IL1A

Domain

The similarity among the IL-1 precursors suggests that the amino ends of these proteins serve some as yet undefined function.

Function

Cytokine constitutively present intracellularly in nearly all resting non-hematopoietic cells that plays an important role in inflammation and bridges the innate and adaptive immune systems (PubMed:26439902). After binding to its receptor IL1R1 together with its accessory protein IL1RAP, forms the high affinity interleukin-1 receptor complex (PubMed:17507369, PubMed:2950091). Signaling involves the recruitment of adapter molecules such as MYD88, IRAK1 or IRAK4 (PubMed:17507369). In turn, mediates the activation of NF-kappa-B and the three MAPK pathways p38, p42/p44 and JNK pathways (PubMed:14687581). Within the cell, acts as an alarmin and cell death results in its liberation in the extracellular space after disruption of the cell membrane to induce inflammation and alert the host to injury or damage (PubMed:15679580). In addition to its role as a danger signal, which occurs when the cytokine is passively released by cell necrosis, directly senses DNA damage and acts as a signal for genotoxic stress without loss of cell integrity (PubMed:26439902).

Post-translational modifications

Acetylated within its nuclear localization sequence, which impacts subcellular localization.

Proteolytic processed by CAPN1 in a calcium-dependent manner. Cleavage from 31 kDa precursor to 18 kDa biologically active molecules.

Phosphorylated. Phosphorylation greatly enhances susceptibility to digestion and promotes the conversion of pre-IL1A alpha to the biologically active IL1A.

Sequence Similarities

Belongs to the IL-1 family.

Cellular localization

• Nucleus
• Cytoplasm
• Secreted
• The lack of a specific hydrophobic segment in the precursor sequence suggests that IL-1 is released by damaged cells or is secreted by a mechanism differing from that used for other secretory proteins. 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 (PubMed:32272059). Recruited to DNA damage sites and secreted after genotoxic stress.

Alternative names

IL1F1, IL1A, Interleukin-1 alpha, IL-1 alpha, Hematopoietin-1

Database links

swissprot:P01583 omim:147760 entrezGene:3552

Other research areas

• Cardiovascular
• Immuno-oncology