Details for: GPBAR1

Gene ID: 151306

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: GPBAR1

Ensembl ID: ENSG00000179921

Description: G protein-coupled bile acid receptor 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • CD14-low, CD16-positive monocyte CL0002396
    CSI 21.99
    rCSI 16.95%
    PRS 95.64
  • type L enteroendocrine cell CL0002279
    CSI 9.02
    rCSI 16.93%
    PRS 94
  • enteroendocrine cell of colon CL0009042
    CSI 5.74
    rCSI 26.91%
    PRS 94.15
  • non-classical monocyte CL0000875
    CSI 5.28
    rCSI 8.46%
    PRS 96.42
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 3.36
    rCSI 4.41%
    PRS 97.52
  • CD14-positive monocyte CL0001054
    CSI 3.31
    rCSI 4.12%
    PRS 97.2
  • microcirculation associated smooth muscle cell CL0008035
    CSI 3.3
    rCSI 9.54%
    PRS 92.5
  • enteroendocrine cell CL0000164
    CSI 3.06
    rCSI 4.19%
    PRS 91.28
  • promyelocyte CL0000836
    CSI 3.05
    rCSI 4.4%
    PRS 94.67
  • myeloid leukocyte CL0000766
    CSI 2.99
    rCSI 2.76%
    PRS 94.25
  • monocyte CL0000576
    CSI 2.73
    rCSI 4.94%
    PRS 94.2
  • promonocyte CL0000559
    CSI 2.67
    rCSI 4.57%
    PRS 94.45
  • basal cell of epidermis CL0002187
    CSI 1.91
    rCSI 3.39%
    PRS 67.04
  • smooth muscle cell CL0000192
    CSI 1.89
    rCSI 4.52%
    PRS 88.1
  • intermediate monocyte CL0002393
    CSI 1.74
    rCSI 2.62%
    PRS 96.25
  • enteric smooth muscle cell CL0002504
    CSI 1.57
    rCSI 2.24%
    PRS 93.05
  • melanocyte of skin CL1000458
    CSI 0.94
    rCSI 1.28%
    PRS 67.02

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [GPBAR1](/details-gene/151306) (G protein-coupled bile acid receptor 1), also known as TGR5, is a protein-coding gene located on chromosome 2q35. It encodes a multi-pass membrane protein that functions as a cell surface receptor for bile acids, first identified in several key studies [Link](https://doi.org/10.1016/s0006-291x(02)02550-0), [Link](https://doi.org/10.1074/jbc.m209706200). As a member of the G protein-coupled receptor (GPCR) superfamily, it plays a crucial role in signal transduction, particularly through G alpha (s) signaling events that lead to the activation of adenylate cyclase. **Overall**, expression data reveals a highly specific enrichment of [GPBAR1](/details-gene/151306) in distinct cell populations, most notably in myeloid lineage cells such as [CD14-low, CD16-positive monocytes](/details-cell/CL0002396) and various [enteroendocrine cells](/details-cell/CL0000164). This dual expression pattern places [GPBAR1](/details-gene/151306) at the intersection of metabolic regulation and innate immunity. ## Cellular Roles and Expression Landscape The expression profile of [GPBAR1](/details-gene/151306) highlights its specialized function in specific cell types. **Overall**, its most significant expression is observed in immune cells of the myeloid lineage, with a particularly high Cell Significance Index (CSI) in [CD14-low, CD16-positive monocytes](/details-cell/CL0002396) (CSI: 21.99) and [non-classical monocytes](/details-cell/CL0000875) (CSI: 5.28). Significant expression is also seen in related cell types including [CD14-positive, CD16-positive monocytes](/details-cell/CL0002397) and their precursors like [promonocytes](/details-cell/CL0000559), suggesting a consistent role for this receptor in monocyte biology. Concurrently, [GPBAR1](/details-gene/151306) is a key marker for specialized sensory cells of the gastrointestinal tract. It shows high significance in [type L enteroendocrine cells](/details-cell/CL0002279) (CSI: 9.02) and [enteroendocrine cells of the colon](/details-cell/CL0009042) (CSI: 5.74). This is consistent with its function as a bile acid sensor in the gut, linking luminal contents to hormonal and metabolic responses. Lower but notable expression is also present in structural cells like [microcirculation associated smooth muscle cells](/details-cell/CL0008035) and [basal cells of the epidermis](/details-cell/CL0002187), indicating broader, albeit less prominent, physiological roles. ## Pathways and Molecular Function Functionally, [GPBAR1](/details-gene/151306) is annotated as a canonical GPCR. Its molecular function is defined as '[G protein-coupled bile acid receptor activity](/details-go/GO:0038182)', initiating the '[adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway](/details-go/GO:0038184)'. This is consistent with its classification within Reactome's '[Class a/1 (rhodopsin-like receptors)](/details-reactome/R-HSA-373076)' and its involvement in '[G alpha (s) signalling events](/details-reactome/R-HSA-418555)' and general '[Gpcr downstream signalling](/details-reactome/R-HSA-388396)'. The biological processes associated with [GPBAR1](/details-gene/151306) signaling are directly tied to its cellular contexts. Its role in the '[cellular response to bile acid](/details-go/GO:1903413)' is fundamental to its function in [enteroendocrine cells](/details-cell/CL0000164), where it contributes to metabolic regulation. Furthermore, it is implicated in tissue homeostasis and development through processes such as the '[positive regulation of cholangiocyte proliferation](/details-go/GO:1904056)' and '[regulation of bicellular tight junction assembly](/details-go/GO:2000810)'. The receptor is predominantly localized to the '[plasma membrane](/details-go/GO:0005886)' as part of a '[receptor complex](/details-go/GO:0043235)', with some presence also noted in the '[cytoplasm](/details-go/GO:0005737)'. ## Research Directions The distinct expression pattern of [GPBAR1](/details-gene/151306) in both metabolic-sensing [enteroendocrine cells](/details-cell/CL0000164) and inflammatory [monocytes](/details-cell/CL0000576) positions it as a key molecular link between metabolism and immunity. This dual role suggests that bile acids, acting through [GPBAR1](/details-gene/151306), may have unappreciated immunomodulatory functions. **Proposed Testable Hypotheses:** 1. Given its high expression in non-classical, or "patrolling", [monocytes](/details-cell/CL0000576), activation of [GPBAR1](/details-gene/151306) by systemic bile acids may directly regulate monocyte function, potentially suppressing pro-inflammatory cytokine production or altering their endothelial surveillance capabilities. 2. In the context of gut inflammation, such as in inflammatory bowel disease, crosstalk between bile acid-activated [GPBAR1](/details-gene/151306) on mucosal [myeloid leukocytes](/details-cell/CL0000766) and epithelial cells may be a critical factor in maintaining or restoring intestinal barrier integrity. **Suggested Experimental Approach:** To test the first hypothesis regarding the immunomodulatory role of [GPBAR1](/details-gene/151306) in monocytes, one could perform an *in vitro* study using primary human monocytes. [GPBAR1](/details-gene/151306) expression could be silenced using siRNA. Control and knockdown cells would then be stimulated with a specific GPBAR1 agonist (e.g., oleanolic acid) in the presence or absence of a pro-inflammatory stimulus like lipopolysaccharide (LPS). The impact on monocyte function could be assessed by measuring the secretion of key cytokines (e.g., TNF-alpha, IL-6, IL-10) via ELISA and analyzing changes in gene expression related to inflammation and cell migration using RT-qPCR or RNA-sequencing. **Therapeutic Potential:** As a cell surface GPCR, [GPBAR1](/details-gene/151306) is an excellent and highly druggable therapeutic target. Its established role in stimulating GLP-1 secretion from [enteroendocrine cells](/details-cell/CL0000164) has already made it a target of interest for metabolic diseases, with **activation** via synthetic agonists being explored for the treatment of type 2 diabetes and non-alcoholic steatohepatitis. The prominent expression on monocyte subsets suggests it could also be targeted to modulate chronic inflammatory disorders. Depending on whether its signaling in these cells is pro- or anti-inflammatory, both agonists and antagonists could be developed for conditions ranging from atherosclerosis to autoimmune diseases.

Genular Protein ID: 15665977

Symbol: GPBAR_HUMAN

Name: G-protein coupled bile acid receptor 1

UniProtKB Accession Codes:

Q8TDU6 B3KV35

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEMBL 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 3 DrugCentral 1 EMBL 7 EMDB 4 Ensembl 4 GO 10 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MINT 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 4 PDBsum 4 PRINTS 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 2 RefSeq 8 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissLipids 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 12419312

Title: Identification of membrane-type receptor for bile acids (M-BAR).

PubMed ID: 12419312

DOI: 10.1016/s0006-291x(02)02550-0

PubMed ID: 12524422

Title: A G protein-coupled receptor responsive to bile acids.

PubMed ID: 12524422

DOI: 10.1074/jbc.m209706200

PubMed ID: 12044878

Title: Identification of G protein-coupled receptor genes from the human genome sequence.

PubMed ID: 12044878

DOI: 10.1016/s0014-5793(02)02775-8

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

Sequence Information:

  • Length: 330
  • Mass: 35248
  • Checksum: B3A1AEDADEAFE021
  • Sequence:
    • MTPNSTGEVP SPIPKGALGL SLALASLIIT ANLLLALGIA WDRRLRSPPA GCFFLSLLLA 
GLLTGLALPT LPGLWNQSRR GYWSCLLVYL APNFSFLSLL ANLLLVHGER YMAVLRPLQP 
PGSIRLALLL TWAGPLLFAS LPALGWNHWT PGANCSSQAI FPAPYLYLEV YGLLLPAVGA 
AAFLSVRVLA TAHRQLQDIC RLERAVCRDE PSALARALTW RQARAQAGAM LLFGLCWGPY 
VATLLLSVLA YEQRPPLGPG TLLSLLSLGS ASAAAVPVAM GLGDQRYTAP WRAAAQRCLQ 
GLWGRASRDS PGPSIAYHPS SQSSVDLDLN