PFN1

This gene encodes a member of the profilin family of small actin-binding proteins. The encoded protein plays an important role in actin dynamics by regulating actin polymerization in response to extracellular signals. Deletion of this gene is associated with Miller-Dieker syndrome, and the encoded protein may also play a role in Huntington disease. Multiple pseudogenes of this gene are located on chromosome 1. [provided by RefSeq, Jul 2012]

Full Name

Profilin 1

Function

Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG. Inhibits androgen receptor (AR) and HTT aggregation and binding of G-actin is essential for its inhibition of AR.

Biological Process

Actin cytoskeleton organizationIEA:InterPro
Modification of postsynaptic actin cytoskeletonIEA:Ensembl
Negative regulation of actin filament bundle assemblyManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of actin filament polymerizationManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of stress fiber assemblyManual Assertion Based On ExperimentIMP:UniProtKB
Neural tube closureIEA:Ensembl
Positive regulation of actin filament bundle assemblyManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of actin filament polymerizationManual Assertion Based On ExperimentIGI:UniProtKB
Positive regulation of ATP-dependent activityManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of epithelial cell migrationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of ruffle assemblyManual Assertion Based On ExperimentIMP:UniProtKB
Protein stabilizationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of actin filament polymerizationManual Assertion Based On ExperimentIBA:GO_Central
Regulation of transcription by RNA polymerase IIIEA:Ensembl
Synapse maturationIEA:Ensembl

Cellular Location

Cytoplasm, cytoskeleton

Involvement in disease

Amyotrophic lateral sclerosis 18 (ALS18):
A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.

PTM

Phosphorylation at Ser-138 reduces its affinity for G-actin and blocks its interaction with HTT, reducing its ability to inhibit androgen receptor (AR) and HTT aggregation.