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Gene Review

SPAG11B  -  sperm associated antigen 11B

Homo sapiens

Synonyms: EDDM2B, EP2, EP2C, EP2D, HE2, ...
 
 
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Disease relevance of SPAG11B

  • Inhibition of E. coli RNA, DNA and protein synthesis by nonlethal concentrations of SPAG11 isoforms indicated an additional mechanism of bacterial killing [1].
  • CONCLUSIONS: The ECL carcinoid tumor cells of Mastomys seem to possess two subtypes of PGE receptor: EP2 linked to cAMP production and EP3 coupled with inhibitory guanosine 5'-triphosphate-binding proteins mediating the inhibition of cAMP production [2].
  • To establish whether PGE(2) has an autocrine/paracrine effect in cervical carcinomas, we investigated the expression of two subtypes of PGE(2) receptors, namely EP2 and EP4, by real-time quantitative RT-PCR [3].
  • Thus, agonism of EP2 and EP4 receptors may provide a basis for treating acute and chronic kidney failure [4].
  • Decreased prostaglandin E2 production by inflammatory cytokine and lower expression of EP2 receptor result in increased collagen synthesis in keloid fibroblasts [5].
 

High impact information on SPAG11B

  • In this study, we have established a primary culture system of human gastric fibroblasts and clearly demonstrated that PGs strongly induce the expression of hepatocyte growth factor (HGF) in the fibroblasts, which is mediated by PGE specific receptor, EP2 or EP4 [6].
  • Protein gel blot analysis showed that the EP2 protein is present in cell walls and conditioned medium of cell cultures [7].
  • Based on the extracellular location of the EP2 protein and the expression pattern of the encoding gene, we propose a role for plant lipid transfer proteins in the transport of cutin monomers through the extracellular matrix to sites of cutin synthesis [7].
  • An EP2 receptor-selective prostaglandin E2 agonist induces bone healing [8].
  • The major PGE2 receptors on epithelial cells, EP2 and EP4, increase cAMP production, which promotes growth and inhibits apoptosis in some cell types [9].
 

Chemical compound and disease context of SPAG11B

 

Biological context of SPAG11B

  • Identical sequences and deletion start and stop points indicate the HE2 isoforms are derived from alternative splicing of 8 or more exons of a single gene [14].
  • This recombinant HE2 protein, as well as an oligopeptide deduced from the open-reading frame, was used to raise polyclonal antisera [15].
  • Localization of HE2 within the defensin gene cluster and prediction that beta-defensin-like modules exist suggest that these peptides have antimicrobial activity and represent components of the innate epithelial defense system of the epididymal duct [16].
  • The anabolic action of PGE2 in bone has been linked to an elevated level of cAMP, thereby implicating the EP2 and/or EP4 receptor subtypes in bone formation [8].
  • After two rounds of screening with 198 AIA patients, multiple SNPs in the prostaglandin E(2) receptor subtype 2 (EP2) gene were associated with AIA (P<0.05) [17].
 

Anatomical context of SPAG11B

  • Three tissue-specific gene probes that had been isolated by differential screening from a human epididymal cDNA library--HE1, HE2, and HE5--were employed to investigate regional specializations in the human epididymis [18].
  • The HE5 mRNA, which was recently shown to encode the peptide backbone of the human leukocyte differentiation antigen CDw52, showed maximum levels in the distal corpus epididymidis and in the vas deferens, whereas the HE2 mRNA was found predominantly in the caput and proximal corpus sections of the epididymis [18].
  • In cell line HE2, the same promoter is permanently shut off and all 5'-CG-3' sequences are methylated in both strands [19].
  • Employing isoform-specific antibodies against the predicted HE2 products, multiple 4- to 8-kDa peptides were detected in human epididymal epithelium, epididymal fluid, and ejaculate [16].
  • A better understanding of these regulatory mechanisms and the crosstalk between TNF-R/TLR and EP2 signaling pathways will provide insight into the regulation of T-cell activation by DCs and may help to improve existing immunotherapy protocols [20].
 

Associations of SPAG11B with chemical compounds

  • Testosterone replacement maintained HE2 mRNA 3- to 5-fold higher than castrate levels, indicating its androgen dependence [14].
  • A novel human cDNA encoding a small secretory glycopeptide specifically expressed within the caput and proximal corpus regions of the human epididymis, HE2, has been cloned and sequenced [15].
  • The effect of PGE2 is mediated by activation of adenylate cyclase via the Gs-protein-coupled receptor E prostanoid-2 (EP2) [20].
  • Furthermore, the EP1 receptor-selective antagonists AH 6809 and SC19220 were more potent than the EP2 receptor-selective agonist butaprost in these competition binding assays [21].
  • If PGE(2), unlike EP2/3 agonists butaprost and sulprostone, was added to fresh medium, COX-2 mRNA levels remained elevated for up to 16 h [22].
 

Other interactions of SPAG11B

 

Analytical, diagnostic and therapeutic context of SPAG11B

  • Similarly, HE2 transcriptional and translational products normally expressed in the caput epididymidis were not affected by vasectomy [23].
  • Molecular cloning and characterization of a novel human sperm antigen (HE2) specifically expressed in the proximal epididymis [15].
  • Immunohistochemistry and immunofluorescence showed that the predicted HE2 peptide is present in the epididymal epithelium and on the sperm surface, where it adopts a typical antigenic pattern with a subacrosomal equatorial distribution on the sperm head [15].
  • In addition, Northern blot analysis using EP2 and EP3 receptor complementary DNAs was conducted [2].
  • RNA gel blot analysis revealed that the EP2 gene is expressed in embryogenic cell cultures, the shoot apex of seedlings, developing flowers, and maturing seeds [7].

References

  1. Antimicrobial actions of human and macaque sperm associated antigen (SPAG) 11 isoforms: influence of the N-terminal peptide. Yenugu, S., Hamil, K.G., French, F.S., Hall, S.H. Mol. Cell. Biochem. (2006) [Pubmed]
  2. Copresence of prostaglandin EP2 and EP3 receptors on gastric enterochromaffin-like cell carcinoid in African rodents. Naribayashi-Inomoto, Y., Ding, M., Nakata, H., Narumiya, S., Sugimoto, Y., Honda, A., Ichikawa, A., Chiba, T., Kinoshita, Y. Gastroenterology (1995) [Pubmed]
  3. Cyclooxygenase-2 expression and prostaglandin E(2) synthesis are up-regulated in carcinomas of the cervix: a possible autocrine/paracrine regulation of neoplastic cell function via EP2/EP4 receptors. Sales, K.J., Katz, A.A., Davis, M., Hinz, S., Soeters, R.P., Hofmeyr, M.D., Millar, R.P., Jabbour, H.N. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  4. Role of EP2 and EP4 receptor-selective agonists of prostaglandin E(2) in acute and chronic kidney failure. Vukicevic, S., Simic, P., Borovecki, F., Grgurevic, L., Rogic, D., Orlic, I., Grasser, W.A., Thompson, D.D., Paralkar, V.M. Kidney Int. (2006) [Pubmed]
  5. Decreased prostaglandin E2 production by inflammatory cytokine and lower expression of EP2 receptor result in increased collagen synthesis in keloid fibroblasts. Hayashi, T., Nishihira, J., Koyama, Y., Sasaki, S., Yamamoto, Y. J. Invest. Dermatol. (2006) [Pubmed]
  6. Hepatocyte growth factor as a key to modulate anti-ulcer action of prostaglandins in stomach. Takahashi, M., Ota, S., Hata, Y., Mikami, Y., Azuma, N., Nakamura, T., Terano, A., Omata, M. J. Clin. Invest. (1996) [Pubmed]
  7. Cell-specific expression of the carrot EP2 lipid transfer protein gene. Sterk, P., Booij, H., Schellekens, G.A., Van Kammen, A., De Vries, S.C. Plant Cell (1991) [Pubmed]
  8. An EP2 receptor-selective prostaglandin E2 agonist induces bone healing. Paralkar, V.M., Borovecki, F., Ke, H.Z., Cameron, K.O., Lefker, B., Grasser, W.A., Owen, T.A., Li, M., DaSilva-Jardine, P., Zhou, M., Dunn, R.L., Dumont, F., Korsmeyer, R., Krasney, P., Brown, T.A., Plowchalk, D., Vukicevic, S., Thompson, D.D. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  9. Inhibition of apoptosis in normal and transformed intestinal epithelial cells by cAMP through induction of inhibitor of apoptosis protein (IAP)-2. Nishihara, H., Kizaka-Kondoh, S., Insel, P.A., Eckmann, L. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  10. In vivo increase in resistance to ciprofloxacin in Escherichia coli associated with deletion of the C-terminal part of MarR. Linde, H.J., Notka, F., Metz, M., Kochanowski, B., Heisig, P., Lehn, N. Antimicrob. Agents Chemother. (2000) [Pubmed]
  11. Expression of COX-2 and PGE synthase and synthesis of PGE(2)in endometrial adenocarcinoma: a possible autocrine/paracrine regulation of neoplastic cell function via EP2/EP4 receptors. Jabbour, H.N., Milne, S.A., Williams, A.R., Anderson, R.A., Boddy, S.C. Br. J. Cancer (2001) [Pubmed]
  12. Effect of rebamipide on acetic acid-induced gastric ulcer in rats: involvement of hepatocyte growth factor. Udagawa, A., Shiota, G., Ichiba, M., Murawaki, Y. Scand. J. Gastroenterol. (2003) [Pubmed]
  13. Spinal prostaglandin E receptors of the EP2 subtype and the glycine receptor alpha3 subunit, which mediate central inflammatory hyperalgesia, do not contribute to pain after peripheral nerve injury or formalin injection. H??sl, K., Reinold, H., Harvey, R.J., M??ller, U., Narumiya, S., Zeilhofer, H.U. Pain (2006) [Pubmed]
  14. HE2beta and HE2gamma, new members of an epididymis-specific family of androgen-regulated proteins in the human. Hamil, K.G., Sivashanmugam, P., Richardson, R.T., Grossman, G., Ruben, S.M., Mohler, J.L., Petrusz, P., O'Rand, M.G., French, F.S., Hall, S.H. Endocrinology (2000) [Pubmed]
  15. Molecular cloning and characterization of a novel human sperm antigen (HE2) specifically expressed in the proximal epididymis. Osterhoff, C., Kirchhoff, C., Krull, N., Ivell, R. Biol. Reprod. (1994) [Pubmed]
  16. Novel antimicrobial peptide of human epididymal duct origin. von Horsten, H.H., Derr, P., Kirchhoff, C. Biol. Reprod. (2002) [Pubmed]
  17. Polymorphisms in the prostaglandin E2 receptor subtype 2 gene confer susceptibility to aspirin-intolerant asthma: a candidate gene approach. Jinnai, N., Sakagami, T., Sekigawa, T., Kakihara, M., Nakajima, T., Yoshida, K., Goto, S., Hasegawa, T., Koshino, T., Hasegawa, Y., Inoue, H., Suzuki, N., Sano, Y., Inoue, I. Hum. Mol. Genet. (2004) [Pubmed]
  18. Region-specific variation of gene expression in the human epididymis as revealed by in situ hybridization with tissue-specific cDNAs. Krull, N., Ivell, R., Osterhoff, C., Kirchhoff, C. Mol. Reprod. Dev. (1993) [Pubmed]
  19. Genomic sequencing reveals a 5-methylcytosine-free domain in active promoters and the spreading of preimposed methylation patterns. Toth, M., Lichtenberg, U., Doerfler, W. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  20. A two-step induction of indoleamine 2,3 dioxygenase (IDO) activity during dendritic-cell maturation. Braun, D., Longman, R.S., Albert, M.L. Blood (2005) [Pubmed]
  21. Cloning and expression of a cDNA for the human prostaglandin E receptor EP1 subtype. Funk, C.D., Furci, L., FitzGerald, G.A., Grygorczyk, R., Rochette, C., Bayne, M.A., Abramovitz, M., Adam, M., Metters, K.M. J. Biol. Chem. (1993) [Pubmed]
  22. Prostaglandin E(2) regulates the level and stability of cyclooxygenase-2 mRNA through activation of p38 mitogen-activated protein kinase in interleukin-1 beta-treated human synovial fibroblasts. Faour, W.H., He, Y., He, Q.W., de Ladurantaye, M., Quintero, M., Mancini, A., Di Battista, J.A. J. Biol. Chem. (2001) [Pubmed]
  23. Vasectomy influences expression of HE1 but not HE2 and HE5 genes in human epididymis. Légaré, C., Verville, N., Sullivan, R. J. Androl. (2004) [Pubmed]
 
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