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FLASH GENE
Symbol ERBIN contributors: mct/npt/pgu - updated : 14-12-2016
HGNC name erbb2 interacting protein
HGNC id 15842
Location 5q12.3      Physical location : -
Synonym name
  • densin-180-like protein
  • erbin
  • Synonym symbol(s) KIAA1225, LAP2, ERBB2IP
    DNA
    TYPE functioning gene
    STRUCTURE 154.47 kb     25 Exon(s)
    regulatory sequence Promoter
    Binding site
    text structure
  • MYB site in the core promoter region of ERBIN
  • MAPPING cloned Y linked N status provisional
    regionally located between D5S427 and D5S647
    RNA
    TRANSCRIPTS type messenger
    text several transcripts caused by alternate splicing between exons 21 and 26
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    25 - 6916 154 1371 - 2015 25521828
    24 - 6709 146 1302 - 2015 25521828
    26 - 7063 - 1419 - 2015 25521828
    26 - 7042 - 1412 - 2015 25521828
    24 - 6844 - 1346 - 2015 25521828
    25 - 6907 - 1367 - 2015 25521828
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveliver   highly
    Endocrinepancreas    
    Nervousbrain    
     spinal cord   highly
    Reproductivemale systemprostate   
    Respiratorylung    
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    Nervouscentral   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Skin/Tegumentkeratinocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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
  • 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