Profilin 1

PFN1
Identifiers
Aliases	PFN1, ALS18, Profilin 1
External IDs	OMIM: 176610; MGI: 97549; GeneCards: PFN1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1AWI, 1CF0, 1CJF, 1FIK, 1FIL, 1PFL, 2PAV, 2PBD, 3CHW, 4X1L, 4X1M, 4X25
Gene location (Human) Chr. Chromosome 17 (human) Band 17p13.2 Start 4,945,652 bp End 4,949,061 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11 B3|11 43.21 cM Start 70,542,676 bp End 70,545,470 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte mucosa of transverse colon muscle layer of sigmoid colon mucosa of ileum monocyte thoracic aorta ascending aorta stromal cell of endometrium Descending thoracic aorta left coronary artery Top expressed in granulocyte yolk sac tail of embryo thymus tibiofemoral joint lymph node mesenteric lymph nodes genital tubercle epiblast ascending aorta More reference expression data BioGPS More reference expression data
Gene ontology Molecular function actin monomer binding protein binding adenyl-nucleotide exchange factor activity actin binding proline-rich region binding RNA binding cadherin binding signaling receptor binding phosphatidylinositol-4,5-bisphosphate binding Cellular component cytosol blood microparticle membrane focal adhesion cell cortex extracellular exosome cytoskeleton cytoplasm nucleus extracellular space neuron projection synapse glutamatergic synapse Biological process positive regulation of actin filament polymerization positive regulation of ATP-dependent activity negative regulation of actin filament polymerization positive regulation of ruffle assembly regulation of transcription by RNA polymerase II protein stabilization positive regulation of epithelial cell migration negative regulation of actin filament bundle assembly neural tube closure positive regulation of actin filament bundle assembly negative regulation of stress fiber assembly actin cytoskeleton organization Wnt signaling pathway, planar cell polarity pathway response to organic substance positive regulation of transcription by RNA polymerase II positive regulation of viral transcription positive regulation of DNA metabolic process positive regulation of stress fiber assembly cellular response to growth factor stimulus regulation of actin filament polymerization synapse maturation modification of postsynaptic actin cytoskeleton Sources:Amigo / QuickGO
Orthologs Databases NCBI: entry; OMA: entry Species Human Mouse Entrez 5216 18643 Ensembl ENSG00000108518 ENSMUSG00000018293 UniProt P07737 P62962 RefSeq (mRNA) NM_005022 NM_001375991 NM_011072 RefSeq (protein) NP_005013 NP_001362920 NP_035202 Location (UCSC) Chr 17: 4.95 – 4.95 Mb Chr 11: 70.54 – 70.55 Mb PubMed search
Wikidata
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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