IRG1_MOUSE
ID IRG1_MOUSE Reviewed; 488 AA.
AC P54987; Q3TAA1; Q3U8E8; Q8CBA6;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 12-DEC-2006, sequence version 2.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=Cis-aconitate decarboxylase;
DE Short=CAD;
DE EC=4.1.1.6 {ECO:0000269|PubMed:23610393};
DE AltName: Full=Aconitate decarboxylase;
DE AltName: Full=Aconitate decarboxylase 1 {ECO:0000312|MGI:MGI:103206};
DE AltName: Full=Cis-aconitic acid decarboxylase;
DE AltName: Full=Immune-responsive gene 1 protein;
GN Name=Acod1 {ECO:0000312|MGI:MGI:103206}; Synonyms=Irg1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ;
RX PubMed=7721348; DOI=10.1007/bf00172150;
RA Lee C.G.L., Jenkins N.A., Gilbert D.J., Copeland N.G., O'Brien W.E.;
RT "Cloning and analysis of gene regulation of a novel LPS-inducible cDNA.";
RL Immunogenetics 41:263-270(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Bone, and Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP FUNCTION, INDUCTION BY PROGESTERONE, AND TISSUE SPECIFICITY.
RX PubMed=14500577; DOI=10.1210/en.2003-0585;
RA Cheon Y.P., Xu X., Bagchi M.K., Bagchi I.C.;
RT "Immune-responsive gene 1 is a novel target of progesterone receptor and
RT plays a critical role during implantation in the mouse.";
RL Endocrinology 144:5623-5630(2003).
RN [4]
RP SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=19014335; DOI=10.1089/jir.2008.0013;
RA Degrandi D., Hoffmann R., Beuter-Gunia C., Pfeffer K.;
RT "The proinflammatory cytokine-induced IRG1 protein associates with
RT mitochondria.";
RL J. Interferon Cytokine Res. 29:55-67(2009).
RN [5]
RP FUNCTION, INDUCTION BY LPS, AND TISSUE SPECIFICITY.
RX PubMed=23609450; DOI=10.1074/jbc.m113.454538;
RA Li Y., Zhang P., Wang C., Han C., Meng J., Liu X., Xu S., Li N., Wang Q.,
RA Shi X., Cao X.;
RT "Immune responsive gene 1 (IRG1) promotes endotoxin tolerance by increasing
RT A20 expression in macrophages through ROS.";
RL J. Biol. Chem. 288:16225-16234(2013).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, INDUCTION BY LPS, AND TISSUE SPECIFICITY.
RX PubMed=23610393; DOI=10.1073/pnas.1218599110;
RA Michelucci A., Cordes T., Ghelfi J., Pailot A., Reiling N., Goldmann O.,
RA Binz T., Wegner A., Tallam A., Rausell A., Buttini M., Linster C.L.,
RA Medina E., Balling R., Hiller K.;
RT "Immune-responsive gene 1 protein links metabolism to immunity by
RT catalyzing itaconic acid production.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:7820-7825(2013).
RN [7]
RP FUNCTION, AND INDUCTION.
RX PubMed=30635240; DOI=10.1016/j.immuni.2018.11.017;
RA Daniels B.P., Kofman S.B., Smith J.R., Norris G.T., Snyder A.G., Kolb J.P.,
RA Gao X., Locasale J.W., Martinez J., Gale M. Jr., Loo Y.M., Oberst A.;
RT "The nucleotide sensor ZBP1 and kinase RIPK3 induce the enzyme IRG1 to
RT promote an antiviral metabolic state in neurons.";
RL Immunity 50:64-76(2019).
CC -!- FUNCTION: Cis-aconitate decarboxylase that catalyzes production of
CC itaconate and is involved in the inhibition of the inflammatory
CC response (PubMed:23609450, PubMed:23610393, PubMed:30635240). Acts as a
CC negative regulator of the Toll-like receptors (TLRs)-mediated
CC inflammatory innate response by stimulating the tumor necrosis factor
CC alpha-induced protein TNFAIP3 expression via reactive oxygen species
CC (ROS) in LPS-tolerized macrophages (PubMed:23609450). Involved in
CC antimicrobial response of innate immune cells; ACOD1-mediated itaconic
CC acid production contributes to the antimicrobial activity of
CC macrophages (PubMed:23610393). Involved in antiviral response following
CC infection by flavivirus in neurons: ACOD1-mediated itaconate production
CC inhibits the activity of succinate dehydrogenase, generating a
CC metabolic state in neurons that suppresses replication of viral genomes
CC (PubMed:30635240). Plays a role in the embryo implantation
CC (PubMed:14500577). {ECO:0000269|PubMed:14500577,
CC ECO:0000269|PubMed:23609450, ECO:0000269|PubMed:23610393,
CC ECO:0000269|PubMed:30635240}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cis-aconitate + H(+) = CO2 + itaconate; Xref=Rhea:RHEA:15253,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16383, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:17240; EC=4.1.1.6;
CC Evidence={ECO:0000269|PubMed:23610393};
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:19014335}.
CC -!- TISSUE SPECIFICITY: Expressed in LPS-tolerized macrophages (at protein
CC level). Expressed in the luminal epithelial cells of pregnant uterus.
CC Expressed in microglia and macrophage cells.
CC {ECO:0000269|PubMed:14500577, ECO:0000269|PubMed:23609450,
CC ECO:0000269|PubMed:23610393}.
CC -!- INDUCTION: Up-regulated after lipopolysaccharide (LPS) stimulation
CC (PubMed:23609450, PubMed:23610393). Up-regulated in LPS-tolerized
CC macrophage by LPS (PubMed:23609450, PubMed:23610393). Up-regulated
CC synergistically by pro-inflammatory cytokines TNF and IFNG
CC (PubMed:19014335). Up-regulated by pro-inflammatory cytokines IL1B and
CC IFNB1 (PubMed:19014335). Up-regulated by progesterone and at the time
CC of the embryo implantation (PubMed:14500577). Expression is activated
CC by IRF1 in neurons in response to flavivirus infection in neurons
CC (PubMed:30635240). {ECO:0000269|PubMed:14500577,
CC ECO:0000269|PubMed:19014335, ECO:0000269|PubMed:23609450,
CC ECO:0000269|PubMed:23610393, ECO:0000269|PubMed:30635240}.
CC -!- SIMILARITY: Belongs to the PrpD family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA74554.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; L38281; AAA74554.1; ALT_SEQ; mRNA.
DR EMBL; AK036446; BAC29433.1; -; mRNA.
DR EMBL; AK152177; BAE31008.1; -; mRNA.
DR EMBL; AK152248; BAE31070.1; -; mRNA.
DR EMBL; AK152332; BAE31131.1; -; mRNA.
DR EMBL; AK152635; BAE31377.1; -; mRNA.
DR EMBL; AK172001; BAE42768.1; -; mRNA.
DR EMBL; AK172298; BAE42932.1; -; mRNA.
DR CCDS; CCDS49558.1; -.
DR PIR; I54546; I54546.
DR RefSeq; NP_032418.1; NM_008392.1.
DR PDB; 6R6T; X-ray; 2.54 A; A/B=2-488.
DR PDB; 7BR9; X-ray; 3.30 A; A/B=1-488.
DR PDBsum; 6R6T; -.
DR PDBsum; 7BR9; -.
DR AlphaFoldDB; P54987; -.
DR SMR; P54987; -.
DR BioGRID; 200787; 2.
DR IntAct; P54987; 3.
DR MINT; P54987; -.
DR STRING; 10090.ENSMUSP00000022722; -.
DR iPTMnet; P54987; -.
DR PhosphoSitePlus; P54987; -.
DR SwissPalm; P54987; -.
DR MaxQB; P54987; -.
DR PaxDb; P54987; -.
DR PeptideAtlas; P54987; -.
DR PRIDE; P54987; -.
DR ProteomicsDB; 269507; -.
DR GeneID; 16365; -.
DR KEGG; mmu:16365; -.
DR UCSC; uc007uwf.2; mouse.
DR CTD; 730249; -.
DR MGI; MGI:103206; Acod1.
DR eggNOG; ENOG502QVEB; Eukaryota.
DR InParanoid; P54987; -.
DR OrthoDB; 822621at2759; -.
DR PhylomeDB; P54987; -.
DR TreeFam; TF332296; -.
DR BRENDA; 4.1.1.6; 3474.
DR BioGRID-ORCS; 16365; 5 hits in 74 CRISPR screens.
DR ChiTaRS; Acod1; mouse.
DR PRO; PR:P54987; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P54987; protein.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0047613; F:aconitate decarboxylase activity; IDA:UniProtKB.
DR GO; GO:0035458; P:cellular response to interferon-beta; IDA:UniProtKB.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IDA:UniProtKB.
DR GO; GO:0071347; P:cellular response to interleukin-1; IDA:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:UniProtKB.
DR GO; GO:0071219; P:cellular response to molecule of bacterial origin; IDA:UniProtKB.
DR GO; GO:0071393; P:cellular response to progesterone stimulus; IDA:UniProtKB.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:UniProtKB.
DR GO; GO:0006952; P:defense response; IDA:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IMP:UniProtKB.
DR GO; GO:0007566; P:embryo implantation; IMP:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IDA:UniProtKB.
DR GO; GO:0045824; P:negative regulation of innate immune response; IDA:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
DR GO; GO:0034136; P:negative regulation of toll-like receptor 2 signaling pathway; IMP:UniProtKB.
DR GO; GO:0034144; P:negative regulation of toll-like receptor 4 signaling pathway; IDA:UniProtKB.
DR GO; GO:0032480; P:negative regulation of type I interferon production; IMP:UniProtKB.
DR GO; GO:0002760; P:positive regulation of antimicrobial humoral response; IDA:UniProtKB.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IDA:UniProtKB.
DR GO; GO:0009617; P:response to bacterium; IEP:MGI.
DR GO; GO:0032496; P:response to lipopolysaccharide; IDA:MGI.
DR GO; GO:0072573; P:tolerance induction to lipopolysaccharide; IDA:UniProtKB.
DR Gene3D; 1.10.4100.10; -; 1.
DR Gene3D; 3.30.1330.120; -; 1.
DR InterPro; IPR036148; MmgE/PrpD_sf.
DR InterPro; IPR042183; MmgE/PrpD_sf_1.
DR InterPro; IPR042188; MmgE/PrpD_sf_2.
DR InterPro; IPR005656; MmgE_PrpD.
DR InterPro; IPR045337; MmgE_PrpD_C.
DR InterPro; IPR045336; MmgE_PrpD_N.
DR PANTHER; PTHR16943; PTHR16943; 1.
DR Pfam; PF03972; MmgE_PrpD; 1.
DR Pfam; PF19305; MmgE_PrpD_C; 1.
DR SUPFAM; SSF103378; SSF103378; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antimicrobial; Immunity; Inflammatory response;
KW Innate immunity; Lyase; Mitochondrion; Reference proteome.
FT CHAIN 1..488
FT /note="Cis-aconitate decarboxylase"
FT /id="PRO_0000084233"
FT CONFLICT 122..123
FT /note="IP -> TL (in Ref. 2; BAE31070/BAE31377/BAE31131/
FT BAE31008)"
FT /evidence="ECO:0000305"
FT CONFLICT 122
FT /note="I -> T (in Ref. 2; BAE42768/BAC29433/BAE42932)"
FT /evidence="ECO:0000305"
FT CONFLICT 248
FT /note="N -> S (in Ref. 2; BAE42768)"
FT /evidence="ECO:0000305"
FT CONFLICT 402
FT /note="R -> G (in Ref. 2; BAE31070/BAE31377/BAE31131/
FT BAE31008)"
FT /evidence="ECO:0000305"
FT HELIX 6..16
FT /evidence="ECO:0007829|PDB:6R6T"
FT HELIX 19..21
FT /evidence="ECO:0007829|PDB:6R6T"
FT HELIX 24..44
FT /evidence="ECO:0007829|PDB:6R6T"
FT HELIX 48..57
FT /evidence="ECO:0007829|PDB:6R6T"
FT HELIX 58..60
FT /evidence="ECO:0007829|PDB:6R6T"
FT STRAND 65..68
FT /evidence="ECO:0007829|PDB:6R6T"
FT STRAND 71..76
FT /evidence="ECO:0007829|PDB:6R6T"
FT HELIX 78..90
FT /evidence="ECO:0007829|PDB:6R6T"
FT TURN 91..93
FT /evidence="ECO:0007829|PDB:7BR9"
FT STRAND 99..101
FT /evidence="ECO:0007829|PDB:6R6T"
FT TURN 106..108
FT /evidence="ECO:0007829|PDB:6R6T"
FT HELIX 109..118
FT /evidence="ECO:0007829|PDB:6R6T"
FT HELIX 127..145
FT /evidence="ECO:0007829|PDB:6R6T"
FT HELIX 149..152
FT /evidence="ECO:0007829|PDB:7BR9"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:7BR9"
FT HELIX 160..176
FT /evidence="ECO:0007829|PDB:6R6T"
FT HELIX 181..192
FT /evidence="ECO:0007829|PDB:6R6T"
FT HELIX 199..203
FT /evidence="ECO:0007829|PDB:6R6T"
FT HELIX 207..226
FT /evidence="ECO:0007829|PDB:6R6T"
FT TURN 233..237
FT /evidence="ECO:0007829|PDB:6R6T"
FT TURN 239..241
FT /evidence="ECO:0007829|PDB:6R6T"
FT HELIX 242..245
FT /evidence="ECO:0007829|PDB:6R6T"
FT STRAND 246..249
FT /evidence="ECO:0007829|PDB:6R6T"
FT TURN 257..259
FT /evidence="ECO:0007829|PDB:6R6T"
FT HELIX 263..266
FT /evidence="ECO:0007829|PDB:6R6T"
FT STRAND 273..276
FT /evidence="ECO:0007829|PDB:6R6T"
FT HELIX 279..291
FT /evidence="ECO:0007829|PDB:6R6T"
FT STRAND 297..299
FT /evidence="ECO:0007829|PDB:6R6T"
FT HELIX 304..306
FT /evidence="ECO:0007829|PDB:6R6T"
FT STRAND 307..313
FT /evidence="ECO:0007829|PDB:6R6T"
FT HELIX 318..320
FT /evidence="ECO:0007829|PDB:6R6T"
FT HELIX 328..331
FT /evidence="ECO:0007829|PDB:6R6T"
FT HELIX 335..345
FT /evidence="ECO:0007829|PDB:6R6T"
FT HELIX 350..353
FT /evidence="ECO:0007829|PDB:6R6T"
FT HELIX 355..358
FT /evidence="ECO:0007829|PDB:6R6T"
FT HELIX 361..367
FT /evidence="ECO:0007829|PDB:6R6T"
FT STRAND 370..373
FT /evidence="ECO:0007829|PDB:6R6T"
FT TURN 382..384
FT /evidence="ECO:0007829|PDB:6R6T"
FT STRAND 387..393
FT /evidence="ECO:0007829|PDB:6R6T"
FT STRAND 398..405
FT /evidence="ECO:0007829|PDB:6R6T"
FT HELIX 416..426
FT /evidence="ECO:0007829|PDB:6R6T"
FT TURN 427..430
FT /evidence="ECO:0007829|PDB:6R6T"
FT HELIX 433..444
FT /evidence="ECO:0007829|PDB:6R6T"
FT HELIX 446..448
FT /evidence="ECO:0007829|PDB:7BR9"
FT HELIX 453..457
FT /evidence="ECO:0007829|PDB:6R6T"
SQ SEQUENCE 488 AA; 53758 MW; 0F573147307DE684 CRC64;
MMLKSVTESF AGMIHGLKVN HLTDGIIRRS KRMILDSLGV GFLGTGTEVF HKVTQYSKIY
SSNTSSTVWG RPDFRLPPTY AAFVNGVAVH SMDFDDTWHP ATHPSGAVLP VLTALSEALP
QIPKFSGLDL LLAFNVGIEV QGRLMHFSKE AKDIPKRFHP PSVVGTLGSA AAASKFLGLS
LTKCREALAI AVSHAGAPIA NAATQTKPLH IGNAAKHGME ATFLAMLGLQ GNKQILDLGS
GFGAFYANYS PEDLPSLDSH IWLLDQQDVA FKSFPAHLAT HWVADAAAAV RKHLVTPERA
LFPADHIERI VLRIPDVQYV NRPFPDSEHE ARHSFQYVAC ASLLDGSITV PSFHSQQVNR
PQVRELLKKV KLEHPPDNPP SFDTLYCEIS ITLKDGTTFT ERSDTFYGHW RKPLSQEDLR
NKFRANASKM LCRDTVESLI TVVEKLEDLE DCSVLTRLLK GPSVQDEASK LSSMSSFDHT
TLPRFTNI
