PMID: 20473317

 

    Legend: Gene, Sites

Title : Mammal-restricted elements predispose human RET to folding impairment by HSCR mutations

Abstract :

1. The maturation of human RET is adversely affected by a range of missense mutations found in patients with Hirschsprung's disease (HSCR), a complex multigenic disease
2. Here we show that two N-terminal cadherin-like domains , CLD1 and CLD2 (CLD(1-2)), from human RET adopt a clam-shell arrangement distinct from that of classical cadherins
3. CLD1 structural elements and disulfide com position are unique to mammals, indicating an unexpected structural diversity within higher and lower vertebrate RET CLD regions
4. We identify two unpaired cysteines that predispose human RET to maturation impediments in the endoplasmic reticulum and establish a quantitative cell-based RET maturation assay that offers a biochemical correlate of HSCR disease severity
5. Our findings provide a key conceptual framework and means of testing and predicting genotype-phenotype correlations in HSCR

Output (sent_index, trigger, protein, sugar, site):

Output(Part-Of) (sent_index, protein, site):

• 2. RET, domains
• 3. RET, regions

*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

Protein	NCBI ID	SENTENCE INDEX
CLD1	9076	2,3
RET	5979	0,1,2,3,4