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formin 1
Symbol FMN1
Alt. symbols LD, FMN
Entrez 342184
HUGO 3768
OMIM 136535
RefSeq NM_001103184
UniProt Q68DA7
Other data
Locus Chr. 15 q13-q14
formin 2
Symbol FMN2
Entrez 56776
HUGO 14074
OMIM 606373
RefSeq XM_371352
UniProt Q9NZ56
Other data
Locus Chr. 1 q43
Domain structure of formin proteins across phyla.[1]
Formin Homology Region 1
Symbol Drf_FH1
Pfam PF06346
InterPro IPR009408
Formin Homology 2 Domain
PDB 1ux4 EBI.jpg
crystal structures of a formin homology-2 domain reveal a tethered-dimer architecture
Symbol FH2
Pfam PF02181
InterPro IPR015425
SCOP 1ux5
Diaphanous FH3 Domain
PDB 1z2c EBI.jpg
crystal structure of mdia1 gbd-fh3 in complex with rhoc-gmppnp
Symbol Drf_FH3
Pfam PF06367
Pfam clan CL0020
InterPro IPR010472
DRF Autoregulatory Domain
PDB 2bap EBI.jpg
crystal structure of the n-terminal mdia1 armadillo repeat region and dimerisation domain in complex with the mdia1 autoregulatory domain (dad)
Symbol Drf_DAD
Pfam PF06345
InterPro IPR010465
Diaphanous GTPase-binding Domain
PDB 1z2c EBI.jpg
crystal structure of mdia1 gbd-fh3 in complex with rhoc-gmppnp
Symbol Drf_GBD
Pfam PF06371
Pfam clan CL0020
InterPro IPR010473

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] and are involved in various cellular functions such as cell polarity, cytokinesis, cell migration and SRF transcriptional activity.[4] Formins are multidomain proteins that interact with diverse signalling molecules and cytoskeletal proteins, although some formins have been assigned functions within the nucleus.


Formins have been found in all eukaryotes studied.[1] In humans, 15 different formin proteins are present that have been classified in 7 subgroups. By contrast, yeasts contain only 2-3 formins.[5]

Structure and interactions[edit]

Formins are characterised 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.[6][7] In addition, other domains are usually present, such as PDZ, DAD, or FHA domains.

The proline-rich FH1 domain mediates interactions with a variety of proteins, including the actin-binding protein profilin, SH3 (Src homology 3) domain proteins,[8] and WW domain proteins. The actin nucleation-promoting activity of S. cerevisiae formins has been localized to the FH2 domain.[3] 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 polymerisation.[9][10] The FH3 domain is less well conserved and is required for directing formins to the correct intracellular location, such the mitotic spindle, or the projection tip during conjugation[disambiguation needed].[11][12] In addition, some formins can contain a GTPase-binding domain (GBD) required for binding to Rho small GTPases, and a C-terminal conserved DRF autoregulatory domain (Dia-autoregulatory domain) (DAD). The GBD domain 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.[13] The DRF autoregulatory domain binds the N-terminal GTPase-binding domain; 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, stabilises microtubules, and activates serum-response mediated transcription.[13] 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.[14]

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.[15][16]


  1. ^ a b Chalkia, D; Nikolaidis, N; Makalowski, W; Klein, J; Nei, M (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.  edit
  2. ^ Evangelista Marie, Zigmond Sally and Boone Charles (July 2003). "Formins: signaling effectors for assembly and polarization of actin filaments". J Cell Sci. 116 (Pt 13): 2603–11. doi:10.1242/jcs.00611. PMID 12775772. 
  3. ^ a b Goode BL, Eck MJ (2007). "Mechanism and function of formins in the control of actin assembly". Annu. Rev. Biochem. 76: 593–627. doi:10.1146/annurev.biochem.75.103004.142647. PMID 17373907. 
  4. ^ Faix J, Grosse R (June 2006). "Staying in shape with formins". Dev. Cell 10 (6): 693–706. doi:10.1016/j.devcel.2006.05.001. PMID 16740473. 
  5. ^ 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". J. Cell. Sci. 116 (Pt 4): 711–23. doi:10.1242/jcs.00265. PMID 12538772. 
  6. ^ Wallar Bradley J and Alberts Arthur S (August 2003). "The formins: active scaffolds that remodel the cytoskeleton". Trends Cell Biol. 13 (8): 435–46. doi:10.1016/S0962-8924(03)00153-3. PMID 12888296. 
  7. ^ Uetz, P; Fumagalli, S; James, D; Zeller, R (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.  edit
  8. ^ 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". J. Cell. Sci. 116 (Pt 22): 4567–75. doi:10.1242/jcs.00769. PMID 14576350. 
  9. ^ 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". Mol. Cell 13 (4): 511–22. doi:10.1016/S1097-2765(04)00059-0. PMID 14992721. 
  10. ^ 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". J. Cell. Sci. 114 (Pt 4): 775–84. PMID 11171383. 
  11. ^ 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". J. Cell Biol. 141 (5): 1217–28. doi:10.1083/jcb.141.5.1217. PMC 2137179. PMID 9606213. 
  12. ^ 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". Curr. Biol. 13 (7): 534–45. doi:10.1016/S0960-9822(03)00170-2. PMID 12676083. 
  13. ^ 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. 
  14. ^ Palazzo AF, Cook TA, Alberts AS, Gundersen GG (Aug 2001). "mDia mediates Rho-regulated formation and orientation of stable microtubules". Nat Cell Biol. 3 (8): 723–9. doi:10.1038/35087035. PMID 11483957. 
  15. ^ Bartolini F, Gundersen GG (Feb 2010). "Formins and Microtubules". Biochim Biophys Acta. 1803 (2): 164–73. doi:10.1016/j.bbamcr.2009.07.006. PMC 2856479. PMID 19631698. 

External links[edit]

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