Disease relevance of FMN1

• Within the screw mode, the formin dimer rotates with respect to the actin filament in the direction opposite to that generated by the stair-stepping mode so that a combination of the two modes prevents persistent torsion strain accumulation [1].
• Both the FMN domain and the soluble reductase are purified in partially reduced, colored form from the Escherichia coli expression system, either as a green reductase or a gray-blue FMN domain [2].
• Purification and characterization of a novel FMN-dependent enzyme. Membrane-bound L-(+)-pantoyl lactone dehydrogenase from Nocardia asteroides [3].
• Moreover, in the case of some algae and cyanobacteria, an FMN-dependent protein, flavodoxin (Fld), has been shown to replace Fd in this function [4].

High impact information on FMN1

• Further, a recent study suggested that profilin and ATP hydrolysis are both required for processive elongation mediated by the formin mDia1 [5].
• Wnt/Frizzled activation of Rho regulates vertebrate gastrulation and requires a novel Formin homology protein Daam1 [6].
• Regulators of the actin cytoskeleton, such as activators of formin and Rho GTPases, are transported to specific sites on the cortex by riding on the plus ends of microtubules [7].
• The Arp2/3 complex and its activator cortactin drive the assembly of branching actin-filament arrays, and formin-1 promotes the nucleation of non-branching actin filaments [8].
• Model of formin-associated actin filament elongation [9].

Biological context of FMN1

• Here, we identified the human FMN1 gene by using bioinformatics [10].
• The Xenopus fmn1 gene was identified within the Xenopus genome sequence CH216-24N20 (AC147835.1) [10].
• FMN1 isoform 1 (exons 1-18) and FMN isoform 2 (exons 1b and 3-18) were transcribed due to alternative splicing of the alternative promoter type [10].
• Formin homology proteins, implicated in organogenesis and carcinogenesis, are actin regulators with scaffold function [11].
• We assume that (1) FH2 domains are in rapid equilibrium among conformations that block or allow actin addition and that (2) profilin-actin is transferred rapidly to the barbed end from multiple profilin binding sites in formin FH1 domains [9].

Anatomical context of FMN1

• Our data suggest that DdVASP is complexed with dDia2 in filopodial tips and support formin-mediated filament elongation by bundling nascent actin filaments [12].
• Recent evidence indicates that the formin family proteins play a crucial role in the reorganization of the cytoskeleton [13].
• Formin' adherens junctions [14].
• Dorsal stress fibers, which are connected to the substrate via a focal adhesion at one end, are assembled through formin (mDia1/DRF1)-driven actin polymerization at focal adhesions [15].
• The Formin mDia Regulates GSK3beta through Novel PKCs to Promote Microtubule Stabilization but Not MTOC Reorientation in Migrating Fibroblasts [16].

Associations of FMN1 with chemical compounds

• However, constitutively active mutants of another Rho target, the formin homology protein mDia1 (Watanabe, N., T. Kato, A. Fujita, T. Ishizaki, and S. Narumiya. 1999. Nat. Cell Biol. 1:136-143), were sufficient to restore force-induced focal contact formation in C3 transferase-treated cells [17].
• Two arginine residues, Arg-181 and Arg-268, are conserved throughout the known family of FMN-containing enzymes that catalyze the oxidation of alpha-hydroxyacids [18].
• The replacement of Arg-268 by lysine also results in a slow conversion of the 8-CH(3)- substituent of FMN to yield 8-formyl-FMN, still tightly bound to the enzyme, and with significantly different physical and chemical properties from those of the FMN-enzyme [18].
• Microsomal P450s utilize an FAD/FMN reductase [19].
• Each flavin titrates through a blue semiquinone state, with the FMN semiquinone being most intense due to larger separation (approximately 200 mV) of its two couples [2].

Regulatory relationships of FMN1

• Formin proteins regulate the actin and microtubule cytoskeletons and also control the activity of the SRF transcription factor through depletion of the G-actin pool [20].

Other interactions of FMN1

• Exon-intron structure was conserved between FMN2 and FMN1 genes [21].
• Various multidomain proteins including members of the Ena/VASP and formin families localize profilin:actin complexes through profilin:poly-L-proline interactions to particular cytoskeletal locations (e.g. focal adhesions, cleavage furrows) [22].
• Formin homology 2 domain containing protein (FHOD1), a mammalian formin, regulates cytoskeletal architecture, enhances cell migration, and induces gene expression from the serum response element [23].
• A novel human gene from the Formin family, denominated human leukocyte formin gene, was cloned [24].
• Ureteric bud development and branching depends on the transcription factor Emx-2, the GDNF-cRet and probably the HGF/cMet, signalling systems, and the intracellular regulatory molecules formin IV and timeless [25].

Analytical, diagnostic and therapeutic context of FMN1

• Studies included brachial artery blood pressure (BP), aortic pulse wave velocity (PWV), B-mode ultrasonography and wave form analysis of the common carotid artery (CCA), with its conversion to the aortic wave formin [26].
• The lack of perturbation of the individual flavin potentials in the FAD and FMN domains indicates that the flavins are located in discrete environments and that these environments are not significantly disrupted by genetic dissection of the domains [2].
• A chemiluminescence (CL) detection of catecholamines [norepinephrine (NE), epinephrine (E), dopamine (DA) and l-dopa (LD)] is described for the flow-injection (FI) and high-performance liquid chromatographic (HPLC) determination of these compounds [27].
• Real-time PCR was used to study the expression pattern of formin genes [28].

References