| Structural highlights
Function
IRG1_MOUSE Cis-aconitate decarboxylase that catalyzes production of itaconate and is involved in the inhibition of the inflammatory response (PubMed:23609450, PubMed:23610393, PubMed:30635240, PubMed:31548418). Acts as a negative regulator of the Toll-like receptors (TLRs)-mediated inflammatory innate response by stimulating the tumor necrosis factor alpha-induced protein TNFAIP3 expression via reactive oxygen species (ROS) in LPS-tolerized macrophages (PubMed:23609450). Involved in antimicrobial response of innate immune cells; ACOD1-mediated itaconic acid production contributes to the antimicrobial activity of macrophages by generating itaconate, leading to alkylation of proteins, such as TFEB (PubMed:23610393, PubMed:35662396). Involved in antiviral response following infection by flavivirus in neurons: ACOD1-mediated itaconate production inhibits the activity of succinate dehydrogenase, generating a metabolic state in neurons that suppresses replication of viral genomes (PubMed:30635240). Plays a role in the embryo implantation (PubMed:14500577).[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
PROTEIN DATA BANK ACCESSION CODES: Coordinate and structural factors were deposited with the Protein Data Bank under PDB ID: 7BR9.
The crystal structure of mouse IRG1 suggests that cis-aconitate decarboxylase has an open and closed conformation.,Chun HL, Lee SY, Kim KH, Lee CS, Oh TJ, Park HH PLoS One. 2020 Dec 1;15(12):e0242383. doi: 10.1371/journal.pone.0242383., eCollection 2020. PMID:33259501[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cheon YP, Xu X, Bagchi MK, Bagchi IC. Immune-responsive gene 1 is a novel target of progesterone receptor and plays a critical role during implantation in the mouse. Endocrinology. 2003 Dec;144(12):5623-30. PMID:14500577 doi:10.1210/en.2003-0585
- ↑ Li Y, Zhang P, Wang C, Han C, Meng J, Liu X, Xu S, Li N, Wang Q, Shi X, Cao X. Immune responsive gene 1 (IRG1) promotes endotoxin tolerance by increasing A20 expression in macrophages through reactive oxygen species. J Biol Chem. 2013 Jun 7;288(23):16225-34. doi: 10.1074/jbc.M113.454538. Epub 2013, Apr 22. PMID:23609450 doi:https://dx.doi.org/10.1074/jbc.M113.454538
- ↑ Michelucci A, Cordes T, Ghelfi J, Pailot A, Reiling N, Goldmann O, Binz T, Wegner A, Tallam A, Rausell A, Buttini M, Linster CL, Medina E, Balling R, Hiller K. Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production. Proc Natl Acad Sci U S A. 2013 May 7;110(19):7820-5. doi:, 10.1073/pnas.1218599110. Epub 2013 Apr 22. PMID:23610393 doi:https://dx.doi.org/10.1073/pnas.1218599110
- ↑ Daniels BP, Kofman SB, Smith JR, Norris GT, Snyder AG, Kolb JP, Gao X, Locasale JW, Martinez J, Gale M Jr, Loo YM, Oberst A. The Nucleotide Sensor ZBP1 and Kinase RIPK3 Induce the Enzyme IRG1 to Promote an Antiviral Metabolic State in Neurons. Immunity. 2019 Jan 15;50(1):64-76.e4. PMID:30635240 doi:10.1016/j.immuni.2018.11.017
- ↑ Chen F, Lukat P, Iqbal AA, Saile K, Kaever V, van den Heuvel J, Blankenfeldt W, Bussow K, Pessler F. Crystal structure of cis-aconitate decarboxylase reveals the impact of naturally occurring human mutations on itaconate synthesis. Proc Natl Acad Sci U S A. 2019 Oct 8;116(41):20644-20654. doi:, 10.1073/pnas.1908770116. Epub 2019 Sep 23. PMID:31548418 doi:https://dx.doi.org/10.1073/pnas.1908770116
- ↑ Zhang Z, Chen C, Yang F, Zeng YX, Sun P, Liu P, Li X. Itaconate is a lysosomal inducer that promotes antibacterial innate immunity. Mol Cell. 2022 Aug 4;82(15):2844-2857.e10. PMID:35662396 doi:10.1016/j.molcel.2022.05.009
- ↑ Chun HL, Lee SY, Kim KH, Lee CS, Oh TJ, Park HH. The crystal structure of mouse IRG1 suggests that cis-aconitate decarboxylase has an open and closed conformation. PLoS One. 2020 Dec 1;15(12):e0242383. PMID:33259501 doi:10.1371/journal.pone.0242383
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