Top ▲
target has curated data in GtoImmuPdb
Target id: 3018
Nomenclature: aconitate decarboxylase 1
Abbreviated Name: IRG1
Family: Itaconate biosynthesis
Gene and Protein Information  |
||||||
| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | - | 481 | 13q22.3 | ACOD1 | aconitate decarboxylase 1 | |
| Mouse | - | 488 | 14 51.67 cM | Acod1 | aconitate decarboxylase 1 | |
| Rat | - | 488 | 15q23 | Acod1 | aconitate decarboxylase 1 | |
| Previous and Unofficial Names |
| immune-responsive gene 1 | immunoresponsive gene 1 | IRG1 | cis-aconitate decarboxylase (CAD) |
| Database Links |
|
| Alphafold | A6NK06 (Hs), P54987 (Mm) |
| BRENDA | 4.1.1.6 |
| Ensembl Gene | ENSG00000102794 (Hs), ENSMUSG00000022126 (Mm), ENSRNOG00000009919 (Rn) |
| Entrez Gene | 730249 (Hs), 16365 (Mm), 306127 (Rn) |
| Human Protein Atlas | ENSG00000102794 (Hs) |
| KEGG Enzyme | 4.1.1.6 |
| KEGG Gene | hsa:730249 (Hs), mmu:16365 (Mm), rno:306127 (Rn) |
| OMIM | 615275 (Hs) |
| Pharos | A6NK06 (Hs) |
| RefSeq Nucleotide | NM_001258406 (Hs), NM_008392 (Mm), NM_001107282 (Rn) |
| RefSeq Protein | NP_001245335 (Hs), NP_032418 (Mm), NP_001100752 (Rn) |
| UniProtKB | A6NK06 (Hs), P54987 (Mm) |
| Wikipedia | ACOD1 (Hs) |
| Enzyme Reaction |
||||||||||
|
||||||||||
| Immunopharmacology Comments |
| Itaconate (itaconic acid) is generated from the citric acid (TCA) cycle intermediate cis-aconitic acid which is produced by mitochondria. Itaconate is synthesised by the enzyme aconitate decarboxylase 1 (referred to as immunoresponsive gene 1 or IRG1). Its synthesis links metabolism to immunity and it plays an important role in the macrophage-based immune response [2-3]. In the cancer setting, tumour cells alter the metabolic state of macrophages and induce their itaconate production. This itaconate potentiates tumour growth, at least as demonstrated in peritoneal tumours [5]. Itaconate-mediated tumour growth may be associated with this metabolite's ability to induce tolerance in human monocytes [3]. As the primary source of itaconate in cells, IRG1 is therefore a target for novel anti-cancer therapeutic design and development. Modulation of immune cell activity by itaconate and/or itaconate derivatives (e.g. dimethyl itaconate) has been suggested as a tractable mechanistic approach for the treatment of IL-17-driven autoimmune diseases [1]. |
| Cell Type Associations | ||||||||
|
| Immuno Process Associations | ||
|
||
|
||
|
||
|
||
|
1. Bambouskova M, Gorvel L, Lampropoulou V, Sergushichev A, Loginicheva E, Johnson K, Korenfeld D, Mathyer ME, Kim H, Huang LH et al.. (2018) Electrophilic properties of itaconate and derivatives regulate the IκBζ-ATF3 inflammatory axis. Nature, 556 (7702): 501-504. [PMID:29670287]
2. Cordes T, Michelucci A, Hiller K. (2015) Itaconic Acid: The Surprising Role of an Industrial Compound as a Mammalian Antimicrobial Metabolite. Annu Rev Nutr, 35: 451-73. [PMID:25974697]
3. Domínguez-Andrés J, Novakovic B, Li Y, Scicluna BP, Gresnigt MS, Arts RJW, Oosting M, Moorlag SJCFM, Groh LA, Zwaag J et al.. (2019) The Itaconate Pathway Is a Central Regulatory Node Linking Innate Immune Tolerance and Trained Immunity. Cell Metab, 29 (1): 211-220.e5. [PMID:30293776]
4. Strelko CL, Lu W, Dufort FJ, Seyfried TN, Chiles TC, Rabinowitz JD, Roberts MF. (2011) Itaconic acid is a mammalian metabolite induced during macrophage activation. J Am Chem Soc, 133 (41): 16386-9. [PMID:21919507]
5. Weiss JM, Davies LC, Karwan M, Ileva L, Ozaki MK, Cheng RY, Ridnour LA, Annunziata CM, Wink DA, McVicar DW. (2018) Itaconic acid mediates crosstalk between macrophage metabolism and peritoneal tumors. J Clin Invest, 128 (9): 3794-3805. [PMID:29920191]
6. Xiao W, Wang L, Xiao R, Wu M, Tan J, He Y. (2011) Expression profile of human immune-responsive gene 1 and generation and characterization of polyclonal antiserum. Mol Cell Biochem, 353 (1-2): 177-87. [PMID:21424586]
Itaconate biosynthesis: aconitate decarboxylase 1. Last modified on 22/10/2018. Accessed on 06/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=3018.
