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Gene Review

FSTL1  -  follistatin-like 1

Homo sapiens

Synonyms: FRP, FSL1, Follistatin-like protein 1, Follistatin-related protein 1, MIR198
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Disease relevance of FSTL1

  • Detection of anti-FRP antibodies, possibly having disease-promoting effects as the blocking antibodies, could be one of the markers for clinical evaluation of systemic rheumatic diseases [1].
  • Synovial fluid anti-FRP antibodies appeared in 44% of RA (n = 18) and none of osteoarthritis (OA) (n = 15) patients [1].
  • FSL-1 also activated macrophages to produce tumor necrosis factor alpha as the Mycoplasma fermentans-derived lipopeptide MALP-2 (Pam(2)CGNNDESNISFKEK), a potent macrophage-activating lipopeptide, did [2].
  • The detection frequencies and relative proportions of Streptococcus mutans increased in the NC and FRP groups, but decreased in the F group [3].
  • A basic premise of administering full-mouth therapy (FDIS or FRP) is to eliminate or reduce bacterial reservoirs within the oral cavity that could inhibit optimal healing of treated sites or cause periodontal disease initiation or progression [4].

Psychiatry related information on FSTL1

  • Paroxysmal extreme pain disorder (PEPD), previously known as familial rectal pain (FRP, OMIM 167400), is an inherited disease causing intense burning rectal, ocular, and submandibular pain and flushing [5].

High impact information on FSTL1

  • Mean atrial ERP and FRP during driving were, respectively, 231+/-15.3 and 264+/-14.9 ms before and 266+/-18.6 and 296+/-19.7 ms after ouabain (P less than 0.01 and P less than 0.01) [6].
  • MyoD inhibits Fstl1 and Utrn expression by inducing transcription of miR-206 [7].
  • Crystal structure of a pair of follistatin-like and EF-hand calcium-binding domains in BM-40 [8].
  • The ERP of the A-V node (seven cases) was prolonged in found and the FRP was increased in three [9].
  • With the same method, a CUB domain-interacting protein was isolated and turned out to be the transmembrane protein with epidermal growth factor-like and two follistatin-like domains 1 (TMEFF1) [10].

Chemical compound and disease context of FSTL1


Biological context of FSTL1


Anatomical context of FSTL1


Associations of FSTL1 with chemical compounds

  • Characterization of a rat C6 glioma-secreted follistatin-related protein (FRP). Cloning and sequence of the human homologue [17].
  • To determine minimal structural requirements for the activity of FSL-1, the diacylglyceryl Cys and the peptide portions were examined for this activity [2].
  • FSL-1 and, to a lesser extent, lipopolysaccharide activated mitogen-activated protein kinases in splenocytes [18].
  • Furthermore, in studies that addressed the utility of FDIS, it was not possible to determine if benefits induced beyond PDIS were due to FRP or administration of multifaceted intraoral chlorhexidine treatments ora combination of both therapies [4].

Physical interactions of FSTL1


Regulatory relationships of FSTL1


Other interactions of FSTL1

  • As a result of this unique combination of the libraries and probes, we cloned follistatin-related protein (FRP) as a novel autoantigen in systemic rheumatic diseases [1].
  • The deletion mutant TLR2(DeltaS40-I64) (a TLR2 mutant with a deletion of the region of Ser(40) to Ile(64)) failed to activate NF-kappaB in response to FSL-1 [21].
  • SPARC is composed of three structural/functional domains: an acidic Ca(2+)-binding, a follistatin-like, and an extracellular calcium-binding domain [22].
  • MyoD directly activates the expression of a muscle-specific microRNA (miRNA), miR-206, which targets sequences in the Fstl1 and Utrn RNA, and these sequences are sufficient to suppress gene expression in the presence of miR-206 [7].
  • It has a unique extracellular domain, containing epidermal growth factor-like and follistatin-like modules [23].

Analytical, diagnostic and therapeutic context of FSTL1

  • METHODS: FRP mRNA expression levels in the synovial tissues from 10 patients with RA and 5 patients with OA were measured using real-time RT-PCR [13].
  • Immunoblotting analyses detected synovial fluid and serum anti-FRP antibodies of IgG class more frequently in RA than any other systemic rheumatic diseases and controls [1].
  • In contrast, recent studies from 2 other treatment centers indicated that there were no significant differences when the efficacy of quadrant-by-quadrant root planing was compared to FRP or FDIS with regard to PD reduction, gains of clinical attachment, and impact on the magnitude and quality of the immune response [4].
  • One investigation that had protocol limitations indicated that similar results were attained by FRP with and without adjunctive chemotherapy [4].
  • When comparing patients with SND and subjects of the control group, we did not find any significant statistical differences in terms of ERP (237 +/- 33 vs 250 +/- 29 ms), FRP (276 +/- 30 vs 280 +/- 32 ms) and S1-A1 (39 +/- 16 vs 33 +/- 11 ms) and S2-A2 latency (69 +/- 24 vs 63 +/- 25 ms) [24].


  1. Cloning of follistatin-related protein as a novel autoantigen in systemic rheumatic diseases. Tanaka, M., Ozaki, S., Osakada, F., Mori, K., Okubo, M., Nakao, K. Int. Immunol. (1998) [Pubmed]
  2. Relationship between structures and biological activities of mycoplasmal diacylated lipopeptides and their recognition by toll-like receptors 2 and 6. Okusawa, T., Fujita, M., Nakamura, J., Into, T., Yasuda, M., Yoshimura, A., Hara, Y., Hasebe, A., Golenbock, D.T., Morita, M., Kuroki, Y., Ogawa, T., Shibata, K. Infect. Immun. (2004) [Pubmed]
  3. Increase in cariogenic bacteria after initial periodontal therapy. De Soete, M., Dekeyser, C., Pauwels, M., Teughels, W., van Steenberghe, D., Quirynen, M. J. Dent. Res. (2005) [Pubmed]
  4. Full-mouth therapy versus individual quadrant root planning: a critical commentary. Greenstein, G. J. Periodontol. (2002) [Pubmed]
  5. Painful channels. Catterall, W.A., Yu, F.H. Neuron (2006) [Pubmed]
  6. The electrophysiological effects of ouabain on sinus node and atrium in man. Dhingra, R.C., Amat-Y-Leon, F., Wyndham, C., Wu, D., Denes, P., Rosen, K.M. J. Clin. Invest. (1975) [Pubmed]
  7. MyoD inhibits Fstl1 and Utrn expression by inducing transcription of miR-206. Rosenberg, M.I., Georges, S.A., Asawachaicharn, A., Analau, E., Tapscott, S.J. J. Cell Biol. (2006) [Pubmed]
  8. Crystal structure of a pair of follistatin-like and EF-hand calcium-binding domains in BM-40. Hohenester, E., Maurer, P., Timpl, R. EMBO J. (1997) [Pubmed]
  9. Surgical bifascicular block. Pahlajani, D.B., Serratto, M., Mehta, A., Miller, R.A., Hastreiter, A., Rosen, K.M. Circulation (1975) [Pubmed]
  10. Protein interaction analysis of ST14 domains and their point and deletion mutants. Ge, W., Hu, H., Ding, K., Sun, L., Zheng, S. J. Biol. Chem. (2006) [Pubmed]
  11. The diacylated lipopeptide FSL-1 enhances phagocytosis of bacteria by macrophages through a Toll-like receptor 2-mediated signalling pathway. Mae, M., Iyori, M., Yasuda, M., Shamsul, H.M., Kataoka, H., Kiura, K., Hasebe, A., Totsuka, Y., Shibata, K. FEMS Immunol. Med. Microbiol. (2007) [Pubmed]
  12. Follistatin-like immunoreactivity in the cytoplasm and nucleus of spermatogenic cells in the rat. Ogawa, K., Hashimoto, O., Kurohmaru, M., Mizutani, T., Sugino, H., Hayashi, Y. Eur. J. Endocrinol. (1997) [Pubmed]
  13. Follistatin-related protein gene (FRP) is expressed in the synovial tissues of rheumatoid arthritis, but its polymorphisms are not associated with genetic susceptibility. Ehara, Y., Sakurai, D., Tsuchiya, N., Nakano, K., Tanaka, Y., Yamaguchi, A., Tokunaga, K. Clinical and experimental rheumatology. (2004) [Pubmed]
  14. Identification and characterization of a novel follistatin-like protein as a binding protein for the TGF-beta family. Tsuchida, K., Arai, K.Y., Kuramoto, Y., Yamakawa, N., Hasegawa, Y., Sugino, H. J. Biol. Chem. (2000) [Pubmed]
  15. The expression and regulation of follistatin and a follistatin-like gene during avian somite compartmentalization and myogenesis. Amthor, H., Connolly, D., Patel, K., Brand-Saberi, B., Wilkinson, D.G., Cooke, J., Christ, B. Dev. Biol. (1996) [Pubmed]
  16. TSC-36/FRP inhibits vascular smooth muscle cell proliferation and migration. Liu, S., Wang, L., Wang, W., Lin, J., Han, J., Sun, H., Guo, H., Sun, R., Wu, Q. Exp. Mol. Pathol. (2006) [Pubmed]
  17. Characterization of a rat C6 glioma-secreted follistatin-related protein (FRP). Cloning and sequence of the human homologue. Zwijsen, A., Blockx, H., Van Arnhem, W., Willems, J., Fransen, L., Devos, K., Raymackers, J., Van de Voorde, A., Slegers, H. Eur. J. Biochem. (1994) [Pubmed]
  18. The diacylated lipopeptide FSL-1 induces TLR2-mediated Th2 responses. Kiura, K., Kataoka, H., Yasuda, M., Inoue, N., Shibata, K. FEMS Immunol. Med. Microbiol. (2006) [Pubmed]
  19. Analysis of human follistatin structure: identification of two discontinuous N-terminal sequences coding for activin A binding and structural consequences of activin binding to native proteins. Wang, Q., Keutmann, H.T., Schneyer, A.L., Sluss, P.M. Endocrinology (2000) [Pubmed]
  20. Signaling pathways induced by lipoproteins derived from Mycoplasma salivarium and a synthetic lipopeptide (FSL-1) in normal human gingival fibroblasts. Nakamura, J., Shibata, K., Hasebe, A., Into, T., Watanabe, T., Ohata, N. Microbiol. Immunol. (2002) [Pubmed]
  21. Involvement of leucine residues at positions 107, 112, and 115 in a leucine-rich repeat motif of human Toll-like receptor 2 in the recognition of diacylated lipoproteins and lipopeptides and Staphylococcus aureus peptidoglycans. Fujita, M., Into, T., Yasuda, M., Okusawa, T., Hamahira, S., Kuroki, Y., Eto, A., Nisizawa, T., Morita, M., Shibata, K. J. Immunol. (2003) [Pubmed]
  22. Porcine SPARC: isolation from dentin, cDNA sequence, and computer model. Chun, Y.H., Yamakoshi, Y., Kim, J.W., Iwata, T., Hu, J.C., Simmer, J.P. Eur. J. Oral Sci. (2006) [Pubmed]
  23. Tomoregulin-2 is found extensively in plaques in Alzheimer's disease brain. Siegel, D.A., Davies, P., Dobrenis, K., Huang, M. J. Neurochem. (2006) [Pubmed]
  24. Electrophysiological characteristics of the atrium in sinus node dysfunction with and without postpacing atrial fibrillation. De Sisti, A., Attuel, P., Manot, S., Fiorello, P., Halimi, F., Leclercq, J.F. Pacing and clinical electrophysiology : PACE. (2000) [Pubmed]
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