Cyclin A1

Cyclin-A1 is a protein that in humans is encoded by the CCNA1 gene.[5]

CCNA1
Identifiers
Aliases	CCNA1, CT146, Cyclin A1
External IDs	OMIM: 604036 MGI: 108042 HomoloGene: 31203 GeneCards: CCNA1
Gene location (Human) Chr. Chromosome 13 (human)[1] Band 13q13.3 Start 36,431,520 bp[1] End 36,442,870 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3|3 C Start 55,045,469 bp[2] End 55,055,501 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0001948 protein binding • protein kinase activity • cyclin-dependent protein serine/threonine kinase regulator activity • protein kinase binding Cellular component • microtubule cytoskeleton • cytosol • cell nucleus • nucleoplasm • cyclin A1-CDK2 complex • cyclin-dependent protein kinase holoenzyme complex • cytoplasm • cyclin A2-CDK2 complex Biological process • cell division • cell cycle • male meiosis I • regulation of transcription involved in G1/S transition of mitotic cell cycle • spermatogenesis • protein deubiquitination • regulation of cyclin-dependent protein serine/threonine kinase activity • GO:0007067 mitotic cell cycle • protein phosphorylation • regulation of mitotic nuclear division • positive regulation of cell proliferation • positive regulation of cell cycle • mitotic cell cycle phase transition Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	8900	12427
Ensembl	ENSG00000133101	ENSMUSG00000027793
UniProt	P78396	Q61456
RefSeq (mRNA)	NM_001111045 NM_001111046 NM_001111047 NM_003914	NM_007628 NM_001305221
RefSeq (protein)	NP_001104515 NP_001104516 NP_001104517 NP_003905	NP_001292150 NP_031654
Location (UCSC)	Chr 13: 36.43 – 36.44 Mb	Chr 3: 55.05 – 55.06 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell division cycle. Cyclins function as activating subunits of enzymatic complex together with cyclin-dependent kinases (CDKs). Different cyclins exhibit distinct expression and degradation patterns that contribute to the temporal coordination of cell cycle events. Cyclin A1 was shown to be expressed in testis and brain, as well as in several leukemic cell lines, and is thought to primarily function in the control of meiosis. This cyclin binds both Cdk1 and Cdk2 kinases, which give two distinct kinase activities, one appearing in S phase, the other in G2, and thus regulate separate functions in cell cycle. This cyclin was found to bind to important cell cycle regulators, such as Rb family proteins, transcription factor E2F1, and the Kip/Cip family of CDK-inhibitor proteins.[6]

Interactions

Cyclin-A1 interacts with:

• CDC20,[7]
• Cyclin-dependent kinase 2,[5][8][9][10]
• E2F1,[11]
• GNB2L1,[12]
• GPS2,[12]
• MYBL2,[9] and
• Retinoblastoma protein.[11]

References

1. GRCh38: Ensembl release 89: ENSG00000133101 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000027793 - 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.
5. Yang R, Morosetti R, Koeffler HP (March 1997). "Characterization of a second human cyclin A that is highly expressed in testis and in several leukemic cell lines". Cancer Res. 57 (5): 913–920. PMID 9041194.
6. "Entrez Gene: CCNA1 cyclin A1".
7. Ohtoshi A, Maeda T, Higashi H, Ashizawa S, Hatakeyama M (February 2000). "Human p55(CDC)/Cdc20 associates with cyclin A and is phosphorylated by the cyclin A-Cdk2 complex". Biochem. Biophys. Res. Commun. 268 (2): 530–534. doi:10.1006/bbrc.2000.2167. PMID 10679238.
8. Sweeney C, Murphy M, Kubelka M, Ravnik SE, Hawkins CF, Wolgemuth DJ, Carrington M (January 1996). "A distinct cyclin A is expressed in germ cells in the mouse". Development. 122 (1): 53–64. PMID 8565853.
9. Müller-Tidow C, Wang W, Idos GE, Diederichs S, Yang R, Readhead C, Berdel WE, Serve H, Saville M, Watson R, Koeffler HP (April 2001). "Cyclin A1 directly interacts with B-myb and cyclin A1/cdk2 phosphorylate B-myb at functionally important serine and threonine residues: tissue-specific regulation of B-myb function". Blood. 97 (7): 2091–2097. doi:10.1182/blood.v97.7.2091. PMID 11264176.
10. Brown NR, Noble ME, Endicott JA, Johnson LN (November 1999). "The structural basis for specificity of substrate and recruitment peptides for cyclin-dependent kinases". Nat. Cell Biol. 1 (7): 438–443. doi:10.1038/15674. PMID 10559988.
11. Yang R, Müller C, Huynh V, Fung YK, Yee AS, Koeffler HP (March 1999). "Functions of cyclin A1 in the cell cycle and its interactions with transcription factor E2F-1 and the Rb family of proteins". Mol. Cell. Biol. 19 (3): 2400–2407. doi:10.1128/mcb.19.3.2400. PMC 84032. PMID 10022926.
12. Diederichs S, Bäumer N, Ji P, Metzelder SK, Idos GE, Cauvet T, Wang W, Möller M, Pierschalski S, Gromoll J, Schrader MG, Koeffler HP, Berdel WE, Serve H, Müller-Tidow C (August 2004). "Identification of interaction partners and substrates of the cyclin A1-CDK2 complex". J. Biol. Chem. 279 (32): 33727–33741. doi:10.1074/jbc.M401708200. PMID 15159402.

Further reading

• Hall M, Bates S, Peters G (1995). "Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to cyclins". Oncogene. 11 (8): 1581–1588. PMID 7478582.
• Xu M, Sheppard KA, Peng CY, Yee AS, Piwnica-Worms H (1994). "Cyclin A/CDK2 binds directly to E2F-1 and inhibits the DNA-binding activity of E2F-1/DP-1 by phosphorylation". Mol. Cell. Biol. 14 (12): 8420–8431. doi:10.1128/MCB.14.12.8420. PMC 359381. PMID 7969176.
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• O'Connor PM, Ferris DK, Pagano M, Draetta G, Pines J, Hunter T, Longo DL, Kohn KW (1993). "G2 delay induced by nitrogen mustard in human cells affects cyclin A/cdk2 and cyclin B1/cdc2-kinase complexes differently". J. Biol. Chem. 268 (11): 8298–8308. PMID 8463339.
• Sweeney C, Murphy M, Kubelka M, Ravnik SE, Hawkins CF, Wolgemuth DJ, Carrington M (1996). "A distinct cyclin A is expressed in germ cells in the mouse". Development. 122 (1): 53–64. PMID 8565853.
• Wang H, Shao N, Ding QM, Cui J, Reddy ES, Rao VN (1997). "BRCA1 proteins are transported to the nucleus in the absence of serum and splice variants BRCA1a, BRCA1b are tyrosine phosphoproteins that associate with E2F, cyclins and cyclin dependent kinases". Oncogene. 15 (2): 143–157. doi:10.1038/sj.onc.1201252. PMID 9244350.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–156. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Liu D, Matzuk MM, Sung WK, Guo Q, Wang P, Wolgemuth DJ (1998). "Cyclin A1 is required for meiosis in the male mouse". Nat. Genet. 20 (4): 377–380. doi:10.1038/3855. PMID 9843212.
• Yang R, Müller C, Huynh V, Fung YK, Yee AS, Koeffler HP (1999). "Functions of cyclin A1 in the cell cycle and its interactions with transcription factor E2F-1 and the Rb family of proteins". Mol. Cell. Biol. 19 (3): 2400–2407. doi:10.1128/mcb.19.3.2400. PMC 84032. PMID 10022926.
• Ravnik SE, Wolgemuth DJ (1999). "Regulation of meiosis during mammalian spermatogenesis: the A-type cyclins and their associated cyclin-dependent kinases are differentially expressed in the germ-cell lineage". Dev. Biol. 207 (2): 408–418. doi:10.1006/dbio.1998.9156. PMID 10068472.
• Yang R, Nakamaki T, Lübbert M, Said J, Sakashita A, Freyaldenhoven BS, Spira S, Huynh V, Müller C, Koeffler HP (1999). "Cyclin A1 expression in leukemia and normal hematopoietic cells". Blood. 93 (6): 2067–2074. PMID 10068680.
• Müller C, Yang R, Beck-von-Peccoz L, Idos G, Verbeek W, Koeffler HP (1999). "Cloning of the cyclin A1 genomic structure and characterization of the promoter region. GC boxes are essential for cell cycle-regulated transcription of the cyclin A1 gene". J. Biol. Chem. 274 (16): 11220–11228. doi:10.1074/jbc.274.16.11220. PMID 10196209.
• Ruffner H, Jiang W, Craig AG, Hunter T, Verma IM (1999). "BRCA1 is phosphorylated at serine 1497 in vivo at a cyclin-dependent kinase 2 phosphorylation site". Mol. Cell. Biol. 19 (7): 4843–4854. doi:10.1128/MCB.19.7.4843. PMC 84283. PMID 10373534.
• Brown NR, Noble ME, Endicott JA, Johnson LN (1999). "The structural basis for specificity of substrate and recruitment peptides for cyclin-dependent kinases". Nat. Cell Biol. 1 (7): 438–443. doi:10.1038/15674. PMID 10559988.
• Liu D, Liao C, Wolgemuth DJ (2000). "A role for cyclin A1 in the activation of MPF and G2-M transition during meiosis of male germ cells in mice". Dev. Biol. 224 (2): 388–400. doi:10.1006/dbio.2000.9776. PMID 10926775.
• Hartley JL, Temple GF, Brasch MA (2000). "DNA cloning using in vitro site-specific recombination". Genome Res. 10 (11): 1788–1795. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
• Müller-Tidow C, Bornemann C, Diederichs S, Westermann A, Klümpen S, Zuo P, Wang W, Berdel WE, Serve H (2001). "Analyses of the genomic methylation status of the human cyclin A1 promoter by a novel real-time PCR-based methodology". FEBS Lett. 490 (1–2): 75–78. doi:10.1016/S0014-5793(01)02128-7. PMID 11172814.
• Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S (2000). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Rep. 1 (3): 287–292. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.
• Müller-Tidow C, Wang W, Idos GE, Diederichs S, Yang R, Readhead C, Berdel WE, Serve H, Saville M, Watson R, Koeffler HP (2001). "Cyclin A1 directly interacts with B-myb and cyclin A1/cdk2 phosphorylate B-myb at functionally important serine and threonine residues: tissue-specific regulation of B-myb function". Blood. 97 (7): 2091–2097. doi:10.1182/blood.V97.7.2091. PMID 11264176.