Profilin 1 Explained

Profilin-1 is a protein that in humans is encoded by the PFN1 gene.^{[1] [2]}

Function

The protein encoded by this gene is a ubiquitous actin monomer-binding protein belonging to the profilin family. It is thought to regulate actin polymerization in response to extracellular signals. Deletion of this gene is associated with Miller-Dieker syndrome.^[3] Mutations in this gene may be a rare cause of amyotrophic lateral sclerosis, also called Lou Gehrig's disease.^{[4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16]}

Interactions

Profilin 1 has been shown to interact with:

• FMNL1,^[17]
• MLLT4^[18]
• Vasodilator-stimulated phosphoprotein,^[19]
• WASF1,^[20] and
• WASL.^{[21] [22]}

Further reading

• Qualmann B, Kessels MM . Endocytosis and the cytoskeleton . Int. Rev. Cytol. . 220 . 93–144 . 2003 . 12224553 . 10.1016/S0074-7696(02)20004-2 . 978-0-12-364624-8 . International Review of Cytology .
• Ampe C, Markey F, Lindberg U, Vandekerckhove J . The primary structure of human platelet profilin: reinvestigation of the calf spleen profilin sequence . FEBS Lett. . 228 . 1 . 17–21 . 1988 . 3342873 . 10.1016/0014-5793(88)80575-1 . 23245396 .
• Gieselmann R, Kwiatkowski DJ, Janmey PA, Witke W . Distinct biochemical characteristics of the two human profilin isoforms . Eur. J. Biochem. . 229 . 3 . 621–8 . 1995 . 7758455 . 10.1111/j.1432-1033.1995.tb20506.x .
• Kato S, Sekine S, Oh SW, Kim NS, Umezawa Y, Abe N, Yokoyama-Kobayashi M, Aoki T . Construction of a human full-length cDNA bank . Gene . 150 . 2 . 243–50 . 1995 . 7821789 . 10.1016/0378-1119(94)90433-2 .
• Metzler WJ, Constantine KL, Friedrichs MS, Bell AJ, Ernst EG, Lavoie TB, Mueller L . Characterization of the three-dimensional solution structure of human profilin: 1H, 13C, and 15N NMR assignments and global folding pattern . Biochemistry . 32 . 50 . 13818–29 . 1994 . 8268157 . 10.1021/bi00213a010 .
• Schutt CE, Myslik JC, Rozycki MD, Goonesekere NC, Lindberg U . The structure of crystalline profilin-beta-actin . Nature . 365 . 6449 . 810–6 . 1993 . 8413665 . 10.1038/365810a0 . 1993Natur.365..810S . 4359724 .
• Mahoney NM, Janmey PA, Almo SC . Structure of the profilin-poly-L-proline complex involved in morphogenesis and cytoskeletal regulation . Nat. Struct. Biol. . 4 . 11 . 953–60 . 1997 . 9360613 . 10.1038/nsb1197-953 . 7492336 .
• Mammoto A, Sasaki T, Asakura T, Hotta I, Imamura H, Takahashi K, Matsuura Y, Shirao T, Takai Y . Interactions of drebrin and gephyrin with profilin . Biochem. Biophys. Res. Commun. . 243 . 1 . 86–9 . 1998 . 9473484 . 10.1006/bbrc.1997.8068 .
• Bhargavi V, Chari VB, Singh SS . Phosphatidylinositol 3-kinase binds to profilin through the p85 alpha subunit and regulates cytoskeletal assembly . Biochem. Mol. Biol. Int. . 46 . 2 . 241–8 . 1998 . 9801792 . 10.1080/15216549800203752 . 1764456 .
• Suetsugu S, Miki H, Takenawa T . The essential role of profilin in the assembly of actin for microspike formation . EMBO J. . 17 . 22 . 6516–26 . 1999 . 9822597 . 1170999 . 10.1093/emboj/17.22.6516 .
• Miki H, Suetsugu S, Takenawa T . WAVE, a novel WASP-family protein involved in actin reorganization induced by Rac . EMBO J. . 17 . 23 . 6932–41 . 1999 . 9843499 . 1171041 . 10.1093/emboj/17.23.6932 .
• Mahoney NM, Rozwarski DA, Fedorov E, Fedorov AA, Almo SC . Profilin binds proline-rich ligands in two distinct amide backbone orientations . Nat. Struct. Biol. . 6 . 7 . 666–71 . 1999 . 10404225 . 10.1038/10722 . 10994213 .
• Nunoi H, Yamazaki T, Tsuchiya H, Kato S, Malech HL, Matsuda I, Kanegasaki S . A heterozygous mutation of β-actin associated with neutrophil dysfunction and recurrent infection . Proc. Natl. Acad. Sci. U.S.A. . 96 . 15 . 8693–8 . 1999 . 10411937 . 17578 . 10.1073/pnas.96.15.8693 . 1999PNAS...96.8693N . free .
• Murphy GA, Solski PA, Jillian SA, Pérez de la Ossa P, D'Eustachio P, Der CJ, Rush MG . Cellular functions of TC10, a Rho family GTPase: regulation of morphology, signal transduction and cell growth . Oncogene . 18 . 26 . 3831–45 . 1999 . 10445846 . 10.1038/sj.onc.1202758 . 13589258 .
• Harbeck B, Hüttelmaier S, Schluter K, Jockusch BM, Illenberger S . Phosphorylation of the vasodilator-stimulated phosphoprotein regulates its interaction with actin . J. Biol. Chem. . 275 . 40 . 30817–25 . 2000 . 10882740 . 10.1074/jbc.M005066200 . free .
• Boettner B, Govek EE, Cross J, Van Aelst L . The junctional multidomain protein AF-6 is a binding partner of the Rap1A GTPase and associates with the actin cytoskeletal regulator profilin . Proc. Natl. Acad. Sci. U.S.A. . 97 . 16 . 9064–9 . 2000 . 10922060 . 16822 . 10.1073/pnas.97.16.9064 . 2000PNAS...97.9064B . free .
• Yayoshi-Yamamoto S, Taniuchi I, Watanabe T . FRL, a Novel Formin-Related Protein, Binds to Rac and Regulates Cell Motility and Survival of Macrophages . Mol. Cell. Biol. . 20 . 18 . 6872–81 . 2000 . 10958683 . 86228 . 10.1128/MCB.20.18.6872-6881.2000 .
• Mellon MB, Frank BT, Fang KC . Mast cell alpha-chymase reduces IgE recognition of birch pollen profilin by cleaving antibody-binding epitopes . J. Immunol. . 168 . 1 . 290–7 . 2002 . 11751973 . 10.4049/jimmunol.168.1.290 . free .

Notes and References

1. Kwiatkowski DJ, Bruns GA . Human profilin. Molecular cloning, sequence comparison, and chromosomal analysis . J Biol Chem . 263 . 12 . 5910–5 . May 1988 . 10.1016/S0021-9258(18)60651-9 . 3356709 . free .
2. Kwiatkowski DJ, Aklog L, Ledbetter DH, Morton CC . 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 . Am J Hum Genet . 46 . 3 . 559–67 . April 1990 . 1968707 . 1683621 .
3. Web site: Entrez Gene: PFN1 profilin 1.
4. Wu CH, Fallini C, Ticozzi N, Keagle PJ, Sapp PC, Piotrowska K, Lowe P, Koppers M, McKenna-Yasek D, Baron DM, Kost JE, Gonzalez-Perez P, Fox AD, Adams J, Taroni F, Tiloca C, Leclerc AL, Chafe SC, Mangroo D, Moore MJ, Zitzewitz JA, Xu ZS, van den Berg LH, Glass JD, Siciliano G, Cirulli ET, Goldstein DB, Salachas F, Meininger V, Rossoll W, Ratti A, Gellera C, Bosco DA, Bassell GJ, Silani V, Drory VE, Brown RH, Landers JE . 6 . Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis . Nature . 488 . 7412 . 499–503 . August 2012 . 22801503 . 3575525 . 10.1038/nature11280 . 2012Natur.488..499W .
5. Daoud H, Dobrzeniecka S, Camu W, Meininger V, Dupré N, Dion PA, Rouleau GA . Mutation analysis of PFN1 in familial amyotrophic lateral sclerosis patients . Neurobiology of Aging . 34 . 4 . 1311.e1–2 . April 2013 . 23062600 . 10.1016/j.neurobiolaging.2012.09.001 . 42137823 .
6. Tiloca C, Ticozzi N, Pensato V, Corrado L, Del Bo R, Bertolin C, Fenoglio C, Gagliardi S, Calini D, Lauria G, Castellotti B, Bagarotti A, Corti S, Galimberti D, Cagnin A, Gabelli C, Ranieri M, Ceroni M, Siciliano G, Mazzini L, Cereda C, Scarpini E, Sorarù G, Comi GP, D'Alfonso S, Gellera C, Ratti A, Landers JE, Silani V . 6 . Screening of the PFN1 gene in sporadic amyotrophic lateral sclerosis and in frontotemporal dementia . Neurobiology of Aging . 34 . 5 . 1517.e9–10 . May 2013 . 23063648 . 3548975 . 10.1016/j.neurobiolaging.2012.09.016 .
7. Ingre C, Landers JE, Rizik N, Volk AE, Akimoto C, Birve A, Hübers A, Keagle PJ, Piotrowska K, Press R, Andersen PM, Ludolph AC, Weishaupt JH . 6 . A novel phosphorylation site mutation in profilin 1 revealed in a large screen of US, Nordic, and German amyotrophic lateral sclerosis/frontotemporal dementia cohorts . Neurobiology of Aging . 34 . 6 . 1708.e1–6 . June 2013 . 23141414 . 10.1016/j.neurobiolaging.2012.10.009 . 6591725 .
8. Lattante S, Le Ber I, Camuzat A, Brice A, Kabashi E . Mutations in the PFN1 gene are not a common cause in patients with amyotrophic lateral sclerosis and frontotemporal lobar degeneration in France . Neurobiology of Aging . 34 . 6 . 1709.e1–2 . June 2013 . 23182804 . 10.1016/j.neurobiolaging.2012.10.026 . 37470475 .
9. Dillen L, Van Langenhove T, Engelborghs S, Vandenbulcke M, Sarafov S, Tournev I, Merlin C, Cras P, Vandenberghe R, De Deyn PP, Jordanova A, Cruts M, Van Broeckhoven C, van der Zee J . 6 . Explorative genetic study of UBQLN2 and PFN1 in an extended Flanders-Belgian cohort of frontotemporal lobar degeneration patients . Neurobiology of Aging . 34 . 6 . 1711.e1–5 . June 2013 . 23312802 . 10.1016/j.neurobiolaging.2012.12.007 . 8448562 .
10. Zou ZY, Sun Q, Liu MS, Li XG, Cui LY . Mutations in the profilin 1 gene are not common in amyotrophic lateral sclerosis of Chinese origin . Neurobiology of Aging . 34 . 6 . 1713.e5–6 . June 2013 . 23357624 . 10.1016/j.neurobiolaging.2012.12.024 . 9675956 .
11. Chen Y, Zheng ZZ, Huang R, Chen K, Song W, Zhao B, Chen X, Yang Y, Yuan L, Shang HF . 6 . PFN1 mutations are rare in Han Chinese populations with amyotrophic lateral sclerosis . Neurobiology of Aging . 34 . 7 . 1922.e1–5 . July 2013 . 23428184 . 10.1016/j.neurobiolaging.2013.01.013 . 25016105 .
12. van Blitterswijk M, Baker MC, Bieniek KF, Knopman DS, Josephs KA, Boeve B, Caselli R, Wszolek ZK, Petersen R, Graff-Radford NR, Boylan KB, Dickson DW, Rademakers R . 6 . Profilin-1 mutations are rare in patients with amyotrophic lateral sclerosis and frontotemporal dementia . Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration . 14 . 5–6 . 463–9 . September 2013 . 23634771 . 3923463 . 10.3109/21678421.2013.787630 .
13. Yang S, Fifita JA, Williams KL, Warraich ST, Pamphlett R, Nicholson GA, Blair IP . 6 . Mutation analysis and immunopathological studies of PFN1 in familial and sporadic amyotrophic lateral sclerosis . Neurobiology of Aging . 34 . 9 . 2235.e7–10 . September 2013 . 23635659 . 10.1016/j.neurobiolaging.2013.04.003 . 19339337 .
14. Fratta P, Charnock J, Collins T, Devoy A, Howard R, Malaspina A, Orrell R, Sidle K, Clarke J, Shoai M, Lu CH, Hardy J, Plagnol V, Fisher EM . 6 . Profilin1 E117G is a moderate risk factor for amyotrophic lateral sclerosis . Journal of Neurology, Neurosurgery, and Psychiatry . 85 . 5 . 506–8 . May 2014 . 24309268 . 3995330 . 10.1136/jnnp-2013-306761 .
15. Syriani E, Salvans C, Salvadó M, Morales M, Lorenzo L, Cazorla S, Gamez J . PFN1 mutations are also rare in the Catalan population with amyotrophic lateral sclerosis . Journal of Neurology . 261 . 12 . 2387–92 . December 2014 . 25249294 . 10.1007/s00415-014-7501-x . 21281429 .
16. Smith BN, Vance C, Scotter EL, Troakes C, Wong CH, Topp S, Maekawa S, King A, Mitchell JC, Lund K, Al-Chalabi A, Ticozzi N, Silani V, Sapp P, Brown RH, Landers JE, Al-Sarraj S, Shaw CE . 6 . Novel mutations support a role for Profilin 1 in the pathogenesis of ALS . Neurobiology of Aging . 36 . 3 . 1602.e17–27 . March 2015 . 25499087 . 4357530 . 10.1016/j.neurobiolaging.2014.10.032 .
17. Yayoshi-Yamamoto S, Taniuchi I, Watanabe T . FRL, a novel formin-related protein, binds to Rac and regulates cell motility and survival of macrophages . Mol. Cell. Biol. . 20 . 18 . 6872–81 . September 2000 . 10958683 . 86228 . 10.1128/mcb.20.18.6872-6881.2000.
18. Boettner B, Govek EE, Cross J, Van Aelst L . The junctional multidomain protein AF-6 is a binding partner of the Rap1A GTPase and associates with the actin cytoskeletal regulator profilin . Proc. Natl. Acad. Sci. U.S.A. . 97 . 16 . 9064–9 . August 2000 . 10922060 . 16822 . 10.1073/pnas.97.16.9064. 2000PNAS...97.9064B . free .
19. Harbeck B, Hüttelmaier S, Schluter K, Jockusch BM, Illenberger S . Phosphorylation of the vasodilator-stimulated phosphoprotein regulates its interaction with actin . J. Biol. Chem. . 275 . 40 . 30817–25 . October 2000 . 10882740 . 10.1074/jbc.M005066200 . free .
20. Miki H, Suetsugu S, Takenawa T . WAVE, a novel WASP-family protein involved in actin reorganization induced by Rac . EMBO J. . 17 . 23 . 6932–41 . December 1998 . 9843499 . 1171041 . 10.1093/emboj/17.23.6932 .
21. Mimuro H, Suzuki T, Suetsugu S, Miki H, Takenawa T, Sasakawa C . Profilin is required for sustaining efficient intra- and intercellular spreading of Shigella flexneri . J. Biol. Chem. . 275 . 37 . 28893–901 . September 2000 . 10867004 . 10.1074/jbc.M003882200 . free .
22. Suetsugu S, Miki H, Takenawa T . The essential role of profilin in the assembly of actin for microspike formation . EMBO J. . 17 . 22 . 6516–26 . November 1998 . 9822597 . 1170999 . 10.1093/emboj/17.22.6516 .