WAS
Domain
The WH1 (Wasp homology 1) domain may bind a Pro-rich ligand.
The CRIB (Cdc42/Rac-interactive-binding) region binds to the C-terminal WH2 domain in the autoinhibited state of the protein. Binding of Rho-type GTPases to the CRIB induces a conformation change and leads to activation.
Function
Effector protein for Rho-type GTPases that regulates actin filament reorganization via its interaction with the Arp2/3 complex (PubMed:12235133, PubMed:12769847, PubMed:16275905). Important for efficient actin polymerization (PubMed:12235133, PubMed:16275905, PubMed:8625410). Possible regulator of lymphocyte and platelet function (PubMed:9405671). Mediates actin filament reorganization and the formation of actin pedestals upon infection by pathogenic bacteria (PubMed:18650809). In addition to its role in the cytoplasmic cytoskeleton, also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA (PubMed:20574068). Promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs) (PubMed:29925947).
Involvement in disease
Wiskott-Aldrich syndrome
WAS
An X-linked recessive immunodeficiency characterized by eczema, thrombocytopenia, recurrent infections, and bloody diarrhea. Death usually occurs before age 10.
None
The disease is caused by variants affecting the gene represented in this entry.
Thrombocytopenia 1
THC1
A form of thrombocytopenia, a hematologic disorder defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting.
None
The disease is caused by variants affecting the gene represented in this entry.
Neutropenia, severe congenital, X-linked
XLN
A disorder of hematopoiesis characterized by maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylated at Tyr-291 by FYN and HCK, inducing WAS effector activity after TCR engagement. Phosphorylation at Tyr-291 enhances WAS activity in promoting actin polymerization and filopodia formation.
Tissue Specificity
Expressed predominantly in the thymus. Also found, to a much lesser extent, in the spleen.
Cellular localization
- Cytoplasm
- Cytoskeleton
- Nucleus
Alternative names
IMD2, WAS, Actin nucleation-promoting factor WAS, Wiskott-Aldrich syndrome protein, WASp