The CCNA1 gene is located at chromosome 13q12.3-q13 (Yang et al., 1997) and made up of 9 exons and 8 introns that extend over ~ 13 kb (Müller et al., 1999).

2,1 kb mRNA; coding region is from 130 to 1527 bp (Yang et al., 1997). The cyclin A1 promoter does not possess a TATA box, whereas the region upstream of the transcriptional start site region contains four GC boxes, with multiple Sp1-binding sites important for the regulation of cyclin A1 expression (Müller et al., 1999). Three different transcript variants exist: isoform "a" is the longest transcript and encodes the longest isoform; isoform "b" has an alternate in-frame splice site in the 5 coding region resulting in a protein that is 1 amino acid shorter than isoform "a"; isoform "c" contains a distinct 5 UTR and lacks an in-frame portion of the 5 coding region, resulting in a 44 aa shorter N-terminus compared to isoform "a".

None described.

MW: 52 kDa. Amino acids (aa): 465 full-length isoform a (464 aa isoform b; 421 aa isoform c). Cyclin A1 is a member of the highly conserved cyclin family whose members are able to control the progression of cells through the cell cycle by activating cyclin-dependent kinases (CDKs). Within the protein the cyclin box is a region of protein sequence homology that is common to all members of the cyclin family and is required for interaction with the CDK partner.

Cyclin A1 expression is tissue-specific and high levels of expression are restricted to testis; a lower expression is reported in other human cell lines and in healthy brain. Cyclin A1 is also expressed in several myeloid leukemia cell lines and various other tumour types (Yang et al., 1997; Wegiel et al., 2008). Cyclin A1 is expressed at low levels in G0 phase and increases in early G1, S and G2/M phases (Yang et al., 1997; Yang et al., 1999).

Mammalian cyclin A1 is primarily localized in the nuclei of spermatocytes in mouse and human (Liu et al., 1998; Liao et al., 2004). Cyclin A1 has an important role in the development of acute myeloid leukemia (AML): its localization in normal hematopoietic cells is nuclear, whereas in leukemic cells from AML patients and cell lines, it is predominantly cytoplasmic (Ekberg et al., 2004).

Cyclin A1 belongs to the A-type cyclin family of proteins originally identified as 60 kDa polypeptides associated to CDK2 and interacting with viral proteins (Giordano et al., 1989; Giordano et al., 1991). Cyclin A family members are characterized by a typical periodicity in protein abundance through the cell division cycle functioning as activating subunits of enzymatic complexes, together with cyclin-dependent kinases (CDKs) (Lapenna and Giordano, 2009). Cyclin A2, also known as cyclin A, is the major A-type cyclin in mammals. Cyclin A1 primarily functions in the meiotic cell cycle, but it also seems to contribute to G1/S cell cycle progression in somatic cells (Ji et al., 2005). Human cyclin A1 interacts with CDK2 in vitro and in vivo (Yang et al., 1997) and the resulting complex is essential for spermatogenesis and contributes to leukemogenesis, although its molecular functions remain largely unclear. Male knockout mice lacking cyclin A1 are infertile owing to a cell cycle arrest before the first meiotic division (Liu et al., 1998). Cyclin A1 interacts also with E2F1 and the retinoblastoma protein (Yang et al., 1999), with GPS2 (Diederichs et al., 2004), binds to and activates B-MYB in leukemic blasts (Müller-Tidow et al., 2001). Moreover the cyclin A1-CDK2 complex regulates DNA double-strand break repair following radiation damage (Müller-Tidow et al., 2004) by competing with CDK2-cyclin A2 for the binding to Ku70, a pivotal player in the non-homologous end-joining double strand break repair pathway, and inhibiting apoptosis through modulating RB functions in leukemia cells (Ji et al., 2007). Consistently, cyclin A1 knockout mice and Xenopus embryos show defects in the DNA repair process and are more prone to undergo apoptosis (Müller-Tidow et al., 2004; Cho et al., 2006). Finally, following exposure to DNA damaging agents, cyclin A1 is strongly upregulated and localizes to the nucleus. Inhibition of this upregulation, through roscovitine treatment, resulted in a significant decrease of DNA repair and an increase of DNA damage over time (Federico et al., 2010).

The percentage of identity below represents identity over an aligned protein region using pairwise alignment function of ClustalW software:
Bos taurus: 87%
Rattus norvegicus: 85%
Mus musculus: 84%
Xenopus tropicalis: 60%
Xenopus laevis: 59%
Danio rerio: 53%

None.

Some mutations in the CCNA1 gene have been found in several tumor types. No insertions, nonsense substitutions or deletions have been described, whereas, some substitutions leading to missense (P50L in skin; A429V in stomach; C452Y in ovary) or silent mutations (Y107Y in stomach; L122L in lung; A391A in ovary) have been reported and were obtained from the Sanger Institute Catalogue Of Somatic Mutations In Cancer web site (Bamford et al., 2004).