HGNC Approved Gene Symbol: IZUMO3
Cytogenetic location: 9p21.3 Genomic coordinates (GRCh38): 9:24,542,952-24,545,897 (from NCBI)
Members of the IZUMO family, such as IZUMO3, are expressed in sperm and have potential roles in sperm-egg fusion (Ellerman et al., 2009; Grayson and Civetta, 2012).
By searching for proteins homologous to IZUMO1 (609278), Ellerman et al. (2009) identified IZUMO2 (618895), IZUMO3, and IZUMO4 (618897) in human, mouse, and other mammals. All IZUMO proteins have a pattern of 8 conserved cysteines and a similar predicted secondary structure consisting of 4 alpha helices between the cysteine motifs. IZUMO1, IZUMO2, and IZUMO3 contain a transmembrane domain, but IZUMO4 lacks the transmembrane domain. Among mammals, IZUMO4 is the most conserved family member, and IZUMO1 is least conserved. EST database analysis indicated that expression of mouse Izumo2 and Izumo3 was restricted to adult testis, whereas mouse Izumo4 was expressed in a broader range of tissues, including testis. Western blot analysis detected nonphosphorylated and phosphorylated Izumo1 proteins with apparent molecular mass of 56 and 60 kD, respectively, on mature mouse sperm. Isoforms of 55 and 37 kD were detected for Izumo3, and isoforms of 50 and 43 kD were detected for Izumo4, likely corresponding to products of the 2 splice variants predicted for both of these genes. Izumo4 was likely an intraacrosomal protein of sperm, whereas Izumo1 and Izumo3 were expressed in sperm head, although some expression in sperm tail was possible.
Gross (2020) mapped the IZUMO3 gene to chromosome 9p21.3 based on an alignment of the IZUMO3 sequence (GenBank NM_001271706) with the genomic sequence (GRCh38).
Using electrophoresis and Western blot analysis, Ellerman et al. (2009) showed that Izumo1 formed several large complexes in mouse sperm, likely corresponding to homodimers, -trimers, and -tetramers. In contrast, Izumo3 and Izumo4 each formed single complexes, likely corresponding to homodimers. Further analysis showed that the N-terminal Izumo domain of Izumo1 and Izumo3 was responsible for dimer formation, and that a region between the transmembrane domain and cytoplasmic tail in Izumo1 was responsible for formation of larger complexes.
Ellerman, D. A., Pei, J., Gupta, S., Snell, W. J., Myles, D., Primakoff, P. Izumo is part of a multiprotein family whose members form large complexes on mammalian sperm. Molec. Reprod. Dev. 76: 1188-1199, 2009. [PubMed: 19658160] [Full Text: https://doi.org/10.1002/mrd.21092]
Grayson, P., Civetta, A. Positive selection and the evolution of izumo genes in mammals. Int. J. Evol. Biol. 2012: 958164, 2012. Note: Electronic Article. [PubMed: 22957301] [Full Text: https://doi.org/10.1155/2012/958164]
Gross, M. B. Personal Communication. Baltimore, Md. 5/27/2020.