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FLASH GENE
Symbol ERBIN contributors: mct/npt/pgu - updated : 14-12-2016
HGNC name erbb2 interacting protein
HGNC id 15842
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • cysteines 14 and 16 at the N-terminal region are palmitoylated
  • multiple leucine-rich repeat domains
  • one C terminal PDZ domain, interacting with SMAD3 , and phosphorylated by cAMP-dependent protein kinase
    • HOMOLOGY
    interspecies homolog to Drosophila Lap1
    homolog to C.elegans let-413
    ortholog to murine Erbb2ip
    Homologene
    FAMILY
  • LAP (leucine-rich repeat (LRR) and PDZ domain) family
  • LAP (leucine-rich repeats and PDZ domain) adaptor proteins
    • CATEGORY adaptor
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,desmosome
        intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm
    text
  • colocalized to lateral membrane with ERBB2/HER2 basement membrane
  • palmitoylation is necessary for its plasma membrane localization
    • basic FUNCTION
  • acting as an adaptor for the receptor ERBB2/HER2
  • regulator of ERBB2/HER2 localization and signaling function
  • inhibits Ras-mediated activation of ERK in response to growth factors
  • may inhibit ERK activation by disrupting the SHOC2-Ras/Raf interaction
  • inhibit the Ras-mediated activation of the mitogen-activated protein kinase pathway
  • has the potential to act as an inhibitor as well as an activator of the beta-catenin-regulated gene expression
  • involved in the regulation of cell polarity
  • via the PDZ domain, binds to and stabilizes ERBB2, which is necessary for NRG1 signaling that has been implicated in tumorigenesis, heart development, and neural function
  • playing a critical role in myelination
  • negatively regulates the MAPK pathway downstream of tyrosine kinases including ERBB2
  • ERBIN may function as a signaling molecule
  • interacting with MAGUK protein
  • negative regulator of the Ras-Raf pathway
  • unappreciated function of ERBIN in cell cycle progression
  • necessary role of ERBIN in remyelination of regenerating axons
  • participates in inhibition of several intracellular signaling pathways
  • is an inhibitor of pathological cardiac hypertrophy, and this inhibition is mediated, at least in part, by modulating ERK signaling
  • ERBIN is an ERBB2 regulator for breast tumor formation and progression
  • scaffold protein that regulates ERBB2 stability
  • ERBIN, LRRC1, and SCRIB act at the post-synaptic membrane of NMJs in a concerted fashion to regulate nicotinic acetylcholine receptors cluster morphology and neural transmission
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    text embryogenesis and morphogenesis ; oncogenesis
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • component of the cytoskeleton
  • core component of post-synaptic densities, the highly complex molecular assemblies that mediate signaling between neuronal cell (Thalhammer 2009)
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to ERBB2/HER2,EBPAG1 and integrin beta 4 subunit
  • binding PKP4 in desmosomes of epithelial cells (interaction crucial for epithelial homeostasis)
    • interacting with LRR1
  • binding with high affinity and specificity to the carboxyl termini of CTNND and ARVCF
  • interacting with SMAD3
  • via the LRR domain, interacts with SHOC2, a scaffold protein necessary for the Ras-Raf complex
  • binding partner of the receptor tyrosine kinase ERBB2, erbin targets this receptor to the basolateral membrane of polarized epithelial cells
  • new ZFYVE9-interacting protein that can be recruited by ZFYVE9 to early endosomes
  • bind and segregate phosphorylated SMAD2 and SMAD3 (SMAD2/3) in the cytoplasm, thereby inhibiting SMAD2/3-dependent transcription
  • is a negative feedback molecule induced by TGFB1 and inhibits TGFB1-induced EMT via ERK signaling pathway
  • interaction of MYB with MYB site in the ERBIN promoter was significantly enhanced in G2/M phase
  • ERBIN is required for remyelination of regenerated axons after injury, probably by regulating ERBB2 and NRG1 levels
  • FRMPD2 interacts with NOD2 via leucine-rich repeats and forms a complex with the membrane-associated protein ERBIN
  • imbalanced NRG1 isoforms and downregulated ERBIN may contribute to the dysregulation of ERBB2 signaling in the development of diabetic peripheral neuropathy (DPN)
  • inhibits RAS-mediated activation of the extracellular signal-regulated kinase (ERK) by binding to Soc-2 suppressor of clear homolog (SHOC2)
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       loss of function
    disrupted ERBIN links polarity loss, hyperproliferation and tumorigenesis
    constitutional     --over  
    dramatically in injured nerves
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS