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FLASH GENE
Symbol LGR5 contributors: mct/npt/pgu - updated : 29-06-2015
HGNC name leucine-rich repeat-containing G protein-coupled receptor 5
HGNC id 4504
Location 12q21.1      Physical location : 71.833.812 - 71.978.619
Synonym name
  • G protein-coupled receptor 49
  • G-protein coupled receptor 67
  • orphan G protein-coupled receptor HG38
  • Synonym symbol(s) HG38, GPR67, GPR49, MGC117008, FEX, GRP49
    DNA
    TYPE functioning gene
    STRUCTURE 144.81 kb     18 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    18 - 2880 99.87 907 - 1998 9642114
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon  
    Endocrinepancreas   highly Homo sapiens
    Nervousbrain    
     spinal cord    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    Epithelialabsorptive excretorydigestive epithelium (mucosa)  
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...) Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text
  • specifically expressed in stem cells of the intestinal crypt and hair follicle
  • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • . N-terminal extracellular domain (ECD) composed of 17 leucine-rich repeats
  • seven transmembrane segments (7TM)
  • canonical GATA binding sites within the LGR5 gene
  • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to murine Lgr5
    Homologene
    FAMILY
  • G protein-coupled receptor 1 family
  • rhodopsin family
  • CATEGORY receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • G protein coupled receptor, orphan receptor
  • may be an important receptor for signals controlling growth and differenciation of specific embryonic tissues
  • may be a target gene activated by Wnt-signaling in hepatocellular carcinoma
  • potential direct target of GATA6 regulation in the process of chondrogenesis
  • involved not only in early events but also in late events in colorectal tumorigenesis
  • may have important functions in uterine biology
  • negative regulator of the Wnt pathway in the developing intestine
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling hormonal , signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • target of GATA6 regulation in differentiating embryonal carcinoma cell
  • target of Wnt signaling
  • LGR4 and LGR5 bind the R-spondins with high affinity and mediate the potentiation of Wnt/CTNNB signaling by enhancing Wnt-induced LRP6 phosphorylation
  • each of the four R-spondins, secreted Wnt pathway agonists, can bind to LGR4, LGR5 and LGR6 (Pubmed 21727895)
  • function as receptors of the R-spondin family of stem cell factors to potentiate WNT/CTNNB1 signaling
  • LGR5 interacts and forms a supercomplex with the Wnt coreceptors LRP6 and FZD5 which is rapidly internalized and then degraded
  • TLR4 is expressed on the LGR5-positive intestinal stem cells
  • LGR5 does not contact RNF43 but increases the affinity of RSPO1 to RNF43, supporting LGR5 as an engagement receptor and RNF43 as an effector receptor
  • LGR5 is regulated by Proneural factor OLIG2, which is important for both neurogenesis and stem-like cells in glioblastoma (GSCs) maintenance
  • ZNRF3 binds RSPO1 and LGR5-RSPO1 with micromolar affinity via RSPO1 furin-like 1 (Fu1) domain
  • RSPO2 interacts with LGR5 to stabilize the membrane-associated zinc and ring finger 3 (ZNRF3)
  • RSPO2 and its receptor LGR5 are WNT-dependent and agrin-independent regulators of acetylcholine receptor (ACHR) clustering at the neuromuscular junction (NMJ)
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in basal cell carcinoma and promotes cell proliferation and tumor formation
    tumoral     --over  
    up-regulation of LGR5 from the early stage of colorectal tumorigenesis
    constitutional       loss of function
    deficiency leads to premature Paneth cell differentiation in the small intestine without detectable effects on differentiation of other cell lineages, nor on epithelial cell proliferation or migration
    Susceptibility
    Variant & Polymorphism
    Candidate gene
  • potential marker of intestinal stem cells in humans (Becker 2008)
  • has potential utility as a biomarker for Barrett esophagus-associated dysplasia and esophageal adenocarcinoma (Becker 2010)
  • Marker
    Therapy target
    ANIMAL & CELL MODELS