WASF1

The protein encoded by this gene, a member of the Wiskott-Aldrich syndrome protein (WASP)-family, plays a critical role downstream of Rac, a Rho-family small GTPase, in regulating the actin cytoskeleton required for membrane ruffling. It has been shown to associate with an actin nucleation core Arp2/3 complex while enhancing actin polymerization in vitro. Wiskott-Aldrich syndrome is a disease of the immune system, likely due to defects in regulation of actin cytoskeleton. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene.

Full Name

WAS protein family, member 1

Function

Downstream effector molecule involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton. Promotes formation of actin filaments. Part of the WAVE complex that regulates lamellipodia formation (PubMed:29961568).
The WAVE complex regulates actin filament reorganization via its interaction with the Arp2/3 complex (By similarity).
As component of the WAVE1 complex, required for BDNF-NTRK2 endocytic trafficking and signaling from early endosomes (By similarity).
Also involved in the regulation of mitochondrial dynamics (PubMed:29961568).

Biological Process

Biological Process actin cytoskeleton organization Source:UniProtKB1 Publication
Biological Process actin filament polymerization Source:ProtInc1 Publication
Biological Process cellular response to brain-derived neurotrophic factor stimulus Source:UniProtKB
Biological Process dendrite extension Source:Ensembl
Biological Process dendritic transport of mitochondrion Source:Ensembl
Biological Process lamellipodium morphogenesis Source:UniProtKB1 Publication
Biological Process mitochondrion morphogenesis Source:UniProtKB1 Publication
Biological Process modification of postsynaptic actin cytoskeleton Source:Ensembl
Biological Process positive regulation of Arp2/3 complex-mediated actin nucleation Source:UniProtKB1 Publication
Biological Process positive regulation of neurotrophin TRK receptor signaling pathway Source:Ensembl
Biological Process protein-containing complex assembly Source:ProtInc1 Publication
Biological Process Rac protein signal transduction Source:UniProtKB1 Publication
Biological Process receptor-mediated endocytosis Source:UniProtKB

Cellular Location

Cytoplasm, cytoskeleton
Synapse
Cell junction, focal adhesion
Dot-like pattern in the cytoplasm. Concentrated in Rac-regulated membrane-ruffling areas (PubMed:9889097).
Partial translocation to focal adhesion sites might be mediated by interaction with SORBS2 (PubMed:18559503).
In neurons, colocalizes with activated NTRK2 after BDNF addition in endocytic sites through the association with TMEM108 (By similarity).

Involvement in disease

Neurodevelopmental disorder with absent language and variable seizures (NEDALVS):
A disorder characterized by neurodevelopmental abnormalities, including moderate to profound intellectual disability, with autistic features, seizures, severe impairments in speech, and gross motor delay.

PTM

Phosphorylated on tyrosine residues by ABL1 and dephosphorylated by PTPN12.