Formins have been found in all eukaryotes studied.[1] In humans, 15 different formin proteins are present that have been classified in 7 subgroups.[6] By contrast, yeasts contain only 2-3 formins.[7]
Structure and interactionsedit
Formins are characterized by the presence of three formin homology (FH) domains (FH1, FH2 and FH3), although members of the formin family do not necessarily contain all three domains.[8][9] In addition, other domains are usually present, such as PDZ, DAD, WH2, or FHA domains.
The proline-rich FH1 domain mediates interactions with a variety of proteins, including the actin-binding proteinprofilin,[10]SH3 (Src homology 3) domain proteins,[11] and WW domain proteins. The actin nucleation-promoting activity of S. cerevisiae formins has been localized to the FH2 domain.[4] The FH2 domain is required for the self-association of formin proteins through the ability of FH2 domains to directly bind each other, and may also act to inhibit actin polymerization.[12][13] The FH3 domain is less well conserved and is required for directing formins to the correct intracellular location, such as the mitotic spindle, or the projection tip during conjugation.[14][15] In addition, some formins can contain a GTPase-binding domain (GBD) required for binding to Rho small GTPases, and a C-terminalconserved Dia-autoregulatory domain (DAD). The GBD is a bifunctional autoinhibitory domain that interacts with and is regulated by activated Rho family members. Mammalian Drf3 contains a CRIB-like motif within its GBD for binding to Cdc42, which is required for Cdc42 to activate and guide Drf3 towards the cell cortex where it remodels the actin skeleton.[16] The DAD binds the N-terminal GBD; this link is broken when GTP-bound Rho binds to the GBD and activates the protein. The addition of the DAD to mammaliancells induces actin filament formation, stabilizes microtubules, and activates SRF mediated transcription.[16] Another commonly found domain is an armadillo repeat region (ARR) located in the FH3 domain.
Formins also directly bind to microtubules via their FH2 domain. This interaction is important in promoting the capture and stabilization of a subset of microtubules oriented towards the leading edge of migrating cells. Formins also promote the capture of microtubules by the kinetochore during mitosis and for aligning microtubules along actin filaments.[19][20]
^ abChalkia D, Nikolaidis N, Makalowski W, Klein J, Nei M (December 2008). "Origins and evolution of the formin multigene family that is involved in the formation of actin filaments". Molecular Biology and Evolution. 25 (12): 2717–33. doi:10.1093/molbev/msn215. PMC2721555. PMID 18840602.
^Evangelista M, Zigmond S, Boone C (July 2003). "Formins: signaling effectors for assembly and polarization of actin filaments". Journal of Cell Science. 116 (Pt 13): 2603–11. doi:10.1242/jcs.00611. PMID 12775772.
^Gunning PW, Ghoshdastider U, Whitaker S, Popp D, Robinson RC (June 2015). "The evolution of compositionally and functionally distinct actin filaments". Journal of Cell Science. 128 (11): 2009–19. doi:10.1242/jcs.165563. PMID 25788699.
^ abGoode BL, Eck MJ (2007). "Mechanism and function of formins in the control of actin assembly". Annual Review of Biochemistry. 76: 593–627. doi:10.1146/annurev.biochem.75.103004.142647. PMID 17373907.
^Faix J, Grosse R (June 2006). "Staying in shape with formins". Developmental Cell. 10 (6): 693–706. doi:10.1016/j.devcel.2006.05.001. PMID 16740473.
^Higgs HN, Peterson KJ (January 2005). "Phylogenetic analysis of the formin homology 2 domain". Molecular Biology of the Cell. 16 (1): 1–13. doi:10.1091/mbc.E04-07-0565. PMC539145. PMID 15509653.
^Kitayama C, Uyeda TQ (February 2003). "ForC, a novel type of formin family protein lacking an FH1 domain, is involved in multicellular development in Dictyostelium discoideum". Journal of Cell Science. 116 (Pt 4): 711–23. doi:10.1242/jcs.00265. PMID 12538772.
^Wallar BJ, Alberts AS (August 2003). "The formins: active scaffolds that remodel the cytoskeleton". Trends in Cell Biology. 13 (8): 435–46. doi:10.1016/S0962-8924(03)00153-3. PMID 12888296.
^Uetz P (1997). Biochemische Studien am limb deformity-Protein der Vertebraten: Inaugural-Dissertation zur Erlangung der Doktorwürde der Naturwissenschaftlich-Mathematischen Gesamtfakultät der Ruprecht-Karls-Universität Heidelberg. Developmental Biology, European Molecular Biology Laboratory. Heidelberg: European Molecular Biology Laboratory.
^Uetz P, Fumagalli S, James D, Zeller R (December 1996). "Molecular interaction between limb deformity proteins (formins) and Src family kinases". The Journal of Biological Chemistry. 271 (52): 33525–30. doi:10.1074/jbc.271.52.33525. PMID 8969217.
^Takeya R, Sumimoto H (November 2003). "Fhos, a mammalian formin, directly binds to F-actin via a region N-terminal to the FH1 domain and forms a homotypic complex via the FH2 domain to promote actin fiber formation". Journal of Cell Science. 116 (Pt 22): 4567–75. doi:10.1242/jcs.00769. PMID 14576350.
^Shimada A, Nyitrai M, Vetter IR, Kühlmann D, Bugyi B, Narumiya S, Geeves MA, Wittinghofer A (February 2004). "The core FH2 domain of diaphanous-related formins is an elongated actin binding protein that inhibits polymerization". Molecular Cell. 13 (4): 511–22. doi:10.1016/S1097-2765(04)00059-0. PMID 14992721.
^Kato T, Watanabe N, Morishima Y, Fujita A, Ishizaki T, Narumiya S (February 2001). "Localization of a mammalian homolog of diaphanous, mDia1, to the mitotic spindle in HeLa cells". Journal of Cell Science. 114 (Pt 4): 775–84. doi:10.1242/jcs.114.4.775. hdl:2433/150544. PMID 11171383.
^Petersen J, Nielsen O, Egel R, Hagan IM (June 1998). "FH3, a domain found in formins, targets the fission yeast formin Fus1 to the projection tip during conjugation". The Journal of Cell Biology. 141 (5): 1217–28. doi:10.1083/jcb.141.5.1217. PMC2137179. PMID 9606213.
^ abPeng J, Wallar BJ, Flanders A, Swiatek PJ, Alberts AS (April 2003). "Disruption of the Diaphanous-related formin Drf1 gene encoding mDia1 reveals a role for Drf3 as an effector for Cdc42". Current Biology. 13 (7): 534–45. Bibcode:2003CBio...13..534P. doi:10.1016/S0960-9822(03)00170-2. PMID 12676083. S2CID 13902104.
^Xu Y, Moseley JB, Sagot I, Poy F, Pellman D, Goode BL, Eck MJ (March 2004). "Crystal structures of a Formin Homology-2 domain reveal a tethered dimer architecture". Cell. 116 (5): 711–23. doi:10.1016/S0092-8674(04)00210-7. PMID 15006353. S2CID 15855545.
This article incorporates text from the public domain Pfam and InterPro: IPR010472
This article incorporates text from the public domain Pfam and InterPro: IPR015425
This article incorporates text from the public domain Pfam and InterPro: IPR010465
This article incorporates text from the public domain Pfam and InterPro: IPR010473
January 01, 1970
formins, formin, homology, proteins, group, proteins, that, involved, polymerization, actin, associate, with, fast, growing, barbed, actin, filaments, most, formins, gtpase, effector, proteins, regulate, actin, microtubule, cytoskeleton, involved, various, cel. Formins formin homology proteins are a group of proteins that are involved in the polymerization of actin and associate with the fast growing end barbed end of actin filaments 2 Most formins are Rho GTPase effector proteins Formins regulate the actin and microtubule cytoskeleton 3 4 and are involved in various cellular functions such as cell polarity cytokinesis cell migration and SRF transcriptional activity 5 Formins are multidomain proteins that interact with diverse signalling molecules and cytoskeletal proteins although some formins have been assigned functions within the nucleus formin 1IdentifiersSymbolFMN1Alt symbolsLD FMNNCBI gene342184HGNC3768OMIM136535RefSeqNM 001103184UniProtQ68DA7Other dataLocusChr 15 q13 q14Search forStructuresSwiss modelDomainsInterPro Formin Homology Region 1IdentifiersSymbolDrf FH1PfamPF06346InterProIPR009408Available protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summary Domain structure of formin proteins across phyla 1 Formin Homology 2 Domaincrystal structures of a formin homology 2 domain reveal a tethered dimer architectureIdentifiersSymbolFH2PfamPF02181InterProIPR015425SMARTFH2SCOP21ux5 SCOPe SUPFAMAvailable protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summary Diaphanous FH3 Domaincrystal structure of mdia1 gbd fh3 in complex with rhoc gmppnpIdentifiersSymbolDrf FH3PfamPF06367Pfam clanCL0020InterProIPR010472Available protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summary DRF Autoregulatory Domaincrystal structure of the n terminal mdia1 armadillo repeat region and dimerisation domain in complex with the mdia1 autoregulatory domain dad IdentifiersSymbolDrf DADPfamPF06345InterProIPR010465Available protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summary Diaphanous GTPase binding Domaincrystal structure of mdia1 gbd fh3 in complex with rhoc gmppnpIdentifiersSymbolDrf GBDPfamPF06371Pfam clanCL0020InterProIPR010473Available protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summary Contents 1 Diversity 2 Structure and interactions 3 See also 4 References 5 External linksDiversity editFormins have been found in all eukaryotes studied 1 In humans 15 different formin proteins are present that have been classified in 7 subgroups 6 By contrast yeasts contain only 2 3 formins 7 Structure and interactions editFormins are characterized by the presence of three formin homology FH domains FH1 FH2 and FH3 although members of the formin family do not necessarily contain all three domains 8 9 In addition other domains are usually present such as PDZ DAD WH2 or FHA domains The proline rich FH1 domain mediates interactions with a variety of proteins including the actin binding protein profilin 10 SH3 Src homology 3 domain proteins 11 and WW domain proteins The actin nucleation promoting activity of S cerevisiae formins has been localized to the FH2 domain 4 The FH2 domain is required for the self association of formin proteins through the ability of FH2 domains to directly bind each other and may also act to inhibit actin polymerization 12 13 The FH3 domain is less well conserved and is required for directing formins to the correct intracellular location such as the mitotic spindle or the projection tip during conjugation 14 15 In addition some formins can contain a GTPase binding domain GBD required for binding to Rho small GTPases and a C terminal conserved Dia autoregulatory domain DAD The GBD is a bifunctional autoinhibitory domain that interacts with and is regulated by activated Rho family members Mammalian Drf3 contains a CRIB like motif within its GBD for binding to Cdc42 which is required for Cdc42 to activate and guide Drf3 towards the cell cortex where it remodels the actin skeleton 16 The DAD binds the N terminal GBD this link is broken when GTP bound Rho binds to the GBD and activates the protein The addition of the DAD to mammalian cells induces actin filament formation stabilizes microtubules and activates SRF mediated transcription 16 Another commonly found domain is an armadillo repeat region ARR located in the FH3 domain The FH2 domain has been shown by X ray crystallography to have an elongated crescent shape containing three helical subdomains 17 18 Formins also directly bind to microtubules via their FH2 domain This interaction is important in promoting the capture and stabilization of a subset of microtubules oriented towards the leading edge of migrating cells Formins also promote the capture of microtubules by the kinetochore during mitosis and for aligning microtubules along actin filaments 19 20 See also editFormin 2References edit a b Chalkia D Nikolaidis N Makalowski W Klein J Nei M December 2008 Origins and evolution of the formin multigene family that is involved in the formation of actin filaments Molecular Biology and Evolution 25 12 2717 33 doi 10 1093 molbev msn215 PMC 2721555 PMID 18840602 Evangelista M Zigmond S Boone C July 2003 Formins signaling effectors for assembly and polarization of actin filaments Journal of Cell Science 116 Pt 13 2603 11 doi 10 1242 jcs 00611 PMID 12775772 Gunning PW Ghoshdastider U Whitaker S Popp D Robinson RC June 2015 The evolution of compositionally and functionally distinct actin filaments Journal of Cell Science 128 11 2009 19 doi 10 1242 jcs 165563 PMID 25788699 a b Goode BL Eck MJ 2007 Mechanism and function of formins in the control of actin assembly Annual Review of Biochemistry 76 593 627 doi 10 1146 annurev biochem 75 103004 142647 PMID 17373907 Faix J Grosse R June 2006 Staying in shape with formins Developmental Cell 10 6 693 706 doi 10 1016 j devcel 2006 05 001 PMID 16740473 Higgs HN Peterson KJ January 2005 Phylogenetic analysis of the formin homology 2 domain Molecular Biology of the Cell 16 1 1 13 doi 10 1091 mbc E04 07 0565 PMC 539145 PMID 15509653 Baarlink C Brandt D Grosse R July 2010 SnapShot Formins Cell 142 1 172 172 e1 doi 10 1016 j cell 2010 06 030 PMID 20603022 S2CID 2914004 Kitayama C Uyeda TQ February 2003 ForC a novel type of formin family protein lacking an FH1 domain is involved in multicellular development in Dictyostelium discoideum Journal of Cell Science 116 Pt 4 711 23 doi 10 1242 jcs 00265 PMID 12538772 Wallar BJ Alberts AS August 2003 The formins active scaffolds that remodel the cytoskeleton Trends in Cell Biology 13 8 435 46 doi 10 1016 S0962 8924 03 00153 3 PMID 12888296 Uetz P 1997 Biochemische Studien am limb deformity Protein der Vertebraten Inaugural Dissertation zur Erlangung der Doktorwurde der Naturwissenschaftlich Mathematischen Gesamtfakultat der Ruprecht Karls Universitat Heidelberg Developmental Biology European Molecular Biology Laboratory Heidelberg European Molecular Biology Laboratory Uetz P Fumagalli S James D Zeller R December 1996 Molecular interaction between limb deformity proteins formins and Src family kinases The Journal of Biological Chemistry 271 52 33525 30 doi 10 1074 jbc 271 52 33525 PMID 8969217 Takeya R Sumimoto H November 2003 Fhos a mammalian formin directly binds to F actin via a region N terminal to the FH1 domain and forms a homotypic complex via the FH2 domain to promote actin fiber formation Journal of Cell Science 116 Pt 22 4567 75 doi 10 1242 jcs 00769 PMID 14576350 Shimada A Nyitrai M Vetter IR Kuhlmann D Bugyi B Narumiya S Geeves MA Wittinghofer A February 2004 The core FH2 domain of diaphanous related formins is an elongated actin binding protein that inhibits polymerization Molecular Cell 13 4 511 22 doi 10 1016 S1097 2765 04 00059 0 PMID 14992721 Kato T Watanabe N Morishima Y Fujita A Ishizaki T Narumiya S February 2001 Localization of a mammalian homolog of diaphanous mDia1 to the mitotic spindle in HeLa cells Journal of Cell Science 114 Pt 4 775 84 doi 10 1242 jcs 114 4 775 hdl 2433 150544 PMID 11171383 Petersen J Nielsen O Egel R Hagan IM June 1998 FH3 a domain found in formins targets the fission yeast formin Fus1 to the projection tip during conjugation The Journal of Cell Biology 141 5 1217 28 doi 10 1083 jcb 141 5 1217 PMC 2137179 PMID 9606213 a b Peng J Wallar BJ Flanders A Swiatek PJ Alberts AS April 2003 Disruption of the Diaphanous related formin Drf1 gene encoding mDia1 reveals a role for Drf3 as an effector for Cdc42 Current Biology 13 7 534 45 Bibcode 2003CBio 13 534P doi 10 1016 S0960 9822 03 00170 2 PMID 12676083 S2CID 13902104 Xu Y Moseley JB Sagot I Poy F Pellman D Goode BL Eck MJ March 2004 Crystal structures of a Formin Homology 2 domain reveal a tethered dimer architecture Cell 116 5 711 23 doi 10 1016 S0092 8674 04 00210 7 PMID 15006353 S2CID 15855545 Thompson ME Heimsath EG Gauvin TJ Higgs HN Kull FJ January 2013 FMNL3 FH2 actin structure gives insight into formin mediated actin nucleation and elongation Nature Structural amp Molecular Biology 20 1 111 8 doi 10 1038 nsmb 2462 PMC 3876896 PMID 23222643 Palazzo AF Cook TA Alberts AS Gundersen GG August 2001 mDia mediates Rho regulated formation and orientation of stable microtubules Nature Cell Biology 3 8 723 9 doi 10 1038 35087035 PMID 11483957 S2CID 7374170 Bartolini F Gundersen GG February 2010 Formins and microtubules Biochimica et Biophysica Acta BBA Molecular Cell Research 1803 2 164 73 doi 10 1016 j bbamcr 2009 07 006 PMC 2856479 PMID 19631698 External links editMBInfo Formin mediated actin nucleation This article incorporates text from the public domain Pfam and InterPro IPR010472 This article incorporates text from the public domain Pfam and InterPro IPR015425 This article incorporates text from the public domain Pfam and InterPro IPR010465 This article incorporates text from the public domain Pfam and InterPro IPR010473 Retrieved from https en wikipedia org w index php title Formins amp oldid 1216310539, wikipedia, wiki, book, books, library,
