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Gene Review

SSFA1  -  sperm specific antigen 1

Homo sapiens

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Disease relevance of SSFA1

  • The exciting findings from the recent trial in immunoinfertile couples indicate that the FA-1 antigen may have clinical application in the treatment of male infertility [1].
  • Unbalanced growth and macromolecular synthesis in Streptococcus mutans FA-1 [2].
  • RESULTS: Sixty-seven blebs were examined by FA 1 hour after surgery, and RPE debridement was confirmed by SEM or LM in 15 blebs from 10 animals [3].
  • Streptococcus rattus FA-1 and Streptococcus sanguis NCTC 10904 underwent phenotypic acid adaptation in batch cultures toward the end of sugar-fueled growth after the culture pH had dropped to triggering values [4].
  • FA-1 displayed greater variation than the CL assay or FA-2 and the highest IC(50) values with zanamivir; FA-2 showed the highest values with oseltamivir, particularly for influenza virus B, and was more variable with zanamivir than was the CL assay [5].
 

High impact information on SSFA1

  • cDNA encoding for a sperm antigen, designated fertilization antigen (FA-1), was cloned and sequenced from murine testis cDNA-lambdagt11 expression library using FA-1 mAb [6].
  • Extensive computer search in the GenBank, National Biomedical Research Foundation, and Swiss sequence banks did not identify any known nucleotide/amino acid sequence having homology with FA-1 cDNA or deduced amino acids, indicating it to be a novel protein [6].
  • The FA-1 cDNA was subcloned into pGEX-2T vector and expressed in glutathione S-transferase gene fusion system to obtain the recombinant protein [6].
  • FA-1 is a sperm-specific glycoprotein having receptor activity for ZP recognition and binding [1].
  • A significant increase in mononuclear cells staining for the neural cell adhesion molecule (N-CAM) and fetal antigen 1 (FA1) were observed within the exercised human vastus lateralis muscle on days 4 and 8 post exercise [7].
 

Chemical compound and disease context of SSFA1

  • The amino acid requirements of Streptococcus mutans strains AHT, OMZ-61, FA-1, BHT, GS-5, JC-2, Ingbritt, At6T, OMZ-176, 6715, Streptococcus salivarius HHT, Streptococcus sanguis OMZ-9, and strain 72x46 were determined in a chemically defined medium [8].
  • Hyperfluorescence and variable central fluorescein leakage were seen 1 week after surgery in 52 of 53 blebs (which includes all 27 blebs from the 1-week timepoint and 26 of 29 blebs from the 4-week timepoint that were studied by FA 1 week after surgery) [3].
  • In contrast to controls of organification of iodide was not inhibited by the addition of 100 microM iodide to the medium in FA-1 adenomas [9].
 

Biological context of SSFA1

  • The Ab caused a significant (P < 0.001) and concentration-dependent inhibition of human sperm capacitation/acrosome reaction by blocking tyrosine phosphorylation of the FA-1 antigen [10].
  • For example, for Streptococcus rattus FA-1, the pH at which arginolysis was reduced to 10% of the maximum was between 2.1 and 2.6, or more than 1 full pH unit below the minimum for glycolysis (pH 3.7), and more than 2 units below the minimum for growth in complex medium (pH 4.7) [11].
  • However, as measured by ELISA, the circulating maternal FA1 levels in complete moles were not different from normal pregnancies [12].
  • The results presented suggest that FA1 is a growth and/or differentiation factor extensively expressed in immature cells and down-regulated during fetal development [12].
 

Anatomical context of SSFA1

  • The rFA-1 Ab specifically recognized a protein band of approximately 50 kDa in human testis extract in the Western blot involving 11 types of human tissue extracts, indicating the testis-specific expression of FA-1 at the protein level [10].
  • The continued synthesis of deoxyribonucleic acid, protein, cell wall peptidoglycan and intracellular iodophilic polysaccharide (IPS) by Streptococcus mutans strain FA-1 after several treatments intended to inhibit protein synthesis was studied [2].
  • A monoclonal antibody (mAb) to the human sperm plasma membrane protein, fertilization antigen-1 (FA-1), was tested for its reactivity with bovine spermatozoa and its effects on bovine fertilization in vitro [13].
  • The concentration of FA1 in fetal serum, maternal serum, urine, and amniotic fluid in rats was determined using an ELISA [14].
  • CONCLUSION(S): The FA-1 sperm antigen appears to significantly free sperm cells coated with autoantibodies in the semen of most infertile men examined [15].
 

Associations of SSFA1 with chemical compounds

  • Three strains (S. mutans OMZ-176, FA-1, and BHT) required glutamate (and/or glutamine) [8].
  • With these incubation conditions, one strain required isoleucine (S. mutans FA-1), another valine (S. mutans AHT), and a third tyrosine (72x46) [8].
  • In order to investigate the relation between the structure and the function, and understand the reaction mechanism of the enzyme, a 3D model of fluoroacetate dehalogenase FAc-DEX FA1 was built by homology-based modeling [16].
  • These antibodies also specifically recognized a single protein band of 51 +/- 2 kDa, corresponding to the dimeric form of FA-1 antigen, on a Western blot of lithium diiodosalicylate (LIS)-solubilized monkey sperm [17].
  • Zinc inhibited alkali production from arginine or urea and was a potent enzyme inhibitor for arginine deiminase of S. rattus FA-1 and for urease of S. salivarius [18].
 

Analytical, diagnostic and therapeutic context of SSFA1

  • The Northern blot and reverse transcription-polymerase chain reaction (RT-PCR)-Southern blot analyses indicated the testis-specific expression of FA-1 antigen at the mRNA level [10].
  • The sperm-specific human FA-1 recombinant antigen may find applications in immunocontraception, and diagnosis and treatment of immunoinfertility in humans [10].
  • Molecular cloning and sequencing of cDNA encoding for human FA-1 antigen [10].
  • Active immunization of animals with recombinant FA-1 antigen causes a long-lasting reversible inhibition in fertility by raising a sperm-specific immune response [1].
  • Immunochemical identity between mouse and rat FA1 was established by crossed tandem immunoelectrophoresis [14].

References

  1. Vaccine for contraception targeting sperm. Naz, R.K. Immunol. Rev. (1999) [Pubmed]
  2. Unbalanced growth and macromolecular synthesis in Streptococcus mutans FA-1. Mattingly, S.J., Dipersio, J.R., Higgins, M.L., Shockman, G.D. Infect. Immun. (1976) [Pubmed]
  3. Clinicopathologic correlation of localized retinal pigment epithelium debridement. Leonard, D.S., Zhang, X.G., Panozzo, G., Sugino, I.K., Zarbin, M.A. Invest. Ophthalmol. Vis. Sci. (1997) [Pubmed]
  4. Arginine deiminase system and acid adaptation of oral streptococci. Curran, T.M., Lieou, J., Marquis, R.E. Appl. Environ. Microbiol. (1995) [Pubmed]
  5. Evaluation of neuraminidase enzyme assays using different substrates to measure susceptibility of influenza virus clinical isolates to neuraminidase inhibitors: report of the neuraminidase inhibitor susceptibility network. Wetherall, N.T., Trivedi, T., Zeller, J., Hodges-Savola, C., McKimm-Breschkin, J.L., Zambon, M., Hayden, F.G. J. Clin. Microbiol. (2003) [Pubmed]
  6. Fertilization antigen-1: cDNA cloning, testis-specific expression, and immunocontraceptive effects. Zhu, X., Naz, R.K. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  7. Changes in satellite cells in human skeletal muscle after a single bout of high intensity exercise. Crameri, R.M., Langberg, H., Magnusson, P., Jensen, C.H., Schrøder, H.D., Olesen, J.L., Suetta, C., Teisner, B., Kjaer, M. J. Physiol. (Lond.) (2004) [Pubmed]
  8. Amino acid requirements of Streptococcus mutans and other oral streptococci. Terleckyj, B., Shockman, G.D. Infect. Immun. (1975) [Pubmed]
  9. Defective iodide transport and normal organification of iodide in cold nodules of the thyroid. Shiroozu, A., Inoue, K., Nakashima, T., Okamura, K., Yoshinari, M., Nishitani, H., Omae, T. Clin. Endocrinol. (Oxf) (1981) [Pubmed]
  10. Molecular cloning and sequencing of cDNA encoding for human FA-1 antigen. Naz, R.K., Zhu, X. Mol. Reprod. Dev. (2002) [Pubmed]
  11. Role of the arginine deiminase system in protecting oral bacteria and an enzymatic basis for acid tolerance. Casiano-Colón, A., Marquis, R.E. Appl. Environ. Microbiol. (1988) [Pubmed]
  12. Does fetal antigen 1 (FA1) identify cells with regenerative, endocrine and neuroendocrine potentials? A study of FA1 in embryonic, fetal, and placental tissue and in maternal circulation. Floridon, C., Jensen, C.H., Thorsen, P., Nielsen, O., Sunde, L., Westergaard, J.G., Thomsen, S.G., Teisner, B. Differentiation (2000) [Pubmed]
  13. Monoclonal antibody to human fertilization antigen-1 (FA-1) inhibits bovine fertilization in vitro: application in immunocontraception. Coonrod, S.A., Westhusin, M.E., Naz, R.K. Biol. Reprod. (1994) [Pubmed]
  14. Purification, characterization, and biological compartmentalization of rat fetal antigen 1. Carlsson, H.E., Persdotter-Hedlund, G., Fries, E., Eriksson, U.J., Hau, J. Biol. Reprod. (2000) [Pubmed]
  15. Fertilization antigen-1 removes antisperm autoantibodies from spermatozoa of infertile men and results in increased rates of acrosome reaction. Menge, A.C., Christman, G.M., Ohl, D.A., Naz, R.K. Fertil. Steril. (1999) [Pubmed]
  16. Homology modeling and S(N)2 displacement reaction of fluoroacetate dehalogenase from Burkholderia sp. FA1. Zhang, Y., Li, Z.S., Wu, J.Y., Sun, M., Zheng, Q.C., Sun, C.C. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  17. Antibodies to sperm-specific human FA-1 inhibit in vitro fertilization in rhesus monkeys: development of a simian model for testing of anti-FA-1 contraceptive vaccine. Naz, R.K., Wolf, D.P. J. Reprod. Immunol. (1994) [Pubmed]
  18. Physiologic actions of zinc related to inhibition of acid and alkali production by oral streptococci in suspensions and biofilms. Phan, T.N., Buckner, T., Sheng, J., Baldeck, J.D., Marquis, R.E. Oral Microbiol. Immunol. (2004) [Pubmed]
 
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