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GPR4 G protein-coupled receptor 4 [ Homo sapiens (human) ]

Gene ID: 2828, updated on 11-Apr-2024

Summary

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Official Symbol
GPR4provided by HGNC
Official Full Name
G protein-coupled receptor 4provided by HGNC
Primary source
HGNC:HGNC:4497
See related
Ensembl:ENSG00000177464 MIM:600551; AllianceGenome:HGNC:4497
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
GPR6C.l
Summary
Enables G protein-coupled receptor activity. Involved in several processes, including G protein-coupled receptor signaling pathway; positive regulation of Rho protein signal transduction; and response to acidic pH. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
Expression
Broad expression in fat (RPKM 4.0), lung (RPKM 2.3) and 22 other tissues See more
Orthologs
mouse all
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Genomic context

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Location:
19q13.32
Exon count:
2
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (45589764..45602212, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (48417036..48429476, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (46093022..46105470, complement)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC107985315 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:46025801-46026353 Neighboring gene vasodilator stimulated phosphoprotein Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10780 Neighboring gene outer mitochondrial membrane lipid metabolism regulator OPA3 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:46056279-46056909 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:46056910-46057539 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:46061287-46061787 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:46065110-46065908 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:46066707-46067504 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr19:46067505-46068302 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr19:46080520-46081155 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:46084233-46084733 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:46085233-46086168 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:46086169-46087104 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14802 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:46100634-46101271 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:46101272-46101908 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:46119367-46120205 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:46120206-46121043 Neighboring gene EMAP like 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:46130698-46131198 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10783 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:46141481-46142332 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:46142333-46143184 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14803 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:46145740-46146591 Neighboring gene EML2 antisense RNA 1 Neighboring gene microRNA 330

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. GPR4 in the pH-dependent migration of melanoma cells in the tumor microenvironment. Stolwijk JA, et al. Exp Dermatol, 2023 Apr. PMID 36562556
  2. Hypoxia-induced GPR4 suppresses trophoblast cell migration and proliferation through the MAPK signaling pathway. Qi H, et al. Reprod Toxicol, 2021 Jan. PMID 33161135
  3. Antagonism of GPR4 with NE 52-QQ57 and the Suppression of AGE-Induced Degradation of Type II Collagen in Human Chondrocytes. Liu H, et al. Chem Res Toxicol, 2020 Jul 20. PMID 32370492
  4. Increased proton-sensing receptor GPR4 signalling promotes colorectal cancer progression by activating the hippo pathway. Yu M, et al. EBioMedicine, 2019 Oct. PMID 31530502, Free PMC Article
  5. Acidosis Activates Endoplasmic Reticulum Stress Pathways through GPR4 in Human Vascular Endothelial Cells. Dong L, et al. Int J Mol Sci, 2017 Jan 27. PMID 28134810, Free PMC Article

See all (35) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. The proton-sensing receptors TDAG8 and GPR4 are differentially expressed in human and mouse oligodendrocytes: Exploring their role in neuroinflammation and multiple sclerosis.
    Title: The proton-sensing receptors TDAG8 and GPR4 are differentially expressed in human and mouse oligodendrocytes: Exploring their role in neuroinflammation and multiple sclerosis.
  2. GPR4 in the pH-dependent migration of melanoma cells in the tumor microenvironment.
    Title: GPR4 in the pH-dependent migration of melanoma cells in the tumor microenvironment.
  3. Hypoxia-induced GPR4 suppresses trophoblast cell migration and proliferation through the MAPK signaling pathway.
    Title: Hypoxia-induced GPR4 suppresses trophoblast cell migration and proliferation through the MAPK signaling pathway.
  4. The evolution and mechanism of GPCR proton sensing.
    Title: The evolution and mechanism of GPCR proton sensing.
  5. Antagonism of GPR4 with NE 52-QQ57 and the Suppression of AGE-Induced Degradation of Type II Collagen in Human Chondrocytes.
    Title: Antagonism of GPR4 with NE 52-QQ57 and the Suppression of AGE-Induced Degradation of Type II Collagen in Human Chondrocytes.
  6. Expression profiles of proton-sensing G-protein coupled receptors in common skin tumors.
    Title: Expression profiles of proton-sensing G-protein coupled receptors in common skin tumors.
  7. The expression of GPR4 is upregulated in colorectal cancer and is associated with shorter overall survival time in CRC patients. These findings reveal the novel roles of GPR4 in CRC progression and suggest GPR4 might be a new therapeutic target for CRC treatment.
    Title: Increased proton-sensing receptor GPR4 signalling promotes colorectal cancer progression by activating the hippo pathway.
  8. Results indicate that GPR4 is expressed by multiple neuronal populations and endothelium and that its pH sensitivity is affected by level of expression and l-lactic acid (LL). GPR4 antagonist NE 52-QQ57 blunts hypercapnic response to CO2 but this effect is absent under anaesthesia, possibly due to the inhibitory effect of LL on GPR4.
    Title: CNS distribution, signalling properties and central effects of G-protein coupled receptor 4.
  9. Proton-sensing GPR4 signaling mediated the proton-induced inhibitory effects on the osteogenesis of BMSCs. YAP was the downstream effector of GPR4 signaling. Extracellular pH modulates the osteogenic responses of BMSCs by regulating the proton-sensing GPR4-YAP pathway.
    Title: Decreased extracellular pH inhibits osteogenesis through proton-sensing GPR4-mediated suppression of yes-associated protein.
  10. These results suggest that zOGR1, but not GPR4, is also a metal-sensing G-protein-coupled receptor in addition to a proton-sensing G-protein-coupled receptor, although not all metals that activate hOGR1 activated zOGR1.
    Title: Manganese and cobalt activate zebrafish ovarian cancer G-protein-coupled receptor 1 but not GPR4.
Submit: New GeneRIF Correction See all GeneRIFs (26)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables G protein-coupled receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables G protein-coupled receptor activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Process Evidence Code Pubs
involved_in G protein-coupled receptor signaling pathway TAS
Traceable Author Statement
more info
 PubMed 
involved_in adenylate cyclase-activating G protein-coupled receptor signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in adenylate cyclase-activating G protein-coupled receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in angiogenesis involved in wound healing IEA
Inferred from Electronic Annotation
more info
  
involved_in glomerular mesangial cell development IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of angiogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in phospholipase C-activating G protein-coupled receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in phospholipase C-activating G protein-coupled receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of Rho protein signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of Rho protein signal transduction IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of Rho protein signal transduction IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of inflammatory response ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of cell adhesion IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of vascular permeability ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in response to acidic pH IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in response to acidic pH IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
G-protein coupled receptor 4
Names
G-protein coupled receptor 19
G-protein coupled receptor 6C.l

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_005282.3 → NP_005273.1  G-protein coupled receptor 4

    See identical proteins and their annotated locations for NP_005273.1

    Status: VALIDATED

    Source sequence(s)
    AC011480, BC038450, BE669939, DA858082
    Consensus CDS
    CCDS12669.1
    UniProtKB/Swiss-Prot
    A8K3T3, B0M0K1, P46093, Q6NWM4
    Related
    ENSP00000319744.3, ENST00000323040.5
    Conserved Domains (1) summary
    cd15366
    Location:18 → 297
    7tmA_GPR4; proton-sensing G protein-coupled receptor 4, member of the class A family of seven-transmembrane G protein-coupled receptors

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

    Range
    45589764..45602212 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060943.1 Alternate T2T-CHM13v2.0

    Range
    48417036..48429476 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054320583.1 → XP_054176558.1  G-protein coupled receptor 4 isoform X1

    UniProtKB/Swiss-Prot
    A8K3T3, B0M0K1, P46093, Q6NWM4
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P46093.2 GenPept UniProtKB/Swiss-Prot:P46093

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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