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FLASH GENE
Symbol DGAT2 contributors: mct - updated : 09-06-2015
HGNC name diacylglycerol O-acyltransferase homolog 2 (mouse)
HGNC id 16940
DNA
TYPE functioning gene
STRUCTURE 32.80 kb     8 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
8 - 2485 - 388 - 2001 11481335
- - 2336 - 345 - 2001 11481335
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveliver    
Nervousnervespinal nervesciatic  
 nervecranial nerve  highly
Skin/Tegumentskin appendagesskin glandsebaceous gland highly
Visualeyeuveachoroid  
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectiveadiposewhite   Homo sapiens
Connectivebonesubchondral  
Epithelialbarrier/liningretinal pigment epithelium (RPE)  
Nervousperipherous   
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticleukocyte
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • ER targeting signal present in the first transmembrane domain (TMD1)
  • has only two transmembrane domains and the loop connecting them is present in the ER lumen
  • HOMOLOGY
    interspecies homolog to murine Dgat2
    Homologene
    FAMILY
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic,microsome
    text
  • reside in the endoplasmic reticulum (ER), but also co-localizes with mitochondria and lipid droplets
  • also localized to near the surface of lipid droplets, where it co-localized with mitochondria
  • resides in the endoplasmic reticulum (ER), but when cells are incubated with fatty acids, DGAT2 interacts with lipid droplets presumably to catalyze localized TG synthesis for lipid droplet expansion
  • transmembrane proteins localized in the endoplasmic reticulum
  • basic FUNCTION
  • catalyzing a reaction in which diacylglycerol is covalently joined to long chain fatty acyl-CoAs, the final step in the production of triacylglycerol
  • mediates the dissociation between fatty liver and insulin resistance and this finding may be important in the prevention and treatment of insulin resistance and Type 2 diabetes in subjects with fatty liver
  • ER-resident transmembrane domain-containing enzyme, also found in mitochondria-associated membranes, where its N terminus may promote its association with mitochondria
  • DGAT1 and DGAT2 account for nearly all triacylglycerol synthesis in adipocytes and appear to be required for lipid droplet formation during adipogenesis
  • is potentially capable of catalyzing triacylglycerol synthesis and promote its storage in cytosolic lipid droplets independent of its localization in the ER
  • DGAT1 and DGAT2 can compensate for each other to synthesize triacylglycerol, but triacylglycerol synthesized by DGAT1 is preferentially channeled to oxidation, whereas DGAT2 synthesizes triacylglycerol destined for very low-density lipoprotein assembly
  • DGAT1 and DGAT2 function coordinately to regulate the process of dietary fat absorption by preferentially synthesizing triacylglycerol(TAG) for incorporation into distinct subcellular TAG pools in enterocytes
  • DGAT2 translocates to the lipid droplet (LD), associates with other proteins, and synthesizes cytosolic and luminal apolipoprotein B associated LD-triacylglycerol (TAG) from both endogenous and exogenous fatty acids
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • evolutionarily conserved SLC27A1-DGAT2 complex acts at the ER-LD interface and couples the synthesis and deposition of triglycerides into lipid droplets (LDs) both physically and functionally
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • two lipogenic genes encoding DGAT2 and FABP4 were induced in ELOVL2-overexpressing cells, whereas no such effect was seen on the fatty acid synthase (FASN) gene
  • SLC27A1 preferentially associated with DGAT2, and they acted synergistically to promote lipid droplets (LDs) expansion in mammalian cells
  • DGAT2 is regulated by AMFR-associated ERAD at the post-translational level
  • DGAT2 interacted with monoacylglycerol acyltransferase MOGAT2, an enzyme that catalyzes the synthesis of diacylglycerol, and interaction of DGAT2 and MOGAT2 serves to channel lipid substrates efficiently for TG biosynthesis
  • interacts with proteins that synthesize its fatty acyl CoA substrates
  • cell & other
  • interaction of DGAT2 with mitochondria depended on 67 N-terminal AAs of DGAT2, which are not conserved in family members that have different catalytic functions
  • REGULATION
    Other regulated in white adipose tissue by central leptin action
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in psoriatic skin
    constitutional     --over  
    plays an important role in the pathogenesis of alcoholic fatty liver disease, and abnormal methionine metabolism contributes, at least partially, to DGAT2 upregulation via suppression of MEK/ERK1/2 activation
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • mice overexpressing hepatic Dgat2 fed a high-fat diet develop fatty liver, but not insulin resistance, suggesting that DGAT2 induces a dissociation between fatty liver and insulin resistance