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FLASH GENE
Symbol IL1A contributors: mct - updated : 02-06-2017
HGNC name interleukin 1, alpha
HGNC id 5991
Location 2q13      Physical location : 113.531.492 - 113.542.971
Synonym name
  • hematopoietin 1
  • IL1-ALPHA
  • preinterleukin 1 alpha
  • Synonym symbol(s) IL1, HMP1, IL1F1, IL1-ALPHA
    DNA
    TYPE functioning gene
    SPECIAL FEATURE component of a cluster
    STRUCTURE 11.48 kb     7 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked Y status confirmed
    Map see IL1RN
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 2943 30.48 271 - -
    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
  • secretion of IL1A, IL1B, IL12B, and CCL4 occurs during gelatinase degranulation, a process controlled by STX3
  • CASP4 and caspase-5 mediate IL1A and IL1B release from human monocytes after lipopolysaccharide (LPS) stimulation
  • 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
  • CTSG is directly engaged in CASP4 activation by a bacterial ligand, which is responsible for cell death and IL1A secretion in human gingival fibroblasts (HGFs)
  • 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