Wiskott-Aldrich syndrome protein (IPR027641)

Short name: WASP

Overlapping homologous superfamilies


Family relationships



This entry represents the Wiskott-Aldrich syndrome protein (WASP). The WASP proteins signal to the cytoskeleton through the Arp2/3 complex, an actin-nucleating assembly that regulates the structure and dynamics of actin filament networks at the leading edge of the cell [PMID: 18650809]. The activity of WASP can be regulated by the Rho-family GTPase, Cdc42 [PMID: 10724160]. Mutations in WASP lead to the Wiskott-Aldrich syndrome, a paediatric disorder characterised by actin cytoskeletal defects in haematopoietic cells, leading clinically to thrombocytopenia, eczema and immunodeficiency [PMID: 8643625].

Similar to mammalian WASP proteins, Wsp1 and Las17 also has a role in regulating actin assembly [PMID: 11076964, PMID: 10512884]. In Saccharomyces cerevisiae, Las17 is the primary activator of Arp2/3-driven actin nucleation and is required for membrane invagination during endocytosis [PMID: 23290554]. Las17 can also nucleate actin filaments independently of Arp2/3 through its polyproline domain [PMID: 23290554].

WASP family members have unique N-terminal regions, followed by a central segment rich in proline, and a common C-terminal region. Their conserved C-terminal VCA domain consists of two WH2 (WASP homology 2) domains ("V" referring to either a single or multiple WH2 domains), followed by a connector domain ("C") and an acidic short extension ("A"). In the VCA region, the WH2 domain(s) bind G-actin, whereas the CA domain binds Arp2/3 complex [PMID: 22847007]. Their distinct N-terminal region enables family members to activate Arp2/3 in response to different upstream signals.

GO terms

Biological Process

GO:0007015 actin filament organization
GO:2000601 positive regulation of Arp2/3 complex-mediated actin nucleation

Molecular Function

GO:0003779 actin binding

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.