MBOAT5

LPCAT3
Identifiers
Aliases	LPCAT3 , C3F, LPCAT, LPLAT 5, LPSAT, MBOAT5, OACT5, nessy, lysophosphatidylcholine acyltransferase 3
External IDs	OMIM: 611950; MGI: 1315211; HomoloGene: 14678; GeneCards: LPCAT3; OMA:LPCAT3 - orthologs
EC number	2.3.1.23
Gene location (Human) Chr. Chromosome 12 (human) [1] Band 12p13.31 Start 6,976,185 bp [1] End 7,018,477 bp [1]
Gene location (Mouse) Chr. Chromosome 6 (mouse) [2] Band 6 F2|6 59.17 cM Start 124,639,990 bp [2] End 124,681,381 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver right adrenal gland mucosa of transverse colon body of stomach rectum right adrenal cortex left adrenal gland body of pancreas left adrenal cortex islet of Langerhans Top expressed in yolk sac lip jejunum right kidney duodenum skin of external ear ileum seminal vesicula epithelium of small intestine transitional epithelium of urinary bladder More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity 1-acylglycerophosphocholine O-acyltransferase activity acyltransferase activity 2-acylglycerol-3-phosphate O-acyltransferase activity 1-acylglycerol-3-phosphate O-acyltransferase activity Cellular component integral component of membrane endoplasmic reticulum membrane membrane endoplasmic reticulum Biological process phosphatidylserine acyl-chain remodeling phosphatidylethanolamine acyl-chain remodeling phosphatidylcholine acyl-chain remodeling regulation of plasma lipoprotein particle levels lipid metabolism phospholipid biosynthetic process phospholipid metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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 Mb Chr 6: 124.64 – 124.68 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/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. GRCh38: Ensembl release 89: ENSG00000111684 – Ensembl, May 2017
2. 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

• Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, et al. (January 2006). "The LIFEdb database in 2006". Nucleic Acids Research. 34 (Database issue): D415 –D418. doi:10.1093/nar/gkj139. PMC   1347501 . PMID   16381901.
• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, et al. (January 2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC   1356129 . PMID   16344560.
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, et al. (October 2004). "From ORFeome to biology: a functional genomics pipeline". Genome Research. 14 (10B): 2136–2144. doi:10.1101/gr.2576704. PMC   528930 . PMID   15489336.
• Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, et al. (March 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research. 11 (3): 422–435. doi:10.1101/gr.GR1547R. PMC   311072 . PMID   11230166.
• Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–1795. doi:10.1101/gr.143000. PMC   310948 . PMID   11076863.
• Maurel-Zaffran C, Chauvet S, Jullien N, Miassod R, Pradel J, Aragnol D (August 1999). "nessy, an evolutionary conserved gene controlled by Hox proteins during Drosophila embryogenesis". Mechanisms of Development. 86 (1–2): 159–163. doi:10.1016/S0925-4773(99)00105-7. PMID   10446276. S2CID   5793636.

External links

• LPCAT3 human gene location in the UCSC Genome Browser .
• LPCAT3 human gene details in the UCSC Genome Browser .