HGNC Approved Gene Symbol: CLGN
Cytogenetic location: 4q31.1 Genomic coordinates (GRCh38): 4:140,388,453-140,427,648 (from NCBI)
The proper folding of newly synthesized membrane proteins in the endoplasmic reticulum (ER) is required for the formation of functional mature proteins. Calmegin is similar to calnexin (114217), a ubiquitous ER chaperone that plays a major role in quality control by retaining incompletely folded or misfolded proteins. In contrast to other known chaperones, such as heat shock proteins (see 140550) and calreticulin (109091), calnexin is an integral membrane protein (Ikawa et al., 1997).
Watanabe et al. (1994) cloned mouse calmegin. Calmegin is a 611-amino acid, testis-specific ER protein.
Tanaka et al. (1997) cloned human CLGN by PCR of human testis total RNA. The deduced 610-amino acid protein contains several conserved regions, including an N-terminal hydrophobic signal peptide, 2 sets of internal repetitive sequences, and a hydrophilic C terminus with a transmembrane domain and an ER retention signal. CLGN shares 80% identity with mouse calmegin. Northern blot analysis of multiple tissues revealed expression of a 3.0-kb transcript only in testis. Western blot analysis of mouse, rat, and human testis showed a single band with an apparent molecular mass of 93 kD.
By FISH, Tanaka et al. (1997) mapped the CLGN gene to chromosome 4q28.3-q31.1.
Ikawa et al. (1997) showed that mouse calmegin binds to nascent polypeptides during spermatogenesis and analyzed its physiologic function by targeted disruption of its gene. Homozygous-null male mice were shown to be nearly sterile even though spermatogenesis was morphologically normal and mating was normal. In vitro, sperm from homozygous-null males did not adhere to the egg extracellular matrix (zona pellucida), and Ikawa et al. (1997) speculated that this defect may explain the observed infertility. These results suggested that calmegin functions as a chaperone for 1 or more sperm surface proteins that mediate the interactions between sperm and egg. The defective zona pellucida adhesion phenotype of sperm from calmegin-deficient mice was reminiscent of certain cases of unexplained infertility in human males.
Ikawa et al. (2001) noted that the infertility and sperm characteristics of Clgn-null mice were similar to those of fertilin-beta (ADAM2; 601533)-null mice. Using immunoprecipitation techniques, they found that Clgn bound to the sperm membrane proteins, fertilin-alpha (see 603712) and -beta. In the Clgn-null mice, heterodimerization between fertilin-alpha and -beta was not observed, and fertilin-beta was not detected in mature sperm.
Ikawa, M., Nakanishi, T., Yamada, S., Wada, I., Kominami, K., Tanaka, H., Nozaki, M., Nishimune, Y., Okabe, M. Calmegin is required for fertilin alpha/beta heterodimerization and sperm fertility. Dev. Biol. 240: 254-261, 2001. [PubMed: 11784061] [Full Text: https://doi.org/10.1006/dbio.2001.0462]
Ikawa, M., Wada, I., Kominami, K., Watanabe, D., Toshimori, K., Nishimune, Y., Okabe, M. The putative chaperone calmegin is required for sperm fertility. Nature 387: 607-611, 1997. [PubMed: 9177349] [Full Text: https://doi.org/10.1038/42484]
Tanaka, H., Ikawa, M., Tsuchida, J., Nozaki, M., Suzuki, M., Fujiwara, T., Okabe, M., Nishimune, Y. Cloning and characterization of the human calmegin gene encoding putative testis-specific chaperone. Gene 204: 159-163, 1997. [PubMed: 9434179] [Full Text: https://doi.org/10.1016/s0378-1119(97)00537-4]
Watanabe, D., Yamada, K., Nishina, Y., Tajima, Y., Koshimizu, U., Nagata, A., Nishimune, Y. Molecular cloning of a novel Ca(2+)-binding protein (calmegin) specifically expressed during male meiotic germ cell development. J. Biol. Chem. 269: 7744-7749, 1994. [PubMed: 8126001]