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Gene Review

PFN1  -  profilin 1

Homo sapiens

Synonyms: Epididymis tissue protein Li 184a, Profilin I, Profilin-1
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Disease relevance of PFN1


High impact information on PFN1

  • In extracts and host cells, profilin is localized to the back half of the surface of motile L. monocytogenes, the site of actin filament assembly in the tail [6].
  • How profilin promotes actin filament assembly in the presence of thymosin beta 4 [7].
  • The movement is more effective when profilin, alpha-actinin and VASP (for Listeria) are also included [8].
  • Proteins that bind to the barbed end, including capping protein, the gelsolin super-family, tensin, and profilin are discussed, as are proteins that bind to the pointed end, including tropomodulin and spectrin/band 4 [9].
  • There is evidence that the polymerization of actin takes place at the plasma membrane, and that profilactin (profilin/actin complex), the unpolymerized form of actin found in extracts of many non-muscle cells, serves as the immediate precursor [10].

Chemical compound and disease context of PFN1

  • Coincubation of chymase-rich BR mastocytoma cells with Ala-Ala-Pro-Phe-chloromethylketone (a chymase inhibitor) blocks profilin cleavage, which does not occur in degranulated HMC-1 mast cells, which are rich in tryptase, but chymase deficient [11].
  • With use of immunoblotting,.serum IgE from 25 patients displaying type I allergic reactions to tree pollens and intolerance to hazelnuts (group I) bound to the 17 kd major hazel pollen allergen Cor a I (100%) and to the 14 kd hazel pollen profilin (16%) [12].
  • CONCLUSION: In clinical settings in which laboratory investigations are not easily accessible, allergy to melon, watermelon, citrus fruits, tomato, and banana can be used as a marker of profilin hypersensitivity once a sensitization to natural rubber latex and lipid transfer protein is ruled out [13].

Biological context of PFN1

  • We conclude that the actin binding site on profilin is instrumental for normal differentiation of human epithelia and the tumor suppressor function of PFN1 [1].
  • The importance of PFN1 for human tissue differentiation has been demonstrated by the findings that human cancer cells, expressing conspicuously low PFN1 levels, adopt a nontumorigenic phenotype upon raising their PFN1 level [1].
  • Profilin IIb appears to be a minor form, and its expression is restricted to a limited number of tissues, indicating that the alternative splicing is tightly regulated [14].
  • VASP contains a central proline-rich sequence which recruits the G-actin binding protein profilin [15].
  • Transfection of PFN1 cDNA into CAL51 cells raised the profilin 1 level, had a prominent effect on cell growth, cytoskeletal organization and spreading, and suppressed tumorigenicity of the stable, PFN1-overexpressing cell clones in nude mice [16].

Anatomical context of PFN1


Associations of PFN1 with chemical compounds

  • Humans express a basic (I) and an acidic (II) isoform of profilin which exhibit different affinities for peptides and proteins rich in proline residues [20].
  • Profilin I and profilin II have similar affinities for PtdIns(4,5)P2 and poly(L-proline), and both accelerate nucleotide exchange on monomeric actin to the same extent [21].
  • In Acanthamoeba, the two isoforms of profilin may have specialized functions on the basis of their identical (approximately 10 microM) affinities for actin monomers and different affinities for PIP2 [22].
  • In light of recent work implicating profilin from human platelets as a possible regulator of both cytoskeletal dynamics and inositol phospholipid-mediated signaling, we have further characterized the interaction of platelet profilin and the two isoforms of Acanthamoeba profilin with inositol phospholipids [22].
  • Characterization of renatured profilin purified by urea elution from poly-L-proline agarose columns [23].
  • The Y6D mutation reduces the affinity of human profilin-I for poly-l-proline by 1000-fold, but overexpression of Y6D profilin in fission yeast is lethal [24].

Physical interactions of PFN1

  • Recent studies have revealed that profilin interacts with VASP, Mena, Bnilp, Bnrlp, and mDia, all of which have the proline-rich domain [25].
  • Like SH3 domains, profilin has a surface-exposed aromatic patch which binds to proline-rich peptides [20].
  • Interestingly, profilin competes with ActA for binding of Arp2/3, but actophorin (cofilin) does not [26].
  • RIAM also interacts with Profilin and Ena/VASP proteins, molecules that regulate actin dynamics [27].
  • To our knowledge, AF-6 is the only integral component in cell-cell junctions discovered thus far that interacts with profilin and thus could modulate actin modeling proximal to adhesion complexes [28].

Co-localisations of PFN1


Regulatory relationships of PFN1

  • Profilin enhances Cdc42-induced nucleation of actin polymerization [17].
  • These data suggest that under conditions present in intact cells, profilin enhances nucleation by activated Arp2/3 complex [17].
  • This mutant profilin I suppresses actin polymerization in microspike formation induced by N-WASP, the essential factor in microspike formation [30].
  • Notably, the antibody displaces a fraction of the Golgi-bound dynamin II indicating that profilin I may indirectly promote vesicle formation by supporting the binding of dynamin II to the Golgi membrane [29].
  • Recombinant plant (birch) profilin was analyzed for its ability to promote actin polymerization from the actin:thymosin beta4 and beta9 complex [31].

Other interactions of PFN1

  • Unmasking of this site serves as a molecular switch that initiates assembly of an actin-based motility complex containing VASP and profilin [32].
  • Potential structural differences of profilin I and profilin II that might explain the difference in actin binding are discussed [21].
  • Profilin catalyzes exchange of ADP for ATP, recycling actin back to a pool of unpolymerized monomers bound to profilin and thymosin-beta 4 that is poised for rapid elongation of new barbed ends [33].
  • The isolated COOH-terminal domain of N-WASP containing a verprolin-homology region, a cofilin-homology sequence, and an acidic terminal segment (VCA) interacts with G-actin in a unique profilin-like functional fashion [34].
  • Indeed, we show that extracellular S100A4 treatments decrease both the amount of polymerized F-actin and the levels of expression of RhoA, mDia and profilin [35].

Analytical, diagnostic and therapeutic context of PFN1


  1. Tumor suppressor activity of profilin requires a functional actin binding site. Wittenmayer, N., Jandrig, B., Rothkegel, M., Schlüter, K., Arnold, W., Haensch, W., Scherneck, S., Jockusch, B.M. Mol. Biol. Cell (2004) [Pubmed]
  2. Vaccinia locomotion in host cells: evidence for the universal involvement of actin-based motility sequences ABM-1 and ABM-2. Zeile, W.L., Condit, R.C., Lewis, J.I., Purich, D.L., Southwick, F.S. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  3. Profilin interacts with the Gly-Pro-Pro-Pro-Pro-Pro sequences of vasodilator-stimulated phosphoprotein (VASP): implications for actin-based Listeria motility. Kang, F., Laine, R.O., Bubb, M.R., Southwick, F.S., Purich, D.L. Biochemistry (1997) [Pubmed]
  4. Shigella interactions with the actin cytoskeleton in the absence of Ena/VASP family proteins. Ally, S., Sauer, N.J., Loureiro, J.J., Snapper, S.B., Gertler, F.B., Goldberg, M.B. Cell. Microbiol. (2004) [Pubmed]
  5. Profilin 1 obtained by proteomic analysis in all-trans retinoic acid-treated hepatocarcinoma cell lines is involved in inhibition of cell proliferation and migration. Wu, N., Zhang, W., Yang, Y., Liang, Y.L., Wang, L.Y., Jin, J.W., Cai, X.M., Zha, X.L. Proteomics (2006) [Pubmed]
  6. Involvement of profilin in the actin-based motility of L. monocytogenes in cells and in cell-free extracts. Theriot, J.A., Rosenblatt, J., Portnoy, D.A., Goldschmidt-Clermont, P.J., Mitchison, T.J. Cell (1994) [Pubmed]
  7. How profilin promotes actin filament assembly in the presence of thymosin beta 4. Pantaloni, D., Carlier, M.F. Cell (1993) [Pubmed]
  8. Reconstitution of actin-based motility of Listeria and Shigella using pure proteins. Loisel, T.P., Boujemaa, R., Pantaloni, D., Carlier, M.F. Nature (1999) [Pubmed]
  9. Control of actin assembly at filament ends. Schafer, D.A., Cooper, J.A. Annu. Rev. Cell Dev. Biol. (1995) [Pubmed]
  10. Specific interaction between phosphatidylinositol 4,5-bisphosphate and profilactin. Lassing, I., Lindberg, U. Nature (1985) [Pubmed]
  11. Mast cell alpha-chymase reduces IgE recognition of birch pollen profilin by cleaving antibody-binding epitopes. Mellon, M.B., Frank, B.T., Fang, K.C. J. Immunol. (2002) [Pubmed]
  12. Identification of common allergenic structures in hazel pollen and hazelnuts: a possible explanation for sensitivity to hazelnuts in patients allergic to tree pollen. Hirschwehr, R., Valenta, R., Ebner, C., Ferreira, F., Sperr, W.R., Valent, P., Rohac, M., Rumpold, H., Scheiner, O., Kraft, D. J. Allergy Clin. Immunol. (1992) [Pubmed]
  13. Detection of clinical markers of sensitization to profilin in patients allergic to plant-derived foods. Asero, R., Mistrello, G., Roncarolo, D., Amato, S., Zanoni, D., Barocci, F., Caldironi, G. J. Allergy Clin. Immunol. (2003) [Pubmed]
  14. Profilin II is alternatively spliced, resulting in profilin isoforms that are differentially expressed and have distinct biochemical properties. Lambrechts, A., Braun, A., Jonckheere, V., Aszodi, A., Lanier, L.M., Robbens, J., Van Colen, I., Vandekerckhove, J., Fässler, R., Ampe, C. Mol. Cell. Biol. (2000) [Pubmed]
  15. The focal adhesion phosphoprotein, VASP. Holt, M.R., Critchley, D.R., Brindle, N.P. Int. J. Biochem. Cell Biol. (1998) [Pubmed]
  16. Suppression of tumorigenicity in breast cancer cells by the microfilament protein profilin 1. Janke, J., Schlüter, K., Jandrig, B., Theile, M., Kölble, K., Arnold, W., Grinstein, E., Schwartz, A., Estevéz-Schwarz, L., Schlag, P.M., Jockusch, B.M., Scherneck, S. J. Exp. Med. (2000) [Pubmed]
  17. Profilin enhances Cdc42-induced nucleation of actin polymerization. Yang, C., Huang, M., DeBiasio, J., Pring, M., Joyce, M., Miki, H., Takenawa, T., Zigmond, S.H. J. Cell Biol. (2000) [Pubmed]
  18. Identification of the functional profilin gene, its localization to chromosome subband 17p13.3, and demonstration of its deletion in some patients with Miller-Dieker syndrome. Kwiatkowski, D.J., Aklog, L., Ledbetter, D.H., Morton, C.C. Am. J. Hum. Genet. (1990) [Pubmed]
  19. The Wiskott-Aldrich syndrome protein-interacting protein (WIP) binds to the adaptor protein Nck. Antón, I.M., Lu, W., Mayer, B.J., Ramesh, N., Geha, R.S. J. Biol. Chem. (1998) [Pubmed]
  20. X-ray structure determination of human profilin II: A comparative structural analysis of human profilins. Nodelman, I.M., Bowman, G.D., Lindberg, U., Schutt, C.E. J. Mol. Biol. (1999) [Pubmed]
  21. Distinct biochemical characteristics of the two human profilin isoforms. Gieselmann, R., Kwiatkowski, D.J., Janmey, P.A., Witke, W. Eur. J. Biochem. (1995) [Pubmed]
  22. The affinities of human platelet and Acanthamoeba profilin isoforms for polyphosphoinositides account for their relative abilities to inhibit phospholipase C. Machesky, L.M., Goldschmidt-Clermont, P.J., Pollard, T.D. Cell Regul. (1990) [Pubmed]
  23. Characterization of renatured profilin purified by urea elution from poly-L-proline agarose columns. Kaiser, D.A., Goldschmidt-Clermont, P.J., Levine, B.A., Pollard, T.D. Cell Motil. Cytoskeleton (1989) [Pubmed]
  24. Incompatibility with formin Cdc12p prevents human profilin from substituting for fission yeast profilin: insights from crystal structures of fission yeast profilin. Ezezika, O.C., Younger, N.S., Lu, J., Kaiser, D.A., Corbin, Z.A., Nolen, B.J., Kovar, D.R., Pollard, T.D. J. Biol. Chem. (2009) [Pubmed]
  25. Interactions of drebrin and gephyrin with profilin. Mammoto, A., Sasaki, T., Asakura, T., Hotta, I., Imamura, H., Takahashi, K., Matsuura, Y., Shirao, T., Takai, Y. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  26. Activation of the Arp2/3 complex by the Listeria acta protein. Acta binds two actin monomers and three subunits of the Arp2/3 complex. Zalevsky, J., Grigorova, I., Mullins, R.D. J. Biol. Chem. (2001) [Pubmed]
  27. RIAM, an Ena/VASP and Profilin ligand, interacts with Rap1-GTP and mediates Rap1-induced adhesion. Lafuente, E.M., van Puijenbroek, A.A., Krause, M., Carman, C.V., Freeman, G.J., Berezovskaya, A., Constantine, E., Springer, T.A., Gertler, F.B., Boussiotis, V.A. Dev. Cell (2004) [Pubmed]
  28. The junctional multidomain protein AF-6 is a binding partner of the Rap1A GTPase and associates with the actin cytoskeletal regulator profilin. Boettner, B., Govek, E.E., Cross, J., Van Aelst, L. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  29. Profilin I attached to the Golgi is required for the formation of constitutive transport vesicles at the trans-Golgi network. Dong, J., Radau, B., Otto, A., Müller, E., Lindschau, C., Westermann, P. Biochim. Biophys. Acta (2000) [Pubmed]
  30. The essential role of profilin in the assembly of actin for microspike formation. Suetsugu, S., Miki, H., Takenawa, T. EMBO J. (1998) [Pubmed]
  31. Plant profilin induces actin polymerization from actin : beta-thymosin complexes and competes directly with beta-thymosins and with negative co-operativity with DNase I for binding to actin. Ballweber, E., Giehl, K., Hannappel, E., Huff, T., Jockusch, B.M., Mannherz, H.G. FEBS Lett. (1998) [Pubmed]
  32. Vinculin proteolysis unmasks an ActA homolog for actin-based Shigella motility. Laine, R.O., Zeile, W., Kang, F., Purich, D.L., Southwick, F.S. J. Cell Biol. (1997) [Pubmed]
  33. Molecular mechanisms controlling actin filament dynamics in nonmuscle cells. Pollard, T.D., Blanchoin, L., Mullins, R.D. Annual review of biophysics and biomolecular structure. (2000) [Pubmed]
  34. Activation of the CDC42 effector N-WASP by the Shigella flexneri IcsA protein promotes actin nucleation by Arp2/3 complex and bacterial actin-based motility. Egile, C., Loisel, T.P., Laurent, V., Li, R., Pantaloni, D., Sansonetti, P.J., Carlier, M.F. J. Cell Biol. (1999) [Pubmed]
  35. Extracellular S100A4 stimulates the migration rate of astrocytic tumor cells by modifying the organization of their actin cytoskeleton. Belot, N., Pochet, R., Heizmann, C.W., Kiss, R., Decaestecker, C. Biochim. Biophys. Acta (2002) [Pubmed]
  36. Molecular cloning and characterization of profilin-3: a novel cytoskeleton-associated gene expressed in rat kidney and testes. Hu, E., Chen, Z., Fredrickson, T., Zhu, Y. Exp. Nephrol. (2001) [Pubmed]
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