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ADGRE1

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Target id: 182

Nomenclature: ADGRE1

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 7 886 19p13.3-p13.2 ADGRE1 adhesion G protein-coupled receptor E1 2
Mouse 7 931 17 29.8 cM Adgre1 adhesion G protein-coupled receptor E1
Rat 7 932 9q12 Adgre1 adhesion G protein-coupled receptor E1 17
Previous and Unofficial Names Click here for help
EMR1 (EGF-like module-containing, mucin-like, hormone receptor-like 1)
Database Links Click here for help
Specialist databases
GPCRdb agre1_human (Hs), agre1_rat (Rn)
Other databases
Alphafold Q14246 (Hs), Q3U9R0 (Mm), Q5Y4N8 (Rn)
Ensembl Gene ENSG00000174837 (Hs), ENSMUSG00000004730 (Mm), ENSRNOG00000046254 (Rn)
Entrez Gene 2015 (Hs), 13733 (Mm), 316137 (Rn)
Human Protein Atlas ENSG00000174837 (Hs)
KEGG Gene hsa:2015 (Hs), mmu:13733 (Mm), rno:316137 (Rn)
OMIM 600493 (Hs)
Pharos Q14246 (Hs)
RefSeq Nucleotide NM_001974 (Hs), NM_001256255 (Hs), NM_001256254 (Hs), NM_001256252 (Hs), NM_001256253 (Hs), NM_010130 (Mm), NM_001007557 (Rn)
RefSeq Protein NP_001243182 (Hs), NP_001243181 (Hs), NP_001243183 (Hs), NP_001243184 (Hs), NP_001965 (Hs), NP_034260 (Mm), NP_001007558 (Rn)
UniProtKB Q14246 (Hs), Q3U9R0 (Mm), Q5Y4N8 (Rn)
Wikipedia ADGRE1 (Hs)
Agonist Comments
No ligands identified: orphan receptor.
Immuno Process Associations
Immuno Process:  T cell (activation)
Immuno Process:  B cell (activation)
Tissue Distribution Click here for help
Eosinophilic granulocytes, not expressed in monocytes, macrophages and myeloid dendritic cells
Species:  Human
Technique:  Flow cytometry
References:  7,10
Northern blot of assorted mouse cell lines detects expression only in cells of the macrophage lineage.
Species:  Mouse
Technique:  Northern blotting.
References:  17
Pan-macrophage marker for mouse tissue macrophages, including liver Kupffer cells, spleen red pulp macrophages, brain microglia cells and resident tissue macrophages in bone marrow, peritoneum, gut lamina propria, kidney and lymph nodes, also expressed in mouse eosinophils and macrophage cell lines, but not in cells of lymphoid lineages, neutrophils and monocyte-derived osteoclasts
Species:  Mouse
Technique:  Immunohistochemistry and flow cytometry
References:  1,4-6,13-15
Tissue Distribution Comments
ADGRE1 and F4/80 are human and mouse orthologous genes, respectively. However, the two receptors have very different tissue distribution/cell expression patterns. F4/80 is a pan-macrophage marker, ubiquitously expressed in most, if not all, mouse resident tissue macrophages. F4/80 expression is also detected in eosinophils. On the other hand, ADGRE1 is restrictedly expressed in human eosinophilic granulocytes, but not monocytes, macrophages or myeloid dendritic cells.
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]

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Physiological Consequences of Altering Gene Expression Click here for help
F4/80-/- mice are viable, fertile, and appear healthy even when maintained under non-SPF (specific pathogen-free) conditions (unpublished results).
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  16
Failure in peripheral immune tolerance. Mice with receptor knockout show the F4/80 receptor is involved in the generation of antigen-specific efferent regulatory T (Treg) cells that suppress antigen-specific immunity, macrophage develoment is not affected
Species:  Mouse
Tissue:  Immune system
Technique:  Gene knockouts
References:  12,19
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Emr1tm1Stst Emr1tm1Stst/Emr1tm1Stst
B6.129S1-Emr1		 MGI:106912  MP:0005000 abnormal immune tolerance PMID: 15883173 
Emr1tm1Stst Emr1tm1Stst/Emr1tm1Stst
B6.129S1-Emr1		 MGI:106912  MP:0004946 abnormal regulatory T cell physiology PMID: 15883173 
Biologically Significant Variants Click here for help
Type:  Splice variant
Species:  Human
Description:  Largest EMR1 isoform with 6 EGF-like domains
Amino acids:  886
Nucleotide accession:  NM_001974
Protein accession:  NP_001965
References:  2,7
Type:  Splice variant
Species:  Human
Description:  This variant lacks the first 2 EGF-like domains and lacks an additional segment in the 3' coding region
Amino acids:  867
Nucleotide accession:  NM_001256252
Protein accession:  NP_001243181
References:  2,7
Type:  Splice variant
Species:  Human
Description:  This variant lacks an in-frame exon in the stalk region, compared to the largest variant
Amino acids:  821
Nucleotide accession:  NM_001256253
Protein accession:  NP_001243182
References:  2,7
Type:  Splice variant
Species:  Human
Description:  This variant lacks the EGF-like domains 2, 3 and 4, compared to the largest variant
Amino acids:  745
Nucleotide accession:  NM_001256254
Protein accession:  NP_001243183
References:  2,7
Type:  Splice variant
Species:  Human
Description:  This variant lacks the EGF-like domains 3, 4, 5 and 6, compared to the largest variant
Amino acids:  709
Nucleotide accession:  NM_001256255
Protein accession:  NP_001243184
References:  2,7
General Comments
ADGRE1 (adhesion G protein-coupled receptor E1, formerly known as EMR1: EGF-like module containing, mucin-like, hormone receptor-like 1) is an orphan receptor that belongs to Family II Adhesion-GPCRs together with ADGRE5 and ADGRE2-4 [3,8]. The genes of Family II Adhesion-GPCRs are syntenically clustered on human chromosome 19 suggesting the evolution from an ancestral gene through gene duplication and exon shuffling [9]. The mouse gene is localized on chromosome 17 [18].

There are 14 well characterised amino acid-changing SNPs.

Full coding sequence human cDNA is publicly available, IMAGE:7447856 [11] in mammalian expression vector pCDNA3.1. This clone differs from the RefSeq and reference genomic sequence at three known SNPs and has the more common allele at each, Val424, Gln496 and Val539.

References

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1. Austyn JM, Gordon S. (1981) F4/80, a monoclonal antibody directed specifically against the mouse macrophage. Eur J Immunol, 11 (10): 805-15. [PMID:7308288]

2. Baud V, Chissoe SL, Viegas-Péquignot E, Diriong S, N'Guyen VC, Roe BA, Lipinski M. (1995) EMR1, an unusual member in the family of hormone receptors with seven transmembrane segments. Genomics, 26 (2): 334-44. [PMID:7601460]

3. 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]

4. Gordon S, Hamann J, Lin HH, Stacey M. (2011) F4/80 and the related adhesion-GPCRs. Eur J Immunol, 41 (9): 2472-6. [PMID:21952799]

5. Gordon S, Lawson L, Rabinowitz S, Crocker PR, Morris L, Perry VH. (1992) Antigen markers of macrophage differentiation in murine tissues. Curr Top Microbiol Immunol, 181: 1-37. [PMID:1424778]

6. Gordon S, Perry VH, Rabinowitz S, Chung LP, Rosen H. (1988) Plasma membrane receptors of the mononuclear phagocyte system. J Cell Sci Suppl, 9: 1-26. [PMID:3077135]

7. Hamann J, Koning N, Pouwels W, Ulfman LH, van Eijk M, Stacey M, Lin HH, Gordon S, Kwakkenbos MJ. (2007) EMR1, the human homolog of F4/80, is an eosinophil-specific receptor. Eur J Immunol, 37 (10): 2797-802. [PMID:17823986]

8. 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]

9. 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]

10. Legrand F, Tomasevic N, Simakova O, Lee CC, Wang Z, Raffeld M, Makiya MA, Palath V, Leung J, Baer M et al.. (2014) The eosinophil surface receptor epidermal growth factor-like module containing mucin-like hormone receptor 1 (EMR1): a novel therapeutic target for eosinophilic disorders. J Allergy Clin Immunol, 133 (5): 1439-47, 1447.e1-8. [PMID:24530099]

11. 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]

12. Lin HH, Faunce DE, Stacey M, Terajewicz A, Nakamura T, Zhang-Hoover J, Kerley M, Mucenski ML, Gordon S, Stein-Streilein J. (2005) The macrophage F4/80 receptor is required for the induction of antigen-specific efferent regulatory T cells in peripheral tolerance. J Exp Med, 201 (10): 1615-25. [PMID:15883173]

13. Lin HH, Stacey M, Stein-Streilein J, Gordon S. (2010) F4/80: the macrophage-specific adhesion-GPCR and its role in immunoregulation. Adv Exp Med Biol, 706: 149-56. [PMID:21618834]

14. Martinez-Pomares L, Platt N, McKnight AJ, da Silva RP, Gordon S. (1996) Macrophage membrane molecules: markers of tissue differentiation and heterogeneity. Immunobiology, 195 (4-5): 407-16. [PMID:8933147]

15. McGarry MP, Stewart CC. (1991) Murine eosinophil granulocytes bind the murine macrophage-monocyte specific monoclonal antibody F4/80. J Leukoc Biol, 50 (5): 471-8. [PMID:1721083]

16. McKnight AJ, Gordon S. (1998) The EGF-TM7 family: unusual structures at the leukocyte surface. J Leukoc Biol, 63 (3): 271-80. [PMID:9500513]

17. McKnight AJ, Macfarlane AJ, Dri P, Turley L, Willis AC, Gordon S. (1996) Molecular cloning of F4/80, a murine macrophage-restricted cell surface glycoprotein with homology to the G-protein-linked transmembrane 7 hormone receptor family. J Biol Chem, 271 (1): 486-9. [PMID:8550607]

18. McKnight AJ, Macfarlane AJ, Seldin MF, Gordon S. (1997) Chromosome mapping of the Emr1 gene. Mamm Genome, 8 (12): 946. [PMID:9383301]

19. Schaller E, Macfarlane AJ, Rupec RA, Gordon S, McKnight AJ, Pfeffer K. (2002) Inactivation of the F4/80 glycoprotein in the mouse germ line. Mol Cell Biol, 22 (22): 8035-43. [PMID:12391169]

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