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Gene Review

SPAG6  -  sperm associated antigen 6

Homo sapiens

Synonyms: CT141, PF16, Protein PF16 homolog, Repro-SA-1, Sperm flagellar protein, ...
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Disease relevance of SPAG6

  • However, the near absence of Dnahc8 expression has been associated with male sterility resulting from an early breakdown in sperm flagellar development [1].
  • In testis and ependymal primary cultures, Wdr16 messenger RNA appears concomitantly with the messages for sperm-associated antigen 6, a kinocilia marker, and for hydin, a protein linked to ciliary function and hydrocephalus [2].

High impact information on SPAG6


Biological context of SPAG6

  • The deduced amino acid sequence of the full-length cDNA revealed striking homology to the product of the Chlamydomonas reinhardtii PF16 locus, which encodes a protein localized to the central pair of the flagellar axoneme [8].
  • Significantly, gene expression associated with ciliogenesis is evident in bronchial epithelium, and includes the expression of transcripts specifying axonemal proteins DNAI2, SPAG6, ASP, and FOXJ1 transcription factor [9].
  • cAMP and calcium are two important regulators of sperm flagellar motility. cAMP stimulates sperm motility by activating cAMP-dependent protein kinase and catalyzing the phosphorylation of sperm proteins [10].
  • ICSI provides a suitable solution for patients with sperm flagellar defects but raises the question of the consequences of a specific (and primary flagellar) abnormality on oocyte fertilization, on embryo and fetal development as well as on live birth [11].

Anatomical context of SPAG6

  • The murine Pf6 gene is expressed in a pattern consistent with a role in flagella and cilia, and the PF6 protein is indeed localized to the central apparatus of the sperm flagellar axoneme [12].
  • The clone, initially designated Repro-SA-1 (HUGO-approved symbol SPAG6), was found to encode a sequence highly enriched in testis [8].
  • These studies indicate that TP-47-induced circular motility of spermatozoa is compound-specific and that the tyrosine phosphorylation status of 45-60 kDa flagellum-localized proteins could be key regulators of sperm flagellar bending pattern, associated with the hyperactivation of hamster spermatozoa [13].
  • In vitro polymerization of tubulin from echinoderm sperm flagellar microtubules [14].
  • Sperm flagellar motion is the outcome of a dynamic interplay between the axonemal cytoskeleton, the peri-axonemal accessory structures, and multiple regulatory networks that coordinate to produce flagellar beat and waveform [15].

Associations of SPAG6 with chemical compounds

  • Myristoylated and nonmyristoylated pools of sea urchin sperm flagellar creatine kinase exist side-by-side: myristoylation is necessary for efficient lipid association [16].
  • When Percoll-separated spermatozoa were treated with hydrogen peroxide, or the combination xanthine and xanthine oxidase (X + XO), there was a progressive decrease, leading to a complete arrest, in sperm flagellar beat frequency [17].
  • Sea urchin sperm flagellar ATPase (EC has magnesium-ATP as an effective substrate and is inhibited by free ATP [18].

Physical interactions of SPAG6


Other interactions of SPAG6

  • To date, the genes encoding four components of the central apparatus have been cloned, PF15, PF16, PF20 and KLP1 [19].


  1. The T complex distorter 2 candidate gene, Dnahc8, encodes at least two testis-specific axonemal dynein heavy chains that differ extensively at their amino and carboxyl termini. Samant, S.A., Ogunkua, O., Hui, L., Fossella, J., Pilder, S.H. Dev. Biol. (2002) [Pubmed]
  2. Biosynthesis of Wdr16, a marker protein for kinocilia-bearing cells, starts at the time of kinocilia formation in rat, and wdr16 gene knockdown causes hydrocephalus in zebrafish. Hirschner, W., Pogoda, H.M., Kramer, C., Thiess, U., Hamprecht, B., Wiesmüller, K.H., Lautner, M., Verleysdonk, S. J. Neurochem. (2007) [Pubmed]
  3. Equimolar heterodimers in microtubules. Stephens, R.E. J. Cell Biol. (1982) [Pubmed]
  4. A sea urchin sperm flagellar adenylate kinase with triplicated catalytic domains. Kinukawa, M., Nomura, M., Vacquier, V.D. J. Biol. Chem. (2007) [Pubmed]
  5. Conserved and specific functions of axoneme components in trypanosome motility. Branche, C., Kohl, L., Toutirais, G., Buisson, J., Cosson, J., Bastin, P. J. Cell. Sci. (2006) [Pubmed]
  6. Functional characterization of a mouse testicular olfactory receptor and its role in chemosensing and in regulation of sperm motility. Fukuda, N., Yomogida, K., Okabe, M., Touhara, K. J. Cell. Sci. (2004) [Pubmed]
  7. Translation and assembly of CABYR coding region B in fibrous sheath and restriction of calcium binding to coding region A. Kim, Y.H., Jha, K.N., Mandal, A., Vanage, G., Farris, E., Snow, P.L., Klotz, K., Naaby-Hansen, S., Flickinger, C.J., Herr, J.C. Dev. Biol. (2005) [Pubmed]
  8. cDNA cloning and characterization of a human sperm antigen (SPAG6) with homology to the product of the Chlamydomonas PF16 locus. Neilson, L.I., Schneider, P.A., Van Deerlin, P.G., Kiriakidou, M., Driscoll, D.A., Pellegrini, M.C., Millinder, S., Yamamoto, K.K., French, C.K., Strauss, J.F. Genomics (1999) [Pubmed]
  9. Identification of novel lung genes in bronchial epithelium by serial analysis of gene expression. Lonergan, K.M., Chari, R., Deleeuw, R.J., Shadeo, A., Chi, B., Tsao, M.S., Jones, S., Marra, M., Ling, V., Ng, R., Macaulay, C., Lam, S., Lam, W.L. Am. J. Respir. Cell Mol. Biol. (2006) [Pubmed]
  10. Cyclic adenosine 3',5' monophosphate, calcium and protein phosphorylation in flagellar motility. Tash, J.S., Means, A.R. Biol. Reprod. (1983) [Pubmed]
  11. Outcome of ICSI with ejaculated spermatozoa in a series of men with distinct ultrastructural flagellar abnormalities. Mitchell, V., Rives, N., Albert, M., Peers, M.C., Selva, J., Clavier, B., Escudier, E., Escalier, D. Hum. Reprod. (2006) [Pubmed]
  12. Dissecting the axoneme interactome: the mammalian orthologue of Chlamydomonas PF6 interacts with sperm-associated antigen 6, the mammalian orthologue of Chlamydomonas PF16. Zhang, Z., Jones, B.H., Tang, W., Moss, S.B., Wei, Z., Ho, C., Pollack, M., Horowitz, E., Bennett, J., Baker, M.E., Strauss, J.F. Mol. Cell Proteomics (2005) [Pubmed]
  13. Tyrphostin-A47 inhibitable tyrosine phosphorylation of flagellar proteins is associated with distinct alteration of motility pattern in hamster spermatozoa. Mariappa, D., Siva, A.B., Shivaji, S., Seshagiri, P.B. Mol. Reprod. Dev. (2006) [Pubmed]
  14. In vitro polymerization of tubulin from echinoderm sperm flagellar microtubules. Kuriyama, R., Linck, R.W. Methods Cell Biol. (1995) [Pubmed]
  15. Absence of tektin 4 causes asthenozoospermia and subfertility in male mice. Roy, A., Lin, Y.N., Agno, J.E., DeMayo, F.J., Matzuk, M.M. FASEB J. (2007) [Pubmed]
  16. Myristoylated and nonmyristoylated pools of sea urchin sperm flagellar creatine kinase exist side-by-side: myristoylation is necessary for efficient lipid association. Quest, A.F., Harvey, D.J., McIlhinney, R.A. Biochemistry (1997) [Pubmed]
  17. Reactive oxygen species and human spermatozoa. I. Effects on the motility of intact spermatozoa and on sperm axonemes. de Lamirande, E., Gagnon, C. J. Androl. (1992) [Pubmed]
  18. Inhibition of axoneme and dynein ATPase from sea urchin sperm by free ATP. Hayashi, M. Biochim. Biophys. Acta (1976) [Pubmed]
  19. The role of central apparatus components in flagellar motility and microtubule assembly. Smith, E.F., Lefebvre, P.A. Cell Motil. Cytoskeleton (1997) [Pubmed]
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