CDK2AP1

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

CDK2AP1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2KW6
Identifiers
Aliases	CDK2AP1, DOC1, DORC1, ST19, doc-1, p12DOC-1, cyclin-dependent kinase 2 associated protein 1, cyclin dependent kinase 2 associated protein 1
External IDs	OMIM: 602198; MGI: 1202069; HomoloGene: 3411; GeneCards: CDK2AP1; OMA:CDK2AP1 - orthologs
Gene location (Human) Chr. Chromosome 12 (human) Band 12q24.31 Start 123,250,112 bp End 123,272,334 bp
Gene location (Mouse) Chr. Chromosome 5 (mouse) Band 5|5 F Start 124,483,480 bp End 124,501,145 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in parotid gland tibia spinal cord C1 segment ganglionic eminence internal globus pallidus superior vestibular nucleus ventricular zone inferior ganglion of vagus nerve dorsal motor nucleus of vagus nerve Top expressed in genital tubercle tail of embryo ganglionic eminence ventricular zone epiblast morula islet of Langerhans quadriceps femoris muscle adrenal gland lip More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding DNA polymerase binding Cellular component perinuclear region of cytoplasm nucleus nucleoplasm cytosol Biological process DNA-dependent DNA replication cell cycle positive regulation of protein phosphorylation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8099 13445 Ensembl ENSG00000111328 ENSMUSG00000029394 UniProt O14519 O35207 RefSeq (mRNA) NM_001270433 NM_001270434 NM_004642 NM_013812 RefSeq (protein) NP_001257362 NP_001257363 NP_004633 NP_038840 Location (UCSC) Chr 12: 123.25 – 123.27 Mb Chr 5: 124.48 – 124.5 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

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.

Interactions

CDK2AP1 has been shown to interact with Cyclin-dependent kinase 2.

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

External links

• Human CDK2AP1 genome location and CDK2AP1 gene details page in the UCSC Genome Browser.

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. S2CID 24498031.
• 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. S2CID 2905417.
• 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. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
• 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.