NCBI Summary:
Calpains are calcium-dependent cysteine proteases involved in signal transduction in a variety of cellular processes. A functional calpain protein consists of an invariant small subunit and 1 of a family of large subunits. CAPN5 is one of the large subunits. Unlike some of the calpains, CAPN5 and CAPN6 lack a calmodulin-like domain IV. Because of the significant similarity to Caenorhabditis elegans sex determination gene tra-3, CAPN5 is also called as HTRA3. [provided by RefSeq, Jul 2008]
General function
Peptidase/Protease
Comment
Cellular localization
Cytoplasmic
Comment
candidate123
Ovarian function
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Expression regulated by
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Ovarian localization
Granulosa, Theca
Comment
HTRA3 expression in non-pregnant rhesus monkey ovary and endometrium, and at the maternal-fetal interface during early pregnancy. Bowden MA et al. ABSTRACT: BACKGROUND: HTRA3 is a recently identified member of the mammalian serine protease family HTRA (high temperature requirement factor A). In both the rodent and the human HTRA3 is transcribed into two mRNA species (long and short) through alternative splicing. We have previously shown that HTRA3 is expressed in the mature rat ovary and may be involved in folliculogenesis and luteinisation. HTRA3 is also upregulated during mouse and human placental development. The current study investigated whether HTRA3 is also localised in the primate ovary (rhesus monkey n = 7). In addition, we examined the non-pregnant rhesus monkey endometrium (n = 4) and maternal-fetal interface during early pregnancy (n = 5) to further investigate expression of HTRA3 in primate endometrium and placentation. METHODS: HTRA3 mRNA levels in several rhesus monkey tissues was determined by semiquantitative RT-PCR. Protein expression and localisation of HTRA3 was determined by immunohistochemistry. RESULTS: Long and short forms of HTRA3 mRNA were detected in the ovary, aorta, bladder, small intestine, skeletal muscle, heart and uterus but not the liver nor the kidney. HTRA3 protein was immunolocalised to the oocyte of all follicular stages in the rhesus monkey ovary. Protein expression in mural and cumulus granulosa cells of late secondary follicles increased significantly compared to granulosa cells of primordial, primary and secondary follicles. Mural and cumulus granulosa cells of antral follicles also showed a significant increase in expression. Staining intensity was higher in the granulosa-lutein cells compared to the theca-lutein cells of corpora lutea (n = 3). In the non-pregnant monkey endometrium, HTRA3 was detected in the glandular epithelium. The basalis endometrial glands showed higher staining intensity than functionalis endometrial glands. During early pregnancy, strong staining for HTRA3 protein was seen in both maternal decidual cells and glands. CONCLUSION: We propose that HTRA3 may be involved in folliculogenesis and luteinisation in the primate ovary. Furthermore, similar to previous findings in the human, HTRA3 is possibly a factor involved in and potentially important for primate placentation.
Follicle stages
Secondary, Antral, Preovulatory, Corpus luteum
Comment
Evolutionary conservation of mammalian HTRA3 and its developmental regulation in the rat ovary. Bowden M et al. The high-temperature requirement factor A (HtrA) family of serine proteases is evolutionarily conserved from bacteria to mammals. We have previously identified Htra3 in the mouse and human (HTRA3) and reported its expression in the ovary. In this study, we analyzed the rat Htra3 gene and determined its developmental regulation in the rat ovary. We localized the rat Htra3 gene on chromosome 14q21 and identified two alternatively spliced mRNA variants. The two protein sequences deduced from these mRNAs enabled the prediction of the domain organization of the two protein isoforms. Our comparative analysis has established that the key gene features of Htra3 including its genomic structure, intron-exon junction and alternative splicing are well conserved among the mouse, rat and human. The similarities are even higher at the levels of primary protein sequence and protein domain architecture, suggesting that the functions of Htra3 are highly conserved during evolution from rodents to primates. We demonstrate that Htra3 expression in the rat ovary is developmentally regulated; expression was initiated on day 12 after birth and up-regulated during ovarian maturation with the highest levels found in the mature cycling ovary. In the mature ovary, Htra3 was expressed in granulosa cells, in a follicle-stage specific manner, with the level of expression being dependent on the positioning of the granulosa cells relative to the oocyte in late stage follicles. The luteinizing granulosa cells of the corpus luteum expressed the highest levels of Htra3. Collectively, these results suggest an important role for Htra3 in ovarian development, granulosa cell differentiation and luteinization. J. Exp. Zool. (Mol. Dev. Evol.) 312B, 2009. (c) 2009 Wiley-Liss, Inc.
Phenotypes
PCO (polycystic ovarian syndrome)
Mutations
1 mutations
Species: human
Mutation name: None
type: naturally occurring fertility: subfertile Comment: Specific haplotypes of the CALPAIN-5 gene are associated with polycystic ovary syndromeGonzalez A, et al .
BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. The aim of the present study was to investigate the role of CALPAIN-5 (CAPN5) gene in PCOS susceptibility. METHODS: We analysed four intronic polymorphisms of the CAPN5 gene in 148 well-characterized women with PCOS and 606 unrelated controls. We performed a case-control study and an intracohort analysis of clinical characteristics associated with PCOS. RESULTS: Analysis of haplotypes distribution between PCOS population compared to controls showed a strong deviation (P = 0.00029). The haplotypes GGCA and GGTG were overrepresented in PCOS patients (P = 0.009 and P = 0.001, respectively). In addition, we identified several CAPN5 haplotypes associated with phenotypic differences observed between PCOS patients, such as the presence of obesity (P = 0.02), cardiovascular complications (P = 0.02), familial antecedents of obesity (P = 0.003) and of hypertension (P = 0.007) and type 2 diabetes mellitus aggregation (P = 0.04). CONCLUSIONS: These results suggest a role of CAPN5 gene in PCOS susceptibility in humans. Moreover, novel candidate risk alleles have been identified, within CAPN5 gene, which could be associated with important phenotypic and prognosis differences observed in PCOS patients.