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FLASH GENE
Symbol IL1A contributors: mct - updated : 02-06-2015
HGNC name interleukin 1, alpha
HGNC id 5991
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularvessel   predominantly
Digestivemouth   moderately
 pharynx   moderately
Lymphoid/Immunelymph node   moderately
Reproductivemale systemtestis  moderately
Skin/Tegumentskin   moderately
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / hematopoietic   predominantly
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticplatelet Homo sapiens
Lymphoid/Immunemacrophage Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period fetal
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • lacks the N-terminal signal peptide
  • mono polymer monomer
    isoforms Precursor
    HOMOLOGY
    interspecies homolog to murine Il1a (62.26 pc)
    homolog to rattus Il1a (65.28 pc)
    intraspecies paralog to IL1AB
    Homologene
    FAMILY
  • IL1 family
  • CATEGORY immunity/defense , signaling cytokine
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,cytosolic
    text
  • endogenous IL1A is essentially found as a chromatin-associated nuclear protein in LPS-stimulated macrophages
  • basic FUNCTION
  • involved in the inflammatory response
  • stimulating osteoclastogenesis
  • inhibiting EPO gene expression
  • playing a crucial role in the regulation of a number of key cellular processes (potent mediator of bodys response to inflammation, microbial invasion, tissue injury, and immunological response)
  • is a key danger signal released from necrotic cells to trigger CXCL1 secretion and recruitment of neutrophils via IL1R/MYD88 on neighboring mesothelial cells
  • cell surface IL1A is an essential cell-autonomous regulator of the senescence-associated IL6/IL8 cytokine network
  • intracellular IL1A is a chromatin-associated cytokine and highly dynamic in the nucleus of living cells
  • in apoptotic cells, is retained within the chromatin fraction and is not released along with the cytoplasmic contents
  • platelets are a key source of IL1A and platelet activation of brain endothelium via IL1A is likely a critical step for the entry of white blood cells, major contributors to inflammation-mediated injury in the brain
  • is a critical regulator of blood-testis barrier (BTB) dynamics
  • IL1A, released from dying cells, initiates sterile inflammation by inducing recruitment of neutrophils
  • IL1B, IL1A both bind to the same IL1 receptor (IL1R1) and are potent proinflammatory cytokines
  • may have a critical function in the development of obesity
  • autophagy has a potentially pivotal role to play in the induction and regulation of inflammatory responses by innate immune cells, largely driven by IL1A, IL1B and its consequential effects on IL23A secretion
  • IL1A and IL23A signaling seems to be closely regulated through MYD88 in both innate and adaptive immune cells
  • in macrophages IL1A primarily acts as an alarmin that is rapidly released upon cell damage to activate early mechanisms of host defense
  • is a key senescence-associated (SA) proinflammatory cytokine that acts as a critical upstream regulator of the senescence-associated (SA) secretory phenotype (SASP)
  • IL1A and IL1B, are central to host responses to infection and to damaging sterile inflammation
  • IL1A, IL1B are important participants in the age-related exhaustion of ovarian reserve in mammalian, possibly by enhancing the expression of inflammatory genes and promoting apoptotic pathways
  • IL1A and IL1B are key players in the innate immune system
  • triggers lung responses requiring macrophage proliferation and maturation from tissue-resident macrophages
  • is a crucial danger signal triggering acute myocardial inflammation during myocardial infarction
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS inflammation
    text
  • after cell injury
  • extracellular fluid calcium homeostasis
  • PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding the IL1 receptor
  • interacting with S100A13
  • stimulates cardiac myofibroblasts (CMF) to express IL1B, TNF, and IL6 via specific signaling pathways
  • IL1B directly binds IL1A thus identifying IL1B as a shuttle for another proinflammatory cytokine
  • MYD88 plays a critical role in integrating IL1A and IL23A signaling for Th17 cell proliferation and expansion
  • as a result of its nuclear activity, IL1A overexpression promotes NFKB1 activity, but also interacts with the histone acetyl transferase (HAT) EP300
  • IL1A regulates CXCL1, CXCL10, and ICAM1 in network form in oral keratinocytes
  • IL1A regulates extracellular domain shedding of SDC2 through regulation of the MAP kinase-mediated MMP7 expression in colon cancer cells
  • S100A7 induces mature IL1A expression in normal human epidermal keratinocytes, which is dependent on AGER/MAPK14 and calpain-1 as the inhibitors or knockdown of them completely decreased the expression of mature IL1A
  • cell & other
  • stimulating osteoclastic activity
  • REGULATION
    Other IL1A and IL1B polyubiquitination and proteasomal degradation are central mechanisms in the regulation of intracellular IL1 levels in dendritic cells
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
  • to end-stage renal disease in NIDDM patients
  • to rheumatoid arthritis
  • Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target antibodies specific as therapeutic targets in rheumatoid arthritis
    ANIMAL & CELL MODELS