Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclin B3 evolution has the unique peculiarity of an abrupt 3-fold increase of the protein size in the mammalian lineage due to the extension of a single exon. We have analyzed the evolution of the gene to define the modalities of this event and the possible consequences on the function of the protein. Database searches can trace the appearance of the gene to the origin of metazoans. Most introns were already present in early metazoans, and the intron-exon structure as well as the protein size were fairly conserved in invertebrates and nonmammalian vertebrates. Although intron gains are considered as rare events, we identified two cases, one at the prochordate-chordate transition and one in murids, resulting from different mechanisms. At the emergence of mammals, the gene was relocated from chromosome 6 of platypus to the X chromosome in marsupials, but the exon extension occurred only in placental mammals. A repetitive structure of 18 amino acids, of uncertain origin, is detectable in the 3,000-nt mammalian exon-encoded sequence, suggesting an extension by multiple internal duplications, some of which are still detectable in the primate lineage. Structure prediction programs suggest that the repetitive structure has no associated three-dimensional structure but rather a tendency for disorder. Splice variant isoforms were detected in several mammalian species but without conserved pattern, notably excluding the constant coexistence of premammalian-like transcripts, without the extension. The yeast two-hybrid method revealed that, in human, the extension allowed new interactions with ten unrelated proteins, most of them with specific three-dimensional structures involved in protein-protein interactions, and some highly expressed in testis, as is cyclin B3. The interactions with activator of cAMP-responsive element modulator in testis (ACT), germ cell-less homolog 1, and chromosome 1 open reading frame 14 remain to be verified in vivo since they may not be expressed at the same stages of spermatogenesis as cyclin B3.
Mol Biol Evol 2012 Dec
PMID:Evolution of cyclin B3 shows an abrupt three-fold size increase, due to the extension of a single exon in placental mammals, allowing for new protein-protein interactions. 2282 62

Male subfertility due to falling sperm counts has become an increasing problem over a short timescale (50-70 years). Recently, bioinformatics analysis of the human testis proteome has revealed the existence of human-testicular-predominantly-expressed-proteins, which are highly associated with spermatogenesis, although the functions of many of these proteins are still unknown. To understand the function of one of these proteins, SHCBP1L (1700012A16RIKEN), a knockout mouse was produced in which this gene was removed. Using this model, we showed that SHCBP1L binds to another protein, HSPA2, and maintains stability of the spindle. We showed that this complex was not present in knockout mice and that an abnormal number of spermatocytes were held in the early stages of meiosis. Many of these cells were undergoing programmed cell-death, or apoptosis, which is highly unusual for cells during the early stages of meiosis. We also found that proteins very similar to SHCBP1L exist in many other mammals. This led us to propose that SHCBP1L plays an important role in spermatogenesis in mammals.
Mol Hum Reprod 2014 Jun
PMID:SHCBP1L, a conserved protein in mammals, is predominantly expressed in male germ cells and maintains spindle stability during meiosis in testis. 2455 41