Formins

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Formins

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.

Quick Facts formin 1, Identifiers ...
formin 1
Identifiers
SymbolFMN1
Alt. symbolsLD, FMN
NCBI gene342184
HGNC3768
OMIM136535
RefSeqNM_001103184
UniProtQ68DA7
Other data
LocusChr. 15 q13-q14
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StructuresSwiss-model
DomainsInterPro
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Quick Facts Formin Homology Region 1, Identifiers ...
Formin Homology Region 1
Identifiers
SymbolDrf_FH1
PfamPF06346
InterProIPR009408
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
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Domain structure of formin proteins across phyla.[1]
Quick Facts Formin Homology 2 Domain, Identifiers ...
Formin Homology 2 Domain
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crystal structures of a formin homology-2 domain reveal a tethered-dimer architecture
Identifiers
SymbolFH2
PfamPF02181
InterProIPR015425
SMARTFH2
SCOP21ux5 / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
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Quick Facts Diaphanous FH3 Domain, Identifiers ...
Diaphanous FH3 Domain
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crystal structure of mdia1 gbd-fh3 in complex with rhoc-gmppnp
Identifiers
SymbolDrf_FH3
PfamPF06367
Pfam clanCL0020
InterProIPR010472
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
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Quick Facts DRF Autoregulatory Domain, Identifiers ...
DRF Autoregulatory Domain
Thumb
crystal structure of the n-terminal mdia1 armadillo repeat region and dimerisation domain in complex with the mdia1 autoregulatory domain (dad)
Identifiers
SymbolDrf_DAD
PfamPF06345
InterProIPR010465
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
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Quick Facts Diaphanous GTPase-binding Domain, Identifiers ...
Diaphanous GTPase-binding Domain
Thumb
crystal structure of mdia1 gbd-fh3 in complex with rhoc-gmppnp
Identifiers
SymbolDrf_GBD
PfamPF06371
Pfam clanCL0020
InterProIPR010473
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
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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.[6] By contrast, yeasts contain only 2-3 formins.[7]

Structure and interactions

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Perspective

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 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

References

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