Gram domain containing 1a
GRAM domain containing 1A also known as Aster-A is a protein that is encoded by the GRAMD1A gene. [5][6] It contains a transmembrane region, a GRAM domain and a VASt domain that can bind cholesterol.[7][8] GRAMD1A has four paralogs: GRAMD1B and GRAMD1C and two without VASt domains, GRAMD2A and GRAMD2B. These proteins are mammalian representatives of the yeast lipid transfer proteins anchored at a membrane contact site (LAM) family.[7]
| GRAMD1A | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | GRAMD1A, KIAA1533, GRAM domain containing 1A, Aster-A | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | MGI: 105490 HomoloGene: 10843 GeneCards: GRAMD1A | ||||||||||||||||||||||||||||||||||||||||||||||||||
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The protein is expressed ubiquitously with higher levels in the central nervous system.[9]
Function
GRAMD1A localizes to the endoplasmic reticulum.[7] Its GRAM domain tethers it to the plasma membrane where it can bind phosphatidylinositol phosphate in areas enriched for it.[7][10]
When the plasma membrane contains high levels of cholesterol, GRAMD1a like GRAMD1b and GRAMD1c moves to sites of contact between the plasma membrane and the endoplasmic reticulum.[8] The VASt domain of GRAMD1A then binds cholesterol and cholesterol is moved from the plasma membrane to the endoplasmic reticulum.[8][11] The VASt domain is responsible for binding cholesterol while the GRAM domain determines the location of the protein through sensing of cholesterol and binding partially negatively charged lipids in the plasma membrane, especially phosphatidylserine.[8][12]
GRAMD1A also is necessary for autophagosome biogenesis.[11]
References
- GRCh38: Ensembl release 89: ENSG00000089351 - Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000001248 - Ensembl, May 2017
- "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Entrez Gene: GRAM domain containing 1A". Retrieved 2017-09-15.
- "UniProtKB - Q8VEF1 (ASTRA_MOUSE)". Retrieved March 6, 2020.
- Besprozvannaya M, Dickson E, Li H, Ginburg KS, Bers DM, Auwerx J, Nunnari J (February 2018). "GRAM domain proteins specialize functionally distinct ER-PM contact sites in human cells". eLife. 22 (7): e31019. doi:10.7554/eLife.31019. PMC 5823543. PMID 29469807.
- Sandhu J, Li S, Fairall L, Pfisterer SG, Gurnett JE, Xiao X, Weston TA, Vashi D, Ferrari A, Orozco JL, Hartman CL, Strugatsky D, Lee SD, He C, Hong C, Jiang H, Bentolila LA, Gatta AT, Levine TP, Ferng A, Lee R, Ford DA, Young SG, Ikonen E, Schwabe JW, Tontonoz P (October 2018). "Aster Proteins Facilitate Nonvesicular Plasma Membrane to ER Cholesterol Transport in Mammalian Cells". Cell. 175 (2): 514–529.e20. doi:10.1016/j.cell.2018.08.033. PMC 6469685. PMID 30220461.
- Naito T, Saheki Y (August 2021). "GRAMD1-mediated accessible cholesterol sensing and transport". Biochim Biophys Acta Mol Cell Biol Lipids. 1866 (8): 158957. doi:10.1016/j.bbalip.2021.158957. PMID 33932585. S2CID 233477388.
- Wu YW, Waldmann H (December 2019). "Toward the role of cholesterol and cholesterol transfer protein in autophagosome biogenesis". Autophagy. 15 (12): 2167–2168. doi:10.1080/15548627.2019.1666595. PMC 6844521. PMID 31512558.
- Laraia L, Friese A, Corkery DP, Konstantinidis G, Erwin N, Hofer W, Karatas H, Klewer L, Brockmeyer A, Metz M, Schölermann B, Dwivedi M, Li L, Rios-Munoz P, Köhn M, Winter R, Vetter IR, Ziegler S, Janning P, Wu YW, Waldmann H (July 2019). "The cholesterol transfer protein GRAMD1A regulates autophagosome biogenesis" (PDF). Nat. Chem. Biol. 15 (7): 710–720. doi:10.1038/s41589-019-0307-5. PMID 31222192. S2CID 195191486.
- Ercan B, Naito T, Hong D, Koh Z, Dharmawan D, Saheki Y (19 February 2021). "Molecular basis of accessible plasma membrane cholesterol recognition by the GRAM domain of GRAMD1b". The EMBO Journal. 40 (6): e106524. doi:10.15252/embj.2020106524. PMC 7957428. PMID 33604931.