Profilin 1

Profilin-1 is a protein that in humans is encoded by the ''PFN1'' gene.

Structure

The PFN1 protein, also known as profilin-1, is a small, monomeric protein composed of 139–140 amino acids with a molecular mass of approximately 15 kDa. Its three-dimensional structure features an antiparallel, seven-stranded β-sheet core flanked by three amphipathic α-helices—two on one side of the sheet and one on the other—forming a compact, globular fold known as the "profilin-like" fold. PFN1 contains three key functional domains: an actin-binding domain, a poly-L-proline (PLP)-binding domain, and a phosphoinositide-binding domain. These domains enable PFN1 to interact with actin monomers, polyproline-rich motifs in various cytoskeletal proteins, and phosphoinositides, respectively, facilitating its central role in actin cytoskeleton dynamics. Structural studies, including NMR and X-ray crystallography, have shown that PFN1’s binding sites for actin and PLP are distinct and flexible, allowing the protein to adopt different conformations when free or bound to its ligands. This structural versatility is essential for PFN1’s function in actin polymerization and its involvement in numerous cellular processes.

Function

The protein encoded by this gene is a ubiquitously expressed actin monomer-binding protein belonging to the profilin family. It is believed to regulate actin polymerization in response to extracellular signals. Profilin-1 also functions as a pseudouridine-binding protein, contributing to the stability and translational efficiency of certain mRNAs.

Profilin 1 (PFN1) is a highly conserved actin-binding protein that plays a central role in regulating actin polymerization and, consequently, the dynamics of the actin cytoskeleton. By binding actin monomers, PFN1 promotes their incorporation into growing actin filaments, thereby influencing key cellular processes such as cell motility, membrane trafficking, endocytosis, cell cycle progression, and cell survival.

In addition to its canonical role in actin dynamics, PFN1 interacts with poly-L-proline–rich motifs found in various signaling and cytoskeletal proteins, as well as with phosphoinositide lipids, thereby linking cytoskeletal regulation to intracellular signaling pathways. Recent studies have expanded the known functions of PFN1 to include roles in microtubule organization, mitochondrial homeostasis, and the regulation of autophagy and mitophagy.

Disruption of PFN1 function through mutation or loss has been implicated in several diseases, including neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), as well as various cancers and cardiovascular conditions. PFN1 thus acts as a key integrator of cytoskeletal dynamics and intracellular signaling, playing a critical role in maintaining normal cell function and viability.

Clinical significance

Deletion of this gene is associated with Miller-Dieker syndrome. Mutations in this gene may be a rare cause of amyotrophic lateral sclerosis, also called Lou Gehrig's disease.

Interactions

Profilin 1 has been shown to interact with:
* FMNL1,
* MLLT4
* Vasodilator-stimulated phosphoprotein,
* WASF1, and
* WASL.

References

Further reading

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{{Cytoskeletal Proteins