Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
17  structures 230  species 1  interaction 1087  sequences 51  architectures

Family: Drf_FH3 (PF06367)

Summary: Diaphanous FH3 Domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

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
Domain structure of formin proteins across phyla.[1]
Formin Homology Region 1
Identifiers
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
Identifiers
Symbol FH2
Pfam PF02181
InterPro IPR015425
SMART FH2
SCOP 1ux5
SUPERFAMILY 1ux5
Diaphanous FH3 Domain
PDB 1z2c EBI.jpg
crystal structure of mdia1 gbd-fh3 in complex with rhoc-gmppnp
Identifiers
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)
Identifiers
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
Identifiers
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.

Diversity

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

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]

References

  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. 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

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

  1. 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

  2. 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

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.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

Alignments

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...

View options

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)
RP15
(194)
RP35
(270)
RP55
(470)
RP75
(649)
Jalview View  View  View  View  View  View  View  View 
HTML View  View  View  View  View  View     
PP/heatmap 1 View  View  View  View  View     
Pfam viewer View  View             

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(37)
Full
(1087)
Representative proteomes NCBI
(1003)
Meta
(4)
RP15
(194)
RP35
(270)
RP55
(470)
RP75
(649)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(37)
Full
(1087)
Representative proteomes NCBI
(1003)
Meta
(4)
RP15
(194)
RP35
(270)
RP55
(470)
RP75
(649)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

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.

Note: You can also download the data file for the tree.

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 View help on the curation process

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 View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.0 20.0
Trusted cut-off 20.1 20.0
Noise cut-off 19.9 19.3
Model length: 197
Family (HMM) version: 11
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Show

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Interactions

There is 1 interaction for this family. More...

Drf_FH3

Structures

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.

Loading structure mapping...