ADGRE4P | Adhesion Class GPCRs | IUPHAR/BPS Guide to PHARMACOLOGY

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ADGRE4P

Target not currently curated in GtoImmuPdb

Target id: 185

Nomenclature: ADGRE4P

Family: Adhesion Class GPCRs

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

Gene and Protein Information
Adhesion G protein-coupled receptor: probable pseudogene
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 232 19p13.3 ADGRE4P adhesion G protein-coupled receptor E4, pseudogene 3,5
Mouse 7 689 17 C Adgre4 adhesion G protein-coupled receptor E4 9
Rat 7 683 9 Adgre4 adhesion G protein-coupled receptor E4
Previous and Unofficial Names
FIRE (F4/80-like-receptor) | EMR4 (EGF-like module-containing mucin-like hormone receptor-like 4) | GPR127 | G protein-coupled receptor 127
Database Links
Specialist databases
GPCRDB agre4_human (Hs), agre4_mouse (Mm), q5y4n7_rat (Rn)
Other databases
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
Comments: Probable pseudogene
Agonist Comments
No ligands identified: orphan receptor.
Tissue Distribution
Thymus, spleen, monocytes, monocyte-derived dendritic cells, splenic CD11b+ dendritic cells, blood BDCA-1+ dendritic cells
Species:  Human
Technique:  Northern blot
References:  3,5
Spleen, liver, thymus, unactivated CD8-negative dendritic cells, peritoneal macrophages (resident, biogel- and thioglycollate-elicited)
Species:  Mouse
Technique:  Northern blot and RT-PCR
References:  2,9
Subpopulation of blood monocytes and splenic CD8-negative dendritic cells and macrophages, peritoneal macrophages (expression lost upon activation), no expression in lymphocytes
Species:  Mouse
Technique:  FACS analysis
References:  2
Subpopulation of denritic cells and (metalophilic) macrophages in spleen and lymph nodes
Species:  Mouse
Technique:  Immunocytochemistry
References:  2
Expression Datasets

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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]

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Functional Assays
ADGRE4-targeted antigen delivery increases immunogenicity of proteins
Species:  Mouse
Tissue:  Dendritic cells
Response measured:  Increased antibody response
References:  4
General Comments
ADGRE4P (adhesion G protein-coupled receptor E4, pseudogene, formaerly EMR4: EGF-like module containing, mucin-like, hormone receptor-like 4) is an orphan receptor that belongs to Family II Adhesion-GPCRs together with ADGRE5 and ADGRE1-3 [1,6]. The genes of all Family II Adhesion-GPCRs are syntenically clustered on human chromosome 19 and mouse chromosome 8 suggesting the evolution from an ancestral gene through gene duplication and exon shuffling [7]. Human ADGRE4 receptor has likely undergone gene inactivation due to a one-nucleotide deletion in exon 8 that generates a premature stop codon and protein truncation. This deletion is not present in other mammals and nonhuman primates, including chimpanzees [3,8]. The putative truncated domain could potentially act as a functional soluble protein.

The human ADGRE4 gene has a deletion of one nucleotide within the eighth coding exon [3,5]. The deletion has been confirmed in genomic DNA from 17 individuals [5] and cDNA from 15 different individuals [3]. The deletion does not occur in chimpanzee, orangutan, macaque or mouse and thus appears to have occured shortly after the evolutionary divergence of humans and the apes.

The deletion results in a single frame shift which would presumably lead to the expression of a truncated amino terminal domain of 232 amino acids. This protein lacks any of the transmembrane domains. There is a second open reading frame capable of encoding a 7 TM GPCR with an 93 amino acid amino terminal domain but there is no evidence for its translation. Thus human ADGRE4 should be considered as a probable GPCR pseudogene although the 232 amino acid secreted protein may have biological function. It is also possible that the 232 amino acid protein is not expressed due to nonsense mediated decay of the mRNA since there are multiple noncoding exons at the 3' end.

References

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1. Bjarnadóttir TK, Fredriksson R, Höglund PJ, Gloriam DE, Lagerström MC, Schiöth HB. (2004) The human and mouse repertoire of the adhesion family of G-protein-coupled receptors. Genomics, 84 (1): 23-33. [PMID:15203201]

2. Caminschi I, Lucas KM, O'Keeffe MA, Hochrein H, Laâbi Y, Köntgen F, Lew AM, Shortman K, Wright MD. (2001) Molecular cloning of F4/80-like-receptor, a seven-span membrane protein expressed differentially by dendritic cell and monocyte-macrophage subpopulations. J. Immunol., 167 (7): 3570-6. [PMID:11564768]

3. Caminschi I, Vandenabeele S, Sofi M, McKnight AJ, Ward N, Brodnicki TC, Toy T, Lahoud M, Maraskovsky E, Shortman K, Wright MD. (2006) Gene structure and transcript analysis of the human and mouse EGF-TM7 molecule, FIRE. DNA Seq, 17: 8-14. [PMID:16753812]

4. Corbett AJ, Caminschi I, McKenzie BS, Brady JL, Wright MD, Mottram PL, Hogarth PM, Hodder AN, Zhan Y, Tarlinton DM et al.. (2005) Antigen delivery via two molecules on the CD8- dendritic cell subset induces humoral immunity in the absence of conventional "danger". Eur. J. Immunol., 35 (10): 2815-25. [PMID:16143986]

5. Hamann J, Kwakkenbos MJ, de Jong EC, Heus H, Olsen AS, van Lier RA. (2003) Inactivation of the EGF-TM7 receptor EMR4 after the Pan-Homo divergence. Eur J Immunol, 33: 1365-1371. [PMID:12731063]

6. Kwakkenbos MJ, Kop EN, Stacey M, Matmati M, Gordon S, Lin HH, Hamann J. (2004) The EGF-TM7 family: a postgenomic view. Immunogenetics, 55 (10): 655-66. [PMID:14647991]

7. Kwakkenbos MJ, Matmati M, Madsen O, Pouwels W, Wang Y, Bontrop RE, Heidt PJ, Hoek RM, Hamann J. (2006) An unusual mode of concerted evolution of the EGF-TM7 receptor chimera EMR2. FASEB J., 20 (14): 2582-4. [PMID:17068111]

8. Mah MW, Priel IE, Humen DP, Brown NE, Sproule BJ. (1989) Idiopathic pulmonary hemosiderosis, complete heart block and celiac disease. Can J Cardiol, 5 (4): 191-4. [PMID:2731063]

9. Stacey M, Chang GW, Sanos SL, Chittenden LR, Stubbs L, Gordon S, Lin HH. (2002) EMR4, a novel epidermal growth factor (EGF)-TM7 molecule up-regulated in activated mouse macrophages, binds to a putative cellular ligand on B lymphoma cell line A20. J. Biol. Chem., 277 (32): 29283-93. [PMID:12023293]

Contributors

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