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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_032564 8 - 2485 NP_115953 - 388 - 2001 11481335 NM_001253891 - - 2336 NP_001240820 - 345 - 2001 11481335

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive liver         Nervous nerve spinal nerve sciatic       nerve cranial nerve     highly Skin/Tegument skin appendages skin gland sebaceous gland   highly Visual eye uvea choroid

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose white     Homo sapiens Connective bone subchondral     Epithelial barrier/lining retinal pigment epithelium (RPE)     Nervous peripherous

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic leukocyte

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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