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FLASH GENE
Symbol ERRFI1 contributors: mct/np - updated : 10-04-2019
HGNC name ERBB receptor feedback inhibitor 1
HGNC id 18185
Location 1p36.23      Physical location : 8.071.779 - 8.086.393
Synonym name
  • mitogen-inducible gene 6 protein
  • receptor-associated late transducer
  • gene 33
  • Synonym symbol(s) MIG-6, GENE-33, RALT, MIG6
    DNA
    TYPE functioning gene
    STRUCTURE 14.61 kb     4 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 3144 - 462 - 2018 29843645
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon moderately
     liver   highly
     pancreas exocrine   moderately
     stomach   highly
    Endocrinethyroid   highly
    Hearing/Equilibriumear   moderately
    Reproductivefemale systemuterus  moderately
    Respiratorylung   moderately
     respiratory tracttrachea  moderately
    Urinarykidney   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  moderately
    Connectivebone  moderately
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an Ack homology domain containing the previously identified EGFR binding domain
  • Cdc42/Rac interaction and binding (CRIB) domain
  • HOMOLOGY
    interspecies ortholog to murine Errfi (82.4pc)
    Homologene
    FAMILY
  • MIG6 family
  • CATEGORY adaptor , regulatory , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    basic FUNCTION
  • multiadaptor protein may be involved in the regulation of RTK and stress signaling
  • acting as a Rho GTPase activator
  • involved in response to stress
  • inhibiting EGFR autophosphorylation
  • specifically blunting epidermal growth factor (EGF)-induced activation and/or phosphorylation of Ras, ERK, JNK, Akt/PKB, and retinoblastoma protein
  • negative regulator of EGFR signaling in skin morphogenesis and is a novel tumor suppressor of EGFR-dependent carcinogenesis
  • immediate early response gene encoding a nonkinase scaffolding adaptor protein (Zhang 2007)
  • may play important roles in regulating stress response, maintaining homeostasis in tissues like joints or cardiac muscle, and functioning as a tumor suppressor (Zhang 2007)
  • negative regulator of epidermal growth factor (EGF) signaling (Zhang 2007)
  • tumor-suppressor gene (Zhang 2007)
  • critical regulator of the response of the endometrium to Estrogen in regulating tissue homeostasis (Jeong 2009)
  • functions to suppress the malignant potential of Glioblastoma multiforme cells by enhancing EGFR trafficking into late endosomes/lysosomes and promoting its degradation (Ying 2010)
  • functions via STX8 to enhance EGF-induced receptor degradation by regulating the trafficking of internalized EGFR into late endosomes and subsequent lysosomes (Ying 2010)
  • induces premature senescence via functioning in regulation of cellular senescence in normal diploid fibroblasts
  • is a cytosolic multiadaptor protein that is best known for its role as a negative feedback regulator of epidermal growth factor receptor (EGFR) mediated signalling
  • involvement in hepatic insulin resistance
  • may regulate cell proliferation and the cell cycle through the P-ERK/CCND1 pathway
  • is an adaptor protein with multiple cellular functions
  • is a proximal regulator of DNA damage response (DDR) that promotes DNA repair
  • is an important tumor suppressor that binds to and negatively regulates epidermal growth factor receptor (EGFR)
  • EGFR-independent function for ERRFI1 as an integral component of the cell cycle machinery
  • critical role of ERRFI1 in cell cycle progression that is likely to contribute to its potent tumor-suppressive properties
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • ligand-activated epidermal growth factor receptor (EGFR)
  • ErbB-4 and ErbB-2.ErbB-3 dimers
  • interacts with and inhibits the kinase domains of EGFR and ERBB2
  • interacts with and inhibits the kinase domains of EGFR and ERBB2 (Zhang 2007)
  • strong interaction with STX8 upon ligand activation therefore ensures recruitment of internalized EGFR to late endosomes and subsequently the lysosomal degradation compartment (Ying 2010)
  • CHEK1 phosphorylates ERRFI1 on Ser 251, resulting in the inhibition of ERRFI1, and CHEK1 acts as a positive regulator of EGF signalling
  • sustained production of ERRFI1 protein exacerbates ER stress-induced beta-cell death
  • SPRY2 and ERRFI1 are important regulators of wild-type and mutant EGFR trafficking
  • participates in the regulation of cell senescence and RB1 protein phosphorylation
  • has an important role in the regulation of cholesterol homeostasis and bile acid synthesis
  • is an important mediator of progesterone (P4) signaling to inhibit estrogen (E2) signaling in the uterus
  • DNAJB1 is a novel ERRFI1-interacting protein, and DNAJB1 positively regulates the epidermal growth factor receptors (EGFR) signaling pathway via destabilization of ERRFI1
  • is a negative regulator of EGF signaling
  • bind to and inhibit the Rho GTPase CDC42 to suppress cytoskeletal rearrangement
  • may regulate the targeting of ABL1 to chromatin
  • ERRFI1 is required for inhibition of CDK1 upon DNA damage and subsequent G2/M cell cycle arrest
  • controls mitotic progression and the G2/M DNA damage checkpoint by stabilizing the WEE1 Kinase
  • cell & other
    REGULATION
    induced by mitogens
    hypoxia
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in ERBB2-amplified breast carcinomas
    constitutional     --over  
    in osteoarthritic cartilage
    tumoral     --low  
    in endometrial cancers (Jeong 2009)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    targeting of EFFRI1 in EGFR-low cancer as a promising therapeutic approach
    ANIMAL & CELL MODELS