Alternative titles; symbols
HGNC Approved Gene Symbol: ADAM2
Cytogenetic location: 8p11.22 Genomic coordinates (GRCh38): 8:39,743,735-39,838,227 (from NCBI)
The ADAMs (a disintegrin and metalloprotease domain) are a family of type I transmembrane glycoproteins that share homology with snake venom metalloprotease/disintegrins and sperm surface proteins. They are important in diverse biologic processes such as cell adhesion and proteolytic shedding of cell surface receptors. Structurally, ADAMs consist of a prodomain that blocks protease activity; a zinc-binding metalloprotease domain; disintegrin and cysteine-rich domains with adhesion activity; an epidermal growth factor (EGF 131530)-like domain with cell fusion activity; a transmembrane domain; and a phosphorylated cytoplasmic regulatory domain. For a review of the ADAM gene family, see Primakoff and Myles (2000).
Gupta et al. (1996) cloned human fertilin-beta (ADAM2). Using a guinea pig fertilin-beta cDNA as a probe to screen a human testis cDNA library, they obtained the 5-prime end of the human fertilin-beta cDNA using RACE PCR. The complete human fertilin-beta cDNA contains an open reading frame of 2,199 bp and a 380-bp 3-prime untranslated region. Gupta et al. (1996) compared the sequence of human fertilin-beta to related proteins and found metalloprotease, disintegrin, cysteine-rich, EGF-like repeat and transmembrane domains, a structural organization consistent with other members of the metalloprotease/disintegrin family. The amino acid sequence of the mature human fertilin-beta is 90% identical to monkey fertilin and 56 to 59% identical to mature mouse and guinea pig fertilin-betas. Gupta et al. (1996) performed Northern blot analysis of human fertilin-beta which detected a 3.2-kb transcript only in testis RNA, suggesting that human fertilin-beta may be specific to the testis.
Independently, Burkin et al. (1997) cloned a human FTNB cDNA. They stated that the cDNA encodes a predicted 735-amino acid precursor protein from which the signal sequence (amino acids 1 to 16) and metalloprotease domain (amino acids 17 to 382) are cleaved during maturation.
Gupta et al. (1996) stated that most snake venom disintegrins contain the consensus integrin-binding sequence RGD. They noted that guinea pig, mouse, monkey, and human fertilin-betas contain tripeptide sequences TDE, QDE, FDE, and FEE at this location, respectively. These tripeptides are believed to mediate interaction with an integrin on the surface of the egg and thus mediate sperm/egg binding.
Burkin et al. (1997) used fluorescence in situ hybridization to map the FTNB gene to 8p11.2. They stated that the mouse Ftnb gene maps to chromosome 14, in a region that is syntenic with human 8p11.2.
Cho et al. (1998) did fertilin-beta knockout experiments in mice and analyzed sperm function in fertilin-beta -/- sperm. They found that these sperm were defective in sperm-egg membrane adhesion, sperm-egg fusion, migration from the uterus into the oviduct, and binding to the egg zona pellucida. Egg activation was unaffected. The results were consistent with the direct role of fertilin in sperm-egg plasma membrane interaction.
Ikawa et al. (2001) noted that the infertility and sperm characteristics of calmegin (CLGN; 601858)-null mice were similar to those of fertilin-beta-null mice. Using immunoprecipitation techniques, they found that Clgn bound to the sperm membrane proteins, fertilin-alpha 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.
Two human ADAM genes, ADAM3A and ADAM3B, cloned and designated cyritestin-1 (CYRN1) and cyritestin-2 (CYRN2) by Adham et al. (1998), were determined to be nonfunctional pseudogenes by Grzmil et al. (2001).
Adham, I. M., Kim, Y., Shamsadin, R., Heinlein, U. A. O., Von Beust, G., Mattei, M.-G., Engel, W. Molecular cloning, chromosomal localization, and expression analysis of CYRN1 and CYRN2, two human genes coding for cyritestin, a sperm protein involved in gamete interaction. DNA Cell Biol. 17: 161-168, 1998. [PubMed: 9502432] [Full Text: https://doi.org/10.1089/dna.1998.17.161]
Burkin, H. R., Burkin, D. J., Davey, P. M., Griffin, D. K., Affara, N. A. Mapping, sequence, and expression analysis of the human fertilin beta gene (FTNB). Genomics 40: 190-192, 1997. [PubMed: 9070941] [Full Text: https://doi.org/10.1006/geno.1996.4531]
Cho, C., Bunch, D. O., Faure, J.-E., Goulding, E. H., Eddy, E. M., Primakoff, P., Myles, D. G. Fertilization defects in sperm from mice lacking fertilin beta. Science 281: 1857-1859, 1998. [PubMed: 9743500] [Full Text: https://doi.org/10.1126/science.281.5384.1857]
Grzmil, P., Kim, Y., Shamsadin, R., Neesen, J., Adham, I. M., Heinlein, U. A. O., Schwarzer, U. J., Engel, W. Human cyritestin genes (CYRN1 and CYRN2) are non-functional. Biochem. J. 357: 551-556, 2001. [PubMed: 11439107] [Full Text: https://doi.org/10.1042/0264-6021:3570551]
Gupta, S. K., Alves, K., O'Neil Palladino, L., Mark, G. E., Hollis, G. F. Molecular cloning of the human fertilin beta subunit. Biochem. Biophys. Res. Commun. 224: 318-326, 1996. [PubMed: 8702389] [Full Text: https://doi.org/10.1006/bbrc.1996.1027]
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]
Primakoff, P., Myles, D. G. The ADAM gene family: surface proteins with adhesion and protease activity. Trends Genet. 16: 83-87, 2000. [PubMed: 10652535] [Full Text: https://doi.org/10.1016/s0168-9525(99)01926-5]