IRG1_HUMAN
ID IRG1_HUMAN Reviewed; 481 AA.
AC A6NK06;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-JUL-2007, sequence version 1.
DT 03-AUG-2022, entry version 102.
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|HGNC:HGNC:33904};
DE AltName: Full=Cis-aconitic acid decarboxylase;
DE AltName: Full=Immune-responsive gene 1 protein;
GN Name=ACOD1 {ECO:0000312|HGNC:HGNC:33904}; Synonyms=IRG1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [2]
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 [3]
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).
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). Acts as a negative
CC regulator of the Toll-like receptors (TLRs)-mediated inflammatory
CC innate response by stimulating the tumor necrosis factor alpha-induced
CC protein TNFAIP3 expression via reactive oxygen species (ROS) in LPS-
CC tolerized macrophages (PubMed:23609450). Involved in antimicrobial
CC response of innate immune cells; ACOD1-mediated itaconic acid
CC production contributes to the antimicrobial activity of macrophages
CC (PubMed:23610393). Involved in antiviral response following infection
CC by flavivirus in neurons: ACOD1-mediated itaconate production inhibits
CC the activity of succinate dehydrogenase, generating a metabolic state
CC in neurons that suppresses replication of viral genomes (By
CC similarity). Plays a role in the embryo implantation (By similarity).
CC {ECO:0000250|UniProtKB:P54987, ECO:0000269|PubMed:23609450,
CC ECO:0000269|PubMed:23610393}.
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:0000250|UniProtKB:P54987}.
CC -!- TISSUE SPECIFICITY: Expressed in LPS-tolerized macrophages (at protein
CC level). Expressed in peripheral blood mononuclear cells (PBMCs),
CC microglia and macrophage cells. {ECO:0000269|PubMed:23609450,
CC ECO:0000269|PubMed:23610393}.
CC -!- INDUCTION: Up-regulated after lipopolysaccharide (LPS) stimulation. Up-
CC regulated in LPS-tolerized macrophage by LPS. Up-regulated in
CC peripheral blood mononuclear cells (PBMC) of patient after acute
CC sepsis. {ECO:0000269|PubMed:23609450, ECO:0000269|PubMed:23610393}.
CC -!- SIMILARITY: Belongs to the PrpD family. {ECO:0000305}.
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DR EMBL; AC000403; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS58299.1; -.
DR RefSeq; NP_001245335.1; NM_001258406.1.
DR PDB; 6R6U; X-ray; 1.71 A; A/B=4-461.
DR PDBsum; 6R6U; -.
DR AlphaFoldDB; A6NK06; -.
DR SMR; A6NK06; -.
DR BioGRID; 610637; 1.
DR STRING; 9606.ENSP00000366682; -.
DR iPTMnet; A6NK06; -.
DR PhosphoSitePlus; A6NK06; -.
DR BioMuta; ACOD1; -.
DR MassIVE; A6NK06; -.
DR PaxDb; A6NK06; -.
DR PeptideAtlas; A6NK06; -.
DR PRIDE; A6NK06; -.
DR ProteomicsDB; 1370; -.
DR Antibodypedia; 50071; 77 antibodies from 15 providers.
DR DNASU; 730249; -.
DR Ensembl; ENST00000377462.6; ENSP00000366682.1; ENSG00000102794.10.
DR GeneID; 730249; -.
DR KEGG; hsa:730249; -.
DR MANE-Select; ENST00000377462.6; ENSP00000366682.1; NM_001258406.2; NP_001245335.1.
DR UCSC; uc031qmi.3; human.
DR CTD; 730249; -.
DR DisGeNET; 730249; -.
DR GeneCards; ACOD1; -.
DR HGNC; HGNC:33904; ACOD1.
DR HPA; ENSG00000102794; Tissue enhanced (lymphoid).
DR MIM; 615275; gene.
DR neXtProt; NX_A6NK06; -.
DR OpenTargets; ENSG00000102794; -.
DR VEuPathDB; HostDB:ENSG00000102794; -.
DR eggNOG; ENOG502QVEB; Eukaryota.
DR GeneTree; ENSGT00390000015700; -.
DR HOGENOM; CLU_026574_2_2_1; -.
DR InParanoid; A6NK06; -.
DR OMA; AKFSMGT; -.
DR OrthoDB; 822621at2759; -.
DR PhylomeDB; A6NK06; -.
DR TreeFam; TF332296; -.
DR BioCyc; MetaCyc:ENSG00000102794-MON; -.
DR BRENDA; 4.1.1.6; 2681.
DR BioGRID-ORCS; 730249; 2 hits in 1052 CRISPR screens.
DR GenomeRNAi; 730249; -.
DR Pharos; A6NK06; Tbio.
DR PRO; PR:A6NK06; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; A6NK06; protein.
DR Bgee; ENSG00000102794; Expressed in nasal cavity epithelium and 41 other tissues.
DR ExpressionAtlas; A6NK06; baseline and differential.
DR Genevisible; A6NK06; HS.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0047613; F:aconitate decarboxylase activity; IDA:UniProtKB.
DR GO; GO:0035458; P:cellular response to interferon-beta; ISS:UniProtKB.
DR GO; GO:0071346; P:cellular response to interferon-gamma; ISS:UniProtKB.
DR GO; GO:0071347; P:cellular response to interleukin-1; ISS:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:UniProtKB.
DR GO; GO:0071219; P:cellular response to molecule of bacterial origin; ISS:UniProtKB.
DR GO; GO:0071393; P:cellular response to progesterone stimulus; ISS:UniProtKB.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; ISS:UniProtKB.
DR GO; GO:0006952; P:defense response; IDA:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; ISS:UniProtKB.
DR GO; GO:0007566; P:embryo implantation; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0045824; P:negative regulation of innate immune response; ISS:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0034136; P:negative regulation of toll-like receptor 2 signaling pathway; ISS:UniProtKB.
DR GO; GO:0034144; P:negative regulation of toll-like receptor 4 signaling pathway; ISS:UniProtKB.
DR GO; GO:0032480; P:negative regulation of type I interferon production; ISS: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; ISS:UniProtKB.
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..481
FT /note="Cis-aconitate decarboxylase"
FT /id="PRO_0000318692"
FT REGION 462..481
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 467..481
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT HELIX 6..16
FT /evidence="ECO:0007829|PDB:6R6U"
FT HELIX 19..21
FT /evidence="ECO:0007829|PDB:6R6U"
FT HELIX 24..44
FT /evidence="ECO:0007829|PDB:6R6U"
FT HELIX 48..57
FT /evidence="ECO:0007829|PDB:6R6U"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:6R6U"
FT STRAND 71..76
FT /evidence="ECO:0007829|PDB:6R6U"
FT HELIX 78..90
FT /evidence="ECO:0007829|PDB:6R6U"
FT STRAND 99..101
FT /evidence="ECO:0007829|PDB:6R6U"
FT HELIX 105..107
FT /evidence="ECO:0007829|PDB:6R6U"
FT HELIX 109..118
FT /evidence="ECO:0007829|PDB:6R6U"
FT HELIX 127..145
FT /evidence="ECO:0007829|PDB:6R6U"
FT HELIX 149..152
FT /evidence="ECO:0007829|PDB:6R6U"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:6R6U"
FT HELIX 160..177
FT /evidence="ECO:0007829|PDB:6R6U"
FT HELIX 181..192
FT /evidence="ECO:0007829|PDB:6R6U"
FT HELIX 199..201
FT /evidence="ECO:0007829|PDB:6R6U"
FT HELIX 207..226
FT /evidence="ECO:0007829|PDB:6R6U"
FT TURN 233..237
FT /evidence="ECO:0007829|PDB:6R6U"
FT TURN 239..241
FT /evidence="ECO:0007829|PDB:6R6U"
FT HELIX 242..245
FT /evidence="ECO:0007829|PDB:6R6U"
FT HELIX 257..259
FT /evidence="ECO:0007829|PDB:6R6U"
FT HELIX 263..265
FT /evidence="ECO:0007829|PDB:6R6U"
FT STRAND 273..276
FT /evidence="ECO:0007829|PDB:6R6U"
FT HELIX 279..296
FT /evidence="ECO:0007829|PDB:6R6U"
FT HELIX 303..305
FT /evidence="ECO:0007829|PDB:6R6U"
FT STRAND 306..312
FT /evidence="ECO:0007829|PDB:6R6U"
FT HELIX 317..319
FT /evidence="ECO:0007829|PDB:6R6U"
FT HELIX 327..331
FT /evidence="ECO:0007829|PDB:6R6U"
FT HELIX 334..344
FT /evidence="ECO:0007829|PDB:6R6U"
FT HELIX 349..352
FT /evidence="ECO:0007829|PDB:6R6U"
FT HELIX 354..357
FT /evidence="ECO:0007829|PDB:6R6U"
FT HELIX 360..366
FT /evidence="ECO:0007829|PDB:6R6U"
FT STRAND 369..372
FT /evidence="ECO:0007829|PDB:6R6U"
FT TURN 381..383
FT /evidence="ECO:0007829|PDB:6R6U"
FT STRAND 386..392
FT /evidence="ECO:0007829|PDB:6R6U"
FT STRAND 397..404
FT /evidence="ECO:0007829|PDB:6R6U"
FT HELIX 415..426
FT /evidence="ECO:0007829|PDB:6R6U"
FT TURN 427..429
FT /evidence="ECO:0007829|PDB:6R6U"
FT HELIX 432..443
FT /evidence="ECO:0007829|PDB:6R6U"
FT HELIX 445..447
FT /evidence="ECO:0007829|PDB:6R6U"
FT HELIX 452..458
FT /evidence="ECO:0007829|PDB:6R6U"
SQ SEQUENCE 481 AA; 52628 MW; 4F612CD6410166F6 CRC64;
MMLKSITESF ATAIHGLKVG HLTDRVIQRS KRMILDTLGA GFLGTTTEVF HIASQYSKIY
SSNISSTVWG QPDIRLPPTY AAFVNGVAIH SMDFDDTWHP ATHPSGAVLP VLTALAEALP
RSPKFSGLDL LLAFNVGIEV QGRLLHFAKE ANDMPKRFHP PSVVGTLGSA AAASKFLGLS
STKCREALAI AVSHAGAPMA NAATQTKPLH IGNAAKHGIE AAFLAMLGLQ GNKQVLDLEA
GFGAFYANYS PKVLPSIASY SWLLDQQDVA FKRFPAHLST HWVADAAASV RKHLVAERAL
LPTDYIKRIV LRIPNVQYVN RPFPVSEHEA RHSFQYVACA MLLDGGITVP SFHECQINRP
QVRELLSKVE LEYPPDNLPS FNILYCEISV TLKDGATFTD RSDTFYGHWR KPLSQEDLEE
KFRANASKML SWDTVESLIK IVKNLEDLED CSVLTTLLKG PSPPEVASNS PACNNSITNL
S
