UniProt functional annotation for Q14116



	UniProt functional annotation for Q14116

UniProt code: Q14116.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: A proinflammatory cytokine primarily involved in polarized T- helper 1 (Th1) cell and natural killer (NK) cell immune responses (Probable). 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). Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells and natural killer (NK) cells (Probable) (PubMed:10653850). {ECO:0000269|PubMed:10653850, ECO:0000269|PubMed:14528293, ECO:0000269|PubMed:25500532, ECO:0000305}.

Subunit: Forms a ternary complex with ligand-binding receptor subunit IL18R1 and signaling receptor subunit IL18RAP at the plasma membrane. Mature IL18 first binds to IL18R1 forming a low affinity binary complex, which then interacts with IL18RAP to form a high affinity ternary complex that signals inside the cell (PubMed:25261253, PubMed:14528293, PubMed:25500532). Interacts with cargo receptor TMED10; the interaction mediates the translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and thereby secretion (PubMed:32272059). {ECO:0000269|PubMed:14528293, ECO:0000269|PubMed:25261253, ECO:0000269|PubMed:25500532, ECO:0000269|PubMed:32272059}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:32272059}. Secreted {ECO:0000269|PubMed:23955712}. Note=The secretion is dependent on protein unfolding and facilitated by the cargo receptor TMED10; it results in protein translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) followed by vesicle entry and secretion. {ECO:0000269|PubMed:32272059}.

Induction: In macrophages, release is increased by endocannabinoid anandamide/AEA. {ECO:0000269|PubMed:23955712}.

Ptm: The pro-IL-18 precursor is processed by CASP1 or CASP4 to yield the active form. {ECO:0000269|PubMed:15326478, ECO:0000269|PubMed:25261253}.

Miscellaneous: [Isoform 2]: Expressed in ovarian carcinoma but undetectable in normal ovarian epithelial cells. Resistant to proteolytic activation by caspase-1 and -4. {ECO:0000305}.

Similarity: Belongs to the IL-1 family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		A proinflammatory cytokine primarily involved in polarized T- helper 1 (Th1) cell and natural killer (NK) cell immune responses (Probable). 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). Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells and natural killer (NK) cells (Probable) (PubMed:10653850). {ECO:0000269\|PubMed:10653850, ECO:0000269\|PubMed:14528293, ECO:0000269\|PubMed:25500532, ECO:0000305}.


Subunit:		Forms a ternary complex with ligand-binding receptor subunit IL18R1 and signaling receptor subunit IL18RAP at the plasma membrane. Mature IL18 first binds to IL18R1 forming a low affinity binary complex, which then interacts with IL18RAP to form a high affinity ternary complex that signals inside the cell (PubMed:25261253, PubMed:14528293, PubMed:25500532). Interacts with cargo receptor TMED10; the interaction mediates the translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and thereby secretion (PubMed:32272059). {ECO:0000269\|PubMed:14528293, ECO:0000269\|PubMed:25261253, ECO:0000269\|PubMed:25500532, ECO:0000269\|PubMed:32272059}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:32272059}. Secreted {ECO:0000269\|PubMed:23955712}. Note=The secretion is dependent on protein unfolding and facilitated by the cargo receptor TMED10; it results in protein translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) followed by vesicle entry and secretion. {ECO:0000269\|PubMed:32272059}.
Induction:		In macrophages, release is increased by endocannabinoid anandamide/AEA. {ECO:0000269\|PubMed:23955712}.
Ptm:		The pro-IL-18 precursor is processed by CASP1 or CASP4 to yield the active form. {ECO:0000269\|PubMed:15326478, ECO:0000269\|PubMed:25261253}.
Miscellaneous:		[Isoform 2]: Expressed in ovarian carcinoma but undetectable in normal ovarian epithelial cells. Resistant to proteolytic activation by caspase-1 and -4. {ECO:0000305}.
Similarity:		Belongs to the IL-1 family. {ECO:0000305}.