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Gene Review

SYTL1  -  synaptotagmin-like 1

Homo sapiens

Synonyms: Exophilin-7, FLJ14996, JFC1, Protein JFC1, SB146, ...
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Disease relevance of SYTL1

  • These observations decisively prove that Rab27a is involved in CFTR channel regulation through protein-protein interactions involving Munc13-4 and SLP-5 effector proteins, and thus could be a potential target for cystic fibrosis therapy [1].

High impact information on SYTL1


Biological context of SYTL1

  • Co-transfection with NF-kappaB expression vectors or stimulation with TNFalpha resulted in significant transactivation of the jfc1 promoter construct, although transactivation of a mutated jfc1 promoter was negligible [5].
  • The jfc1 promoter was transcriptionally active in various cell lines, as determined by luciferase reporter assays following transfection with a jfc1 promoter luciferase vector [5].
  • The human promoter region of JFC1, a phosphatidylinositol 3,4,5-trisphosphate binding ATPase, was isolated by amplification of a 549 bp region upstream of the jfc1 gene by the use of a double-PCR system [5].
  • Although the SHD of Slp4-a interacts with three distinct Rab species (Rab3A, Rab8A, and Rab27A) in vitro, in contrast to other Slp members, which only recognize Rab27 isoforms, Slp4-a functions as a Rab27A effector during DCV exocytosis under physiological conditions [6].
  • Akt regulates the subcellular localization of the Rab27a-binding protein JFC1 by phosphorylation [7].

Anatomical context of SYTL1


Associations of SYTL1 with chemical compounds

  • The Rab27a-binding protein, JFC1, regulates androgen-dependent secretion of prostate-specific antigen and prostatic-specific acid phosphatase [9].
  • In contrast to synaptotagmins, JFC1 was unable to bind to inositol 1,3,4,5-tetrakisphosphate but did bind to phosphatidylinositol 3,4,5-trisphosphate and to a lesser extent to phosphatidylinositol 3,4-diphosphate [4].
  • By mutagenesis analysis and subsequent immunoprecipitation (IP), we established that Akt phosphorylates JFC1 at serine 241 [7].
  • Using the phosphatase and tensin homolog-null LNCaP cells and the phosphatidylinositol 3-kinase inhibitor LY294002, we show that the phosphorylation of endogenous JFC1 is dependent on the phosphatidylinositol 3-kinase/Akt pathway [7].

Regulatory relationships of SYTL1

  • Androgen-dependent PSAP secretion was significantly inhibited in cells that expressed the C2A domain of JFC1 [PtdIns(3,4,5)P3-binding-domain], but was unaffected by JFC1 overexpression [9].

Other interactions of SYTL1


Analytical, diagnostic and therapeutic context of SYTL1


  1. Rab27a negatively regulates CFTR chloride channel function in colonic epithelia: involvement of the effector proteins in the regulatory mechanism. Saxena, S.K., Kaur, S. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  2. Characterization of the nucleotide-binding capacity and the ATPase activity of the PIP3-binding protein JFC1. Catz, S.D., Johnson, J.L., Babior, B.M. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  3. Synaptotagmin-like protein (Slp) homology domain 1 of Slac2-a/melanophilin is a critical determinant of GTP-dependent specific binding to Rab27A. Fukuda, M. J. Biol. Chem. (2002) [Pubmed]
  4. JFC1, a novel tandem C2 domain-containing protein associated with the leukocyte NADPH oxidase. McAdara Berkowitz, J.K., Catz, S.D., Johnson, J.L., Ruedi, J.M., Thon, V., Babior, B.M. J. Biol. Chem. (2001) [Pubmed]
  5. JFC1 is transcriptionally activated by nuclear factor-kappaB and up-regulated by tumour necrosis factor alpha in prostate carcinoma cells. Catz, S.D., Babior, B.M., Johnson, J.L. Biochem. J. (2002) [Pubmed]
  6. Analysis of the role of Rab27 effector Slp4-a/Granuphilin-a in dense-core vesicle exocytosis. Fukuda, M., Kanno, E. Meth. Enzymol. (2005) [Pubmed]
  7. Akt regulates the subcellular localization of the Rab27a-binding protein JFC1 by phosphorylation. Johnson, J.L., Pacquelet, S., Lane, W.S., Eam, B., Catz, S.D. Traffic (2005) [Pubmed]
  8. Putative neurohemal release zones in the stomatogastric nervous system of decapod crustaceans. Skiebe, P., Wollenschläger, T. J. Comp. Neurol. (2002) [Pubmed]
  9. The Rab27a-binding protein, JFC1, regulates androgen-dependent secretion of prostate-specific antigen and prostatic-specific acid phosphatase. Johnson, J.L., Ellis, B.A., Noack, D., Seabra, M.C., Catz, S.D. Biochem. J. (2005) [Pubmed]
  10. Rab27a regulates epithelial sodium channel (ENaC) activity through synaptotagmin-like protein (SLP-5) and Munc13-4 effector mechanism. Saxena, S.K., Horiuchi, H., Fukuda, M. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
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