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Gene Review

REEP5  -  receptor accessory protein 5

Homo sapiens

Synonyms: C5orf18, D5S346, DP1, Polyposis locus protein 1, Protein TB2, ...
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Disease relevance of REEP5


High impact information on REEP5

  • The second, provisionally designated DP1 (deleted in polyposis 1), was found to be transcribed in the same orientation as MCC [6].
  • Loss of heterozygosity frequency around DP1 also was examined [2].
  • DP1 played a tumor-suppressor role in colon tumorigenesis (ie, DP1-transfected RKO cells showed growth inhibition, apoptosis, decreased telomerase activity, and up-regulation of p53) [2].
  • By contrast, BW245C, a DP1-selective agonist, induced vasodilation in mice, and MK-0524, a DP1-selective antagonist, blocked both PGD(2)- and NA-induced vasodilation [7].
  • Our data do not indicate that selection operated at I1307K (D5S346, P=.114; D5S135, P=.373), providing compelling evidence that the high frequency of disease-susceptibility alleles in the Ashkenazim is due to genetic drift, not selection [8].

Chemical compound and disease context of REEP5

  • These results suggested that prostaglandin D2 plays a physiological role in inhibiting pruritis of NC/Nga mice via their specific prostanoid DP1 receptors, and that prostaglandin D2 and/or a prostanoid DP1 receptor agonist may have therapeutic effects for cases of consecutive skin inflammation [5].
  • Using a murine model of atopic dermatitis, a chronic Th2-type allergic inflammatory disease, we demonstrate that the potent DP1 agonist BW245C dramatically decreases the Ag-specific T cell activation in the skin draining lymph nodes and markedly prevents the skin lesions following repeated epicutaneous sensitization with OVA [9].
  • Pemphigus blister fluid was distinguished by high IL-1-like activity, proteolytic activity, and high concentrations of TB2 and LTB4, while pemphigoid blister fluid was characterized by higher IL-2-like activity, antiprotease activity, and high PGE2 concentration [10].
  • The aim of the present study was to investigate the loss of heterozygosity (LOH), mainly at tumour suppressor loci (using markers D1S2883, D2S123, D3S1611, D5S346, D7S501, D8S254, TP53, NM23), microsatellite instability (BAT25, 26, 40) and <hidden chromosome instability> (bleomycin test) in patients with squamous cell larynx cancer [11].

Biological context of REEP5


Anatomical context of REEP5

  • Triggering of murine mast cells by IgE plus antigen results in a decrease of TB2/DP1 mRNA up to 60% after 2 h implying a possible role of this gene in regulation of the allergic effector cell [1].
  • The balance between DP1 and DP2 receptors could determine the degree to which prostaglandin D2 can activate eosinophils and may play a role in eosinophil recruitment in asthma [17].
  • Unlike DP1, there appear to be multiple transcripts for DP2 and their distribution appears to vary in different tissues and cell lines [13].
  • METHODS AND RESULTS: DNA extracted from 28 paired blood and formalin-fixed, paraffin-embedded normal mucosal tissue was amplified using the DP1 microsatellite marker, consisting of a variable number of CA repeats [18].
  • DP1 receptor transcripts were present only in HT-29 cells [19].

Associations of REEP5 with chemical compounds

  • Effects of prostaglandin D2, 15-deoxy-Delta12,14-prostaglandin J2, and selective DP1 and DP2 receptor agonists on pulmonary infiltration of eosinophils in Brown Norway rats [4].
  • On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, polyacrylamide gel isoelectric focusing and amino acid analysis, both DP1 and DP2 were demonstrated to have close physicochemical similarity with DF1 and DF2, respectively [20].
  • In cells prelabeled with [14C] arachidonic acid, phytohemagglutinin (PHA) produced substantial (3.5- to 12-fold) increases in 5-HETE, 12-HETE, and TB2 radiolabeling [21].
  • Binding to TB2 was ablated by the presence of N-terminal domains (encoded by exons 1-8) and reduced after deleting the proline-rich region [22].
  • DES in the diet reduced and testosterone injections elevated relative prostate weights and perimeters of the dorsal, LP1, lateral prostate type 2 and DP1 expression [23].

Other interactions of REEP5

  • We report on a family with a submicroscopic deletion of about 200 kb including more than the 3' half of the APC gene and the adjacent DP1 gene [24].
  • Allelic imbalance in the cancers at D5S346 and D17S938 suggested allelic loss of both p53 and APC, as well as at the loci D13S263, D13S174, D13S159, and D18S49 [25].
  • Normal and tumor cells were microdissected from paraffin embedded tissues and PCR amplification was performed utilising the specific markers D5S299 and D5S346 at 5q21 and PYGM at 11q13, respectively [26].
  • Polymerase chain reaction using four APC microsatellite markers-D5S210, D5S299, D5S82, and D5S346-was performed and the products analysed [27].
  • METHODS: We examined 104 invasive ovarian cancers for MSI with six microsatellite markers (BAT25, BAT26, D5S346, D2S123, D17S250 and NME1) [28].

Analytical, diagnostic and therapeutic context of REEP5


  1. The murine homolog of TB2/DP1, a gene of the familial adenomatous polyposis (FAP) locus. Prieschl, E.E., Pendl, G.G., Harrer, N.E., Baumruker, T. Gene (1996) [Pubmed]
  2. HCCR-1-interacting molecule "deleted in polyposis 1" plays a tumor-suppressor role in colon carcinogenesis. Shin, S.M., Chung, Y.J., Oh, S.T., Jeon, H.M., Hwang, L.J., Namkoong, H., Kim, H.K., Cho, G.W., Hur, S.Y., Kim, T.E., Lee, Y.S., Park, Y.G., Ko, J., Kim, J.W. Gastroenterology (2006) [Pubmed]
  3. Identification of a synovial fibroblast-specific protein transduction domain for delivery of apoptotic agents to hyperplastic synovium. Mi, Z., Lu, X., Mai, J.C., Ng, B.G., Wang, G., Lechman, E.R., Watkins, S.C., Rabinowich, H., Robbins, P.D. Mol. Ther. (2003) [Pubmed]
  4. Effects of prostaglandin D2, 15-deoxy-Delta12,14-prostaglandin J2, and selective DP1 and DP2 receptor agonists on pulmonary infiltration of eosinophils in Brown Norway rats. Almishri, W., Cossette, C., Rokach, J., Martin, J.G., Hamid, Q., Powell, W.S. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
  5. Prostanoid DP1 receptor agonist inhibits the pruritic activity in NC/Nga mice with atopic dermatitis. Arai, I., Takano, N., Hashimoto, Y., Futaki, N., Sugimoto, M., Takahashi, N., Inoue, T., Nakaike, S. Eur. J. Pharmacol. (2004) [Pubmed]
  6. Identification of deletion mutations and three new genes at the familial polyposis locus. Joslyn, G., Carlson, M., Thliveris, A., Albertsen, H., Gelbert, L., Samowitz, W., Groden, J., Stevens, J., Spirio, L., Robertson, M. Cell (1991) [Pubmed]
  7. Antagonism of the prostaglandin D2 receptor 1 suppresses nicotinic acid-induced vasodilation in mice and humans. Cheng, K., Wu, T.J., Wu, K.K., Sturino, C., Metters, K., Gottesdiener, K., Wright, S.D., Wang, Z., O'neill, G., Lai, E., Waters, M.G. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  8. Genetic anthropology of the colorectal cancer-susceptibility allele APC I1307K: evidence of genetic drift within the Ashkenazim. Niell, B.L., Long, J.C., Rennert, G., Gruber, S.B. Am. J. Hum. Genet. (2003) [Pubmed]
  9. Activation of the D prostanoid receptor 1 regulates immune and skin allergic responses. Angeli, V., Staumont, D., Charbonnier, A.S., Hammad, H., Gosset, P., Pichavant, M., Lambrecht, B.N., Capron, M., Dombrowicz, D., Trottein, F. J. Immunol. (2004) [Pubmed]
  10. Mediators of inflammation in blister fluids from patients with pemphigus vulgaris and bullous pemphigoid. Grando, S.A., Glukhenky, B.T., Drannik, G.N., Epshtein, E.V., Kostromin, A.P., Korostash, T.A. Archives of dermatology. (1989) [Pubmed]
  11. Microsatellite and chromosome instability in squamous cell laryngeal carcinoma. Sasiadek, M., Stembalska-Kozlowska, A., Smigiel, R., Krecicki, T., Blin, N., Mirghomizadeh, F. Int. J. Oncol. (2001) [Pubmed]
  12. A CA-repeat polymorphism close to the adenomatous polyposis coli (APC) gene offers improved diagnostic testing for familial APC. Spirio, L., Nelson, L., Ward, K., Burt, R., White, R., Leppert, M. Am. J. Hum. Genet. (1993) [Pubmed]
  13. Cloning and characterization of human DP2, a novel dimerization partner of E2F. Zhang, Y., Chellappan, S.P. Oncogene (1995) [Pubmed]
  14. Turcot's syndrome: evidence for linkage to the adenomatous polyposis coli (APC) locus. Lasser, D.M., DeVivo, D.C., Garvin, J., Wilhelmsen, K.C. Neurology (1994) [Pubmed]
  15. Possible association between tumor-suppressor gene mutations and hMSH2/hMLH1 inactivation in alveolar soft part sarcoma. Saito, T., Oda, Y., Kawaguchi, K., Takahira, T., Yamamoto, H., Sakamoto, A., Tamiya, S., Iwamoto, Y., Tsuneyoshi, M. Hum. Pathol. (2003) [Pubmed]
  16. Improved predictive carrier testing for familial adenomatous polyposis using DNA from a single archival specimen and polymorphic markers with multiple alleles. Bapat, B., Mitri, A., Greenberg, C.R. Hum. Pathol. (1993) [Pubmed]
  17. Prostaglandin D2 is a potent chemoattractant for human eosinophils that acts via a novel DP receptor. Monneret, G., Gravel, S., Diamond, M., Rokach, J., Powell, W.S. Blood (2001) [Pubmed]
  18. Comparison of allelic ratios from paired blood and paraffin-embedded normal tissue for use in a polymerase chain reaction to assess loss of heterozygosity. Zauber, N.P., Sabbath-Solitare, M., Marotta, S.P., McMahon, L., Bishop, D.T. Mol. Diagn. (1999) [Pubmed]
  19. Expression of prostaglandin D2 receptors DP1 and DP2 by human colorectal cancer cells. Hawcroft, G., Gardner, S.H., Hull, M.A. Cancer Lett. (2004) [Pubmed]
  20. Comparative analysis of physicochemical and immunochemical properties of the two major allergens from Dermatophagoides pteronyssinus and the corresponding allergens from Dermatophagoides farinae. Yasueda, H., Mita, H., Yui, Y., Shida, T. Int. Arch. Allergy Appl. Immunol. (1989) [Pubmed]
  21. Formation of thromboxane B2 and hydroxyarachidonic acids in purified human lymphocytes in the presence and absence of PHA. Parker, C.W., Stenson, W.F., Huber, M.G., Kelly, J.P. J. Immunol. (1979) [Pubmed]
  22. Molecular basis of elastic fiber formation. Critical interactions and a tropoelastin-fibrillin-1 cross-link. Rock, M.J., Cain, S.A., Freeman, L.J., Morgan, A., Mellody, K., Marson, A., Shuttleworth, C.A., Weiss, A.S., Kielty, C.M. J. Biol. Chem. (2004) [Pubmed]
  23. Genistein alters growth but is not toxic to the rat prostate. Fritz, W.A., Eltoum, I.E., Cotroneo, M.S., Lamartiniere, C.A. J. Nutr. (2002) [Pubmed]
  24. Familial adenomatous polyposis: a submicroscopic deletion at the APC locus in a family with mentally normal patients. Mandl, M., Caspari, R., Jauch, A., Böker, T., Raschke, H., Sengteller, M., Propping, P., Friedl, W. Hum. Genet. (1996) [Pubmed]
  25. Colorectal carcinomas arising in the hyperplastic polyposis syndrome progress through the chromosomal instability pathway. Hawkins, N.J., Gorman, P., Tomlinson, I.P., Bullpitt, P., Ward, R.L. Am. J. Pathol. (2000) [Pubmed]
  26. LOH at the APC/MCC gene (5Q21) is frequent in early stages of non-small cell lung cancer. Sanz-Ortega, J., Bryant, B., Sanz-Esponera, J., Asenjo, J.A., Saez, M.C., Torres, A., Balibrea, J.L., Sobel, M.E., Merino, M.J. Pathol. Res. Pract. (1999) [Pubmed]
  27. Microsatellite analysis of the adenomatous polyposis coli (APC) gene and immunoexpression of beta catenin in nephroblastoma: a study including 83 cases treated with preoperative chemotherapy. Ramburan, A., Oladiran, F., Smith, C., Hadley, G.P., Govender, D. J. Clin. Pathol. (2005) [Pubmed]
  28. Genomic instability is associated with lack of telomerase activation in ovarian cancer. Landen, C.N., Klingelhutz, A., Coffin, J.E., Sorosky, J.I., Sood, A.K. Cancer Biol. Ther. (2004) [Pubmed]
  29. Microsatellite analysis of the APC gene and immunoexpression of E-cadherin, catenin, and tubulin in esophageal squamous cell carcinoma. Nair, K.S., Naidoo, R., Chetty, R. Hum. Pathol. (2006) [Pubmed]
  30. Diabetic polyneuropathy. Axonal or demyelinating? Valls-Canals, J., Povedano, M., Montero, J., Pradas, J. Electromyography and clinical neurophysiology. (2002) [Pubmed]
  31. A proapoptotic peptide for the treatment of solid tumors. Mai, J.C., Mi, Z., Kim, S.H., Ng, B., Robbins, P.D. Cancer Res. (2001) [Pubmed]
  32. A monoclonal antibody recognizing desmosomes: use in human pathology. Osborn, M., Weber, K. J. Invest. Dermatol. (1985) [Pubmed]
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