MBOAT5

LPCAT3
Identifiers
AliasesLPCAT3, C3F, LPCAT, LPLAT 5, LPSAT, MBOAT5, OACT5, nessy, lysophosphatidylcholine acyltransferase 3
External IDsOMIM: 611950; MGI: 1315211; HomoloGene: 14678; GeneCards: LPCAT3; OMA:LPCAT3 - orthologs
EC number2.3.1.23
Orthologs
SpeciesHumanMouse
Entrez

10162

14792

Ensembl

ENSG00000111684

ENSMUSG00000004270

UniProt

Q6P1A2

Q91V01

RefSeq (mRNA)

NM_005768

NM_145130

RefSeq (protein)

NP_005759

NP_660112

Location (UCSC)Chr 12: 6.98 – 7.02 MbChr 6: 124.64 – 124.68 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Lysophospholipid acyltransferase 5 is an enzyme that in humans is encoded by the LPCAT3 gene.[5][6][7][8] It is homologous to other membrane-bound O-acyltransferases.

Structure and function

Based on the crystalographic and cryo-EM studies of its homolog in chicken (cLPCAT3),[9] humane MBOAT5 has a typical MBOAT folding as other members such as SOAT1 and DGAT1,[10][11] and the transmembrane helices hold a "T"-shape reaction chamber allowing the co-occupancy of a lysophosphatidylcholine (lysoPC) and a long polyunsaturated acyl-CoA, such as arachidonic acyl CoA. With the assistance of catalytic residues H374 and N338, the acyl chain could be transferred from the acyl CoA to the sn-2 position of lysoPC, thereby generating a new, polyunsaturated phospholipid.

Inhibition of LPCAT3 has been found to alter the cellular lipidome and is partially protective against ferroptosis.[12]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000111684 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000004270 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Ansari-Lari MA, Muzny DM, Lu J, Lu F, Lilley CE, Spanos S, et al. (April 1996). "A gene-rich cluster between the CD4 and triosephosphate isomerase genes at human chromosome 12p13". Genome Research. 6 (4): 314–326. doi:10.1101/gr.6.4.314. PMID 8723724.
  6. ^ Ansari-Lari MA, Shen Y, Muzny DM, Lee W, Gibbs RA (March 1997). "Large-scale sequencing in human chromosome 12p13: experimental and computational gene structure determination". Genome Research. 7 (3): 268–280. doi:10.1101/gr.7.3.268. PMID 9074930.
  7. ^ Zhao Y, Chen YQ, Bonacci TM, Bredt DS, Li S, Bensch WR, et al. (March 2008). "Identification and characterization of a major liver lysophosphatidylcholine acyltransferase". The Journal of Biological Chemistry. 283 (13): 8258–8265. doi:10.1074/jbc.M710422200. PMID 18195019.
  8. ^ "Entrez Gene: MBOAT5 membrane bound O-acyltransferase domain containing 5".
  9. ^ Zhang Q, Yao D, Rao B, Jian L, Chen Y, Hu K, et al. (November 2021). "The structural basis for the phospholipid remodeling by lysophosphatidylcholine acyltransferase 3". Nature Communications. 12 (1): 6869. Bibcode:2021NatCo..12.6869Z. doi:10.1038/s41467-021-27244-1. PMC 8617236. PMID 34824256.
  10. ^ Qian H, Zhao X, Yan R, Yao X, Gao S, Sun X, et al. (May 2020). "Structural basis for catalysis and substrate specificity of human ACAT1". Nature. 581 (7808): 333–338. Bibcode:2020Natur.581..333Q. doi:10.1038/s41586-020-2290-0. PMID 32433614. S2CID 214190451.
  11. ^ Wang L, Qian H, Nian Y, Han Y, Ren Z, Zhang H, et al. (May 2020). "Structure and mechanism of human diacylglycerol O-acyltransferase 1". Nature. 581 (7808): 329–332. Bibcode:2020Natur.581..329W. doi:10.1038/s41586-020-2280-2. PMC 7255049. PMID 32433610.
  12. ^ Reed A, Ichu TA, Milosevich N, Melillo B, Schafroth MA, Otsuka Y, et al. (June 2022). "LPCAT3 Inhibitors Remodel the Polyunsaturated Phospholipid Content of Human Cells and Protect from Ferroptosis". ACS Chemical Biology. 17 (6): 1607–1618. doi:10.1021/acschembio.2c00317. PMID 35658397. S2CID 249396449.

Further reading


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