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ADGRF4

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Target id: 195

Nomenclature: ADGRF4

Family: Adhesion Class GPCRs

Contents:

Gene and Protein Information Click here for help
Adhesion G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 695 6p12.3 ADGRF4 adhesion G protein-coupled receptor F4
Mouse 7 698 17 B3 Adgrf4 adhesion G protein-coupled receptor F4
Rat 7 - 9q12 Adgrf4 adhesion G protein-coupled receptor F4
Previous and Unofficial Names Click here for help
GPR115 (G protein-coupled receptor 115) | PGR18
Database Links Click here for help
Specialist databases
GPCRdb agrf4_human (Hs), agrf4_mouse (Mm)
Other databases
Alphafold Q8IZF3 (Hs), Q9D2L6 (Mm)
ChEMBL Target CHEMBL4523889 (Hs)
Ensembl Gene ENSG00000153294 (Hs), ENSMUSG00000023918 (Mm), ENSRNOG00000012535 (Rn)
Entrez Gene 221393 (Hs), 78249 (Mm), 501106 (Rn)
Human Protein Atlas ENSG00000153294 (Hs)
KEGG Gene hsa:221393 (Hs), mmu:78249 (Mm), rno:501106 (Rn)
OMIM 614268 (Hs)
Pharos Q8IZF3 (Hs)
RefSeq Nucleotide NM_153838 (Hs), NM_030067 (Mm)
RefSeq Protein NP_722580 (Hs), NP_084343 (Mm)
UniProtKB Q8IZF3 (Hs), Q9D2L6 (Mm)
Wikipedia ADGRF4 (Hs)
Endogenous agonists
Peptides derived from the ADGRF5 (GPR116) Stachel sequence: TSFSILMSPDSPD  [2]
Agonist Comments
Peptides derived from the ADGRF5 (GPR116) Stachel sequence (TSFSILMSPDSPD) agonist, have agonist activity at ADGRF4 [2].
Immuno Process Associations
Immuno Process:  Immune regulation
Immuno Process:  Immune system development
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gq/G11 family
References:  2,5
Tissue Distribution Click here for help
Unigene expression profile highest in mouth, heart, uterus, vascular.
Species:  Human
Technique: 
References: 
Unigene expression profile highest in skin, female genital, head and neck.
Species:  Mouse
Technique: 
References: 
Lung, heart, skin, kidney, testis, brain, ovaries, epididymis, thymus
Species:  Mouse
Technique:  RT-PCR
References:  7
Adgrf3 is expressed in mature ameloblasts.
Species:  Mouse
Technique: 
References:  1
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

Created with Highcharts 10.3.3Log average relative​abundanceChart context menuLog average relative transcript abundance for Adgrf4 in mouse tissuesOlfactory epitheliumBrainstemCerebellumCerebral cortexHippocampusHypothalamusOlfactory bulbPituitary glandStriatumRetinaWhole eyeAdrenal glandIsletThyroid/ParathyroidAortaVena cavaHeart atriumHeart ventricleLungTracheaBrown adiposeKidneyLiverSkeletal muscleWhite adiposeAdipocyteTongueEsophagusGall bladderLarge intestinePancreasSmall intestineStomachUrinary bladderSpleenThymusBone marrowOvaryTestesUterusSkin0123Highcharts.com
Functional Assays Click here for help
Elevated levels of IP3
Species:  Human
Tissue:  293T cell line
Response measured:  Receptor causes constitutive activation of Gα15 G protein
References:  5
ADGRF3 couples to Gq proteins in COS-7 cells
Species:  Human
Tissue:  COS-7 cells.
Response measured:  Change in IP1 level.
References:  2
Physiological Consequences of Altering Gene Expression Click here for help
AdgrF3 deficiency results in hypo-mineralized enamel.
Species:  Mouse
Tissue:  In vivo, dental epithelial cell ameloblasts.
Technique: 
References:  1
Physiological Consequences of Altering Gene Expression Comments
Gpr115 knockout mice do not show defects in development or fertility [7].
General Comments
ADGRF4 (formerly GPR115) is an orphan receptor that belongs to Family VI Adhesion-GPCRs together with ADGRF1-3, 5 and 6 [3]. The genes of Family VI Adhesion-GPCRs except ADGRF3 are syntenically clustered on human chromosome 6 and mouse chromosome 17 suggesting the evolution from an ancestral gene through gene duplication and exon shuffling [7].

Full coding sequence human cDNA is publicly available, IMAGE:8317335 [6] in mammalian expression vector pCDNA3.1.

Original gene prediction, AY140957 [4] incorrectly predicts the first two and last exons and includes two exons derived from the ADGRF2 gene. The predicted protein (Swiss-Prot ID: Q8IZF3) is longer than that predicted from the observed cDNAs. ADGRF2 is immediately upstream of the ADGRF4 gene.

References

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1. Chiba Y, Yoshizaki K, Saito K, Ikeuchi T, Iwamoto T, Rhodes C, Nakamura T, de Vega S, Morell RJ, Boger ET et al.. (2020) G protein-coupled receptor Gpr115 (Adgrf4) is required for enamel mineralization mediated by ameloblasts. J Biol Chem, 295 (45): 15328-15341. [PMID:32868297]

2. Demberg LM, Winkler J, Wilde C, Simon KU, Schön J, Rothemund S, Schöneberg T, Prömel S, Liebscher I. (2017) Activation of Adhesion G Protein-coupled Receptors: AGONIST SPECIFICITY OF STACHEL SEQUENCE-DERIVED PEPTIDES. J Biol Chem, 292 (11): 4383-4394. [PMID:28154189]

3. Fredriksson R, Gloriam DE, Höglund PJ, Lagerström MC, Schiöth HB. (2003) There exist at least 30 human G-protein-coupled receptors with long Ser/Thr-rich N-termini. Biochem Biophys Res Commun, 301 (3): 725-34. [PMID:12565841]

4. Fredriksson R, Lagerström MC, Höglund PJ, Schiöth HB. (2002) Novel human G protein-coupled receptors with long N-terminals containing GPS domains and Ser/Thr-rich regions. FEBS Lett, 531 (3): 407-14. [PMID:12435584]

5. Gupte J, Swaminath G, Danao J, Tian H, Li Y, Wu X. (2012) Signaling property study of adhesion G-protein-coupled receptors. FEBS Lett, 586 (8): 1214-9. [PMID:22575658]

6. Lennon G, Auffray C, Polymeropoulos M, Soares MB. (1996) The I.M.A.G.E. Consortium: an integrated molecular analysis of genomes and their expression. Genomics, 33 (1): 151-2. [PMID:8617505]

7. Prömel S, Waller-Evans H, Dixon J, Zahn D, Colledge WH, Doran J, Carlton MB, Grosse J, Schöneberg T, Russ AP et al.. (2012) Characterization and functional study of a cluster of four highly conserved orphan adhesion-GPCR in mouse. Dev Dyn, 241 (10): 1591-602. [PMID:22837050]

Contributors

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How to cite this page

Arac-Ozkan D, Aust G, Bonner TI, Cappallo-Obermann H, Formstone C, Hamann J, Harty B, Heyne H, Kirchhoff C, Knapp B, Krishnan A, Langenhan T, Le Duc D, Lin HH, Martinelli DC, Monk K, Piao X, Prömel S, Schiöth H, Schöneberg T, Singer K, Stacey M, Ushkaryov Y, Wolfrum U, Xu L. Adhesion Class GPCRs in GtoPdb v.2023.1. IUPHAR/BPS Guide to Pharmacology CITE. 2023; 2023(1). Available from: https://doi.org/10.2218/gtopdb/F17/2023.1.