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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001077191 2 splicing 2023 NP_001070659 35 330 - 2002 12419312 encoding the same protein than the other variants 2 exons NM_001077194 2 splicing 1515 NP_001070662 35 330 - 2002 12419312 encoding the same protein than the other variants 2 exons differing in the 5' UTR compared to variant 1 NP_001070662 2 splicing 1402 NP_733800 35 330 - 2002 12419312 encoding the same protein than the other variants 2 exons differing in the 5' UTR compared to variant 1 NM_001321950 2 - 1889 NP_001308879 35 330 - 2002 12419312

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive gallbladder         Homo sapiens   liver         Homo sapiens Endocrine pancreas         Homo sapiens Lymphoid/Immune spleen       highly Nervous brain         Homo sapiens Reproductive female system placenta     highly Urinary kidney       highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose       Homo sapiens Muscular smooth muscularis mucosa (tractus digestif)     Homo sapiens Muscular striatum skeletal     Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Digestive epithelial cell Homo sapiens Endocrine islet cell (alpha,beta...) Homo sapiens Nervous neuron 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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed cancer     may serve as an attractive therapeutic tool for cancer immunology inflammatory   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 digestive liver steatosis activation of both NR1H4 and GPBAR1 may represent an effective therapy for managing hepatic steatosis, obesity, and diabetes miscelleaneous urinary   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