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
Identifiers
Aliases	GRAMD1A, KIAA1533, GRAM domain containing 1A, Aster-A
External IDs	MGI: 105490; HomoloGene: 10843; GeneCards: GRAMD1A; OMA:GRAMD1A - orthologs
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19q13.11 Start 34,994,784 bp[1] End 35,026,471 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7 B1|7 19.3 cM Start 30,829,552 bp[2] End 30,855,321 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in body of pancreas upper lobe of left lung right uterine tube left uterine tube canal of the cervix left ovary right ovary gastric mucosa appendix right lung Top expressed in granulocyte thymus lymph node superior frontal gyrus ganglionic eminence muscle of thigh visual cortex primary visual cortex ventricular zone interventricular septum 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 intrinsic component of endoplasmic reticulum membrane extrinsic component of cytoplasmic side of plasma membrane organelle membrane contact site endoplasmic reticulum endoplasmic reticulum membrane plasma membrane endoplasmic reticulum-plasma membrane contact site Biological process cholesterol transport cellular response to cholesterol intermembrane sterol transfer lipid transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 57655 52857 Ensembl ENSG00000089351 ENSMUSG00000001248 UniProt Q96CP6 Q8VEF1 RefSeq (mRNA) NM_001136199 NM_020895 NM_001320034 NM_001320035 NM_001320036 NM_027898 NM_001360351 RefSeq (protein) NP_001129671 NP_001306963 NP_001306964 NP_001306965 NP_065946 NP_082174 NP_001347280 Location (UCSC) Chr 19: 34.99 – 35.03 Mb Chr 7: 30.83 – 30.86 Mb PubMed search [3] [4]
Wikidata
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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]