SAR1B
Function
Small GTPase that cycles between an active GTP-bound and an inactive GDP-bound state and mainly functions in vesicle-mediated endoplasmic reticulum (ER) to Golgi transport. The active GTP-bound form inserts into the endoplasmic reticulum membrane where it recruits the remainder of the coat protein complex II/COPII (PubMed:23433038, PubMed:32358066, PubMed:33186557, PubMed:36369712). The coat protein complex II assembling and polymerizing on endoplasmic reticulum membrane is responsible for both the sorting of cargos and the deformation and budding of membranes into vesicles destined to the Golgi (PubMed:23433038, PubMed:32358066, PubMed:33186557). In contrast to SAR1A, SAR1B specifically interacts with the cargo receptor SURF4 to mediate the transport of lipid-carrying lipoproteins including APOB and APOA1 from the endoplasmic reticulum to the Golgi and thereby, indirectly regulates lipid homeostasis (PubMed:32358066, PubMed:33186557). In addition to its role in vesicle trafficking, can also function as a leucine sensor regulating TORC1 signaling and more indirectly cellular metabolism, growth and survival. In absence of leucine, interacts with the GATOR2 complex via MIOS and inhibits TORC1 signaling. The binding of leucine abrogates the interaction with GATOR2 and the inhibition of the TORC1 signaling. This function is completely independent of the GTPase activity of SAR1B (PubMed:34290409).
Involvement in disease
Chylomicron retention disease
CMRD
An autosomal recessive disorder of severe fat malabsorption associated with failure to thrive in infancy. The condition is characterized by deficiency of fat-soluble vitamins, low blood cholesterol levels, and a selective absence of chylomicrons from blood. Affected individuals accumulate chylomicron-like particles in membrane-bound compartments of enterocytes, which contain large cytosolic lipid droplets.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the small GTPase superfamily. SAR1 family.
Tissue Specificity
Expressed in many tissues including small intestine, liver, muscle and brain.
Cellular localization
- Endoplasmic reticulum membrane
- Peripheral membrane protein
- Golgi apparatus
- Golgi stack membrane
- Peripheral membrane protein
- Cytoplasm
- Cytosol
- Lysosome membrane
- Active at endoplasmic reticulum exit sites (ERES) where it inserts into the membrane and recruits the remainder of the coat protein complex II/COPII (PubMed:23433038). Upon leucine deprivation, associates with lysosomal membranes to repress TORC1 signaling (PubMed:34290409).
Alternative names
SARA2, SARB, SAR1B, Small COPII coat GTPase SAR1B, GTP-binding protein B, Secretion-associated Ras-related GTPase 1B, GTBPB