GRAMD1C

GRAMD1C
Identifiers
Aliases	GRAMD1C , GRAM domain containing 1C, Aster-C
External IDs	MGI: 2443024; HomoloGene: 9726; GeneCards: GRAMD1C; OMA:GRAMD1C - orthologs
Gene location (Human) Chr. Chromosome 3 (human) [1] Band 3q13.31 Start 113,828,182 bp [1] End 113,947,174 bp [1]
Gene location (Mouse) Chr. Chromosome 16 (mouse) [2] Band 16|16 B4 Start 43,800,713 bp [2] End 43,883,708 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in jejunal mucosa bronchial epithelial cell epithelium of nasopharynx germinal epithelium sperm right uterine tube kidney tubule palpebral conjunctiva body of pancreas renal medulla Top expressed in olfactory epithelium spermatocyte otolith organ utricle spermatid seminiferous tubule zygote primary oocyte vestibular sensory epithelium esophagus More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding cholesterol binding cholesterol transfer activity lipid binding Cellular component membrane integral component of membrane endoplasmic reticulum membrane plasma membrane endoplasmic reticulum-plasma membrane contact site endoplasmic reticulum Biological process cholesterol transport cellular response to cholesterol intermembrane sterol transfer lipid transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 54762 207798 Ensembl ENSG00000178075 ENSMUSG00000036292 UniProt Q8IYS0 Q8CI52 RefSeq (mRNA) NM_001172105 NM_017577 NM_001172107 NM_153528 NM_001359085 RefSeq (protein) NP_001165576 NP_060047 NP_001165578 NP_705756 NP_001346014 NP_001395263 NP_001395264 NP_001395265 Location (UCSC) Chr 3: 113.83 – 113.95 Mb Chr 16: 43.8 – 43.88 Mb PubMed search [3] [4]
Wikidata
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GRAM domain containing 1C also known as Aster-C is a cholesterol transport protein that is encoded by the GRAMD1C gene. ^{[5] [6]} It contains a transmembrane region, a GRAM domain and a VASt domain. It is anchored to the endoplasmic reticulum through its transmembrane domain. ^[7]

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. ^[7]

The protein is expressed in the liver and testes. ^[7]

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. ^[8] GRAMD1 proteins then facilitate the transport of cholesterol into the endoplasmic reticulum. ^{[7] [8]} Reduction of GRAMD1B and GRAMD1C suppresses the onset of a form of non-alcoholic fatty liver disease, non-alcoholic steatohepatitis (NASH) in mice. ^[7] 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] [9]}

References

1. GRCh38: Ensembl release 89: ENSG00000178075 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000036292 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: GRAM domain containing 1C" . Retrieved 2018-10-17.
6. "UniProtKB - Q8IYS0 (ASTRC_HUMAN)" . Retrieved March 6, 2020.
7. 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.
8. 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.
9. 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.