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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
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