Espin dating site
Espin and small espin share a 167-amino acid C-terminal peptide that includes a 116-amino acid C-terminal actin-bundling module that is necessary and sufficient for actin bundle formation in vitro; however, they contain different N termini. PCR analysis of human fetal inner ear c DNA revealed expression of ESPN in the inner ear.
ESPN expression constructs lacking either one or both of the actin-binding sites were unable to crosslink actin filaments when transfected into BHK fibroblasts. (1999) confirmed that mouse espin and small espin are splice variants of a single gene.
The tissues of jerker mice did not accumulate espin proteins but contained normal levels of espin m RNAs.
In a small Italian kindred in which 2 affected individuals in 2 generations showed autosomal dominant progressive sensorineural hearing impairment (see 609006), 15930085, images] [Full Text]" pmid="15930085"Donaudy et al. (2006) found heterozygosity for a G-to-A transition at nucleotide 2230 of the ESPN gene that caused an asp744-to-asn amino acid substitution (D744N). Hearing loss was mainly high frequency, but some involvement was found at all frequencies. (2006) detected a sporadic 3-nucleotide deletion in the ESPN gene (2541-2543del AAG) leading to loss of lys848 in the C-terminal peptide (del K848).The results were consistent with a loss-of-function effect. (2006) reported 4 ESPN mutations in patients affected by autosomal dominant hearing loss without vestibular involvement (see 609006): S719R (606351.0003), D744N (606351.0004), R774Q (606351.0005), and K848del (606351.0006).To determine whether the mutated ESPN alleles affected the biologic activity of the corresponding espin proteins in vivo, their ability to target and elongate the parallel actin bundles of brush border microvilli was investigated in transfected epithelial cells.CO;2-I" target="_blank" onclick="ga('send', 'event', ' Outbound', ' Publisher')"Zheng et al.(2000) determined that espins are present in hair cell stereocilia and uncovered a connection between the espin gene and jerker mouse, a recessive mutation that causes hair cell degeneration, deafness, and vestibular dysfunction.(2006) detected an A-to-C transversion at nucleotide position 2155 in the ESPN gene that led to a substitution of arg for ser at codon 719 (S719R). The lys848 residue of the ESPN protein is highly conserved across species. (2008) identified a homozygous 1-bp insertion (1757ins G) in the ESPN gene, predicted to result in a frameshift and premature protein truncation.Hearing loss started in the second decade and led to mild to moderate hearing loss in the fourth decade. If translated, the mutant protein would lack the WH2 domain, which is important for binding actin monomers.In 2 consanguineous Pakistani families segregating recessively inherited deafness and vestibular areflexia (DFNB36; 609006), Naz et al.(2004) identified 2 different homozygous frameshift mutations in the ESPN gene (606351.0001-606351.0002). (2008) identified a homozygous mutation in the ESPN gene (606351.0007) in 6 affected members of a consanguineous Moroccan family with autosomal recessive deafness without vestibular involvement (609006).The 836-amino acid espin protein had a molecular mass of approximately 110 k D in SDS gels. The deduced 854-amino acid protein has 8 ankyrin-like repeats at the N terminus, 2 proline-rich regions, a consensus site for ATP or GTP binding (P loop), which is contained within an actin-binding WH2 motif, and a coiled coil domain.Northern blot analysis detected a 2.9-kb espin transcript only in rat testis; a minor 1.7-kb transcript was detected in small intestine and kidney. (1998) identified a 30-k D, 253-amino acid isoform of rat espin that localized to brush border microvilli in the intestine and kidney. (1999) determined that unlike many actin-bundling proteins, the rat espins bind actin filaments with high affinity, and their actin-bundling activities are not inhibited by calcium. The human protein shares 83% and 86% sequence identity with the mouse and rat homologs, respectively.