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Gene Review

SPAM1  -  sperm adhesion molecule 1 (PH-20...

Homo sapiens

Synonyms: HEL-S-96n, HYA1, HYAL1, HYAL3, HYAL5, ...
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Disease relevance of SPAM1

  • Transcription of the human and rodent SPAM1 / PH-20 genes initiates within an ancient endogenous retrovirus [1].
  • Hyal1 is implicated as an inducer of prostate cancer metastatic progression [2].
  • After calculating the counts in VOI using the product of probability of SPAM images and counts in FDG images, asymmetric indices (AI) were calculated and used for finding epileptogenic zones in mesial temporal lobe epilepsy (mTLE) [3].
  • We also found a positive trend in the risk of lung cancer in women with increasing intake of some processed meats (bacon, Spam) and desserts (cakes, custard/cream pies) [4].
  • CONCLUSION: This is the first study to demonstrate the cellular localization of HA and its synthases and that Hyal 3 mRNA is predominant in endometrial cancer [5].

High impact information on SPAM1

  • The guinea pig sperm surface protein PH-20 is essential in sperm adhesion to the extracellular coat (zona pellucida) of the egg, a necessary initial step in fertilization [6].
  • A hyaluronidase activity of the sperm plasma membrane protein PH-20 enables sperm to penetrate the cumulus cell layer surrounding the egg [7].
  • These results, indicating that PH-20 enables acrosome intact sperm to penetrate the cumulus barrier, reveal a mechanism for cumulus penetration, and thus provide the missing element in the current model [7].
  • cDNA cloning reveals the molecular structure of a sperm surface protein, PH-20, involved in sperm-egg adhesion and the wide distribution of its gene among mammals [8].
  • Northern blots of tissues other than testis are negative for PH-20, indicating that human PH-20 is testis-specific [9].

Chemical compound and disease context of SPAM1


Biological context of SPAM1

  • Southern blot analysis of human genomic DNA and DNA from somatic cell hybrids indicates that the gene (SPAM1) is unique and does not form part of a larger family and that it maps to chromosome 7 [11].
  • 0. In the proximal promoter of SPAM1 were uncovered putative epididymal transcription factor binding sites including androgen receptor elements (AREs), consistent with epididymal expression [12].
  • SPAM1 (PH-20) was detectable only in testis by Northern blot as previously reported, but was detectable in fetal and placental cDNA libraries by PCR, suggesting a possible role for this gene during embryonic development [13].
  • In the human cluster, SPAM1 is the only functional hyaluronidase and of all six hyaluronidases in the genome it is the best characterized, both structurally and functionally [14].
  • Like testicular SPAM1, epididymal SPAM1 (ES) has hyaluronidase activity and is conserved in at least five species (mouse, rat, bull, macaque, and human) all of which have putative androgen response elements in the gene promoters, consistent with androgen regulation [14].

Anatomical context of SPAM1

  • SPAM1 protein is present in all three regions of the epididymis, as well as the vas deferens, and is localized similarly to the transcripts [12].
  • RESULTS: We demonstrate that mRNA unique to SPAM1 is present in the principal cells of the epididymal epithelium in all individuals of both species studied [12].
  • The similar response of human and mouse sperm to these agonists of the acrosome reaction, underscores the usefulness of the mouse as a model to study physiological aspects of SPAM1 in humans where, unlike the mouse, it is the only sperm hyaluronidase [15].
  • While SPAM1 transcripts are abundantly expressed only in the testis, specifically in spermatids, the RNA and protein are present in the male reproductive tract and accessory organs and in the female tract of mice [14].
  • Acrosome intact mouse sperm incubated with anti-PH-20 antibodies can not pass through the cumulus layer and thus can not reach the zona pellucida [7].

Associations of SPAM1 with chemical compounds

  • It is suggested that a soluble form of SPAM1 glycoprotein is synthesized and released in the epididymis and that in addition to androgens, its regulation may involve a cross-talk between the tubule epithelium and lumicrine factors, the latter possibly of testicular origin [16].
  • A widely conserved sperm antigen, the sperm adhesion molecule 1 (SPAM1 or PH-20) is a glycosylphosphatidyl inositol-linked protein with multiple roles in mammalian fertilization [17].
  • Several sperm antigens, such as lactate dehydrogenase C4, PH-20, sperm protein (SP)-10, fertilization antigen (FA)-1, FA-2, cleavage signal (CS)-1, NZ-1, and NZ-2 have been proposed as potential candidates for the vaccine development [18].
  • Dol m 2 has 56% sequence identity with the honey bee venom allergen hyaluronidase and 27% identity with PH-20, a human sperm protein with hyaluronidase activity [19].
  • In addition, novel isoforms of actin, beta-tubulin, PH-20, and several phosphotyrosine-containing proteins were identified in human sperm [20].

Other interactions of SPAM1


Analytical, diagnostic and therapeutic context of SPAM1


  1. Transcription of the human and rodent SPAM1 / PH-20 genes initiates within an ancient endogenous retrovirus. Dunn, C.A., Mager, D.L. BMC Genomics (2005) [Pubmed]
  2. Hyaluronidase expression induces prostate tumor metastasis in an orthotopic mouse model. Kovar, J.L., Johnson, M.A., Volcheck, W.M., Chen, J., Simpson, M.A. Am. J. Pathol. (2006) [Pubmed]
  3. Quantification of F-18 FDG PET images in temporal lobe epilepsy patients using probabilistic brain atlas. Kang, K.W., Lee, D.S., Cho, J.H., Lee, J.S., Yeo, J.S., Lee, S.K., Chung, J.K., Lee, M.C. Neuroimage (2001) [Pubmed]
  4. High-fat foods and the risk of lung cancer. Goodman, M.T., Hankin, J.H., Wilkens, L.R., Kolonel, L.N. Epidemiology (Cambridge, Mass.) (1992) [Pubmed]
  5. Expression patterns of hyaluronan, hyaluronan synthases and hyaluronidases indicate a role for hyaluronan in the progression of endometrial cancer. Paiva, P., Van Damme, M.P., Tellbach, M., Jones, R.L., Jobling, T., Salamonsen, L.A. Gynecol. Oncol. (2005) [Pubmed]
  6. Fully effective contraception in male and female guinea pigs immunized with the sperm protein PH-20. Primakoff, P., Lathrop, W., Woolman, L., Cowan, A., Myles, D. Nature (1988) [Pubmed]
  7. A hyaluronidase activity of the sperm plasma membrane protein PH-20 enables sperm to penetrate the cumulus cell layer surrounding the egg. Lin, Y., Mahan, K., Lathrop, W.F., Myles, D.G., Primakoff, P. J. Cell Biol. (1994) [Pubmed]
  8. cDNA cloning reveals the molecular structure of a sperm surface protein, PH-20, involved in sperm-egg adhesion and the wide distribution of its gene among mammals. Lathrop, W.F., Carmichael, E.P., Myles, D.G., Primakoff, P. J. Cell Biol. (1990) [Pubmed]
  9. Molecular cloning of the human and monkey sperm surface protein PH-20. Lin, Y., Kimmel, L.H., Myles, D.G., Primakoff, P. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  10. The modulation of granulomatous tissue and tumour angiogenesis by diclofenac in combination with hyaluronan (HYAL EX-0001). Freemantle, C., Alam, C.A., Brown, J.R., Seed, M.P., Willoughby, D.A. International journal of tissue reactions. (1995) [Pubmed]
  11. Expression analysis, genomic structure, and mapping to 7q31 of the human sperm adhesion molecule gene SPAM1. Jones, M.H., Davey, P.M., Aplin, H., Affara, N.A. Genomics (1995) [Pubmed]
  12. SPAM1 (PH-20) protein and mRNA expression in the epididymides of humans and macaques: utilizing laser microdissection/RT-PCR. Evans, E.A., Zhang, H., Martin-DeLeon, P.A. Reprod. Biol. Endocrinol. (2003) [Pubmed]
  13. Expression analysis of six paralogous human hyaluronidase genes clustered on chromosomes 3p21 and 7q31. Csóka, A.B., Scherer, S.W., Stern, R. Genomics (1999) [Pubmed]
  14. Epididymal SPAM1 and its impact on sperm function. Martin-Deleon, P.A. Mol. Cell. Endocrinol. (2006) [Pubmed]
  15. Cytoplasmic localization during testicular biogenesis of the murine mRNA for Spam1 (PH-20), a protein involved in acrosomal exocytosis. Morales, C.R., Badran, H., El-Alfy, M., Men, H., Zhang, H., Martin-DeLeon, P.A. Mol. Reprod. Dev. (2004) [Pubmed]
  16. Expression and secretion of rat SPAM1(2B1 or PH-20) in the epididymis: role of testicular lumicrine factors. Zhang, H., Jones, R., Martin-DeLeon, P.A. Matrix Biol. (2004) [Pubmed]
  17. Spam1 (PH-20) expression in the extratesticular duct and accessory organs of the mouse: a possible role in sperm fluid reabsorption. Zhang, H., Morales, C.R., Badran, H., El-Alfy, M., Martin-DeLeon, P.A. Biol. Reprod. (2004) [Pubmed]
  18. Vaccine for contraception targeting sperm. Naz, R.K. Immunol. Rev. (1999) [Pubmed]
  19. Sequence identity and antigenic cross-reactivity of white face hornet venom allergen, also a hyaluronidase, with other proteins. Lu, G., Kochoumian, L., King, T.P. J. Biol. Chem. (1995) [Pubmed]
  20. Two-dimensional gel electrophoretic analysis of vectorially labeled surface proteins of human spermatozoa. Naaby-Hansen, S., Flickinger, C.J., Herr, J.C. Biol. Reprod. (1997) [Pubmed]
  21. Hyaluronidases and CD44 undergo differential modulation during chondrogenesis. Nicoll, S.B., Barak, O., Csóka, A.B., Bhatnagar, R.S., Stern, R. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  22. Sperm adhesion molecules: structure and function. Jansen, S., Ekhlasi-Hundrieser, M., Töpfer-Petersen, E. Cells Tissues Organs (Print) (2001) [Pubmed]
  23. Purification and microsequencing of hyaluronidase isozymes from human urine. Csóka, A.B., Frost, G.I., Wong, T., Stern, R., Csóka, T.B. FEBS Lett. (1997) [Pubmed]
  24. Structural organization and chromosomal localization of Hyal2, a gene encoding a lysosomal hyaluronidase. Strobl, B., Wechselberger, C., Beier, D.R., Lepperdinger, G. Genomics (1998) [Pubmed]
  25. PH20: a novel tumor marker for laryngeal cancer. Godin, D.A., Fitzpatrick, P.C., Scandurro, A.B., Belafsky, P.C., Woodworth, B.A., Amedee, R.G., Beech, D.J., Beckman, B.S. Arch. Otolaryngol. Head Neck Surg. (2000) [Pubmed]
  26. Hyalp1 in murine sperm function: evidence for unique and overlapping functions with other reproductive hyaluronidases. Miller, K.A., Shao, M., Martin-Deleon, P.A. J. Androl. (2007) [Pubmed]
  27. Expression of tumor markers hyaluronic acid and hyaluronidase (HYAL1) in head and neck tumors. Franzmann, E.J., Schroeder, G.L., Goodwin, W.J., Weed, D.T., Fisher, P., Lokeshwar, V.B. Int. J. Cancer (2003) [Pubmed]
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