Nomenclature: EMR2

Family: Adhesion Class GPCRs

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

Contents

Gene and Protein Information
Adhesion G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 823 19p13.1 EMR2 egf-like module containing, mucin-like, hormone receptor-like 2 12,14,17
Previous and Unofficial Names
egf-like module containing, mucin-like, hormone receptor-like 2
CD312
EGF-like module-containing mucin-like hormone receptor-like 2
EGF-like module EMR2
CD312 antigen
egf-like module containing, mucin-like, hormone receptor-like sequence 2
Database Links
Ensembl Gene
Entrez Gene
GPCRDB
GeneCards
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Agonist Comments
No ligands identified: orphan receptor. No data found to show chondroitin sulfate B can act as an agonist at this receptor when tested by [15,19].
Primary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family
Comments:  Induces inositiol phosphate accumulation when co-transfected with Gα15.
References:  9
Tissue Distribution
Spleen, lymph node, peripheral blood leukocyte, lung, bone marrow, fetal liver
Species:  Human
Technique:  Northern blot
References:  17
All types of myeloid cells including monocytes, monocyte-derived macrophages, myeloid dendritic cells and neutrophilic, basophilic and eosinophilic granulocytes, upregulated during differentiation and maturation of macrophages and in neutrophils in patients with systemic inflammation, expressed by hematopoietic stem and progenitor cells
Species:  Human
Technique:  Flow cytometry
References:  4,7-8,12,21
Tissue macrophages in skin, spleen (red-pulp macrophages), tonsil, lung and placenta (interstitial macrophages)
Species:  Human
Technique:  Immunohistochemistry
References:  12
Subsets of infiltrating macrophages, dendritic cells and neutrophilic granulocytes in rheumatoid arthritis, in liver and lung abscesses, in severe acute suppurative appendicitis and in atherosclerosis
Species:  Human
Technique:  Immunohistochemistry
References:  4,11,20
Expression in breast carcinomas, weak expression in colorectal adenocarcinomas, not expressed in esophageal, gastric and pancreatic carcinomas
Species:  Human
Technique:  Immunocytochemistry
References:  1-2,6
Functional Assays
Elevated neutrophil migration, and augmented superoxide production/proteolytic enzyme degranulation
Species:  Human
Tissue:  Neutrophils
Response measured:  Elevated in-vitro migration/superoxide production
References:  5,21
Activates monocytes and macrophages to secrete inflammatory cytokines (IL-8, TNF)
Species:  Human
Tissue:  Monocytes, macrophages
Response measured:  Elevated cytokine secretion
References:  10
Physiological Functions
Increases neutrophil adhesion and migration, and augments superoxide production and proteolytic enzyme degranulation by potentiating the effects of proinflammatory mediators
Species:  Human
Tissue:  Neutrophilic granulocytes
References:  5,21
Biologically Significant Variants
Type:  Splice variant
Species:  Human
Description:  Full-length isoform with 5 EGF-like domains (EGF1-5), binds chondroitin sulfate B
Amino acids:  823
Nucleotide accession: 
Protein accession: 
References:  1,17-19
Type:  Splice variant
Species:  Human
Description:  Isoform with 4 EGF-like domains (EGF1,2,3,5), does not bind chondroitin sulfate B
Amino acids:  774
References:  1,17-19
Type:  Splice variant
Species:  Human
Description:  Isoform with 3 EGF-like domains (EGF1,2,5), does not bind chondroitin sulfate B
Amino acids:  730
References:  1,17-19
Type:  Splice variant
Species:  Human
Description:  Isoform with 2 EGF-like domains (EGF1,2), does not bind chondroitin sulfate B
Amino acids:  681
References:  1,17-19
Biologically Significant Variant Comments
The interaction with chondroitin sulfate B is mediated by the 4th EGF-like domain [1].
General Comments
EMR2 (EGF-like module containing, mucin-like, hormone receptor-like 2) is a receptor that belongs to Family II Adhesion-GPCRs together with CD97 and EMR1, EMR3 and EMR4 [3,13]. 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 [14]. No mouse or rat EMR2 orthologue exists. EMR2 possesses a chimeric structure with a seven-span transmembrane region most related to EMR3 and an EGF-like domain region nearly identical to CD97 [17]. This structure has evolved by gene conversion between the EMR2 gene and the oppositely orientated and physically adjacent genes CD97 and EMR3 [14]. Most highly conserved between EMR2 and CD97 is the 4th EGF-like domain, which mediates binding to chondroitin sulfate, a ligand shared by both receptors [19].

There are three well characterized amino acid-changing SNPs.

Full coding sequence human cDNA is publicly available, IMAGE:8317326 [16] in mammalian expression vector pCDNA3.1. This clone differs from the RefSeq and human reference genomic sequence at a know SNP. It has the less common Phe614 allele.

REFERENCES

1. Aust G, Hamann J, Schilling N, Wobus M. (2003) Detection of alternatively spliced EMR2 mRNAs in colorectal tumor cell lines but rare expression of the molecule in colorectal adenocarcinomas. Virchows Arch.443 (1): 32-7. [PMID:12761622]

2. Aust G, Steinert M, Schütz A, Boltze C, Wahlbuhl M, Hamann J, Wobus M. (2002) CD97, but not its closely related EGF-TM7 family member EMR2, is expressed on gastric, pancreatic, and esophageal carcinomas. Am. J. Clin. Pathol.118 (5): 699-707. [PMID:12428789]

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. Genomics84: 23-33. [PMID:15203201]

4. Chang GW, Davies JQ, Stacey M, Yona S, Bowdish DM, Hamann J, Chen TC, Lin CY, Gordon S, Lin HH. (2007) CD312, the human adhesion-GPCR EMR2, is differentially expressed during differentiation, maturation, and activation of myeloid cells. Biochem. Biophys. Res. Commun.353 (1): 133-8. [PMID:17174274]

5. Chen TY, Hwang TL, Lin CY, Lin TN, Lai HY, Tsai WP, Lin HH. (2011) EMR2 receptor ligation modulates cytokine secretion profiles and cell survival of lipopolysaccharide-treated neutrophils. Chang Gung Med J34 (5): 468-77. [PMID:22035891]

6. Davies JQ, Lin HH, Stacey M, Yona S, Chang GW, Gordon S, Hamann J, Campo L, Han C, Chan P et al.. (2011) Leukocyte adhesion-GPCR EMR2 is aberrantly expressed in human breast carcinomas and is associated with patient survival. Oncol. Rep.25 (3): 619-27. [PMID:21174063]

7. Florian S, Sonneck K, Czerny M, Hennersdorf F, Hauswirth AW, Bühring HJ, Valent P. (2006) Detection of novel leukocyte differentiation antigens on basophils and mast cells by HLDA8 antibodies. Allergy61 (9): 1054-62. [PMID:16918507]

8. Glaeser RM, Zilker A, Radermacher M, Gaub HE, Hartmann T, Baumeister W. (1991) Interfacial energies and surface-tension forces involved in the preparation of thin, flat crystals of biological macromolecules for high-resolution electron microscopy. J Microsc161 (Pt 1): 21-45. [PMID:2016735]

9. 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]

10. Huang YS, Chiang NY, Hu CH, Hsiao CC, Cheng KF, Tsai WP, Yona S, Stacey M, Gordon S, Chang GW et al.. (2012) Activation of myeloid cell-specific adhesion class G protein-coupled receptor EMR2 via ligation-induced translocation and interaction of receptor subunits in lipid raft microdomains. Mol. Cell. Biol.32 (8): 1408-20. [PMID:22310662]

11. Kop EN, Kwakkenbos MJ, Teske GJ, Kraan MC, Smeets TJ, Stacey M, Lin HH, Tak PP, Hamann J. (2005) Identification of the epidermal growth factor-TM7 receptor EMR2 and its ligand dermatan sulfate in rheumatoid synovial tissue. Arthritis Rheum.52 (2): 442-50. [PMID:15693006]

12. Kwakkenbos MJ, Chang GW, Lin HH, Pouwels W, de Jong EC, van Lier RA, Gordon S, Hamann J. (2002) The human EGF-TM7 family member EMR2 is a heterodimeric receptor expressed on myeloid cells. J Leukoc Biol71: 854-862. [PMID:11994511]

13. Kwakkenbos MJ, Kop EN, Stacey M, Matmati M, Gordon S, Lin HH, Hamann J. (2004) The EGF-TM7 family: a postgenomic view. Immunogenetics55 (10): 655-66. [PMID:14647991]

14. 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 J20: 2582-2584. [PMID:17068111]

15. Kwakkenbos MJ, Pouwels W, Matmati M, Stacey M, Lin HH, Gordon S, van Lier RA, Hamann J. (2005) Expression of the largest CD97 and EMR2 isoforms on leukocytes facilitates a specific interaction with chondroitin sulfate on B cells. J. Leukoc. Biol.77 (1): 112-9. [PMID:15498814]

16. 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. Genomics33: 151-152. [PMID:8617505]

17. Lin HH, Stacey M, Hamann J, Gordon S, McKnight AJ. (2000) Human EMR2, a novel EGF-TM7 molecule on chromosome 19p13.1, is closely related to CD97. Genomics67: 188-200. [PMID:10903844]

18. Lin HH, Stacey M, Saxby C, Knott V, Chaudhry Y, Evans D, Gordon S, McKnight AJ, Handford P, Lea S. (2001) Molecular analysis of the epidermal growth factor-like short consensus repeat domain-mediated protein-protein interactions: dissection of the CD97-CD55 complex. J. Biol. Chem.276 (26): 24160-9. [PMID:11297558]

19. Stacey M, Chang GW, Davies JQ, Kwakkenbos MJ, Sanderson RD, Hamann J, Gordon S, Lin HH. (2003) The epidermal growth factor-like domains of the human EMR2 receptor mediate cell attachment through chondroitin sulfate glycosaminoglycans. Blood102 (8): 2916-24. [PMID:12829604]

20. van Eijk M, Aust G, Brouwer MS, van Meurs M, Voerman JS, Dijke IE, Pouwels W, Sändig I, Wandel E, Aerts JM, Boot RG, Laman JD, Hamann J. (2010) Differential expression of the EGF-TM7 family members CD97 and EMR2 in lipid-laden macrophages in atherosclerosis, multiple sclerosis and Gaucher disease. Immunol. Lett.129 (2): 64-71. [PMID:20167235]

21. Yona S, Lin HH, Dri P, Davies JQ, Hayhoe RP, Lewis SM, Heinsbroek SE, Brown KA, Perretti M, Hamann J et al.. (2008) Ligation of the adhesion-GPCR EMR2 regulates human neutrophil function. FASEB J.22 (3): 741-51. [PMID:17928360]

To cite this database page, please use the following:

Hsi-Hsien Lin, Jörg Hamann, Martin Stacey, Gabriela Aust, Tom I. Bonner.
Adhesion Class GPCRs: EMR2. Last modified on 23/07/2013. Accessed on 25/10/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=183.

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