A Member of Ⅱ Transmembrane Serine,TMPRSS3 and Hereditary Deafness
- VernacularTitle:跨膜丝氨酸蛋白酶TMPRSS3与遗传性耳聋
- Author:
Shenglei GE
;
Yan YI
;
Dinghua XIE
- Publication Type:Journal Article
- Keywords:
transmembrane protease, serine 3 (TMPRSS3), type Ⅱ transmembrane serine proteases (TTSPs), inner ear, substrate, signaling transduction pathway
- From:
Progress in Biochemistry and Biophysics
2006;0(08):-
- CountryChina
- Language:Chinese
-
Abstract:
TMPRSS3 (transmembrane protease, serine 3) is a member of Ⅱ transmembrane serine proteases (TTSPs), and like the other members of this family, it contains typical domains including a serine protease domain, a transmembrane domain, a LDL receptor-like domain (LDLRA), and a scavenger receptor cysteine-rich domain (SRCR). Four alternative protein isoforms have been described, and isoform A is thought to be primary isoform which is expressed in many tissues, especially in the cochlea. TMPRSS3 protein is primarily localized in the endoplasmic reticulum membranes where it may be anchored by its transmembrane domain. TMPRSS3 is mutated in non-syndromic autosomal recessive deafness (DFNB8/10). Therefore TMPRSS3 is thought to be involved in the development and maintenance of the inner ear, and isoform D may be proposed as a novel diagnostic marker in ovarian carcinoma. TMPRSS3 protein is the first protease which mutation could lead to deafness. These data indicate that important signaling pathways in the inner ear are controlled by proteolytic cleavage. However, it is not clear about TMPRSS3 substrates and its function. The epithelial amiloride-sensitive sodium channel (ENaC) which is regulated by membrane-bound channel activating serine proteases (CAPs), a member of TTSPs, may be a potential substrate of TMPRSS3, but this hypothesis is still to be verified in vivo. With the development of protease research and the application of protease proteomics, substrate degradomes of a protease may therefore represent an important tool for the research of TMPRSS3 function and its molecular mechanism.