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Gene and Protein Information | ||||||
Adhesion G protein-coupled receptor | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | 7 | 835 | 19p13.12 | ADGRE5 | adhesion G protein-coupled receptor E5 | |
Mouse | 7 | 818 | 8 40.22 cM | Adgre5 | adhesion G protein-coupled receptor E5 | 10 |
Rat | - | 825 | 19q11 | Adgre5 | adhesion G protein-coupled receptor E5 |
Previous and Unofficial Names |
CD97 (cluster of differentiation 97) | BL-Ac (F2) |
Database Links | |
Specialist databases | |
GPCRdb | cd97_human (Hs), cd97_mouse (Mm), q5xi36_rat (Rn) |
Other databases | |
Alphafold | P48960 (Hs), Q9Z0M6 (Mm), Q5XI36 (Rn) |
ChEMBL Target | CHEMBL4523865 (Hs) |
Ensembl Gene | ENSG00000123146 (Hs), ENSMUSG00000002885 (Mm), ENSRNOG00000004489 (Rn) |
Entrez Gene | 976 (Hs), 26364 (Mm), 361383 (Rn) |
Human Protein Atlas | ENSG00000123146 (Hs) |
KEGG Gene | hsa:976 (Hs), mmu:26364 (Mm), rno:361383 (Rn) |
OMIM | 601211 (Hs) |
Pharos | P48960 (Hs) |
RefSeq Nucleotide | NM_001025160 (Hs), NM_001784 (Hs), NM_078481 (Hs), NM_011925 (Mm), NM_001163030 (Mm), NM_001163029 (Mm), NM_001012164 (Rn) |
RefSeq Protein | NP_001020331 (Hs), NP_510966 (Hs), NP_001775 (Hs), NP_001156502 (Mm), NP_036055 (Mm), NP_001156501 (Mm), NP_001012164 (Rn) |
UniProtKB | P48960 (Hs), Q9Z0M6 (Mm), Q5XI36 (Rn) |
Wikipedia | ADGRE5 (Hs) |
Agonist Comments | ||
Agents tested for their properties as agonists at this receptor include CD55, α5β1 integrin, chrondroitin sulfate B and CD90 (Thy1); however, while each was able to bind to the receptor as a ligand none were found to have agonist activity at the receptor [17-19,30-31,36,39,46,49]. |
Immunopharmacology Comments |
ADGRE5 is included in GtoImmuPdb because its tissue expression profile and the phenotypes expressed by mouse ADGRE5 knockouts suggest an involvement in inflammation. |
Primary Transduction Mechanisms | |
Transducer | Effector/Response |
G12/G13 family | |
Comments: In a ligation-independent manner, ADGRE5 forms heterodimers with and potentiates ligation-dependent signaling of the lysophosphatidic acid (LPA) receptor. Yeast-based assay data confirmed these findings [7]. | |
References: 47,50-51 |
Tissue Distribution | ||||||||
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Expression Datasets | |
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Functional Assays | ||||||||||
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Physiological Functions | ||||||||
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Physiological Consequences of Altering Gene Expression | ||||||||||
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Phenotypes, Alleles and Disease Models | Mouse data from MGI | ||||||||||||||||||||||||||||||||||||
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Biologically Significant Variants | ||||||||||||||
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Biologically Significant Variant Comments | ||||||||||||||
The interaction with CD55 is mediated by the N-terminal EGF-like domains and requires 3 tandemly arranged EGF-like domains; additional EGF-like domains lower the affinity for CD55 [17,31]. The interaction with chondroitin sulfate B is mediated by the 4th EGF-like domain [3]. Lack of N-glycosylation in the EGF domain region prevents CD55 binding in normal smooth muscle cells [5]. |
General Comments |
ADGRE5 (previous gene symbol CD97) is a receptor that belongs to Family II Adhesion-GPCRs together with ADGRE1-4 (formerly EMR1-4) [8,28]. 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 [29]. |
1. Aust G. (2010) Adhesion-GPCRS in tumorigenesis. Adv Exp Med Biol, 706: 109-20. [PMID:21618830]
2. Aust G, Eichler W, Laue S, Lehmann I, Heldin NE, Lotz O, Scherbaum WA, Dralle H, Hoang-Vu C. (1997) CD97: a dedifferentiation marker in human thyroid carcinomas. Cancer Res, 57 (9): 1798-806. [PMID:9135025]
3. 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]
4. 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]
5. Aust G, Wandel E, Boltze C, Sittig D, Schütz A, Horn LC, Wobus M. (2006) Diversity of CD97 in smooth muscle cells. Cell Tissue Res, 324 (1): 139-47. [PMID:16408199]
6. Becker S, Wandel E, Wobus M, Schneider R, Amasheh S, Sittig D, Kerner C, Naumann R, Hamann J, Aust G. (2010) Overexpression of CD97 in intestinal epithelial cells of transgenic mice attenuates colitis by strengthening adherens junctions. PLoS ONE, 5 (1): e8507. [PMID:20084281]
7. Bhudia N, Desai S, King N, Ancellin N, Grillot D, Barnes AA, Dowell SJ. (2020) Author Correction: G Protein-Coupling of Adhesion GPCRs ADGRE2/EMR2 and ADGRE5/CD97, and Activation of G Protein Signalling by an Anti-EMR2 Antibody. Sci Rep, 10 (1): 5097. [PMID:32184438]
8. 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]
9. Boltze C, Schneider-Stock R, Aust G, Mawrin C, Dralle H, Roessner A, Hoang-Vu C. (2002) CD97, CD95 and Fas-L clearly discriminate between chronic pancreatitis and pancreatic ductal adenocarcinoma in perioperative evaluation of cryocut sections. Pathol Int, 52 (2): 83-8. [PMID:11940212]
10. Carver EA, Hamann J, Olsen AS, Stubbs L. (1999) Physical mapping of EMR1 and CD97 in human Chromosome 19 and assignment of Cd97 to mouse Chromosome 8 suggest an ancient genomic duplication. Mamm Genome, 10 (10): 1039-40. [PMID:10501980]
11. Chidambaram A, Fillmore HL, Van Meter TE, Dumur CI, Broaddus WC. (2012) Novel report of expression and function of CD97 in malignant gliomas: correlation with Wilms tumor 1 expression and glioma cell invasiveness. J Neurosurg, 116 (4): 843-53. [PMID:22313360]
12. Eichler W, Aust G, Hamann D. (1994) Characterization of an early activation-dependent antigen on lymphocytes defined by the monoclonal antibody BL-Ac(F2). Scand J Immunol, 39 (1): 111-5. [PMID:8290889]
13. Eichler W, Hamann J, Aust G. (1997) Expression characteristics of the human CD97 antigen. Tissue Antigens, 50 (5): 429-38. [PMID:9389316]
14. Fitzmaurice CJ, Brown LE, Kronin V, Jackson DC. (2000) The geometry of synthetic peptide-based immunogens affects the efficiency of T cell stimulation by professional antigen-presenting cells. Int Immunol, 12 (4): 527-35. [PMID:10744654]
15. Galle J, Sittig D, Hanisch I, Wobus M, Wandel E, Loeffler M, Aust G. (2006) Individual cell-based models of tumor-environment interactions: Multiple effects of CD97 on tumor invasion. Am J Pathol, 169 (5): 1802-11. [PMID:17071601]
16. Gray JX, Haino M, Roth MJ, Maguire JE, Jensen PN, Yarme A, Stetler-Stevenson MA, Siebenlist U, Kelly K. (1996) CD97 is a processed, seven-transmembrane, heterodimeric receptor associated with inflammation. J Immunol, 157 (12): 5438-47. [PMID:8955192]
17. Hamann J, Stortelers C, Kiss-Toth E, Vogel B, Eichler W, van Lier RA. (1998) Characterization of the CD55 (DAF)-binding site on the seven-span transmembrane receptor CD97. Eur J Immunol, 28 (5): 1701-7. [PMID:9603477]
18. Hamann J, van Zeventer C, Bijl A, Molenaar C, Tesselaar K, van Lier RA. (2000) Molecular cloning and characterization of mouse CD97. Int Immunol, 12 (4): 439-48. [PMID:10744645]
19. Hamann J, Vogel B, van Schijndel GM, van Lier RA. (1996) The seven-span transmembrane receptor CD97 has a cellular ligand (CD55, DAF). J Exp Med, 184 (3): 1185-9. [PMID:9064337]
20. Hamann J, Wishaupt JO, van Lier RA, Smeets TJ, Breedveld FC, Tak PP. (1999) Expression of the activation antigen CD97 and its ligand CD55 in rheumatoid synovial tissue. Arthritis Rheum, 42 (4): 650-8. [PMID:10211878]
21. Han SL, Xu C, Wu XL, Li JL, Liu Z, Zeng QQ. (2010) The impact of expressions of CD97 and its ligand CD55 at the invasion front on prognosis of rectal adenocarcinoma. Int J Colorectal Dis, 25 (6): 695-702. [PMID:20339853]
22. Hoang-Vu C, Bull K, Schwarz I, Krause G, Schmutzler C, Aust G, Köhrle J, Dralle H. (1999) Regulation of CD97 protein in thyroid carcinoma. J Clin Endocrinol Metab, 84 (3): 1104-9. [PMID:10084602]
23. Hoek RM, de Launay D, Kop EN, Yilmaz-Elis AS, Lin F, Reedquist KA, Verbeek JS, Medof ME, Tak PP, Hamann J. (2010) Deletion of either CD55 or CD97 ameliorates arthritis in mouse models. Arthritis Rheum, 62 (4): 1036-42. [PMID:20131275]
24. Jaspars LH, Vos W, Aust G, Van Lier RA, Hamann J. (2001) Tissue distribution of the human CD97 EGF-TM7 receptor. Tissue Antigens, 57 (4): 325-31. [PMID:11380941]
25. 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]
26. Kop EN, Matmati M, Pouwels W, Leclercq G, Tak PP, Hamann J. (2009) Differential expression of CD97 on human lymphocyte subsets and limited effect of CD97 antibodies on allogeneic T-cell stimulation. Immunol Lett, 123 (2): 160-8. [PMID:19428565]
27. 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 Biol, 71 (5): 854-62. [PMID:11994511]
28. 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]
29. 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]
30. 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]
31. 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]
32. Loberg RD, Wojno KJ, Day LL, Pienta KJ. (2005) Analysis of membrane-bound complement regulatory proteins in prostate cancer. Urology, 66 (6): 1321-6. [PMID:16360477]
33. Martin GH, Roy N, Chakraborty S, Desrichard A, Chung SS, Woolthuis CM, Hu W, Berezniuk I, Garrett-Bakelman FE, Hamann J et al.. (2019) CD97 is a critical regulator of acute myeloid leukemia stem cell function. J Exp Med, 216 (10): 2362-2377. [PMID:31371381]
34. Matmati M, Pouwels W, van Bruggen R, Jansen M, Hoek RM, Verhoeven AJ, Hamann J. (2007) The human EGF-TM7 receptor EMR3 is a marker for mature granulocytes. J Leukoc Biol, 81 (2): 440-8. [PMID:17108056]
35. Mustafa T, Klonisch T, Hombach-Klonisch S, Kehlen A, Schmutzler C, Koehrle J, Gimm O, Dralle H, Hoang-Vu C. (2004) Expression of CD97 and CD55 in human medullary thyroid carcinomas. Int J Oncol, 24 (2): 285-94. [PMID:14719104]
36. Qian YM, Haino M, Kelly K, Song WC. (1999) Structural characterization of mouse CD97 and study of its specific interaction with the murine decay-accelerating factor (DAF, CD55). Immunology, 98 (2): 303-11. [PMID:10540231]
37. Regard JB, Sato IT, Coughlin SR. (2008) Anatomical profiling of G protein-coupled receptor expression. Cell, 135 (3): 561-71. [PMID:18984166]
38. Schebesta A, McManus S, Salvagiotto G, Delogu A, Busslinger GA, Busslinger M. (2007) Transcription factor Pax5 activates the chromatin of key genes involved in B cell signaling, adhesion, migration, and immune function. Immunity, 27 (1): 49-63. [PMID:17658281]
39. 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. Blood, 102 (8): 2916-24. [PMID:12829604]
40. Steinert M, Wobus M, Boltze C, Schütz A, Wahlbuhl M, Hamann J, Aust G. (2002) Expression and regulation of CD97 in colorectal carcinoma cell lines and tumor tissues. Am J Pathol, 161 (5): 1657-67. [PMID:12414513]
41. 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]
42. van Pel M, Hagoort H, Hamann J, Fibbe WE. (2008) CD97 is differentially expressed on murine hematopoietic stem-and progenitor-cells. Haematologica, 93 (8): 1137-44. [PMID:18603564]
43. Veninga H, Becker S, Hoek RM, Wobus M, Wandel E, van der Kaa J, van der Valk M, de Vos AF, Haase H, Owens B et al.. (2008) Analysis of CD97 expression and manipulation: antibody treatment but not gene targeting curtails granulocyte migration. J Immunol, 181 (9): 6574-83. [PMID:18941248]
44. Veninga H, Hoek RM, de Vos AF, de Bruin AM, An FQ, van der Poll T, van Lier RA, Medof ME, Hamann J. (2011) A novel role for CD55 in granulocyte homeostasis and anti-bacterial host defense. PLoS ONE, 6 (10): e24431. [PMID:21984892]
45. Visser L, de Vos AF, Hamann J, Melief MJ, van Meurs M, van Lier RA, Laman JD, Hintzen RQ. (2002) Expression of the EGF-TM7 receptor CD97 and its ligand CD55 (DAF) in multiple sclerosis. J Neuroimmunol, 132 (1-2): 156-63. [PMID:12417446]
46. Wandel E, Saalbach A, Sittig D, Gebhardt C, Aust G. (2012) Thy-1 (CD90) is an interacting partner for CD97 on activated endothelial cells. J Immunol, 188 (3): 1442-50. [PMID:22210915]
47. Wang N, Qian Y, Xia R, Zhu X, Xiong Y, Zhang A, Guo C, He Y. (2023) Structural basis of CD97 activation and G-protein coupling. Cell Chem Biol, 30 (11): 1343-1353.e5. [PMID:37673067]
48. Wang T, Tian L, Haino M, Gao JL, Lake R, Ward Y, Wang H, Siebenlist U, Murphy PM, Kelly K. (2007) Improved antibacterial host defense and altered peripheral granulocyte homeostasis in mice lacking the adhesion class G protein receptor CD97. Infect Immun, 75 (3): 1144-53. [PMID:17158902]
49. Wang T, Ward Y, Tian L, Lake R, Guedez L, Stetler-Stevenson WG, Kelly K. (2005) CD97, an adhesion receptor on inflammatory cells, stimulates angiogenesis through binding integrin counterreceptors on endothelial cells. Blood, 105 (7): 2836-44. [PMID:15576472]
50. Ward Y, Lake R, Martin PL, Killian K, Salerno P, Wang T, Meltzer P, Merino M, Cheng SY, Santoro M et al.. (2013) CD97 amplifies LPA receptor signaling and promotes thyroid cancer progression in a mouse model. Oncogene, 32 (22): 2726-38. [PMID:22797060]
51. Ward Y, Lake R, Yin JJ, Heger CD, Raffeld M, Goldsmith PK, Merino M, Kelly K. (2011) LPA receptor heterodimerizes with CD97 to amplify LPA-initiated RHO-dependent signaling and invasion in prostate cancer cells. Cancer Res, 71 (23): 7301-11. [PMID:21978933]
52. Wobus M, Vogel B, Schmücking E, Hamann J, Aust G. (2004) N-glycosylation of CD97 within the EGF domains is crucial for epitope accessibility in normal and malignant cells as well as CD55 ligand binding. Int J Cancer, 112 (5): 815-22. [PMID:15386373]
53. Wu J, Lei L, Wang S, Gu D, Zhang J. (2012) Immunohistochemical expression and prognostic value of CD97 and its ligand CD55 in primary gallbladder carcinoma. J Biomed Biotechnol, 2012: 587672. [PMID:22547928]