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FLASH GENE
Symbol LRIG1 contributors: mct - updated : 08-01-2020
HGNC name leucine-rich repeats and immunoglobulin-like domains 1
HGNC id 17360
DNA
TYPE functioning gene
STRUCTURE 121.62 kb     19 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
19 - 4812 119 1093 - 2003 12684867
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Nervousbrain   predominantly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscular     Homo sapiens
Nervouscentral   
cells
SystemCellPubmedSpeciesStageRna symbol
Nervousneuron Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period fetal
Text kidney
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • leucine-rich repeats
  • Ig-like domains in its extracellular region
    • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to murine Lig-1
    homolog to Drosophila Kekkon-1
    Homologene
    FAMILY
  • leucine-rich repeat and the immunoglobulin superfamily
    • CATEGORY receptor membrane
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
    basic FUNCTION
  • playing a role as a growth and tumor suppressor
  • functioning as a cell type-specific adhesion molecule or receptor at the glial cell surface
  • playing a role in the nervous system in neuroglial differentiation, development, and/or maintenance of neural functions where it is expressed
  • plays an essential role in Met degradation
  • suppressor of Met function, serving to regulate cellular receptor levels by promoting Met degradation in a ligand- and cbl-independent manner
  • acting in a negative feedback loop to regulate the activity of RET receptor tyrosine kinase
  • endogenous inhibitor of RET receptor tyrosine kinase activation, downstream signaling, and biological responses to GDNF
  • negative regulator of growth factor signaling
  • possible role for LRIG1 and LRIG2 proteins in meningioma pathogenesis
  • LRIG1 and LRIG3 overlap prominently in the developing vestibular apparatus and simultaneous removal of both genes disrupts inner ear morphogenesis
  • LRIG genes appear to act both redundantly and independently, with LRIG2 emerging as the most functionally distinct family member
  • LRIG1 is a negative regulator of the STAT3-dependent inflammatory pathway
  • is an independent prognostic factor in patients with non-small cell lung cancer that could be important in future decision-making algorithms for adjuvant lung cancer treatment
  • important homeostatic role of LRIG1 in skin
  • essential role of LRIG1 in regulating morphogenic events that shape the hippocampal circuits
  • is a tumor suppressor and a negative regulator of several receptor tyrosine kinases
  • LRIG1 functions as a thyroid tumor suppressor
  • negatively regulates receptor tyrosine kinases and functions as a tumor suppressor
  • participate in the aggressive progression of several tumors, where its expression is frequently decreased
  • acts as a critical regulator of melanoma cell invasion, migration, and vasculogenic mimicry upon hypoxia
  • tumor suppressor in gastrointestinal tract and epidermis
  • represents a pleiotropic AR-regulated feedback tumor suppressor that functions to restrict oncogenic signaling from AR
    • CELLULAR PROCESS cell life, differentiation
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling signal transduction
    growth factor receptor
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • negative regulator of EGF receptor and its relatives, ERBB2, ERBB3, and ERBB4, and LRIG1-mediated receptor ubiquitination and degradation may contribute to the suppression of ErbB receptor function
  • interacting with MET (LRIG1 destabilizes the Met receptor in a cbl-independent manner)
  • capable of physically interacting with RET and LRIG1/RET association inhibits GDNF binding, recruitment of Ret to lipid rafts, receptor autophosphorylation, and mitogen-activated protein kinase (MAPK) activation in response to GDNF
  • USP8 is involved in deubiquitination of LRIG1, influencing the efficiency of MET degradation
  • LRIG1 physically interacts with NTRK2 and attenuates BDNF signaling
  • is a suppressor of various receptor tyrosine kinases, including RET
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    in various cancers
    tumoral     --low  
    in renal cell carcinoma
    tumoral     --over  
    destabilizes endogenous Met receptor in breast cancer cells and impairs their ability to respond to hepatocyte growth factor
    tumoral     --over  
    suppresses malignant glioma cell growth by attenuating EGFR activity
    tumoral     --low  
    in squamous cell carcinoma of the uterine cervix, with high LRIG2 expression identified women with a very poor prognosis
    tumoral     --over  
    in prostate cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • prognostic biomarker in non-small cell lung cancer
    • Therapy target
    SystemTypeDisorderPubmed
    cancerbrain 
    feedback negative attenuator of EGFR and could offer a novel therapeutic target to treat patients with malignant gliomas
    ANIMAL & CELL MODELS
  • Lrig1-deficient mice display morphological changes in proximal dendrite arborization and defects in social interaction