IL18
entrez
3606
canonical
uniprot
Q14116
canonical
ensembl
ENSG00000150782
resolver
ensp
ENSP00000280357
resolver
ensp
ENSP00000434161
resolver
ensp
ENSP00000434561
resolver
ensp
ENSP00000615906
resolver
ensp
ENSP00000615907
resolver
genesymbol
IL18
resolver
genesymbol_syn
IGIF
resolver
genesymbol_syn
IL1F4
resolver
hgnc
HGNC:5986
resolver
uniprot
O75599
resolver
uniprot
Q6FGY3
resolver
uniprot
Q6WWJ7
resolver
uniprot_entry
IL18_HUMAN
resolver
uniprot_sec
O75599
resolver
uniprot_sec
Q6FGY3
resolver
uniprot_sec
Q6WWJ7
resolver
amino_acid_sequence
MAAEPVEDNCINFVAMKFIDNTLYFIAEDDENLESDYFGKLESKLSVIRNLNDQVLFIDQGNRPLFEDMTDSDCRDNAPRTIFIISMYKDSQPRGMAVTISVKCEKISTLSCENKIISFKEMNPPDNIKDTKSDIIFFQRSVPGHDNKMQFESSSYEGYFLACEKERDLFKLILKKEDELGDRSIMFTVQNED
uniprot
proteins
function
FUNCTION: Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (PubMed:10653850). Upon binding to IL18R1 and IL18RAP, forms a signaling ternary complex which activates NF-kappa-B, triggering synthesis of inflammatory mediators (PubMed:14528293, PubMed:25500532, PubMed:37993714). Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells and natural killer (NK) cells (PubMed:10653850). Involved in transduction of inflammation downstream of pyroptosis: its mature form is specifically released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore (PubMed:33883744). {ECO:0000269|PubMed:10653850, ECO:0000269|PubMed:14528293, ECO:0000269|PubMed:25500532, ECO:0000269|PubMed:33883744, ECO:0000269|PubMed:37993714}.
uniprot
proteins
mass_dalton
22326
uniprot
proteins
mutagenesis
MUTAGEN 12; /note="N->A: Strongly decreased processing by CASP4 or CASP5; when associated with A-28."; /evidence="ECO:0000269|PubMed:37993714"; MUTAGEN 28; /note="E->A: Strongly decreased processing by CASP4 or CASP5; when associated with A-12."; /evidence="ECO:0000269|PubMed:37993714"; MUTAGEN 33..35; /note="LES->AAA: Abolished processing by CASP1, CASP4 or CASP5 and maturation."; /evidence="ECO:0000269|PubMed:37993712, ECO:0000269|PubMed:37993714"; MUTAGEN 36; /note="D->A: Abolished processing by CASP1 or CASP4 or CASP5 and maturation."; /evidence="ECO:0000269|PubMed:37993714"; MUTAGEN 37..38; /note="YF->AA: Does not strongly affect cleavage by CASP4."; /evidence="ECO:0000269|PubMed:37993714"; MUTAGEN 38; /note="F->D: Abolished ability to bind the IL18R1 receptor without affecting its processing by CASP4."; /evidence="ECO:0000269|PubMed:37993714"; MUTAGEN 40; /note="K->A: Reduces binding to IL18R1 and the ability to induce IFNG production."; /evidence="ECO:0000269|PubMed:14528293"; MUTAGEN 41; /note="L->A: Impairs binding to IL18R1 and the ability to induce IFNG production."; /evidence="ECO:0000269|PubMed:14528293"; MUTAGEN 44; /note="K->A: Reduces binding to IL18R1 and the ability to induce IFNG production."; /evidence="ECO:0000269|PubMed:14528293"; MUTAGEN 47..48; /note="VI->NN: Decreased binding to CASP4."; /evidence="ECO:0000269|PubMed:37993712"; MUTAGEN 49; /note="R->A: Reduces binding to IL18R1 and the ability to induce IFNG production."; /evidence="ECO:0000269|PubMed:14528293"; MUTAGEN 53; /note="D->A: Reduces binding to IL18R1 and the ability to induce IFNG production."; /evidence="ECO:0000269|PubMed:14528293"; MUTAGEN 69; /note="M->A: Impairs binding to IL18R1 and the ability to induce IFNG production."; /evidence="ECO:0000269|PubMed:14528293"; MUTAGEN 70..77; /note="Missing: Abolished ability to bind the IL18R1 receptor without affecting its processing by CASP4."; /evidence="ECO:0000269|PubMed:37993714"; MUTAGEN 71; /note="D->A: Impairs binding to IL18R1 and the ability to induce IFNG production. Abolished cleavage by CASP3."; /evidence="ECO:0000269|PubMed:14528293, ECO:0000269|PubMed:37993714"; MUTAGEN 94; /note="R->A: Impairs binding to IL18R1 and the ability to induce IFNG production."; /evidence="ECO:0000269|PubMed:14528293"; MUTAGEN 96; /note="M->A: Impairs binding to IL18R1 and the ability to induce IFNG production."; /evidence="ECO:0000269|PubMed:14528293"; MUTAGEN 115; /note="K->A: Reduces binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP resulting in impaired IFNG production."; /evidence="ECO:0000269|PubMed:14528293"; MUTAGEN 120; /note="K->A: Reduces binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP resulting in impaired IFNG production."; /evidence="ECO:0000269|PubMed:14528293"; MUTAGEN 134; /note="D->A: Reduces binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP resulting in impaired IFNG production."; /evidence="ECO:0000269|PubMed:14528293"; MUTAGEN 140; /note="R->A: Reduces binding to IL18R1 and the ability to induce IFNG production."; /evidence="ECO:0000269|PubMed:14528293"; MUTAGEN 144; /note="G->A: Abolishes binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP."; /evidence="ECO:0000269|PubMed:25500532"; MUTAGEN 145; /note="H->A: Abolishes binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP."; /evidence="ECO:0000269|PubMed:25500532"; MUTAGEN 146; /note="D->A: Reduces binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP."; /evidence="ECO:0000269|PubMed:25500532"; MUTAGEN 148; /note="K->A: Abolishes binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP."; /evidence="ECO:0000269|PubMed:25500532"; MUTAGEN 168; /note="D->A: Reduces binding to IL18R1 and the ability to induce IFNG production."; /evidence="ECO:0000269|PubMed:14528293"; MUTAGEN 183; /note="R->A: Reduces binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP."; /evidence="ECO:0000269|PubMed:25500532"; MUTAGEN 186; /note="M->A: Reduces binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP."; /evidence="ECO:0000269|PubMed:25500532"; MUTAGEN 192..193; /note="ED->KK: Decreased binding to Casp4/Casp11."; /evidence="ECO:0000269|PubMed:37993712
uniprot
proteins
post_translational_modification
PTM: The pro-IL-18 precursor is processed by CASP1, CASP4 or CASP5 to yield its mature, active form (PubMed:15326478, PubMed:25261253, PubMed:37993712, PubMed:37993714, PubMed:9334240). The pro-IL-18 precursor features autoinhibitory interactions between the propeptide and the post-cleavage-site region, preventing recognition by the IL18R1 receptor (PubMed:37993714). Processing by CASP1, CASP4 or CASP5 induces conformational changes to generate critical receptor-binding sites (PubMed:37993714). The mature form is then secreted and released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore (PubMed:33883744, PubMed:37993714). In contrast, cleavage by CASP3 inactivates IL18 (PubMed:37993714, PubMed:9334240). {ECO:0000269|PubMed:15326478, ECO:0000269|PubMed:25261253, ECO:0000269|PubMed:33883744, ECO:0000269|PubMed:37993712, ECO:0000269|PubMed:37993714, ECO:0000269|PubMed:9334240}.
uniprot
proteins
protein_family
IL-1 family
uniprot
proteins
pubmed
10653850
uniprot
proteins
pubmed
14528293
uniprot
proteins
pubmed
15326478
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
23955712
uniprot
proteins
pubmed
25261253
uniprot
proteins
pubmed
25500532
uniprot
proteins
pubmed
32272059
uniprot
proteins
pubmed
33883744
uniprot
proteins
pubmed
37993712
uniprot
proteins
pubmed
37993714
uniprot
proteins
pubmed
8666798
uniprot
proteins
pubmed
9334240
uniprot
proteins
sequence_length
193
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:32272059, ECO:0000269|PubMed:33883744, ECO:0000269|PubMed:9334240}. Secreted {ECO:0000269|PubMed:23955712, ECO:0000269|PubMed:32272059, ECO:0000269|PubMed:33883744, ECO:0000269|PubMed:37993712, ECO:0000269|PubMed:37993714}. Note=The precursor is cytosolic (PubMed:33883744). In response to inflammasome-activating signals, cleaved and secreted (PubMed:33883744, PubMed:37993712, PubMed:37993714). Mature form is secreted and released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore (PubMed:33883744, PubMed:37993714). In contrast, the precursor form is not released, due to the presence of an acidic region that is proteolytically removed by CASP1, CASP4 or CASP5 during maturation (PubMed:33883744, PubMed:37993714). The secretion is dependent on protein unfolding and facilitated by the cargo receptor TMED10 (PubMed:32272059). {ECO:0000269|PubMed:32272059, ECO:0000269|PubMed:33883744, ECO:0000269|PubMed:37993712, ECO:0000269|PubMed:37993714}.
uniprot
proteins