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FLASH GENE
Symbol GPBAR1 contributors: mct - updated : 21-03-2018
HGNC name G protein-coupled bile acid receptor 1
HGNC id 19680
Location 2q35      Physical location : 219.125.737 - 219.128.582
Synonym name
  • G-protein coupled bile acid receptor BG37
  • Takeda G-protein receptor 5
  • Synonym symbol(s) BG37, GPR131, GPCR, TGR5, M-BAR, GPCR19
    DNA
    TYPE functioning gene
    STRUCTURE 4.37 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    TNS 2q35-q36 tensin FLJ46536 2q35 FLJ46536 protein IL8RB 2q35 interleukin 8 receptor, beta IL8RA 2q35 interleukin 8 receptor, alpha ARPC2 13q12-q13 actin related protein 2/3 complex, subunit 2, 34kDa GPBAR1 2q36.1 G protein-coupled bile acid receptor 1 AAMP 2q36.1 angio-associated, migratory cell protein MR-1 2q35 myofibrillogenesis regulator 1 PP1201 2p24.3-p24.1 PP1201 protein MGC50811 2q35 hypothetical gene supported by BC052750 SLC11A1 2q35 solute carrier family 11 (proton-coupled divalent metal ion transporters), member 1 CTDSP1 2q35 CTD (carboxy-terminal domain, RNA polymerase II, polypeptide A) small phosphatase 1 VIL1 2q35 villin 1 USP37 2q35 ubiquitin specific protease 37 RQCD1 2q36.1 RCD1 required for cell differentiation1 homolog (S. pombe) PLCD4 2q35 phospholipase C, delta 4 ZNF142 2q34-q35 zinc finger protein 142 (clone pHZ-49) BCS1L 2q33 BCS1-like (yeast) RNF25 2q36.1 ring finger protein 25 STK36 2q35 serine/threonine kinase 36 (fused homolog, Drosophila) KIAA0173 2p24.3-p24.1 serine/threonine kinase 36 (fused homolog, Drosophila) CYP27A1 2q35-q36 cytochrome P450, family 27, subfamily A, polypeptide 1 PRKAG3 2q35 protein kinase, AMP-activated, gamma 3 non-catalytic subunit LOC391484 2 similar to 60S ribosomal protein L23a WNT6 2q35 wingless-type MMTV integration site family, member 6 WNT10A 2q35 wingless-type MMTV integration site family, member 10A LOC391485 2 similar to cytokeratin 8 CDK5R2 2q35 cyclin-dependent kinase 5, regulatory subunit 2 (p39) HSRNAFEV 2q33 cyclin-dependent kinase 5, regulatory subunit 2 (p39)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 splicing 2023 35 330 - 2002 12419312
  • encoding the same protein than the other variants
  • 2 exons
  • 2 splicing 1515 35 330 - 2002 12419312
  • encoding the same protein than the other variants
  • 2 exons
  • differing in the 5' UTR compared to variant 1
  • 2 splicing 1402 35 330 - 2002 12419312
  • encoding the same protein than the other variants
  • 2 exons
  • differing in the 5' UTR compared to variant 1
  • 2 - 1889 35 330 - 2002 12419312
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivegallbladder     Homo sapiens
     liver     Homo sapiens
    Endocrinepancreas     Homo sapiens
    Lymphoid/Immunespleen   highly
    Nervousbrain     Homo sapiens
    Reproductivefemale systemplacenta  highly
    Urinarykidney   highly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose    Homo sapiens
    Muscularsmoothmuscularis mucosa (tractus digestif)   Homo sapiens
    Muscularstriatumskeletal   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestiveepithelial cell Homo sapiens
    Endocrineislet cell (alpha,beta...) Homo sapiens
    Nervousneuron Homo sapiens
    cell lineage
    cell lines
    fluid/secretion moderately in blood
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • seven transmembrane domains
  • C terminus of GPBAR1 lacks any known sorting motif such that other factors must determine its trafficking, and the secondary structure of the GPBAR1 membrane-proximal C terminus is the determining factor for plasma membrane localization and responsiveness towards extracellular ligands
  • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to murine Gpbar1 (83.8 pc)
    homolog to rattus Gpbar1 (82.4 pc)
    Homologene
    FAMILY G-protein coupled receptor 1 family
    CATEGORY receptor membrane G
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    text
  • internalized into the cytoplasm in response to bile acids
  • highly expressed in cholangiocytes , and is localized in the primary cilium of human cholangiocytes
  • basic FUNCTION
  • responsive activity to bile acids regulates proglucagon gene expression in enteroendocrine cells
  • acting as a receptor for bile acid
  • bile acid-binding induces its internalization, activation of extracellular signal-regulated kinase and intracellular cAMP production
  • involved in the suppression of macrophage functions by bile acids
  • acting as a rhodopsin-like receptor
  • may play a protective role in obstructive cholestasis preventing excessive cytokine production thereby reducing liver injury
  • stimulates gallbladder filling
  • significant immune modulating function to GPBAR1 activation in the prevention of atherosclerosis
  • expressed in the pancreatic beta cells, regulates likely insulin secretion
  • bile salts promote glucose-mediated insulin release via GPBAR1
  • GPBAR1 agonism induces NO production via AKT1 activation and intracellular Ca(2+) increase in vascular endothelial cells, and this function inhibits monocyte adhesion in response to inflammatory stimuli
  • mediates likely the BA-induced pro-inflammatory cytokine production in Kupffer cells through JNK-dependent pathway
  • appears to be crucial for protecting the regenerating liver from bile acid (BA) overload
  • GPBAR1 signaling reduces neuroinflammation during hepatic encephalopathy
  • is an important mediator of bile acid (BA)-induced cholangiocyte proliferation, and protects cholangiocytes from death receptor-mediated apoptosis
  • activation of GPBAR1 in pancreatic beta cells by bile acids induces insulin secretion
  • because GPBAR1 promotes energy expenditure and improves glucose homeostasis, it is recognized as a key target in treating metabolic diseases
  • is a suppressor of kidney cancer cell proliferation and migration
  • bile acids have emerged as important for renal pathophysiology by activating NR1H4 and GPBAR1 and transcription factors relevant for lipid, cholesterol and carbohydrate metabolism, as well as genes involved in inflammation and renal fibrosis (
  • bile acid activated receptor for secondary bile acids
  • is a druggable target to promote beiging with potential applications in the management of metabolic disorders
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS immunity/defense
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule other,
    bile acids
    protein
    cell & other
    REGULATION
    Other activation of GPBAR1 increases insulin secretion under both low and high ambient glucose levels (
    GPBAR1 activation induces mitochondrial biogenesis and prevents renal oxidative stress and lipid accumulation, establishing a role for TGR5 in inhibiting kidney disease in obesity and diabetes mellitus
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    GPBAR1 and NR1H4 expression levels are decreased in the aging kidney and caloric restriction prevents these age-related decreases
    constitutional       gain of function
    bile acids evoke placental inflammation by activating GPBAR1/NFKB1 pathway in intrahepatic cholestasis of pregnancy
    constitutional       gain of function
    bile acids, which are elevated in the circulation and tissues during cholestasis, cause itch and analgesia by activating GPBAR1
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    may serve as an attractive therapeutic tool for cancer
    immunologyinflammatory 
    may serve as an attractive therapeutic tool for human renal inflammation related diseases
    diabete  
    activation of both NR1H4 and GPBAR1 may represent an effective therapy for managing diabetes
    obesity  
    activation of both NR1H4 and GPBAR1 may represent an effective therapy for managing obesity
    digestiveliversteatosis
    activation of both NR1H4 and GPBAR1 may represent an effective therapy for managing hepatic steatosis, obesity, and diabetes
    miscelleaneousurinary 
    NR1H4 and GPBAR1 agonists play an important role in preventing progression of kidney disease, atherosclerosis, and vascular calcification
    ANIMAL & CELL MODELS
  • Gpbar1 agonism ameliorates liver histology in a rodent model of steatohepatitis (NASH) and promotes the browning of white adipose tissue