CDK2AP1

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)
End	123,272,334 bp
Gene location (Mouse)
Chr.	Chromosome 5 (mouse)
End	124,501,145 bp
RNA expression pattern
	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
	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
	8099
	13445
	ENSG00000111328
	ENSMUSG00000029394
	O14519
	O35207
	NM_001270433 ; NM_001270434 ; NM_004642
	NM_013812
	NP_001257362 ; NP_001257363 ; NP_004633
	NP_038840
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated October 14, 2024

Cyclin-dependent kinase 2-associated protein 1 is an enzyme that in humans is encoded by the CDK2AP1 gene.^[5]^[6]^[7]

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.^[7]

Interactions

CDK2AP1 has been shown to interact with Cyclin-dependent kinase 2.^[8]

It interacts with unnamed protein product (BC006130) which may mediate inhibitory effect of CDK2AP1 on cell proliferation.^[9]

Related Research Articles

Cyclin A is a member of the cyclin family, a group of proteins that function in regulating progression through the cell cycle. The stages that a cell passes through that culminate in its division and replication are collectively known as the cell cycle Since the successful division and replication of a cell is essential for its survival, the cell cycle is tightly regulated by several components to ensure the efficient and error-free progression through the cell cycle. One such regulatory component is cyclin A which plays a role in the regulation of two different cell cycle stages.

Cyclin E is a member of the cyclin family.

Cyclin-dependent kinase 2, also known as cell division protein kinase 2, or Cdk2, is an enzyme that in humans is encoded by the CDK2 gene. The protein encoded by this gene is a member of the cyclin-dependent kinase family of Ser/Thr protein kinases. This protein kinase is highly similar to the gene products of S. cerevisiae cdc28, and S. pombe cdc2, also known as Cdk1 in humans. It is a catalytic subunit of the cyclin-dependent kinase complex, whose activity is restricted to the G1-S phase of the cell cycle, where cells make proteins necessary for mitosis and replicate their DNA. This protein associates with and is regulated by the regulatory subunits of the complex including cyclin E or A. Cyclin E binds G1 phase Cdk2, which is required for the transition from G1 to S phase while binding with Cyclin A is required to progress through the S phase. Its activity is also regulated by phosphorylation. Multiple alternatively spliced variants and multiple transcription initiation sites of this gene have been reported. The role of this protein in G1-S transition has been recently questioned as cells lacking Cdk2 are reported to have no problem during this transition.

Cyclin-dependent kinase inhibitor 1B (p27^Kip1) is an enzyme inhibitor that in humans is encoded by the CDKN1B gene. It encodes a protein which belongs to the Cip/Kip family of cyclin dependent kinase (Cdk) inhibitor proteins. The encoded protein binds to and prevents the activation of cyclin E-CDK2 or cyclin D-CDK4 complexes, and thus controls the cell cycle progression at G1. It is often referred to as a cell cycle inhibitor protein because its major function is to stop or slow down the cell division cycle.

Transcription factor E2F1 is a protein that in humans is encoded by the E2F1 gene.

G1/S-specific cyclin-D2 is a protein that in humans is encoded by the CCND2 gene.

Myb-related protein B is a protein that in humans is encoded by the MYBL2 gene.

G1/S-specific cyclin-E1 is a protein that in humans is encoded by the CCNE1 gene.

Transcription factor E2F3 is a protein that in humans is encoded by the E2F3 gene.

Transcription factor E2F2 is a protein that in humans is encoded by the E2F2 gene.

Cyclin-A2 is a protein that in humans is encoded by the CCNA2 gene. It is one of the two types of cyclin A: cyclin A1 is expressed during meiosis and embryogenesis while cyclin A2 is expressed in the mitotic division of somatic cells.

Cyclin-dependent kinase 4 inhibitor B also known as multiple tumor suppressor 2 (MTS-2) or p15^INK4b is a protein that is encoded by the CDKN2B gene in humans.

Cyclin-dependent kinases regulatory subunit 1 is a protein that in humans is encoded by the CKS1B gene.

Cell division protein kinase 3 is an enzyme that in humans is encoded by the CDK3 gene.

Cyclin-dependent kinase inhibitor 3 is an enzyme that in humans is encoded by the CDKN3 gene.

Protein phosphatase 1B is an enzyme that in humans is encoded by the PPM1B gene.

G protein pathway suppressor 2 is a protein that in humans is encoded by the GPS2 gene.

Dual specificity protein phosphatase CDC14A is an enzyme that in humans is encoded by the CDC14A gene.

Histone H4 transcription factor is a protein that in humans is encoded by the HINFP gene.

The CIP/KIP family is one of two families of mammalian cyclin dependent kinase (CDK) inhibitors (CKIs) involved in regulating the cell cycle. The CIP/KIP family is made up of three proteins: p21^cip1/waf1, P27^kip1, p57^kip2 These proteins share sequence homology at the N-terminal domain which allows them to bind to both the cyclin and CDK. Their activity primarily involves the binding and inhibition of G1/S- and S-Cdks; however, they have also been shown to play an important role in activating the G1-CDKs CDK4 and CDK6. In addition, more recent work has shown that CIP/KIP family members have a number of CDK-independent roles involving regulation of transcription, apoptosis, and the cytoskeleton.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000111328 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000029394 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ 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. S2CID 9615947.
↑ 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.
1 2 "Entrez Gene: CDK2AP1 CDK2-associated protein 1".
↑ 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.
↑ 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". Mol Med Rep. 9 (1): 156–62. doi: 10.3892/mmr.2013.1801 . PMID 24248101.

External links

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

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.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000111328 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000029394 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid9331572-5] 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. S2CID 9615947.

[pmid9506968-6] 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.

[entrez-7] 1 2 "Entrez Gene: CDK2AP1 CDK2-associated protein 1".

[pmid10938106-8] 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.

[pmid24248101-9] 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". Mol Med Rep. 9 (1): 156–62. doi: 10.3892/mmr.2013.1801 . PMID 24248101.

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