CDK2AP1

Cyclin-dependent kinase 2 associated protein 1
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2KW6​
Identifiers
Symbols	CDK2AP1 ; DOC1; DORC1; ST19; doc-1; p12DOC-1
External IDs	OMIM: 602198 MGI: 1202069 HomoloGene: 3411 ChEMBL: 5578 GeneCards: CDK2AP1 Gene
Gene ontology Molecular function • protein binding • DNA polymerase binding Cellular component • nucleus • perinuclear region of cytoplasm Biological process • positive regulation of protein phosphorylation • DNA-dependent DNA replication • cell cycle Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8099	13445
Ensembl	ENSG00000111328	ENSMUSG00000029394
UniProt	O14519	O35207
RefSeq (mRNA)	NM_001270433	NM_013812
RefSeq (protein)	NP_001257362	NP_038840
Location (UCSC)	Chr 12: 123.26 – 123.27 Mb	Chr 5: 124.35 – 124.36 Mb
PubMed search

Cyclin-dependent kinase 2-associated protein 1 is an enzyme that in humans is encoded by the CDK2AP1 gene.^[1][2][3]

Function

The protein encoded by this gene is a specific CDK2-associated protein, which is thought to negatively regulate CDK2 activity by sequestering monomeric CDK2, and targeting CDK2 for proteolysis. This protein was found to also interact with DNA polymerase alpha/primase and mediate the phosphorylation of the large p180 subunit, which suggested the regulatory role in DNA replication during S phase of the cell cycle. A similar gene in hamster was isolated from, and functions as a growth suppressor of normal keratinocytes.^[3]

Interactions

CDK2AP1 has been shown to interact with Cyclin-dependent kinase 2.^[4]

It interacts with unnamed protein product (BC006130) which may mediate inhibitory effect of CDK2AP1 on cell proliferation. ^[5]

References

1. Daigo Y, Suzuki K, Maruyama O, Miyoshi Y, Yasuda T, Kabuto T, Imaoka S, Fujiwara T, Takahashi E, Fujino MA, Nakamura Y (November 1997). "Isolation, mapping and mutation analysis of a human cDNA homologous to the doc-1 gene of the Chinese hamster, a candidate tumor suppressor for oral cancer". Genes Chromosomes Cancer 20 (2): 204–7. doi:10.1002/(SICI)1098-2264(199710)20:2<204::AID-GCC12>3.0.CO;2-Q. PMID 9331572.
2. Tsuji T, Duh FM, Latif F, Popescu NC, Zimonjic DB, McBride J, Matsuo K, Ohyama H, Todd R, Nagata E, Terakado N, Sasaki A, Matsumura T, Lerman MI, Wong DT (April 1998). "Cloning, mapping, expression, function, and mutation analyses of the human ortholog of the hamster putative tumor suppressor gene Doc-1". J Biol Chem 273 (12): 6704–9. doi:10.1074/jbc.273.12.6704. PMID 9506968.
3. "Entrez Gene: CDK2AP1 CDK2-associated protein 1".
4. Shintani S, Ohyama H, Zhang X, McBride J, Matsuo K, Tsuji T, Hu MG, Hu G, Kohno Y, Lerman M, Todd R, Wong DT (September 2000). "p12DOC-1 Is a Novel Cyclin-Dependent Kinase 2-Associated Protein". Mol. Cell. Biol. 20 (17): 6300–7. doi:10.1128/MCB.20.17.6300-6307.2000. PMC 86104. PMID 10938106.
5. Liu L, Yang X, Ni Q, Xiao Z, Zhao Y, Han J, Sun M, Chen B (Jan 2014). "Interaction between p12CDK2AP1 and a novel unnamed protein product inhibits cell proliferation by regulating the cell cycle.". J Mol Med Rep 9 (1): 156–62. doi:10.3892/mmr.2013.1801. PMID 24248101.

Further reading

• Matsuo K, Shintani S, Tsuji T, Nagata E, Lerman M, McBride J, Nakahara Y, Ohyama H, Todd R, Wong DT (2000). "p12(DOC-1), a growth suppressor, associates with DNA polymerase alpha/primase". FASEB J. 14 (10): 1318–24. doi:10.1096/fj.14.10.1318. PMID 10877824.
• Shintani S, Ohyama H, Zhang X, McBride J, Matsuo K, Tsuji T, Hu MG, Hu G, Kohno Y, Lerman M, Todd R, Wong DT (2000). "p12DOC-1 Is a Novel Cyclin-Dependent Kinase 2-Associated Protein". Mol. Cell. Biol. 20 (17): 6300–7. doi:10.1128/MCB.20.17.6300-6307.2000. PMC 86104. PMID 10938106.
• Yuan Z, Sotsky Kent T, Weber TK (2003). "Differential expression of DOC-1 in microsatellite-unstable human colorectal cancer". Oncogene 22 (40): 6304–10. doi:10.1038/sj.onc.1206609. PMID 13679870.
• Hu MG, Hu GF, Kim Y, Tsuji T, McBride J, Hinds P, Wong DT (2004). "Role of p12(CDK2-AP1) in transforming growth factor-beta1-mediated growth suppression". Cancer Res. 64 (2): 490–9. doi:10.1158/0008-5472.CAN-03-2284. PMID 14744761.
• Buajeeb W, Zhang X, Ohyama H, Han D, Surarit R, Kim Y, Wong DT (2004). "Interaction of the CDK2-associated protein-1, p12(DOC-1/CDK2AP1), with its homolog, p14(DOC-1R)". Biochem. Biophys. Res. Commun. 315 (4): 998–1003. doi:10.1016/j.bbrc.2004.02.003. PMID 14985111.
• Kim Y, Ohyama H, Patel V, Figueiredo M, Wong DT (2005). "Mutation of Cys105 inhibits dimerization of p12CDK2-AP1 and its growth suppressor effect". J. Biol. Chem. 280 (24): 23273–9. doi:10.1074/jbc.M412929200. PMID 15840587.
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
• Peng H, Shintani S, Kim Y, Wong DT (2007). "Loss of p12CDK2-AP1 Expression in Human Oral Squamous Cell Carcinoma with Disrupted Transforming Growth Factor-β-Smad Signaling Pathway". Neoplasia 8 (12): 1028–36. doi:10.1593/neo.06580. PMC 1783720. PMID 17217620.
• Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein–protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
• Shin J, Yuan Z, Fordyce K, Sreeramoju P, Kent TS, Kim J, Wang V, Schneyer D, Weber TK (2007). "A del T poly T (8) mutation in the 3' untranslated region (UTR) of the CDK2-AP1 gene is functionally significant causing decreased mRNA stability resulting in decreased CDK2-AP1 expression in human microsatellite unstable (MSI) colorectal cancer (CRC)". Surgery 142 (2): 222–7. doi:10.1016/j.surg.2007.04.002. PMID 17689689.