Summary: Diaphanous GTPase-binding Domain
This is the Wikipedia entry entitled "Formins". More...
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Formins Edit Wikipedia article
|Alt. symbols||LD, FMN|
|Locus||Chr. 15 q13-q14|
|Locus||Chr. 1 q43|
|Formin Homology Region 1|
|Formin Homology 2 Domain|
crystal structures of a formin homology-2 domain reveal a tethered-dimer architecture
|Diaphanous FH3 Domain|
crystal structure of mdia1 gbd-fh3 in complex with rhoc-gmppnp
|DRF Autoregulatory Domain|
crystal structure of the n-terminal mdia1 armadillo repeat region and dimerisation domain in complex with the mdia1 autoregulatory domain (dad)
|Diaphanous GTPase-binding Domain|
crystal structure of mdia1 gbd-fh3 in complex with rhoc-gmppnp
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. Most formins are Rho-GTPase effector proteins. Formins regulate the actin and microtubule cytoskeleton and are involved in various cellular functions such as cell polarity, cytokinesis, cell migration and SRF transcriptional activity. Formins are multidomain proteins that interact with diverse signalling molecules and cytoskeletal proteins, although some formins have been assigned functions within the nucleus. Formins are characterised by the presence of three FH domains (FH1, FH2 and FH3), although members of the formin family do not necessarily contain all three 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, and WW domain proteins. The actin nucleation-promoting activity of S. cerevisiae formins has been localized to the FH2 domain. 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. 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]. 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. 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. 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Shimada A, Nyitrai M, Vetter IR, KÃ¼hlmann 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- MBInfo - Formin mediated nucleation
- Baarlink C, Brandt D, Grosse R (July 2010). "SnapShot: Formins". Cell 172 (1): e1. doi:10.1016/j.cell.2010.06.030. PMID 20603022.
Diaphanous GTPase-binding Domain Provide feedback
This domain is bound to by GTP-attached Rho proteins, leading to activation of the Drf protein.
Peng J, Wallar BJ, Flanders A, Swiatek PJ, Alberts AS; , Curr Biol 2003;13:534-545.: Disruption of the Diaphanous-Related Formin Drf1 Gene Encoding mDia1 Reveals a Role for Drf3 as an Effector for Cdc42. PUBMED:12676083 EPMC:12676083
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR010473
Diaphanous-related formins (Drfs) are a family of formin homology (FH) proteins that act as effectors of Rho small GTPases during growth factor-induced cytoskeletal remodelling, stress fibre formation, and cell division [PUBMED:10631086]. Drf proteins are characterised by a variety of shared domains: an N-terminal GTPase-binding domain (GBD), formin-homology domains FH1, FH2 (INTERPRO) and FH3 (INTERPRO), and a C-terminal conserved Dia-autoregulatory domain (DAD) that binds the GBD.
This entry represents the GBD, which 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 [PUBMED:12676083].
|Molecular function||actin binding (GO:0003779)|
|Rho GTPase binding (GO:0017048)|
|Biological process||actin cytoskeleton organization (GO:0030036)|
- the number of sequences which exhibit this architecture
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This example describes an architecture with one
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Tetratricopeptide-like repeats are found in a numerous and diverse proteins involved in such functions as cell cycle regulation, transcriptional control, mitochondrial and peroxisomal protein transport, neurogenesis and protein folding.
The clan contains the following 117 members:Adaptin_N Alkyl_sulf_dimr Apc3 Apc5 API5 Arm Arm_2 Avirulence BTAD CAS_CSE1 ChAPs CLASP_N Clathrin Clathrin-link Clathrin_propel Cnd1 Cnd3 Coatomer_E Cohesin_HEAT Cohesin_load CRM1_C Cse1 DNA_alkylation Drf_FH3 Drf_GBD DUF1822 DUF2225 DUF3385 DUF3458 DUF3808 DUF3856 EST1_DNA_bind FAT Fis1_TPR_C Fis1_TPR_N Foie-gras_1 GUN4 HAT HEAT HEAT_2 HEAT_EZ HEAT_PBS HemY_N IBB IBN_N IFRD KAP Leuk-A4-hydro_C LRV LRV_FeS MA3 MIF4G MIF4G_like MIF4G_like_2 MMS19_C Mo25 MRP-S27 NARP1 Neurochondrin Nro1 NSF Paf67 ParcG PC_rep PHAT PI3Ka PPP5 PPR PPR_1 PPR_2 PPR_3 Proteasom_PSMB PUF Rab5-bind Rapsyn_N RPN7 Sel1 SHNi-TPR SNAP SPO22 ST7 Suf SusD SusD-like SusD-like_2 SusD-like_3 Tcf25 TOM20_plant TPR_1 TPR_10 TPR_11 TPR_12 TPR_14 TPR_15 TPR_16 TPR_17 TPR_18 TPR_19 TPR_2 TPR_20 TPR_21 TPR_3 TPR_4 TPR_5 TPR_6 TPR_7 TPR_8 TPR_9 Upf2 V-ATPase_H_C V-ATPase_H_N Vac14_Fab1_bd Vitellogenin_N Vps39_1 W2 Xpo1 YfiO
We make a range of alignments for each Pfam-A family:
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Curation and family details
|Number in seed:||20|
|Number in full:||1367|
|Average length of the domain:||151.50 aa|
|Average identity of full alignment:||21 %|
|Average coverage of the sequence by the domain:||17.18 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||8|
|Download:||download the raw HMM for this family|
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There is 1 interaction for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Drf_GBD domain has been found. There are 17 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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