mb
PubMed search

Cyclin-dependent kinase inhibitor 3 is an enzyme that in humans is encoded by the CDKN3 gene.^[1][2][3]

The protein encoded by this gene belongs to the dual specificity protein phosphatase family. It was identified as a cyclin-dependent kinase inhibitor, and has been shown to interact with, and dephosphorylate CDK2 kinase, thus prevent the activation of CDK2 kinase. This gene was reported to be deleted, mutated, or overexpressed in several kinds of cancers.^[3]

Interactions

CDKN3 has been shown to interact with Cyclin-dependent kinase 2,^[4][5][6] Cdk1^[5][1] and MS4A3.^[7]

References

1. Gyuris J, Golemis E, Chertkov H, Brent R (Dec 1993). "Cdi1, a human G1 and S phase protein phosphatase that associates with Cdk2". Cell 75 (4): 791–803. doi:10.1016/0092-8674(93)90498-F. PMID 8242750.
2. Demetrick DJ, Matsumoto S, Hannon GJ, Okamoto K, Xiong Y, Zhang H, Beach DH (May 1995). "Chromosomal mapping of the genes for the human cell cycle proteins cyclin C (CCNC), cyclin E (CCNE), p21 (CDKN1) and KAP (CDKN3)". Cytogenet Cell Genet 69 (3–4): 190–2. doi:10.1159/000133960. PMID 7698009.
3. "Entrez Gene: CDKN3 cyclin-dependent kinase inhibitor 3 (CDK2-associated dual specificity phosphatase)".
4. Yeh, Chau-Ting; Lu Su-Chuan; Chao Chung-Hao; Chao Mei-Ling (May 2003). "Abolishment of the interaction between cyclin-dependent kinase 2 and Cdk-associated protein phosphatase by a truncated KAP mutant". Biochem. Biophys. Res. Commun. (United States) 305 (2): 311–4. doi:10.1016/S0006-291X(03)00757-5. ISSN 0006-291X. PMID 12745075.
5. Hannon, G J; Casso D; Beach D (Mar 1994). "KAP: a dual specificity phosphatase that interacts with cyclin-dependent kinases". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 91 (5): 1731–5. doi:10.1073/pnas.91.5.1731. ISSN 0027-8424. PMC 43237. PMID 8127873.
6. Harper, J W; Adami G R; Wei N; Keyomarsi K; Elledge S J (Nov 1993). "The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases". Cell (UNITED STATES) 75 (4): 805–16. doi:10.1016/0092-8674(93)90499-G. ISSN 0092-8674. PMID 8242751.
7. Donato, José L; Ko Jon; Kutok Jeffery L; Cheng Tao; Shirakawa Taro; Mao Xiao-Quan; Beach David; Scadden David T; Sayegh Mohamed H; Adra Chaker N (Jan 2002). "Human HTm4 is a hematopoietic cell cycle regulator". J. Clin. Invest. (United States) 109 (1): 51–8. doi:10.1172/JCI14025. ISSN 0021-9738. PMC 150822. PMID 11781350.

Further reading

• Poon RY, Hunter T (1995). "Dephosphorylation of Cdk2 Thr160 by the cyclin-dependent kinase-interacting phosphatase KAP in the absence of cyclin". Science 270 (5233): 90–3. doi:10.1126/science.270.5233.90. PMID 7569954.
• Hannon GJ, Casso D, Beach D (1994). "KAP: a dual specificity phosphatase that interacts with cyclin-dependent kinases". Proc. Natl. Acad. Sci. U.S.A. 91 (5): 1731–5. doi:10.1073/pnas.91.5.1731. PMC 43237. PMID 8127873.
• Harper JW, Adami GR, Wei N; et al. (1993). "The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases". Cell 75 (4): 805–16. doi:10.1016/0092-8674(93)90499-G. PMID 8242751.
• Sexl V, Diehl JA, Sherr CJ; et al. (1999). "A rate limiting function of cdc25A for S phase entry inversely correlates with tyrosine dephosphorylation of Cdk2". Oncogene 18 (3): 573–82. doi:10.1038/sj.onc.1202362. PMID 9989807.
• Lee SW, Reimer CL, Fang L; et al. (2000). "Overexpression of kinase-associated phosphatase (KAP) in breast and prostate cancer and inhibition of the transformed phenotype by antisense KAP expression". Mol. Cell. Biol. 20 (5): 1723–32. doi:10.1128/MCB.20.5.1723-1732.2000. PMC 85355. PMID 10669749.
• Yeh CT, Lu SC, Chen TC; et al. (2000). "Aberrant transcripts of the cyclin-dependent kinase-associated protein phosphatase in hepatocellular carcinoma". Cancer Res. 60 (17): 4697–700. PMID 10987270.
• Song H, Hanlon N, Brown NR; et al. (2001). "Phosphoprotein-protein interactions revealed by the crystal structure of kinase-associated phosphatase in complex with phosphoCDK2". Mol. Cell 7 (3): 615–26. doi:10.1016/S1097-2765(01)00208-8. PMID 11463386.
• Wang H, Iakova P, Wilde M; et al. (2001). "C/EBPalpha arrests cell proliferation through direct inhibition of Cdk2 and Cdk4". Mol. Cell 8 (4): 817–28. doi:10.1016/S1097-2765(01)00366-5. PMID 11684017.
• Donato JL, Ko J, Kutok JL; et al. (2002). "Human HTm4 is a hematopoietic cell cycle regulator". J. Clin. Invest. 109 (1): 51–8. doi:10.1172/JCI14025. PMC 150822. PMID 11781350.
• Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Yeh CT, Lu SC, Chao CH, Chao ML (2003). "Abolishment of the interaction between cyclin-dependent kinase 2 and Cdk-associated protein phosphatase by a truncated KAP mutant". Biochem. Biophys. Res. Commun. 305 (2): 311–4. doi:10.1016/S0006-291X(03)00757-5. PMID 12745075.
• Niculescu MD; Yamamuro Y; Zeisel SH (2004). "Choline availability modulates human neuroblastoma cell proliferation and alters the methylation of the promoter region of the cyclin-dependent kinase inhibitor 3 gene". J. Neurochem. 89 (5): 1252–9. doi:10.1111/j.1471-4159.2004.02414.x. PMC 1592524. PMID 15147518.
• Chinami M, Yano Y, Yang X; et al. (2005). "Binding of HTm4 to cyclin-dependent kinase (Cdk)-associated phosphatase (KAP).Cdk2.cyclin A complex enhances the phosphatase activity of KAP, dissociates cyclin A, and facilitates KAP dephosphorylation of Cdk2". J. Biol. Chem. 280 (17): 17235–42. doi:10.1074/jbc.M413437200. PMID 15671017.
• Hsieh MJ, Yao YL, Lai IL, Yang WM (2006). "Transcriptional repression activity of PAX3 is modulated by competition between corepressor KAP1 and heterochromatin protein 1". Biochem. Biophys. Res. Commun. 349 (2): 573–81. doi:10.1016/j.bbrc.2006.08.064. PMID 16945326.
• Okamoto K, Kitabayashi I, Taya Y (2006). "KAP1 dictates p53 response induced by chemotherapeutic agents via Mdm2 interaction". Biochem. Biophys. Res. Commun. 351 (1): 216–22. doi:10.1016/j.bbrc.2006.10.022. PMID 17056014.

External links

• CDKN3 human gene location in the UCSC Genome Browser.
• CDKN3 human gene details in the UCSC Genome Browser.