EMR1

Last updated
ADGRE1
Identifiers
Aliases ADGRE1 , TM7LN3, EMR1, adhesion G protein-coupled receptor E1
External IDs OMIM: 600493 MGI: 106912 HomoloGene: 1493 GeneCards: ADGRE1
Orthologs
SpeciesHumanMouse
Entrez

2015

13733

Ensembl

ENSG00000174837

ENSMUSG00000004730

UniProt

Q14246

Q61549

RefSeq (mRNA)

NM_001256252
NM_001256253
NM_001256254
NM_001256255
NM_001974

Contents

NM_010130
NM_001355722
NM_001355723

RefSeq (protein)

NP_001243181
NP_001243182
NP_001243183
NP_001243184
NP_001965

NP_034260
NP_001342651
NP_001342652

Location (UCSC) Chr 19: 6.89 – 6.94 Mb Chr 17: 57.67 – 57.79 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

EGF-like module-containing mucin-like hormone receptor-like 1 also known as F4/80 is a protein encoded by the ADGRE1 gene. [5] [6] [7] [8] [9] EMR1 is a member of the adhesion GPCR family. [10] [11] Adhesion GPCRs are characterized by an extended extracellular region often possessing N-terminal protein modules that is linked to a TM7 region via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain. [12]

EMR1 expression in human is restricted to eosinophils and is a specific marker for these cells. [13] The murine homolog of EMR1, F4/80, is a well-known and widely used marker of murine macrophage populations. [14] The N-terminal fragment (NTF) of EMR1 contains 4-6 Epidermal Growth Factor-like (EGF-like) domains in human and 4-7 EGF-like domains in the mouse. [15]

Function

Utilizing F4/80 knockout mice, Lin et al. showed that F4/80 is not necessary for the development of tissue macrophages but is required for the induction of efferent CD8+ regulatory T cells needed for peripheral tolerance. [16]

Clinical significance

Legrand et al. demonstrated that EMR1 can serve as a therapeutic target for depletion of these cells in eosinophilic disorders by using afucosylated antibodies. [17]

See also

Related Research Articles

The EGF module-containing Mucin-like hormone Receptors (EMRs) are closely related subgroup of G protein-coupled receptors (GPCRs). These receptors have a unique hybrid structure in which an extracellular epidermal growth factor (EGF)-like domain is fused to a GPCR domain through a mucin-like stalk. There are four variants of EMR labeled 1-4, each encoded by a separate gene. These receptors are predominantly expressed in cells of the immune system and bind ligands such as CD55.

EMR2 Protein-coding gene in the species Homo sapiens

EGF-like module-containing mucin-like hormone receptor-like 2 also known as CD312 is a protein encoded by the ADGRE2 gene. EMR2 is a member of the adhesion GPCR family. Adhesion GPCRs are characterized by an extended extracellular region often possessing N-terminal protein modules that is linked to a TM7 region via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain.

EMR3 Protein-coding gene in the species Homo sapiens

EGF-like module-containing mucin-like hormone receptor-like 3 is a protein encoded by the ADGRE3 gene. EMR3 is a member of the adhesion GPCR family. Adhesion GPCRs are characterized by an extended extracellular region often possessing N-terminal protein modules that is linked to a TM7 region via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain.

ICAM3 Mammalian protein found in Homo sapiens

Intercellular adhesion molecule 3 (ICAM3) also known as CD50, is a protein that in humans is encoded by the ICAM3 gene. The protein is constitutively expressed on the surface of leukocytes, which are also called white blood cells and are part of the immune system. ICAM3 mediates adhesion between cells by binding to specific integrin receptors. It plays an important role in the immune cell response through its facilitation of interactions between T cells and dendritic cells, which allows for T cell activation. ICAM3 also mediates the clearance of cells undergoing apoptosis by attracting and binding macrophages, a type of cell that breaks down infected or dying cells through a process known as phagocytosis, to apoptotic cells.

CD69

CD69 is a human transmembrane C-Type lectin protein encoded by the CD69 gene. It is an early activation marker that is expressed in hematopoietic stem cells, T cells, and many other cell types in the immune system. It is also implicated in T cell differentiation as well as lymphocyte retention in lymphoid organs.

CD97 Mammalian protein found in Homo sapiens

Cluster of differentiation 97 is a protein also known as BL-Ac[F2] encoded by the ADGRE5 gene. CD97 is a member of the adhesion G protein-coupled receptor (GPCR) family. Adhesion GPCRs are characterized by an extended extracellular region often possessing N-terminal protein modules that is linked to a TM7 region via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain.

GPR64 Protein-coding gene in the species Homo sapiens

G protein-coupled receptor 64 also known as HE6 is a protein encoded by the ADGRG2 gene. GPR64 is a member of the adhesion GPCR family. Adhesion GPCRs are characterized by an extended extracellular region often possessing N-terminal protein modules that is linked to a TM7 region via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain.

Latrophilin 1 Protein-coding gene in the species Homo sapiens

Latrophilin 1 is a protein that in humans is encoded by the ADGRL1 gene. It is a member of the adhesion-GPCR family of receptors. Family members are characterized by an extended extracellular region with a variable number of protein domains coupled to a TM7 domain via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain.

GPR126

G protein-coupled receptor 126 also known as VIGR and DREG is a protein encoded by the ADGRG6 gene. GPR126 is a member of the adhesion GPCR family. Adhesion GPCRs are characterized by an extended extracellular region often possessing N-terminal protein modules that is linked to a TM7 region via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain.

GPR128

G protein-coupled receptor 128 is a protein encoded by the ADGRG7 gene. GPR128 is a member of the adhesion GPCR family. Adhesion GPCRs are characterized by an extended extracellular region often possessing N-terminal protein modules that is linked to a TM7 region via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain.

GPR112 Protein-coding gene in the species Homo sapiens

G protein-coupled receptor 112 is a protein encoded by the ADGRG4 gene. GPR112 is a member of the adhesion GPCR family. Adhesion GPCRs are characterized by an extended extracellular region often possessing N-terminal protein modules that is linked to a TM7 region via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain.

GPR114

G protein-coupled receptor 114 is a protein encoded by the ADGRG5 gene. GPR114 is a member of the adhesion GPCR family. Adhesion GPCRs are characterized by an extended extracellular region often possessing N-terminal protein modules that is linked to a TM7 region via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain.

GPR97

G-protein coupled receptor 97 also known as adhesion G protein-coupled receptor G3 (ADGRG3) is a protein that in humans is encoded by the ADGRG3 gene. GPR97 is a member of the adhesion GPCR family. Adhesion GPCRs are characterized by an extended extracellular region often possessing N-terminal protein modules that is linked to a TM7 region via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain.

GPR56 Protein-coding gene in the species Homo sapiens

G protein-coupled receptor 56 also known as TM7XN1 is a protein encoded by the ADGRG1 gene. GPR56 is a member of the adhesion GPCR family. Adhesion GPCRs are characterized by an extended extracellular region often possessing N-terminal protein modules that is linked to a TM7 region via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain.

Relaxin/insulin-like family peptide receptor 2 Protein-coding gene in the species Homo sapiens

Relaxin/insulin-like family peptide receptor 2, also known as RXFP2, is a human G-protein coupled receptor.

Secretin family receptor proteins, also known as Family B or family 2 of G-protein coupled receptors are regulated by peptide hormones from the glucagon hormone family. The family is different from adhesion G protein-coupled receptors.

STAB1 Protein-coding gene in the species Homo sapiens

Stabilin-1 is a protein that in humans is encoded by the STAB1 gene.

CLEC12A Protein-coding gene in humans

C-type lectin domain family 12 member A is a protein that in humans is encoded by the CLEC12A gene.

Adhesion G protein-coupled receptor Class of 33 human protein receptors

Adhesion G protein-coupled receptors are a class of 33 human protein receptors with a broad distribution in embryonic and larval cells, cells of the reproductive tract, neurons, leukocytes, and a variety of tumours. Adhesion GPCRs are found throughout metazoans and are also found in single-celled colony forming choanoflagellates such as Monosiga brevicollis and unicellular organisms such as Filasterea. The defining feature of adhesion GPCRs that distinguishes them from other GPCRs is their hybrid molecular structure. The extracellular region of adhesion GPCRs can be exceptionally long and contain a variety of structural domains that are known for the ability to facilitate cell and matrix interactions. Their extracellular region contains the membrane proximal GAIN domain. Crystallographic and experimental data has shown this structurally conserved domain to mediate autocatalytic processing at a GPCR-proteolytic site (GPS) proximal to the first transmembrane helix. Autocatalytic processing gives rise to an extracellular (α) and a membrane-spanning (β) subunit, which are associated non-covalently, resulting in expression of a heterodimeric receptor at the cell surface. Ligand profiles and in vitro studies have indicated a role for adhesion GPCRs in cell adhesion and migration. Work utilizing genetic models confined this concept by demonstrating that the primary function of adhesion GPCRs may relate to the proper positioning of cells in a variety of organ systems. Moreover, growing evidence implies a role of adhesion GPCRs in tumour cell metastasis. Formal G protein-coupled signalling has been demonstrated for a number for adhesion GPCRs, however, the orphan receptor status of many of the receptors still hampers full characterisation of potential signal transduction pathways. In 2011, the adhesion GPCR consortium was established to facilitate research of the physiological and pathological functions of adhesion GPCRs.

GAIN domain

The GAIN domain is a protein domain found in a number of cell surface receptors, including adhesion-GPCRs and polycystic kidney disease proteins PKD1 and PKD2. The domain is involved in the self-cleavage of these transmembrane receptors, and has been shown to be crucial for their function. Point mutations within the GAIN domain of PKD1 and GPR56 are known to cause polycystic kidney disease and polymicrogyria, respectively.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000174837 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000004730 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Baud V, Chissoe SL, Viegas-Péquignot E, Diriong S, N'Guyen VC, Roe BA, Lipinski M (March 1995). "EMR1, an unusual member in the family of hormone receptors with seven transmembrane segments". Genomics. 26 (2): 334–44. doi:10.1016/0888-7543(95)80218-B. PMID   7601460.
  6. ↑ McKnight AJ, Gordon S (March 1998). "The EGF-TM7 family: unusual structures at the leukocyte surface". Journal of Leukocyte Biology. 63 (3): 271–80. doi:10.1002/jlb.63.3.271. PMID   9500513. S2CID   6497890.
  7. ↑ "Entrez Gene: EMR1 egf-like module containing, mucin-like, hormone receptor-like 1".
  8. ↑ Leenen PJ, de Bruijn MF, Voerman JS, Campbell PA, van Ewijk W (September 1994). "Markers of mouse macrophage development detected by monoclonal antibodies". Journal of Immunological Methods. 174 (1–2): 5–19. doi:10.1016/0022-1759(94)90005-1. hdl: 1765/71089 . PMID   8083537.
  9. ↑ Hamann, J; Aust, G; Araç, D; Engel, FB; Formstone, C; Fredriksson, R; Hall, RA; Harty, BL; Kirchhoff, C; Knapp, B; Krishnan, A; Liebscher, I; Lin, HH; Martinelli, DC; Monk, KR; Peeters, MC; Piao, X; Prömel, S; Schöneberg, T; Schwartz, TW; Singer, K; Stacey, M; Ushkaryov, YA; Vallon, M; Wolfrum, U; Wright, MW; Xu, L; Langenhan, T; Schiöth, HB (April 2015). "International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors". Pharmacological Reviews. 67 (2): 338–67. doi:10.1124/pr.114.009647. PMC   4394687 . PMID   25713288.
  10. ↑ Stacey M, Yona S (2011). Adhesion-GPCRs: Structure to Function (Advances in Experimental Medicine and Biology). Berlin: Springer. ISBN   978-1-4419-7912-4.
  11. ↑ Langenhan, T; Aust, G; Hamann, J (21 May 2013). "Sticky signaling--adhesion class G protein-coupled receptors take the stage". Science Signaling. 6 (276): re3. doi:10.1126/scisignal.2003825. PMID   23695165. S2CID   6958640.
  12. ↑ Araç D, Boucard AA, Bolliger MF, Nguyen J, Soltis SM, Südhof TC, Brunger AT (March 2012). "A novel evolutionarily conserved domain of cell-adhesion GPCRs mediates autoproteolysis". The EMBO Journal. 31 (6): 1364–78. doi:10.1038/emboj.2012.26. PMC   3321182 . PMID   22333914.
  13. ↑ Hamann J, Koning N, Pouwels W, Ulfman LH, van Eijk M, Stacey M, Lin HH, Gordon S, Kwakkenbos MJ (October 2007). "EMR1, the human homolog of F4/80, is an eosinophil-specific receptor". European Journal of Immunology. 37 (10): 2797–802. doi: 10.1002/eji.200737553 . PMID   17823986.
  14. ↑ Austyn JM, Gordon S (October 1981). "F4/80, a monoclonal antibody directed specifically against the mouse macrophage". European Journal of Immunology. 11 (10): 805–15. doi:10.1002/eji.1830111013. PMID   7308288. S2CID   8426640.
  15. ↑ Gordon S, Hamann J, Lin HH, Stacey M (September 2011). "F4/80 and the related adhesion-GPCRs". European Journal of Immunology. 41 (9): 2472–6. doi: 10.1002/eji.201141715 . PMID   21952799.
  16. ↑ Lin HH, Faunce DE, Stacey M, Terajewicz A, Nakamura T, Zhang-Hoover J, Kerley M, Mucenski ML, Gordon S, Stein-Streilein J (May 2005). "The macrophage F4/80 receptor is required for the induction of antigen-specific efferent regulatory T cells in peripheral tolerance". The Journal of Experimental Medicine. 201 (10): 1615–25. doi:10.1084/jem.20042307. PMC   2212925 . PMID   15883173.
  17. ↑ Legrand F, Tomasevic N, Simakova O, Lee CC, Wang Z, Raffeld M, Makiya MA, Palath V, Leung J, Baer M, Yarranton G, Maric I, Bebbington C, Klion AD (May 2014). "The eosinophil surface receptor epidermal growth factor-like module containing mucin-like hormone receptor 1 (EMR1): a novel therapeutic target for eosinophilic disorders". The Journal of Allergy and Clinical Immunology. 133 (5): 1439–47, 1447.e1–8. doi:10.1016/j.jaci.2013.11.041. PMC   4113341 . PMID   24530099.

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