EMR2: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
m (Bot: Automated text replacement (-{{SIB}} + & -{{EJ}} + & -{{EH}} + & -{{Editor Join}} + & -{{Editor Help}} +))
 
imported>Ser Amantio di Nicolao
 
(2 intermediate revisions by 2 users not shown)
Line 1: Line 1:
{{Infobox_gene}}
'''EGF-like module-containing mucin-like hormone receptor-like 2''' also known as '''CD312''' ([[cluster of differentiation]] 312) is a [[protein]] encoded by the ''ADGRE2'' [[gene]].<ref>{{cite journal | vauthors = 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 | display-authors = 6 | title = International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors | journal = Pharmacological Reviews | volume = 67 | issue = 2 | pages = 338–67 | date = April 2015 | pmid = 25713288 | doi = 10.1124/pr.114.009647 | pmc=4394687}}</ref>  EMR2 is a member of the [[adhesion-GPCRs|adhesion GPCR]] family.<ref name="isbn1-4419-7912-3">{{cite book | author = Stacey M, Yona S | title = Adhesion-GPCRs: Structure to Function (Advances in Experimental Medicine and Biology) | publisher = Springer | location = Berlin | year = 2011 | pages = | isbn = 1-4419-7912-3 }}</ref><ref>{{cite journal | vauthors = Langenhan T, Aust G, Hamann J | title = Sticky signaling--adhesion class G protein-coupled receptors take the stage | journal = Science Signaling | volume = 6 | issue = 276 | pages = re3 | date = May 2013 | pmid = 23695165 | doi = 10.1126/scisignal.2003825 }}</ref>
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|(GAIN)]] domain.<ref name="pmid22333914">{{cite journal | vauthors = Araç D, Boucard AA, Bolliger MF, Nguyen J, Soltis SM, Südhof TC, Brunger AT | title = A novel evolutionarily conserved domain of cell-adhesion GPCRs mediates autoproteolysis | journal = The EMBO Journal | volume = 31 | issue = 6 | pages = 1364–78 | date = March 2012 | pmid = 22333914 | pmc = 3321182 | doi = 10.1038/emboj.2012.26 }}</ref>


EMR2 is expressed by monocytes/macrophages, dendritic cells and all types of granulocytes.<ref>{{cite journal | vauthors = Lin HH, Stacey M, Hamann J, Gordon S, McKnight AJ | title = Human EMR2, a novel EGF-TM7 molecule on chromosome 19p13.1, is closely related to CD97 | journal = Genomics | volume = 67 | issue = 2 | pages = 188–200 | date = July 2000 | pmid = 10903844 | doi = 10.1006/geno.2000.6238 }}</ref> In the case of EMR2 the N-terminal domains consist of alternatively spliced epidermal growth factor-like ([[EGF-like domain|EGF-like]]) domains.  EMR2 is closely related to CD97 with 97% amino-acid identity in the EGF-like domains. The N-terminal fragment (NTF) of EMR2 presents 2-5 EGF-like domains in human.<ref>{{cite journal | vauthors = Gordon S, Hamann J, Lin HH, Stacey M | title = F4/80 and the related adhesion-GPCRs | journal = European Journal of Immunology | volume = 41 | issue = 9 | pages = 2472–6 | date = September 2011 | pmid = 21952799 | doi = 10.1002/eji.201141715 }}</ref> Mice lack the ''Emr2'' gene.<ref>{{cite journal | vauthors = Kwakkenbos MJ, Matmati M, Madsen O, Pouwels W, Wang Y, Bontrop RE, Heidt PJ, Hoek RM, Hamann J | title = An unusual mode of concerted evolution of the EGF-TM7 receptor chimera EMR2 | journal = FASEB Journal | volume = 20 | issue = 14 | pages = 2582–4 | date = December 2006 | pmid = 17068111 | doi = 10.1096/fj.06-6500fje }}</ref> This gene is closely linked to the gene encoding EGF-like molecule containing mucin-like hormone receptor 3 [[EMR3]] on chromosome 19.


<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
== Ligand ==
{{PBB_Controls
Like the related [[CD97]] protein, the fourth EGF-like domain of EMR2 binds chondroitin sulfate B to mediate cell attachment.<ref>{{cite journal | vauthors = Stacey M, Chang GW, Davies JQ, Kwakkenbos MJ, Sanderson RD, Hamann J, Gordon S, Lin HH | title = The epidermal growth factor-like domains of the human EMR2 receptor mediate cell attachment through chondroitin sulfate glycosaminoglycans | journal = Blood | volume = 102 | issue = 8 | pages = 2916–24 | date = October 2003 | pmid = 12829604 | doi = 10.1182/blood-2002-11-3540 }}</ref> However, unlike [[CD97]] EMR2 does not interact with the complement regulatory protein, decay accelerating factor [[CD55]], and indicating that these very closely related proteins likely have nonredundant functions.<ref>{{cite journal | vauthors = Kwakkenbos MJ, Chang GW, Lin HH, Pouwels W, de Jong EC, van Lier RA, Gordon S, Hamann J | title = The human EGF-TM7 family member EMR2 is a heterodimeric receptor expressed on myeloid cells | journal = Journal of Leukocyte Biology | volume = 71 | issue = 5 | pages = 854–62 | date = May 2002 | pmid = 11994511 }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
== Signaling ==
{{GNF_Protein_box
Inositol phosphate (IP3) accumulation assays in overexpressing HEK293 cells have demonstrated coupling of EMR2 to Gα<sub>15</sub>.<ref>{{cite journal | vauthors = Gupte J, Swaminath G, Danao J, Tian H, Li Y, Wu X | title = Signaling property study of adhesion G-protein-coupled receptors | journal = FEBS Letters | volume = 586 | issue = 8 | pages = 1214–9 | date = April 2012 | pmid = 22575658 | doi = 10.1016/j.febslet.2012.03.014 }}</ref> EGF-like module-containing mucin-like hormone receptor-like 2 (EMR2) is an adhesion GPCR that undergoes GPS autoproteolysis before being trafficked to the plasma membrane.<ref>{{cite journal | vauthors = Lin HH, Chang GW, Davies JQ, Stacey M, Harris J, Gordon S | title = Autocatalytic cleavage of the EMR2 receptor occurs at a conserved G protein-coupled receptor proteolytic site motif | journal = The Journal of Biological Chemistry | volume = 279 | issue = 30 | pages = 31823–32 | date = July 2004 | pmid = 15150276 | doi = 10.1074/jbc.M402974200 }}</ref> Further, distribution, translocation, co-localization of the N-terminal fragment (NTF) and N-terminal fragment (CTF) of EMR2 within lipid rafts may affect cell signaling.<ref name="ReferenceA">{{cite journal | vauthors = Huang YS, Chiang NY, Hu CH, Hsiao CC, Cheng KF, Tsai WP, Yona S, Stacey M, Gordon S, Chang GW, Lin HH | title = 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 | journal = Molecular and Cellular Biology | volume = 32 | issue = 8 | pages = 1408–20 | date = April 2012 | pmid = 22310662 | doi = 10.1128/MCB.06557-11 | pmc=3318590}}</ref> Mutations in the GPS have shown that EMR2 does not need to undergo autoproteolysis to be trafficked, but loses function.  EMR2 has been shown to be necessary for ''in vitro'' cell migration. Upon cleavage the N-terminus has been shown to associate with the 7TM, but to also dissociate, giving two possible functions.  When the N-terminus dissociates it can be found in lipid rafts.  Additionally, the cleaved EMR2 protein 7TM has been found to associate with EMR4 N-terminus.
| image = PBB_Protein_EMR2_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 2bo2.
| PDB = {{PDB2|2bo2}}, {{PDB2|2bou}}, {{PDB2|2box}}
| Name = Egf-like module containing, mucin-like, hormone receptor-like 2
| HGNCid = 3337
| Symbol = EMR2
| AltSymbols =; CD312; DKFZp781B135
| OMIM = 606100
| ECnumber =
| Homologene = 69138
| MGIid =
| GeneAtlas_image1 = PBB_GE_EMR2_207610_s_at_tn.png
| Function = {{GNF_GO|id=GO:0004872 |text = receptor activity}} {{GNF_GO|id=GO:0004930 |text = G-protein coupled receptor activity}} {{GNF_GO|id=GO:0005509 |text = calcium ion binding}}
| Component = {{GNF_GO|id=GO:0016020 |text = membrane}} {{GNF_GO|id=GO:0016021 |text = integral to membrane}}
| Process = {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0007186 |text = G-protein coupled receptor protein signaling pathway}} {{GNF_GO|id=GO:0007218 |text = neuropeptide signaling pathway}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 30817
    | Hs_Ensembl = ENSG00000127507
    | Hs_RefseqProtein = NP_038475
    | Hs_RefseqmRNA = NM_013447
    | Hs_GenLoc_db =
    | Hs_GenLoc_chr = 19
    | Hs_GenLoc_start = 14704205
    | Hs_GenLoc_end = 14750353
    | Hs_Uniprot = Q9UHX3
    | Mm_EntrezGene = 
    | Mm_Ensembl = 
    | Mm_RefseqmRNA = 
    | Mm_RefseqProtein = 
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 
    | Mm_GenLoc_start = 
    | Mm_GenLoc_end = 
    | Mm_Uniprot = 
  }}
}}
'''Egf-like module containing, mucin-like, hormone receptor-like 2''', also known as '''EMR2''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: EMR2 egf-like module containing, mucin-like, hormone receptor-like 2| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=30817| accessdate = }}</ref> EMR2 has also been designated as '''CD312''' ([[cluster of differentiation]] 312).


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
== Function ==
{{PBB_Summary
The expression of EMR2 and CD97 on activated lymphocytes and myeloid cells promotes binding with their ligand chondroitin sulfate B on peripheral B cells, indicating a role in leukocyte interaction.<ref>{{cite journal | vauthors = Kwakkenbos MJ, Pouwels W, Matmati M, Stacey M, Lin HH, Gordon S, van Lier RA, Hamann J | title = Expression of the largest CD97 and EMR2 isoforms on leukocytes facilitates a specific interaction with chondroitin sulfate on B cells | journal = Journal of Leukocyte Biology | volume = 77 | issue = 1 | pages = 112–9 | date = January 2005 | pmid = 15498814 | doi = 10.1189/jlb.0704402 }}</ref> The interaction between EMR2 and chondroitin sulfate B in inflamed rheumatoid synovial tissue suggests a role of the receptors in the recruitment and retention of leukocytes in synovium of arthritis patients.<ref>{{cite journal | vauthors = Kop EN, Kwakkenbos MJ, Teske GJ, Kraan MC, Smeets TJ, Stacey M, Lin HH, Tak PP, Hamann J | title = Identification of the epidermal growth factor-TM7 receptor EMR2 and its ligand dermatan sulfate in rheumatoid synovial tissue | journal = Arthritis and Rheumatism | volume = 52 | issue = 2 | pages = 442–50 | date = February 2005 | pmid = 15693006 | doi = 10.1002/art.20788 }}</ref> Upon neutrophil activation, EMR2 rapidly moves to membrane ruffles and the leading edge of the cell. Additionally, ligation of EMR2 by antibody promotes neutrophil and macrophage effector functions suggesting a role in potentiating inflammatory responses.<ref name="ReferenceA"/><ref>{{cite journal | vauthors = Yona S, Lin HH, Dri P, Davies JQ, Hayhoe RP, Lewis SM, Heinsbroek SE, Brown KA, Perretti M, Hamann J, Treacher DF, Gordon S, Stacey M | title = Ligation of the adhesion-GPCR EMR2 regulates human neutrophil function | journal = FASEB Journal | volume = 22 | issue = 3 | pages = 741–51 | date = March 2008 | pmid = 17928360 | doi = 10.1096/fj.07-9435com }}</ref>
| section_title =  
| summary_text = This gene encodes a member of the class B seven-span transmembrane (TM7) receptor family expressed predominantly by cells of the immune system. Family members are characterized by an extended extracellular region with a variable number of N-terminal epidermal growth factor (EGF)-like domains coupled to a TM7 domain via a mucin-like spacer domain. This gene is closely linked to the gene encoding egf-like molecule containing mucin-like hormone receptor 3 on chromosome 19. This protein does not interact with the ligand decay accelerating factor for complement, unlike the related CD97 antigen, and indicates that these very closely related proteins likely have nonredundant functions. This gene results in multiple transcripts encoding distinct isoforms.<ref name="entrez">{{cite web | title = Entrez Gene: EMR2 egf-like module containing, mucin-like, hormone receptor-like 2| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=30817| accessdate = }}</ref>
}}


==See also==
== Clinical significance ==
EMR2 is rarely expressed by tumor cell lines and tumors, but has been found on breast and colorectal adenocarcinoma.<ref>{{cite journal | vauthors = Aust G, Hamann J, Schilling N, Wobus M | title = Detection of alternatively spliced EMR2 mRNAs in colorectal tumor cell lines but rare expression of the molecule in colorectal adenocarcinomas | journal = Virchows Archiv | volume = 443 | issue = 1 | pages = 32–7 | date = July 2003 | pmid = 12761622 | doi = 10.1007/s00428-003-0812-4 }}</ref><ref>{{cite journal | vauthors = Aust G, Steinert M, Schütz A, Boltze C, Wahlbuhl M, Hamann J, Wobus M | title = CD97, but not its closely related EGF-TM7 family member EMR2, is expressed on gastric, pancreatic, and esophageal carcinomas | journal = American Journal of Clinical Pathology | volume = 118 | issue = 5 | pages = 699–707 | date = November 2002 | pmid = 12428789 | doi = 10.1309/A6AB-VF3F-7M88-C0EJ }}</ref> In breast cancer, robust expression and different distribution of EMR2 is inversely correlated with survival.<ref>{{cite journal | vauthors = Davies JQ, Lin HH, Stacey M, Yona S, Chang GW, Gordon S, Hamann J, Campo L, Han C, Chan P, Fox SB | title = Leukocyte adhesion-GPCR EMR2 is aberrantly expressed in human breast carcinomas and is associated with patient survival | journal = Oncology Reports | volume = 25 | issue = 3 | pages = 619–27 | date = March 2011 | pmid = 21174063 | doi = 10.3892/or.2010.1117 }}</ref>
Gain of function mutations within the GAIN domain of EMR2 of certain patient cohorts were shown to result in excessive degranulation by mast cells resulting in vibratory [[urticaria]]<ref>{{cite journal | vauthors = Boyden SE, Desai A, Cruse G, Young ML, Bolan HC, Scott LM, Eisch AR, Long RD, Lee CC, Satorius CL, Pakstis AJ, Olivera A, Mullikin JC, Chouery E, Mégarbané A, Medlej-Hashim M, Kidd KK, Kastner DL, Metcalfe DD, Komarow HD | title = Vibratory Urticaria Associated with a Missense Variant in ADGRE2 | journal = The New England Journal of Medicine | volume = 374 | issue = 7 | pages = 656–63 | date = February 2016 | pmid = 26841242 | doi = 10.1056/NEJMoa1500611 | pmc=4782791}}</ref>
 
== See also ==
* [[EGF module-containing mucin-like hormone receptor]]
* [[EGF module-containing mucin-like hormone receptor]]


==References==
== References ==
{{reflist}}
{{reflist|33em}}


==Further reading==
== External links ==
{{refbegin | 2}}
* [http://www.adhesiongpcr.org/Adhesion GPCR consortium]
{{PBB_Further_reading
| citations =  
*{{cite journal  | author=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1-2 |pages= 171-4 |year= 1994 |pmid= 8125298 |doi=  }}
*{{cite journal  | author=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, ''et al.'' |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1-2 |pages= 149-56 |year= 1997 |pmid= 9373149 |doi=  }}
*{{cite journal  | author=Lin HH, Stacey M, Hamann J, ''et al.'' |title=Human EMR2, a novel EGF-TM7 molecule on chromosome 19p13.1, is closely related to CD97. |journal=Genomics |volume=67 |issue= 2 |pages= 188-200 |year= 2000 |pmid= 10903844 |doi= 10.1006/geno.2000.6238 }}
*{{cite journal  | author=Lin HH, Stacey M, Saxby C, ''et al.'' |title=Molecular analysis of the epidermal growth factor-like short consensus repeat domain-mediated protein-protein interactions: dissection of the CD97-CD55 complex. |journal=J. Biol. Chem. |volume=276 |issue= 26 |pages= 24160-9 |year= 2001 |pmid= 11297558 |doi= 10.1074/jbc.M101770200 }}
*{{cite journal  | author=Kwakkenbos MJ, Chang GW, Lin HH, ''et al.'' |title=The human EGF-TM7 family member EMR2 is a heterodimeric receptor expressed on myeloid cells. |journal=J. Leukoc. Biol. |volume=71 |issue= 5 |pages= 854-62 |year= 2002 |pmid= 11994511 |doi=  }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal  | author=Stacey M, Chang GW, Davies JQ, ''et al.'' |title=The epidermal growth factor-like domains of the human EMR2 receptor mediate cell attachment through chondroitin sulfate glycosaminoglycans. |journal=Blood |volume=102 |issue= 8 |pages= 2916-24 |year= 2003 |pmid= 12829604 |doi= 10.1182/blood-2002-11-3540 }}
*{{cite journal  | author=Chang GW, Stacey M, Kwakkenbos MJ, ''et al.'' |title=Proteolytic cleavage of the EMR2 receptor requires both the extracellular stalk and the GPS motif. |journal=FEBS Lett. |volume=547 |issue= 1-3 |pages= 145-50 |year= 2003 |pmid= 12860403 |doi=  }}
*{{cite journal  | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{cite journal  | author=Grimwood J, Gordon LA, Olsen A, ''et al.'' |title=The DNA sequence and biology of human chromosome 19. |journal=Nature |volume=428 |issue= 6982 |pages= 529-35 |year= 2004 |pmid= 15057824 |doi= 10.1038/nature02399 }}
*{{cite journal  | author=Lin HH, Chang GW, Davies JQ, ''et al.'' |title=Autocatalytic cleavage of the EMR2 receptor occurs at a conserved G protein-coupled receptor proteolytic site motif. |journal=J. Biol. Chem. |volume=279 |issue= 30 |pages= 31823-32 |year= 2004 |pmid= 15150276 |doi= 10.1074/jbc.M402974200 }}
*{{cite journal  | author=Bjarnadóttir TK, Fredriksson R, Höglund PJ, ''et al.'' |title=The human and mouse repertoire of the adhesion family of G-protein-coupled receptors. |journal=Genomics |volume=84 |issue= 1 |pages= 23-33 |year= 2005 |pmid= 15203201 |doi= 10.1016/j.ygeno.2003.12.004 }}
*{{cite journal  | author=Chang GW, Davies JQ, Stacey M, ''et al.'' |title=CD312, the human adhesion-GPCR EMR2, is differentially expressed during differentiation, maturation, and activation of myeloid cells. |journal=Biochem. Biophys. Res. Commun. |volume=353 |issue= 1 |pages= 133-8 |year= 2007 |pmid= 17174274 |doi= 10.1016/j.bbrc.2006.11.148 }}
}}
{{refend}}


{{NLM content}}
{{PDB Gallery|geneid=30817}}
{{Clusters of differentiation}}
{{Clusters of differentiation}}
{{G protein-coupled receptors}}
{{G protein-coupled receptors}}


[[Category:Clusters of differentiation]]
[[Category:Clusters of differentiation]]
[[Category:G protein coupled receptors]]
[[Category:G protein-coupled receptors]]
 
[[Category:Adhesion GPCRs]]
{{WH}}
{{WS}}

Latest revision as of 18:00, 24 September 2018

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

n/a

n/a

Ensembl

n/a

n/a

UniProt

n/a

n/a

RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

EGF-like module-containing mucin-like hormone receptor-like 2 also known as CD312 (cluster of differentiation 312) is a protein encoded by the ADGRE2 gene.[1] EMR2 is a member of the adhesion GPCR family.[2][3] 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.[4]

EMR2 is expressed by monocytes/macrophages, dendritic cells and all types of granulocytes.[5] In the case of EMR2 the N-terminal domains consist of alternatively spliced epidermal growth factor-like (EGF-like) domains. EMR2 is closely related to CD97 with 97% amino-acid identity in the EGF-like domains. The N-terminal fragment (NTF) of EMR2 presents 2-5 EGF-like domains in human.[6] Mice lack the Emr2 gene.[7] This gene is closely linked to the gene encoding EGF-like molecule containing mucin-like hormone receptor 3 EMR3 on chromosome 19.

Ligand

Like the related CD97 protein, the fourth EGF-like domain of EMR2 binds chondroitin sulfate B to mediate cell attachment.[8] However, unlike CD97 EMR2 does not interact with the complement regulatory protein, decay accelerating factor CD55, and indicating that these very closely related proteins likely have nonredundant functions.[9]

Signaling

Inositol phosphate (IP3) accumulation assays in overexpressing HEK293 cells have demonstrated coupling of EMR2 to Gα15.[10] EGF-like module-containing mucin-like hormone receptor-like 2 (EMR2) is an adhesion GPCR that undergoes GPS autoproteolysis before being trafficked to the plasma membrane.[11] Further, distribution, translocation, co-localization of the N-terminal fragment (NTF) and N-terminal fragment (CTF) of EMR2 within lipid rafts may affect cell signaling.[12] Mutations in the GPS have shown that EMR2 does not need to undergo autoproteolysis to be trafficked, but loses function. EMR2 has been shown to be necessary for in vitro cell migration. Upon cleavage the N-terminus has been shown to associate with the 7TM, but to also dissociate, giving two possible functions. When the N-terminus dissociates it can be found in lipid rafts. Additionally, the cleaved EMR2 protein 7TM has been found to associate with EMR4 N-terminus.

Function

The expression of EMR2 and CD97 on activated lymphocytes and myeloid cells promotes binding with their ligand chondroitin sulfate B on peripheral B cells, indicating a role in leukocyte interaction.[13] The interaction between EMR2 and chondroitin sulfate B in inflamed rheumatoid synovial tissue suggests a role of the receptors in the recruitment and retention of leukocytes in synovium of arthritis patients.[14] Upon neutrophil activation, EMR2 rapidly moves to membrane ruffles and the leading edge of the cell. Additionally, ligation of EMR2 by antibody promotes neutrophil and macrophage effector functions suggesting a role in potentiating inflammatory responses.[12][15]

Clinical significance

EMR2 is rarely expressed by tumor cell lines and tumors, but has been found on breast and colorectal adenocarcinoma.[16][17] In breast cancer, robust expression and different distribution of EMR2 is inversely correlated with survival.[18] Gain of function mutations within the GAIN domain of EMR2 of certain patient cohorts were shown to result in excessive degranulation by mast cells resulting in vibratory urticaria[19]

See also

References

  1. ↑ Hamann J, Aust G, Araç D, Engel FB, Formstone C, Fredriksson R, et al. (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.
  2. ↑ Stacey M, Yona S (2011). Adhesion-GPCRs: Structure to Function (Advances in Experimental Medicine and Biology). Berlin: Springer. ISBN 1-4419-7912-3.
  3. ↑ Langenhan T, Aust G, Hamann J (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.
  4. ↑ 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.
  5. ↑ Lin HH, Stacey M, Hamann J, Gordon S, McKnight AJ (July 2000). "Human EMR2, a novel EGF-TM7 molecule on chromosome 19p13.1, is closely related to CD97". Genomics. 67 (2): 188–200. doi:10.1006/geno.2000.6238. PMID 10903844.
  6. ↑ 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.
  7. ↑ Kwakkenbos MJ, Matmati M, Madsen O, Pouwels W, Wang Y, Bontrop RE, Heidt PJ, Hoek RM, Hamann J (December 2006). "An unusual mode of concerted evolution of the EGF-TM7 receptor chimera EMR2". FASEB Journal. 20 (14): 2582–4. doi:10.1096/fj.06-6500fje. PMID 17068111.
  8. ↑ Stacey M, Chang GW, Davies JQ, Kwakkenbos MJ, Sanderson RD, Hamann J, Gordon S, Lin HH (October 2003). "The epidermal growth factor-like domains of the human EMR2 receptor mediate cell attachment through chondroitin sulfate glycosaminoglycans". Blood. 102 (8): 2916–24. doi:10.1182/blood-2002-11-3540. PMID 12829604.
  9. ↑ Kwakkenbos MJ, Chang GW, Lin HH, Pouwels W, de Jong EC, van Lier RA, Gordon S, Hamann J (May 2002). "The human EGF-TM7 family member EMR2 is a heterodimeric receptor expressed on myeloid cells". Journal of Leukocyte Biology. 71 (5): 854–62. PMID 11994511.
  10. ↑ Gupte J, Swaminath G, Danao J, Tian H, Li Y, Wu X (April 2012). "Signaling property study of adhesion G-protein-coupled receptors". FEBS Letters. 586 (8): 1214–9. doi:10.1016/j.febslet.2012.03.014. PMID 22575658.
  11. ↑ Lin HH, Chang GW, Davies JQ, Stacey M, Harris J, Gordon S (July 2004). "Autocatalytic cleavage of the EMR2 receptor occurs at a conserved G protein-coupled receptor proteolytic site motif". The Journal of Biological Chemistry. 279 (30): 31823–32. doi:10.1074/jbc.M402974200. PMID 15150276.
  12. ↑ 12.0 12.1 Huang YS, Chiang NY, Hu CH, Hsiao CC, Cheng KF, Tsai WP, Yona S, Stacey M, Gordon S, Chang GW, Lin HH (April 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". Molecular and Cellular Biology. 32 (8): 1408–20. doi:10.1128/MCB.06557-11. PMC 3318590. PMID 22310662.
  13. ↑ Kwakkenbos MJ, Pouwels W, Matmati M, Stacey M, Lin HH, Gordon S, van Lier RA, Hamann J (January 2005). "Expression of the largest CD97 and EMR2 isoforms on leukocytes facilitates a specific interaction with chondroitin sulfate on B cells". Journal of Leukocyte Biology. 77 (1): 112–9. doi:10.1189/jlb.0704402. PMID 15498814.
  14. ↑ Kop EN, Kwakkenbos MJ, Teske GJ, Kraan MC, Smeets TJ, Stacey M, Lin HH, Tak PP, Hamann J (February 2005). "Identification of the epidermal growth factor-TM7 receptor EMR2 and its ligand dermatan sulfate in rheumatoid synovial tissue". Arthritis and Rheumatism. 52 (2): 442–50. doi:10.1002/art.20788. PMID 15693006.
  15. ↑ Yona S, Lin HH, Dri P, Davies JQ, Hayhoe RP, Lewis SM, Heinsbroek SE, Brown KA, Perretti M, Hamann J, Treacher DF, Gordon S, Stacey M (March 2008). "Ligation of the adhesion-GPCR EMR2 regulates human neutrophil function". FASEB Journal. 22 (3): 741–51. doi:10.1096/fj.07-9435com. PMID 17928360.
  16. ↑ Aust G, Hamann J, Schilling N, Wobus M (July 2003). "Detection of alternatively spliced EMR2 mRNAs in colorectal tumor cell lines but rare expression of the molecule in colorectal adenocarcinomas". Virchows Archiv. 443 (1): 32–7. doi:10.1007/s00428-003-0812-4. PMID 12761622.
  17. ↑ Aust G, Steinert M, Schütz A, Boltze C, Wahlbuhl M, Hamann J, Wobus M (November 2002). "CD97, but not its closely related EGF-TM7 family member EMR2, is expressed on gastric, pancreatic, and esophageal carcinomas". American Journal of Clinical Pathology. 118 (5): 699–707. doi:10.1309/A6AB-VF3F-7M88-C0EJ. PMID 12428789.
  18. ↑ Davies JQ, Lin HH, Stacey M, Yona S, Chang GW, Gordon S, Hamann J, Campo L, Han C, Chan P, Fox SB (March 2011). "Leukocyte adhesion-GPCR EMR2 is aberrantly expressed in human breast carcinomas and is associated with patient survival". Oncology Reports. 25 (3): 619–27. doi:10.3892/or.2010.1117. PMID 21174063.
  19. ↑ Boyden SE, Desai A, Cruse G, Young ML, Bolan HC, Scott LM, Eisch AR, Long RD, Lee CC, Satorius CL, Pakstis AJ, Olivera A, Mullikin JC, Chouery E, Mégarbané A, Medlej-Hashim M, Kidd KK, Kastner DL, Metcalfe DD, Komarow HD (February 2016). "Vibratory Urticaria Associated with a Missense Variant in ADGRE2". The New England Journal of Medicine. 374 (7): 656–63. doi:10.1056/NEJMoa1500611. PMC 4782791. PMID 26841242.

External links

Retrieved from "https://www.wikidoc.org/index.php?title=EMR2&oldid=1529711"