ABHD5 explained

1-acylglycerol-3-phosphate O-acyltransferase ABHD5, also known as comparative gene identification-58 (CGI-58),[1] is an enzyme that in humans is encoded by the ABHD5 gene.[2] [3]

Function

The protein encoded by this gene belongs to a large family of proteins defined by an alpha/beta hydrolase fold, and contains three sequence motifs that correspond to a catalytic triad found in the esterase/lipase/thioesterase subfamily. It differs from other members of this subfamily in that its putative catalytic triad contains an asparagine instead of the serine residue. Mutations in this gene have been associated with Chanarin-Dorfman syndrome, a triglyceride storage disease with impaired long-chain fatty acid oxidation.[3] [4]

CGI-58 is known to be a co-activator of adipose triglyceride lipase (ATGL/PNPLA2) that associates with lipid droplets in association with perilipin proteins.[1] Phosphorylation of certain perilipins by protein kinase A causes dissociation of CGI-58 from the perilipins and permits interaction with ATGL.[1] CGI-58 additionally interacts with beclin 1,[1] [5] and CGI-58 has been shown to promote autophagy in colorectal cancer in a PNPLA2-independent manner.[5] [6]

Further reading

Notes and References

  1. Book: Yu L, Li Y, Grisé A, Wang H. CGI-58: Versatile Regulator of Intracellular Lipid Droplet Homeostasis. Lipid Transfer in Lipoprotein Metabolism and Cardiovascular Disease. 2020. 978-981-15-6081-1. Jiang XC. Advances in Experimental Medicine and Biology. Springer. 197–222. 1276. 10.1007/978-981-15-6082-8_13. Singapore. 32705602. 8063591.
  2. Ghosh AK, Ramakrishnan G, Chandramohan C, Rajasekharan R . CGI-58, the causative gene for Chanarin-Dorfman syndrome, mediates acylation of lysophosphatidic acid . The Journal of Biological Chemistry . 283 . 36 . 24525–33 . Sep 2008 . 18606822 . 3259832 . 10.1074/jbc.M801783200 . free .
  3. Web site: Entrez Gene: ABHD5 abhydrolase domain containing 5.
  4. Lefèvre C, Jobard F, Caux F, Bouadjar B, Karaduman A, Heilig R, Lakhdar H, Wollenberg A, Verret JL, Weissenbach J, Ozgüc M, Lathrop M, Prud'homme JF, Fischer J . Mutations in CGI-58, the gene encoding a new protein of the esterase/lipase/thioesterase subfamily, in Chanarin-Dorfman syndrome . American Journal of Human Genetics . 69 . 5 . 1002–12 . Nov 2001 . 11590543 . 1274347 . 10.1086/324121 .
  5. Peng Y, Miao H, Wu S, Yang W, Zhang Y, Xie G, Xie X, Li J, Shi C, Ye L, Sun W, Wang L, Liang H, Ou J. 2016. Autophagy. 12. 11. 2167–2182. 10.1080/15548627.2016.1217380. free. 27559856. 5103361. ABHD5 interacts with BECN1 to regulate autophagy and tumorigenesis of colon cancer independent of PNPLA2.
  6. ABHD5 blunts the sensitivity of colorectal cancer to fluorouracil via promoting autophagic uracil yield. Nature Communications. 2019. Ou J, Peng Y, Yang W, Zhang Y, Hao J, Li F, Chen Y, Zhao Y, Xie X, Wu S, Zha L, Luo X, Xie G, Wang L, Sun W, Zhou Q, Li J, Liang H. 10. 1. 1078 . 1078. 10.1038/s41467-019-08902-x. 30842415. 6403256. 2019NatCo..10.1078O . free.