SIL1

This gene encodes a resident endoplasmic reticulum (ER), N-linked glycoprotein with an N-terminal ER targeting sequence, 2 putative N-glycosylation sites, and a C-terminal ER retention signal. This protein functions as a nucleotide exchange factor for another unfolded protein response protein. Mutations in this gene have been associated with Marinesco-Sjogren syndrome. Alternate transcriptional splice variants have been characterized.

Full Name

SIL1 Nucleotide Exchange Factor

Function

Required for protein translocation and folding in the endoplasmic reticulum (ER). Functions as a nucleotide exchange factor for the ER lumenal chaperone HSPA5.

Biological Process

Biological Process cotranslational protein targeting to membraneISS:FlyBase
Biological Process intracellular protein transport1 PublicationNAS:UniProtKB
Biological Process protein folding1 PublicationNAS:UniProtKB

Cellular Location

Endoplasmic reticulum lumen

Involvement in disease

Marinesco-Sjoegren syndrome (MSS):
Autosomal recessive multisystem disorder which is characterized by cerebellar ataxia due to cerebellar atrophy, with Purkinje and granule cell loss and myopathy featuring marked muscle replacement with fat and connective tissue. Other cardinal features include bilateral cataracts, hypergonadotrophic hypogonadism and mild to severe intellectual disability. Skeletal abnormalities, short stature, dysarthria, strabismus and nystagmus are also frequent findings. Mutational inactivation of this protein may result in ER stress-induced cell death signaling or malfunctioning chaperone machineries that mishandle client proteins which are critical for the organs targeted in MSS.

PTM

N-glycosylated.
Ubiquitinated by the CRL2(FEM1A) and CRL2(FEM1C) complexes, which recognize the -Lys-Xaa-Xaa-Arg C-degron at the C-terminus, leading to its degradation.