2.3.1.- Acyltransferases

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2.3.1.- Acyltransferases

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Enzymes

3211

fatty acid synthase Show summary »« Hide summary More detailed page go icon to follow link

Target Id

2608

Nomenclature

fatty acid synthase

Previous and unofficial names

FAS

Genes

FASN (Hs), Fasn (Mm), Fasn (Rn)

Ensembl ID

ENSG00000169710 (Hs), ENSMUSG00000025153 (Mm), ENSRNOG00000045636 (Rn)

UniProtKB AC

P49327 (Hs), P19096 (Mm), P12785 (Rn)

EC number

2.3.1.85

Comment

Fatty acid synthase (FAS; FASN) is a component of the fatty acid biosynthesis pathway. Pharmacological inhibition of FAS using the FAS/gastric lipases inhibitor orlistat has been shown to decrease replication SARS-CoV-2 in vitro [1,9].

diacylglycerol O-acyltransferase 1 Show summary »« Hide summary More detailed page go icon to follow link

Target Id

2821

Nomenclature

diacylglycerol O-acyltransferase 1

Previous and unofficial names

ARGP1 | DGAT

Genes

DGAT1 (Hs), Dgat1 (Mm), Dgat1 (Rn)

Ensembl ID

ENSG00000185000 (Hs), ENSMUSG00000022555 (Mm), ENSRNOG00000028711 (Rn)

UniProtKB AC

O75907 (Hs), Q9Z2A7 (Mm), Q9ERM3 (Rn)

EC number

2.3.1.20
Conversion of diacylglycerol and fatty acyl CoA to triacylglycerol. Acyl-CoA + 1,2-diacylglycerol <=> CoA + triacylglycerol

diacylglycerol O-acyltransferase 2 Show summary »« Hide summary

Target Id

3211

Nomenclature

diacylglycerol O-acyltransferase 2

Genes

DGAT2 (Hs), Dgat2 (Mm), Dgat2 (Rn)

Ensembl ID

ENSG00000062282 (Hs), ENSMUSG00000030747 (Mm), ENSRNOG00000016573 (Rn)

UniProtKB AC

Q96PD7 (Hs), Q9DCV3 (Mm), Q5FVP8 (Rn)

EC number

2.3.1.20

2.3.1.76

Inhibitors

PF-07202954 pIC₅₀ 8.0 [2]

ervogastat pIC₅₀ 7.8 [3]

ervogastat pIC₅₀ 6.1 [3] - Rat

Comment

DGAT2 is expressed in liver and adipose tissues where its substrate is exclusively diacylglycerol (DAG). Gene knock-out of Dgat2 in rodent models is lethal (in the early post-natal period), but inhibition of hepatic DGAT2 in adult animals induces an improved plasma lipoprotein profile that is translatable to therapeutic benefit in metabolic disease. Based in this latter discovery, DGAT2 is an active pharmacological target for the treatment of metabolic diseases such as non-alcoholic steatohepatitis. Inhibitors like ervogastat are predicted to reduce accumulation of fibrosis-inducing triglycerides in the liver. The enzyme has also been implicated in amyloid-β induced lipid droplet-mediated microglial dysfunction and neuronal damage in Alzheimer's disease model mice [6].

monoacylglycerol O-acyltransferase 2 C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

2881

Nomenclature

monoacylglycerol O-acyltransferase 2

Previous and unofficial names

DGAT2L5 | MGAT2

Genes

MOGAT2 (Hs), Mogat2 (Mm), Mogat2 (Rn)

Ensembl ID

ENSG00000166391 (Hs), ENSMUSG00000052396 (Mm), ENSRNOG00000027228 (Rn)

UniProtKB AC

Q3SYC2 (Hs), Q80W94 (Mm)

EC number

2.3.1.22
Acyl-CoA + 2-acylglycerol <=> CoA + diacylglycerol [5]

Comment

MOGAT2 is involved in the synthesis of diacylglycerol and triacylglycerol from monoacylglycerols (azalanstat, 2-monoacylglycerol).

N-acetyltransferase 8 like Show summary »« Hide summary More detailed page go icon to follow link

Target Id

3144

Nomenclature

N-acetyltransferase 8 like

Previous and unofficial names

CML3 | aspartate N-acetyltransferase | ANAT

Genes

NAT8L (Hs), Nat8l (Mm), Nat8l (Rn)

Ensembl ID

ENSG00000185818 (Hs), ENSMUSG00000048142 (Mm), ENSRNOG00000049351 (Rn)

UniProtKB AC

Q8N9F0 (Hs), Q3UGX3 (Mm)

EC number

2.3.1.17

Acetyl-CoA + L-aspartate <=> CoA + N-acetyl-L-aspartate (NAA)

Comment

N-acetyltransferase 8 like is a neuron-specific GCN5 related N-acetyltransferase. It is essential for the biosynthesis of N-acetylaspartate (NAA) from L-aspartate and acetyl-CoA.

zDHHC palmitoyltransferase 3 Show summary »« Hide summary

Target Id

3271

Nomenclature

zDHHC palmitoyltransferase 3

Previous and unofficial names

zinc finger DHHC-type palmitoyltransferase 3 | DHHC3 | GODZ | ZNF373

Genes

ZDHHC3 (Hs), Zdhhc3 (Mm), Zdhhc3 (Rn)

Ensembl ID

ENSG00000163812 (Hs), ENSMUSG00000025786 (Mm), ENSRNOG00000004344 (Rn)

UniProtKB AC

Q9NYG2 (Hs), Q6EMK3 (Mm)

EC number

2.3.1.225

Inhibitors

benzosceptrin C (Binding) pK_d 6.4 [8]

Comment

Catalyses post-translational palmitoylation of a wide range of substrate proteins within the Golgi apparatus.

zDHHC palmitoyltransferase 6 Show summary »« Hide summary

Target Id

3188

Nomenclature

zDHHC palmitoyltransferase 6

Previous and unofficial names

DHHC palmitoyl transferase | Protein S-acyltransferase | zinc finger DHHC-type palmitoyltransferase 6

Genes

ZDHHC6 (Hs), Zdhhc6 (Mm), Zdhhc6 (Rn)

Ensembl ID

ENSG00000023041 (Hs), ENSMUSG00000024982 (Mm), ENSRNOG00000036576 (Rn)

UniProtKB AC

Q9H6R6 (Hs), Q9CPV7 (Mm)

EC number

2.3.1.225

Comment

Catalyses protein S-palmitoylation of substrate proteins. ZDHHC6 substrates include calnexin (CANX), thioredoxin related transmembrane protein 1 (TMX1) [4], and the oncogenic NRAS GTPase [7]. The antimalarial drug artemisinin inhibits ZDHHC6-mediated palmitoylation of NRAS and calnexin [7]. Blocking NRAS palmitoylation with artemisinin disrupts its subcellular localisation and downstream proliferative signalling, and contributes towards the anticancer activity of artemisinin and its analogues [7].

References

Show »« Hide

1. Chu J, Xing C, Du Y, Duan T, Liu S, Zhang P, Cheng C, Henley J, Liu X, Qian C et al.. (2021) Pharmacological inhibition of fatty acid synthesis blocks SARS-CoV-2 replication. Nat Metab, 3 (11): 1466-1475. [PMID:34580494]

2. Filipski KJ, Edmonds DJ, Garnsey MR, Smaltz DJ, Coffman K, Futatsugi K, Lee J, O'Neil SV, Wright A, Nason D et al.. (2023) Design of Next-Generation DGAT2 Inhibitor PF-07202954 with Longer Predicted Half-Life. ACS Med Chem Lett, 14 (10): 1427-1433. [PMID:37849537]

3. Futatsugi K, Cabral S, Kung DW, Huard K, Lee E, Boehm M, Bauman J, Clark RW, Coffey SB, Crowley C et al.. (2022) Discovery of Ervogastat (PF-06865571): A Potent and Selective Inhibitor of Diacylglycerol Acyltransferase 2 for the Treatment of Non-alcoholic Steatohepatitis. J Med Chem, 65 (22): 15000-15013. [PMID:36322383]

4. Lynes EM, Bui M, Yap MC, Benson MD, Schneider B, Ellgaard L, Berthiaume LG, Simmen T. (2012) Palmitoylated TMX and calnexin target to the mitochondria-associated membrane. EMBO J, 31 (2): 457-70. [PMID:22045338]

5. Manganaro F, Kuksis A. (1985) Purification and preliminary characterization of 2-monoacylglycerol acyltransferase from rat intestinal villus cells. Can J Biochem Cell Biol, 63 (5): 341-7. [PMID:4016575]

6. Prakash P, Manchanda P, Paouri E, Bisht K, Sharma K, Rajpoot J, Wendt V, Hossain A, Wijewardhane PR, Randolph CE et al.. (2025) Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer's disease. Immunity, [Epub ahead of print]. [PMID:40393454]

7. Qiu N, Abegg D, Guidi M, Gilmore K, Seeberger PH, Adibekian A. (2022) Artemisinin inhibits NRas palmitoylation by targeting the protein acyltransferase ZDHHC6. Cell Chem Biol, 29 (3): 530-537.e7. [PMID:34358442]

8. Wang Q, Wang J, Yu D, Zhang Q, Hu H, Xu M, Zhang H, Tian S, Zheng G, Lu D et al.. (2024) Benzosceptrin C induces lysosomal degradation of PD-L1 and promotes antitumor immunity by targeting DHHC3. Cell Rep Med, 5 (2): 101357. [PMID:38237597]

9. Williams CG, Jureka AS, Silvas JA, Nicolini AM, Chvatal SA, Carlson-Stevermer J, Oki J, Holden K, Basler CF. (2021) Inhibitors of VPS34 and fatty-acid metabolism suppress SARS-CoV-2 replication. Cell Rep, 36 (5): 109479. [PMID:34320401]

How to cite this family page

Database page citation:

2.3.1.- Acyltransferases. Accessed on 01/07/2025. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=844.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Enzymes. Br J Pharmacol. 180 Suppl 2:S289-373.