Alternative titles; symbolsNONERYTHROID PROTEIN 4.1, GENERAL TYPE; 4.1GHGNC Approved Gene Symbol: EPB41L2Cytogenetic location: 6q23.1-q23.2 Genomic coordinat...
Alternative titles; symbols
HGNC Approved Gene Symbol: EPB41L2
Cytogenetic location: 6q23.1-q23.2 Genomic coordinates (GRCh38): 6:130,839,346-131,063,244 (from NCBI)
EPB41L2 is a member of the protein 4.1 family (see 607619). Members of this family function as adaptors linking transmembrane proteins to the cytoskeleton (summary by Yang et al., 2011).
▼ Cloning and Expression
Erythrocyte membrane protein 4.1 (EPB41; 130500) is a well-characterized cytoskeletal protein. Several nonerythroid protein 4.1 homologs have been identified, including ezrin (123900), radixin (179410), and moesin (309845). Parra et al. (1998) used EST database searches and PCR to identify and clone a novel protein 4.1 homolog, termed 4.1G. The longest assembled cDNA sequence encoded a 1,005-amino acid polypeptide. 4.1G has a high level of similarity to EPB41 in its membrane-binding domain, spectrin/actin-binding domain, and C terminus. Northern blot analysis detected wide 4.1G gene expression among human tissues, with most tissues exhibiting a prominent mRNA of approximately 5 kb. Expression of 4.1G in COS cells revealed diffuse cytoplasmic and more intense perinuclear localization, a staining pattern significantly different from that of EPB41.
By RT-PCR of mouse testis, Yang et al. (2011) identified 3 splice variants of 4.1G that differed from one another due to alternative splicing involving exons 16 through 18. None of the variants contained exons 14 and 15, and all downstream exons were spliced in-frame. Western blot analysis detected 4.1G expression in brain, lung, and testis, but not in liver, prostate, small intestine, kidney, or skeletal muscle. Multiple 4.1G bands were detected in lung and brain. Electron microscopy and immunofluorescence analysis of mouse testis revealed 4.1G expression along the membranes of seminiferous epithelium, where it colocalized with Necl4 (IGSF4C; 609744).
Parra et al. (1998) used fluorescence in situ hybridization to map the EPB41L2 gene to chromosome 6q22-q23.
▼ Gene Function
Using coimmunoprecipitation analysis, Yang et al. (2011) found that 4.1G and Necl4 interacted directly in mouse testis. Mutation analysis revealed that full-length 4.1G bound to the cytoplasmic domain of Necl4.
▼ Animal Model
Yang et al. (2011) found that 4.1G knockout had no effect on embryonic development, health, or fertility of C57BL/6 mice. However, 4.1G knockout caused male sterility in C57BL/6 and 129/Sv hybrid mice. 4.1G -/- hybrid mice showed reduced testis weight, with abnormal seminiferous epithelia, absence of Sertoli/germ cell contacts, and immature or degenerated spermatogenic cells. 4.1G -/- hybrid testis showed normal Necl4 mRNA content, but reduced Necl4 protein and lack of Necl4 expression at Sertoli cell membranes. Yang et al. (2011) concluded that 4.1G is required for Necl4 protein stability and formation of Sertoli/germ cell contacts.