Summary: Diaphanous FH3 Domain
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This is the Wikipedia entry entitled "Formins". More...
Formins Edit Wikipedia article
| formin 1 | |
|---|---|
| Identifiers | |
| 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 | |
|---|---|
| Identifiers | |
| Symbol | FMN2 |
| Entrez | 56776 |
| HUGO | 14074 |
| OMIM | 606373 |
| RefSeq | XM_371352 |
| UniProt | Q9NZ56 |
| Other data | |
| Locus | Chr. 1 q43 |
| Formin Homology Region 1 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | Drf_FH1 | ||||||||
| Pfam | PF06346 | ||||||||
| InterPro | IPR009408 | ||||||||
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| Formin Homology 2 Domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 crystal structures of a formin homology-2 domain reveal a tethered-dimer architecture |
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| Identifiers | |||||||||
| Symbol | FH2 | ||||||||
| Pfam | PF02181 | ||||||||
| InterPro | IPR015425 | ||||||||
| SMART | FH2 | ||||||||
| SCOP | 1ux5 | ||||||||
| SUPERFAMILY | 1ux5 | ||||||||
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| Diaphanous FH3 Domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 crystal structure of mdia1 gbd-fh3 in complex with rhoc-gmppnp |
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| Identifiers | |||||||||
| Symbol | Drf_FH3 | ||||||||
| Pfam | PF06367 | ||||||||
| Pfam clan | CL0020 | ||||||||
| InterPro | IPR010472 | ||||||||
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| DRF Autoregulatory Domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 crystal structure of the n-terminal mdia1 armadillo repeat region and dimerisation domain in complex with the mdia1 autoregulatory domain (dad) |
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| Identifiers | |||||||||
| Symbol | Drf_DAD | ||||||||
| Pfam | PF06345 | ||||||||
| InterPro | IPR010465 | ||||||||
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| Diaphanous GTPase-binding Domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
crystal structure of mdia1 gbd-fh3 in complex with rhoc-gmppnp |
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| Identifiers | |||||||||
| Symbol | Drf_GBD | ||||||||
| Pfam | PF06371 | ||||||||
| Pfam clan | CL0020 | ||||||||
| InterPro | IPR010473 | ||||||||
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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.[1] Most formins are Rho-GTPase effector proteins. Formins regulate the actin and microtubule cytoskeleton[2] and are involved in various cellular functions such as cell polarity, cytokinesis, cell migration and SRF transcriptional activity.[3] 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.[4][5]
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.[2] 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.[6][7] 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].[8][9] 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.[10] 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.[10] 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.[11]
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.[12][13]
[edit] References
- ^ 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.
- ^ 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.
- ^ 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, 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.
- ^ 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.
- ^ 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.
- ^ 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.
[edit] External links
- 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.
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
This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
Diaphanous FH3 Domain Provide feedback
This region is found in the Formin-like and and diaphanous proteins [1,2].
Literature references
-
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
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Petersen J, Nielsen O, Egel R, Hagan IM; , J Cell Biol 1998;141:1217-1228.: FH3, a domain found in formins, targets the fission yeast formin Fus1 to the projection tip during conjugation. PUBMED:9606213 EPMC:9606213
External database links
| PANDIT: | PF06367 |
| Pseudofam: | PF06367 |
| SYSTERS: | Drf_FH3 |
This tab holds annotation information from the InterPro database.
InterPro entry IPR010472
Formin homology (FH) proteins play a crucial role in the reorganisation of the actin cytoskeleton, which mediates various functions of the cell cortex including motility, adhesion, and cytokinesis [PUBMED:10631086]. 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 [PUBMED:12538772]. 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 FH2 domain (INTERPRO) is required 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 [PUBMED:11171383], or the projection tip during conjugation [PUBMED:9606213]. In addition, some formins can contain a GTPase-binding domain (GBD) (INTERPRO) required for binding to Rho small GTPases, and a C-terminal conserved Dia-autoregulatory domain (DAD).
This entry represents the FH3 domain.
Gene Ontology
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
| Molecular function | actin binding (GO:0003779) |
| Biological process | cellular component organization (GO:0016043) |
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan TPR (CL0020), which 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 YfiOAlignments
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...
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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
| Seed (37) |
Full (1087) |
Representative proteomes | NCBI (1003) |
Meta (4) |
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| RP15 (194) |
RP35 (270) |
RP55 (470) |
RP75 (649) |
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| Jalview | ||||||||
| HTML | ||||||||
| PP/heatmap | 1 | |||||||
| Pfam viewer | ||||||||
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
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| Seed (37) |
Full (1087) |
Representative proteomes | NCBI (1003) |
Meta (4) |
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|---|---|---|---|---|---|---|---|---|
| RP15 (194) |
RP35 (270) |
RP55 (470) |
RP75 (649) |
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| Raw Stockholm | ||||||||
| Gzipped | ||||||||
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
External links
MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.
HMM logo
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
Trees
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
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Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
| Seed source: | ADDA_2536 |
| Previous IDs: | none |
| Type: | Domain |
| Author: | Yeats C |
| Number in seed: | 37 |
| Number in full: | 1087 |
| Average length of the domain: | 187.70 aa |
| Average identity of full alignment: | 26 % |
| Average coverage of the sequence by the domain: | 17.15 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 197 | ||||||||||||
| Family (HMM) version: | 11 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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Interactions
There is 1 interaction for this family. More...
Drf_FH3Structures
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_FH3 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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