aconitate decarboxylase 1

Immunopharmacology Ligand Target has curated data in GtoImmuPdb

Target id: 3018

Nomenclature: aconitate decarboxylase 1

Abbreviated Name: IRG1

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

EC Number: 4.1.1.6
	Description	Reaction	Reference
	Generates itaconic acid via decarboxylation of cis-aconitate (a TCA cycle intermediate).	Cis-aconitate <=> itaconate + CO(2)	4

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].

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 Cell Type:	Macrophages & monocytes
Cell Ontology Term:	macrophage (CL:0000235)
Comment:	Expressed by macrophages.
References:	6

Immuno Process Associations

Immuno Process:

Cellular signalling

Immuno Process:

Cytokine production & signalling

Immuno Process:

Immune regulation

Immuno Process:

Immune system development

Immuno Process:

Inflammation

References

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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]

How to cite this page

Itaconate biosynthesis: aconitate decarboxylase 1. Last modified on 22/10/2018. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=3018.

aconitate decarboxylase 1

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References

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