Wiskott-Aldrich syndrome protein

Wiskott-Aldrich syndrome (eczema-thrombocytopenia)
PDB rendering based on 1cee.
Available structures: 1cee, 1ej5, 1t84
Identifiers
Symbol(s)	WAS; IMD2; THC; WASP
External IDs	OMIM: 300392 MGI: 105059 Homologene: 30970
Gene Ontology Molecular Function: • small GTPase regulator activity • identical protein binding Cellular Component: • vesicle membrane • actin cytoskeleton Biological Process: • protein complex assembly • defense response • immune response • blood coagulation • epidermis development • endosome transport • actin filament polymerization • actin filament-based movement • T cell activation
RNA expression pattern
More reference expression data
Orthologs
	Human	Mouse
Entrez	7454	22376
Ensembl	ENSG00000015285	ENSMUSG00000031165
Uniprot	P42768	Q53WY0
Refseq	NM_000377 (mRNA) NP_000368 (protein)	XM_976759 (mRNA) XP_981853 (protein)
Location	Chr X: 48.43 - 48.43 Mb	Chr X: 7.24 - 7.25 Mb
Pubmed search	[1]	[2]

The Wiskott-Aldrich Syndrome Protein (WASp) is a 502-amino acid protein that is expressed in cells of the hematopoietic system. In the inactive state, WASp exists in an auto-inhibited conformation with sequences near its C-terminus binding to a region near its N-terminus. Its activation is dependent upon Cdc42 and PIP2 acting to disrupt this interaction causing the WASp protein to 'open'. This exposes a domain near the WASp C-Terminus that binds to and activates the Arp2/3 complex. Activated Arp2/3 nucleates new F-actin. WASp is the founding member of a gene family which also includes the broadly expressed N-WASP (neuronal Wiskott-Aldrich Syndrome protein), and Scar.

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.^[1]

Genetic diseases associated with WASp

WASp is a product of the WAS gene and mutations in the WAS gene can lead to Wiskott-Aldrich syndrome (an X-linked disease that mainly affects males with symptoms that include thrombocytopenia, eczema, recurrent infections, and small-sized platelets). Other, less inactivating mutations affecting the WAS gene cause X-linked thrombocytopeia, or XLT.

See also

• cortactin

References

Further reading

External links

• Online 'Mendelian Inheritance in Man' (OMIM) 300392
• Online 'Mendelian Inheritance in Man' (OMIM) 313900
• MeSH Wiskott-Aldrich+Syndrome+Protein