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SIL1

Developmental stage

Expressed in fetal kidney, fetal lung, fetal liver and at low levels in fetal brain.

Function

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

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

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.

Sequence Similarities

Belongs to the SIL1 family.

Tissue Specificity

Highly expressed in tissues which produce large amounts of secreted proteins such as kidney, liver and placenta. Also expressed in colon, heart, lung, ovary, pancreas, peripheral leukocyte, prostate, spleen and thymus. Expressed at low levels throughout the brain.

Cellular localization

Alternative names

UNQ545/PRO836, SIL1, Nucleotide exchange factor SIL1, BiP-associated protein, BAP

swissprot:Q9H173 entrezGene:64374 omim:608005