| Structural highlights
Disease
SAR1B_HUMAN Chylomicron retention disease. The disease is caused by variants affecting the gene represented in this entry.
Function
SAR1B_HUMAN 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).[1] [2] [3] [4] [5]
References
- ↑ Cutrona MB, Beznoussenko GV, Fusella A, Martella O, Moral P, Mironov AA. Silencing of mammalian Sar1 isoforms reveals COPII-independent protein sorting and transport. Traffic. 2013 Jun;14(6):691-708. PMID:23433038 doi:10.1111/tra.12060
- ↑ Melville DB, Studer S, Schekman R. Small sequence variations between two mammalian paralogs of the small GTPase SAR1 underlie functional differences in coat protein complex II assembly. J Biol Chem. 2020 Jun 19;295(25):8401-8412. PMID:32358066 doi:10.1074/jbc.RA120.012964
- ↑ Wang X, Wang H, Xu B, Huang D, Nie C, Pu L, Zajac GJM, Yan H, Zhao J, Shi F, Emmer BT, Lu J, Wang R, Dong X, Dai J, Zhou W, Wang C, Gao G, Wang Y, Willer C, Lu X, Zhu Y, Chen XW. Receptor-Mediated ER Export of Lipoproteins Controls Lipid Homeostasis in Mice and Humans. Cell Metab. 2021 Feb 2;33(2):350-366.e7. doi: 10.1016/j.cmet.2020.10.020. Epub , 2020 Nov 12. PMID:33186557 doi:https://dx.doi.org/10.1016/j.cmet.2020.10.020
- ↑ Chen J, Ou Y, Luo R, Wang J, Wang D, Guan J, Li Y, Xia P, Chen PR, Liu Y. SAR1B senses leucine levels to regulate mTORC1 signalling. Nature. 2021 Aug;596(7871):281-284. PMID:34290409 doi:10.1038/s41586-021-03768-w
- ↑ Huang Q, Szebenyi DME. The alarmone ppGpp selectively inhibits the isoform A of the human small GTPase Sar1. Proteins. 2022 Nov 11. doi: 10.1002/prot.26445. PMID:36369712 doi:https://dx.doi.org/10.1002/prot.26445
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