GRAMD1C

GRAM domain containing 1C also known as Aster-C is a cholesterol transport protein that is encoded by the GRAMD1C gene.[3][4] It contains a transmembrane region, a GRAM domain and a VASt domain. It is anchored to the endoplasmic reticulum through its transmembrane domain.[5]

GRAMD1C
Identifiers
AliasesGRAMD1C, GRAM domain containing 1C, Aster-C
External IDsHomoloGene: 9726 GeneCards: GRAMD1C
Orthologs
SpeciesHumanMouse
Entrez

54762

n/a

Ensembl

ENSG00000178075

n/a

UniProt

Q8IYS0

n/a

RefSeq (mRNA)

NM_001172105
NM_017577

n/a

RefSeq (protein)

NP_001165576
NP_060047

n/a

Location (UCSC)Chr 3: 113.83 – 113.95 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

GRAMD1C has four paralogs: GRAMD1B and GRAMD1A and two without VASt domains, GRAMD2A and GRAMD2B. Homologs of GramD proteins (Lam/Ltc proteins) are found in yeast.[5]

The protein is expressed in the liver and testes.[5]

Function

When the plasma membrane contains high levels of cholesterol, GRAMD1c as well as GRAMD1a and GRAMD1b move to sites of contact between the plasma membrane and the endoplasmic reticulum.[6] GRAMD1 proteins then facilitate the transport of cholesterol into the endoplasmic reticulum.[5][6] Reduction of GRAMD1B and GRAMD1C suppresses the onset of a form of non-alcoholic fatty liver disease, non-alcoholic steatohepatitis (NASH) in mice.[5] 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.[6][7]

References
  1. GRCh38: Ensembl release 89: ENSG00000178075 - Ensembl, May 2017
  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. "Entrez Gene: GRAM domain containing 1C". Retrieved 2018-10-17.
  4. "UniProtKB - Q8IYS0 (ASTRC_HUMAN)". Retrieved March 6, 2020.
  5. 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.
  6. Sandhu J, Li S, Fairall L, et al. (4 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.
  7. 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.
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