Mutations within a furin consensus sequence block proteolytic release of ectodysplasin-A and cause X-linked hypohidrotic ectodermal dysplasia.

ABSTRACT: X-linked hypohidrotic ectodermal dysplasia (XLHED) is a heritable disorder of the ED-1 gene disrupting the morphogenesis of ectodermal structures. The ED-1 gene product, ectodysplasin-A (EDA), is a tumor necrosis factor (TNF) family member and is synthesized as a membrane-anchored precursor protein with the TNF core motif located in the C-terminal domain. The stalk region of EDA contains the sequence -Arg-Val-Arg-Arg156-Asn-Lys-Arg159-, representing overlapping consensus cleavage sites (Arg-X-Lys/Arg-Arg( downward arrow)) for the proprotein convertase furin. Missense mutations in four of the five basic residues within this sequence account for approximately 20% of all known XLHED cases, with mutations occurring most frequently at Arg156, which is shared by the two consensus furin sites. Th

SUBMITTER: Chen Y 

PROVIDER: S-EPMC34649 | biostudies-literature | 2001 Jun

REPOSITORIES: biostudies-literature