WAS

The Wiskott-Aldrich syndrome (WAS) family of proteins share similar domain structure, and are involved in transduction of signals from receptors on the cell surface to the actin cytoskeleton. The presence of a number of different motifs suggests that they are regulated by a number of different stimuli, and interact with multiple proteins. Recent studies have demonstrated that these proteins, directly or indirectly, associate with the small GTPase, Cdc42, known to regulate formation of actin filaments, and the cytoskeletal organizing complex, Arp2/3. Wiskott-Aldrich syndrome is a rare, inherited, X-linked, recessive disease characterized by immune dysregulation and microthrombocytopenia, and is caused by mutations in the WAS gene. The WAS gene product is a cytoplasmic protein, expressed exclusively in hematopoietic cells, which show signalling and cytoskeletal abnormalities in WAS patients. A transcript variant arising as a result of alternative promoter usage, and containing a different 5' UTR sequence, has been described, however, its full-length nature is not known. [provided by RefSeq]

Wiskott-Aldrich syndrome (eczema-thrombocytopenia)

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:8625410, PubMed:12235133, PubMed:16275905).
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).

Biological Process actin filament polymerization Source:UniProtKB1 Publication
Biological Process actin filament-based movement Source:GO_Central1 Publication
Biological Process actin polymerization or depolymerization Source:ProtInc1 Publication
Biological Process blood coagulation Source:ProtInc1 Publication
Biological Process Cdc42 protein signal transduction Source:CAFA1 Publication
Biological Process cellular response to type II interferon Source:Ensembl
Biological Process defense response Source:ProtInc1 Publication
Biological Process endosomal transport Source:Ensembl
Biological Process epidermis development Source:ProtInc1 Publication
Biological Process immune response Source:HGNC-UCL1 Publication
Biological Process negative regulation of cell motility Source:CACAO1 Publication
Biological Process negative regulation of stress fiber assembly Source:CAFA1 Publication
Biological Process positive regulation of Arp2/3 complex-mediated actin nucleation Source:InterPro
Biological Process positive regulation of double-strand break repair via homologous recombination Source:UniProtKB1 Publication
Biological Process positive regulation of transcription by RNA polymerase II Source:UniProtKB1 Publication
Biological Process protein-containing complex assembly Source:ProtInc1 Publication
Biological Process regulation of actin polymerization or depolymerization Source:CAFA1 Publication
Biological Process regulation of lamellipodium assembly Source:CAFA2 Publications
Biological Process regulation of stress fiber assembly Source:CAFA2 Publications
Biological Process regulation of T cell antigen processing and presentation Source:CACAO1 Publication
Biological Process T cell activation Source:Ensembl

Cytoplasm, cytoskeleton
Nucleus

Wiskott-Aldrich syndrome (WAS):
An X-linked recessive immunodeficiency characterized by eczema, thrombocytopenia, recurrent infections, and bloody diarrhea. Death usually occurs before age 10.
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.
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.

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.