Diacylglycerol O-acyltransferase 2

Details

Name

Diacylglycerol O-acyltransferase 2

Synonyms

• 2.3.1.20
• Acyl-CoA retinol O-fatty-acyltransferase
• ARAT
• Diglyceride acyltransferase 2
• Retinol O-fatty-acyltransferase

Gene Name

DGAT2

UniProtKB Entry

Q96PD7Swiss-Prot

Organism

Humans

NCBI Taxonomy ID

9606

Amino acid sequence

>lcl|BSEQ0049585|Diacylglycerol O-acyltransferase 2
MKTLIAAYSGVLRGERQAEADRSQRSHGGPALSREGSGRWGTGSSILSALQDLFSVTWLN
RSKVEKQLQVISVLQWVLSFLVLGVACSAILMYIFCTDCWLIAVLYFTWLVFDWNTPKKG
GRRSQWVRNWAVWRYFRDYFPIQLVKTHNLLTTRNYIFGYHPHGIMGLGAFCNFSTEATE
VSKKFPGIRPYLATLAGNFRMPVLREYLMSGGICPVSRDTIDYLLSKNGSGNAIIIVVGG
AAESLSSMPGKNAVTLRNRKGFVKLALRHGADLVPIYSFGENEVYKQVIFEEGSWGRWVQ
KKFQKYIGFAPCIFHGRGLFSSDTWGLVPYSKPITTVVGEPITIPKLEHPTQQDIDLYHT
MYMEALVKLFDKHKTKFGLPETEVLEVN

Number of residues

388

Molecular Weight

43830.475

Theoretical pI

Not Available

GO Classification

Functions

2-acylglycerol O-acyltransferase activity / diacylglycerol O-acyltransferase activity / protein homodimerization activity / retinol O-fatty-acyltransferase activity

Processes

cellular response to oleic acid / cholesterol homeostasis / diacylglycerol metabolic process / fat pad development / fatty acid homeostasis / glycerol metabolic process / lipid storage / long-chain fatty-acyl-CoA metabolic process / low-density lipoprotein particle clearance / regulation of plasma lipoprotein particle levels / triglyceride biosynthetic process

Components

endoplasmic reticulum / endoplasmic reticulum membrane / mitochondrion / perinuclear region of cytoplasm

General Function

Essential acyltransferase that catalyzes the terminal and only committed step in triacylglycerol synthesis by using diacylglycerol and fatty acyl CoA as substrates. Required for synthesis and storage of intracellular triglycerides (PubMed:27184406). Probably plays a central role in cytosolic lipid accumulation. In liver, is primarily responsible for incorporating endogenously synthesized fatty acids into triglycerides (By similarity). Functions also as an acyl-CoA retinol acyltransferase (ARAT) (By similarity). Also able to use 1-monoalkylglycerol (1-MAkG) as an acyl acceptor for the synthesis of monoalkyl-monoacylglycerol (MAMAG) (PubMed:28420705)

Specific Function

2-acylglycerol O-acyltransferase activity

Pfam Domain Function

• DAGAT (PF03982)

Signal Regions

Not Available

Transmembrane Regions

70-88 93-112

Cellular Location

Endoplasmic reticulum membrane

Gene sequence

>lcl|BSEQ0049586|Diacylglycerol O-acyltransferase 2 (DGAT2)
ATGAAGACCCTCATAGCCGCCTACTCCGGGGTCCTGCGCGGCGAGCGTCAGGCCGAGGCT
GACCGGAGCCAGCGCTCTCACGGAGGACCTGCGCTGTCGCGCGAGGGGTCTGGGAGATGG
GGCACTGGATCCAGCATCCTCTCCGCCCTCCAGGACCTCTTCTCTGTCACCTGGCTCAAT
AGGTCCAAGGTGGAAAAGCAGCTACAGGTCATCTCAGTGCTCCAGTGGGTCCTGTCCTTC
CTTGTACTGGGAGTGGCCTGCAGTGCCATCCTCATGTACATATTCTGCACTGATTGCTGG
CTCATCGCTGTGCTCTACTTCACTTGGCTGGTGTTTGACTGGAACACACCCAAGAAAGGT
GGCAGGAGGTCACAGTGGGTCCGAAACTGGGCTGTGTGGCGCTACTTTCGAGACTACTTT
CCCATCCAGCTGGTGAAGACACACAACCTGCTGACCACCAGGAACTATATCTTTGGATAC
CACCCCCATGGTATCATGGGCCTGGGTGCCTTCTGCAACTTCAGCACAGAGGCCACAGAA
GTGAGCAAGAAGTTCCCAGGCATACGGCCTTACCTGGCTACACTGGCAGGCAACTTCCGA
ATGCCTGTGTTGAGGGAGTACCTGATGTCTGGAGGTATCTGCCCTGTCAGCCGGGACACC
ATAGACTATTTGCTTTCAAAGAATGGGAGTGGCAATGCTATCATCATCGTGGTCGGGGGT
GCGGCTGAGTCTCTGAGCTCCATGCCTGGCAAGAATGCAGTCACCCTGCGGAACCGCAAG
GGCTTTGTGAAACTGGCCCTGCGTCATGGAGCTGACCTGGTTCCCATCTACTCCTTTGGA
GAGAATGAAGTGTACAAGCAGGTGATCTTCGAGGAGGGCTCCTGGGGCCGATGGGTCCAG
AAGAAGTTCCAGAAATACATTGGTTTCGCCCCATGCATCTTCCATGGTCGAGGCCTCTTC
TCCTCCGACACCTGGGGGCTGGTGCCCTACTCCAAGCCCATCACCACTGTTGTGGGAGAG
CCCATCACCATCCCCAAGCTGGAGCACCCAACCCAGCAAGACATCGACCTGTACCACACC
ATGTACATGGAGGCCCTGGTGAAGCTCTTCGACAAGCACAAGACCAAGTTCGGCCTCCCG
GAGACTGAGGTCCTGGAGGTGAACTGA

Chromosome Location

11

Locus

11q13.5

External Identifiers

Resource	Link
UniProtKB ID	Q96PD7
UniProtKB Entry Name	DGAT2_HUMAN
GeneCard ID	DGAT2
HGNC ID	HGNC:16940
KEGG ID	hsa:84649
IUPHAR/Guide To Pharmacology ID	3211
NCBI Gene ID	84649

General References

1. Cases S, Stone SJ, Zhou P, Yen E, Tow B, Lardizabal KD, Voelker T, Farese RV Jr: Cloning of DGAT2, a second mammalian diacylglycerol acyltransferase, and related family members. J Biol Chem. 2001 Oct 19;276(42):38870-6. Epub 2001 Jul 31. [Article]
2. Wakimoto K, Chiba H, Michibata H, Seishima M, Kawasaki S, Okubo K, Mitsui H, Torii H, Imai Y: A novel diacylglycerol acyltransferase (DGAT2) is decreased in human psoriatic skin and increased in diabetic mice. Biochem Biophys Res Commun. 2003 Oct 17;310(2):296-302. [Article]
3. Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res. 2003 Oct;13(10):2265-70. Epub 2003 Sep 15. [Article]
4. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [Article]
5. Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, Dewar K, Lloyd C, Itoh T, Takeda T, Kim DW, She X, Barlow KF, Bloom T, Bruford E, Chang JL, Cuomo CA, Eichler E, FitzGerald MG, Jaffe DB, LaButti K, Nicol R, Park HS, Seaman C, Sougnez C, Yang X, Zimmer AR, Zody MC, Birren BW, Nusbaum C, Fujiyama A, Hattori M, Rogers J, Lander ES, Sakaki Y: Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature. 2006 Mar 23;440(7083):497-500. [Article]
6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
7. Yamada S, Ohira M, Horie H, Ando K, Takayasu H, Suzuki Y, Sugano S, Hirata T, Goto T, Matsunaga T, Hiyama E, Hayashi Y, Ando H, Suita S, Kaneko M, Sasaki F, Hashizume K, Ohnuma N, Nakagawara A: Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas. Oncogene. 2004 Aug 5;23(35):5901-11. [Article]
8. Orland MD, Anwar K, Cromley D, Chu CH, Chen L, Billheimer JT, Hussain MM, Cheng D: Acyl coenzyme A dependent retinol esterification by acyl coenzyme A: diacylglycerol acyltransferase 1. Biochim Biophys Acta. 2005 Oct 15;1737(1):76-82. Epub 2005 Sep 20. [Article]
9. Hong YB, Kang J, Kim JH, Lee J, Kwak G, Hyun YS, Nam SH, Hong HD, Choi YR, Jung SC, Koo H, Lee JE, Choi BO, Chung KW: DGAT2 Mutation in a Family with Autosomal-Dominant Early-Onset Axonal Charcot-Marie-Tooth Disease. Hum Mutat. 2016 May;37(5):473-80. doi: 10.1002/humu.22959. Epub 2016 Feb 9. [Article]

Associated Data

Bio-Entities

Bio-Entity	Type
Diacylglycerol O-acyltransferase 2 (Humans)	protein primary

Drug Relations

Drug	Drug group	Pharmacological action?	Type	Actions	Details
Inositol nicotinate	approved, withdrawn	no	enzyme	inhibitor	Details
Omega-3-carboxylic acids	approved, investigational	yes	target	antagonist	Details
Fish oil	approved, nutraceutical	yes	target	agonist	Details
Niacin	approved, investigational, nutraceutical	yes	target	inhibitor	Details