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FLASH GENE
Symbol AREG contributors: mct - updated : 30-03-2016
HGNC name amphiregulin
HGNC id 651
Location 4q13.3      Physical location : 75.310.852 - 75.490.482
Synonym name
  • colorectum cell-derived growth factor
  • amphiregulin B
  • schwannoma-derived growth factor
  • Synonym symbol(s) ARB, SDGF, CRDGF, MGC13647, AREGB
    DNA
    TYPE functioning gene
    STRUCTURE 10.86 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 1270 - 252 - 2007 17369357
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessel   moderately
    Digestiveesophagus   predominantly
     liver   moderately
     stomach   highly
    Reproductivefemale systemplacenta  moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  moderately Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticbasophil Homo sapiens
    Lymphoid/Immunemacrophage Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a C terminal EGF-like domain, required for autocrine keratinocyte growth
  • is cleaved at Lysine 187, a site homologous to the cleavage site reported in the mouse protein
  • conjugated GlycoP
    isoforms Precursor synthesized as a pro-protein which requires cleavage at the cell surface to release the active signaling domain
    HOMOLOGY
    interspecies homolog to rattus Areg (73.4pc)
    homolog to murine Areg (72.2pc)
    Homologene
    FAMILY
  • amphiregulin family
  • epidermal growth factor family
  • CATEGORY signaling cytokine growth factor
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,nucleus
    basic FUNCTION
  • bifunctional growth-modulating glycoprotein
  • inhibiting growth of several human carcinoma cells in culture
  • stimulating proliferation of human fibroblasts and certain other tumor cells
  • important paracrine mediator of estrogen function specifically required for puberty-induced ductal elongation, but not for any earlier or later developmental stages
  • involved in neurite outgrowth, early neuronal cell development, neuropeptide signaling/synthesis and neuronal receptor
  • TGFA and EREG lead to complete receptor recycling, and AREG does not target EGFR for lysosomal degradation but causes fast as well as slow EGFR recycling
  • may play a significant role in the proliferation of osseous dysplasia
  • YAP1-dependent secretion of AREG indicates that activation of EGFR signalling is an important non-cell-autonomous effector of the Hippo pathway, which has implications for the regulation of both physiological and malignant cell proliferation
  • plays critical roles in intestinal epithelial growth
  • can increase epidermal growth factor receptor (EGFR) stability and promote EGFR localization to the plasma membrane
  • functions in regulating the invasive phenotype in cancers, and this regulation may be through altered signaling that occurs when AREG activates plasma membrane localized EGFR
  • critical for efficient Treg cell function and in addition, mast cell-derived AREG fully restored optimal Treg cell function
  • mediates progesterone-induced mammary ductal development during puberty
  • induces ovarian cancer cell invasion by down-regulating CDH1 expression
  • induces hepatic stellate cells fibrogenic activity via multiple mitogenic signaling pathways
  • participates in tissue repair and inflammation regulation
  • may be an effective new biomarker of M1 macrophages
  • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    cell-cell signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • EGF/TGF-alpha receptor
  • heparin
  • transcriptional target of YAP1, whose induction contributes to YAP1-mediated cell proliferation and migration, but not EMT
  • binding of CREB1 to the AREG promoter is reduced by CCDC6 expression
  • BRCA1 regulates AREG transcription directly through binding to the AREG promoter
  • AGR2 regulates AREG RNA and protein expression
  • AGR2 induces expression of amphiregulin (AREG), a growth promoting EGFR ligand, through YAP1
  • AGR2 localization in the ER by KTEL is required for its ability to induce AREG or CDX2 expression
  • enhances regulatory T cell-suppressive function via EGFR
  • WDR92 could prevent AREG-mediated invasion by degrading AREG mRNA
  • WDR92 specifically interacted with both the 3prime-UTR of AREG mRNA and the RNA degrading exosome, and enhanced decay of AREG transcripts
  • AREG, BTC, and EREG induced prostaglandin E2 (PGE2) production by upregulating PTGS2 expression through ERK1/2 signaling in granulosa cells
  • cell & other
    REGULATION
    induced by phorbol 12-myristate 13-acetate (PMA)
    parathyroid hormone
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in psoriatic epidermis
    tumoral     --over  
    in pancreatic, colon, and prostate cancer, renal cell carcinoma and cholangiocarcinoma cells
    constitutional     --over  
    in non-alcoholic steatohepatitis (NASH)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • AREG accumulation is a useful marker of gonadotrophin stimulation and oocyte competence
  • Therapy target
    SystemTypeDisorderPubmed
    digestive  
    Modulation of levels of AREG by targeting intestinal subepithelial myofibroblasts (ISEMF) represents a novel strategy for treatment of certain intestinal disorders
    ANIMAL & CELL MODELS
  • Areg -/- mice develop spasmolytic polypeptide expressing metaplasia and intestinal metaplasia, which gives rise to goblet cell intestinal metaplasia and invasive fundic dysplastic lesions