Wiskott-Aldrich Syndrome Neural Protein

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Wiskott-Aldrich Syndrome Neural Protein
Wiskott-Aldrich Syndrome Neural Protein
according to PDB  2FF3
other names

N-WASP

Existing structural data : PDB  2LNH , PDB  2VCP

Properties of human protein
Mass / length primary structure 505 amino acids , 54,827 Da
Identifier
Gene name WASL
External IDs
Orthologue
human House mouse
Entrez 8976 73178
Ensemble ENSG00000106299 ENSMUSG00000029684
UniProt O00401 Q91YD9
Refseq (mRNA) NM_003941 NM_001167745
Refseq (protein) NP_003932 NP_001161217
Gene locus Chr 7: 123.68 - 123.75 Mb Chr 6: 24.61 - 24.66 Mb
PubMed search 8976 73178

The neural Wiskott-Aldrich syndrome protein , abbreviated N-WASP, is a regulatory protein from the family of Wiskott-Aldrich syndrome proteins , which is encoded in humans by the WASL gene on the seventh chromosome . It is particularly expressed in nerve tissue.

Structure and function

N-WASP exerts like all proteins of the WASP / WAVE family a function in the regulation of actin cytoskeleton out by the Arp 2/3 complex regulated in its activity and so the actin nucleation affected. At the C terminus there is a highly conserved VCA domain (VCA for Verproline homology, Coflin homology and acidic section), which is used to recur and activate the complex. If you go in the direction of the N terminus , you will find a proline-rich ( PPP ) region, a binding domain for Rho-GTPases ( GBD ), a basic region and the WH1 (WASP homology) domain, which connects the protein to the WASP proteins within the WASP-WAVE family. This WH1 domain can be attached to proline-rich regions, e.g. B. bind in the WASP-interacting protein ( WIP ). The GBD domain can bind directly with the Cdc42 activated .

There are several models of protein and its activation. The most common one assumes that the protein is in an autoinhibitory ground state. The binding of CDC42, of signal proteins carrying SH3 domains and of PIP2 have a positive effect on the activation probability of N-WASP, and the protein can open. Recent studies also suggest an influence of WIP (WASP-interacting protein).

By regulating the Arp 2/3 complex, neural WASP takes part in mitosis and cytokinesis . It also binds to the transcription factor HSF1 / HSTF1 ( heat shock transcription factor ) and forms HSE-promoter complexes that down-regulate the transcription of HSP90 .

Mutations that cause Wiskott-Aldrich syndrome are found more frequently in the VCA domain. By gene targeting induced deletions of the gene in the mouse are embryonic lethal.

Web links

Individual evidence

  1. ↑ WASL
  2. ↑ a b actin dynamics and WASP / WAVE proteins (PDF). biospektrum.de. Retrieved August 7, 2016.
  3. ↑ UniProt O00401
  4. ↑ S. Suetsugu, T. Takenawa: Translocation of N-WASP by Nuclear Localization and export signal into the nucleus modulates expression of HSP90. In: Journal of Biological Chemistry. 278, 2003, p. 42515, doi : 10.1074 / jbc.M302177200 .
  5. ↑ Scott B. Snapper, Fuminao Takeshima, Inés Antón, Ching-Hui Liu, Sheila M. Thomas, Deanna Nguyen, Darryll Dudley, Hunter Fraser, Daniel Purich, Marco Lopez-Ilasaca, Christoph Klein, Laurie Davidson, Roderick Bronson, Richard C Mulligan, Fred Southwick, Raif Geha, Marcia B. Goldberg, Fred S. Rosen, John H. Hartwig, Frederick W. Alt: N-WASP deficiency reveals distinct pathways for cell surface projections and microbial actin-based motility. In: Nature Cell Biology. 3, p. 897, doi : 10.1038 / ncb1001-897 .