P70315
SS
Gene name |
Was (Wasp) |
Protein name |
Wiskott-Aldrich syndrome protein homolog |
Names |
WASp |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:22376 |
EC number |
|
Protein Class |
|
Descriptions
The Rho-family GTPase, Cdc42, can regulate the actin cytoskeleton through activation of Wiskott-Aldrich syndrome protein (WASP) family members. Activation relieves an autoinhibitory contact between the GTPase-binding domain and the carboxyterminal region of WASP proteins. In the autoinhibited complex of human WASP (P42768), intramolecular interactions with the GTPase-binding domain occlude residues of the C terminal VCA domain that regulates the Arp2/3 actin-nucleating complex. Binding of Cdc42 to the GTPase-binding domain causes a dramatic conformational change, resulting in disruption of the hydrophobic core and release of the C terminus, enabling its interaction with the actin regulatory machinery.
Autoinhibitory domains (AIDs)
Target domain |
465-484 (Central region in the C-terminal VCA domain) |
Relief mechanism |
Partner binding |
Assay |
|
Accessory elements
No accessory elements
References
- Kim AS et al. (2000) "Autoinhibition and activation mechanisms of the Wiskott-Aldrich syndrome protein", Nature, 404, 151-8
- Padrick SB et al. (2010) "Physical mechanisms of signal integration by WASP family proteins", Annual review of biochemistry, 79, 707-35
- Papayannopoulos V et al. (2005) "A polybasic motif allows N-WASP to act as a sensor of PIP(2) density", Molecular cell, 17, 181-91
- Prehoda KE et al. (2000) "Integration of multiple signals through cooperative regulation of the N-WASP-Arp2/3 complex", Science (New York, N.Y.), 290, 801-6
- Pinyol R et al. (2007) "Regulation of N-WASP and the Arp2/3 complex by Abp1 controls neuronal morphology", PloS one, 2, e400
- Panchal SC et al. (2003) "A conserved amphipathic helix in WASP/Scar proteins is essential for activation of Arp2/3 complex", Nature structural biology, 10, 591-8
- Padrick SB et al. (2008) "Hierarchical regulation of WASP/WAVE proteins", Molecular cell, 32, 426-38
- Cheng HC et al. (2008) "Structural mechanism of WASP activation by the enterohaemorrhagic E. coli effector EspF(U)", Nature, 454, 1009-13
- Peterson JR et al. (2004) "Autoinhibited proteins as promising drug targets", Journal of cellular biochemistry, 93, 68-73
- Mauricio RP et al. (2017) "The Shigella Virulence Factor IcsA Relieves N-WASP Autoinhibition by Displacing the Verprolin Homology/Cofilin/Acidic (VCA) Domain", The Journal of biological chemistry, 292, 134-145
Autoinhibited structure
Activated structure
1 structures for P70315
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-P70315-F1 | Predicted | AlphaFoldDB |
6 variants for P70315
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs216086976 | 20 | V>I | No | Ensembl | |
| rs222994590 | 114 | P>Q | No | Ensembl | |
| rs248193481 | 162 | P>L | No | Ensembl | |
| rs212170025 | 184 | G>S | No | Ensembl | |
| rs580128145 | 343 | P>L | No | Ensembl | |
| rs223221022 | 514 | E>D | No | Ensembl |
No associated diseases with P70315
8 GO annotations of cellular component
| Name | Definition |
|---|---|
| actin filament | A filamentous structure formed of a two-stranded helical polymer of the protein actin and associated proteins. Actin filaments are a major component of the contractile apparatus of skeletal muscle and the microfilaments of the cytoskeleton of eukaryotic cells. The filaments, comprising polymerized globular actin molecules, appear as flexible structures with a diameter of 5-9 nm. They are organized into a variety of linear bundles, two-dimensional networks, and three dimensional gels. In the cytoskeleton they are most highly concentrated in the cortex of the cell just beneath the plasma membrane. |
| cell-cell junction | A cell junction that forms a connection between two or more cells of an organism; excludes direct cytoplasmic intercellular bridges, such as ring canals in insects. |
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| nucleus | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. |
| phagocytic vesicle | A membrane-bounded intracellular vesicle that arises from the ingestion of particulate material by phagocytosis. |
| plasma membrane | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. |
| site of double-strand break | A region of a chromosome at which a DNA double-strand break has occurred. DNA damage signaling and repair proteins accumulate at the lesion to respond to the damage and repair the DNA to form a continuous DNA helix. |
| vesicle membrane | The lipid bilayer surrounding any membrane-bounded vesicle in the cell. |
6 GO annotations of molecular function
| Name | Definition |
|---|---|
| actin binding | Binding to monomeric or multimeric forms of actin, including actin filaments. |
| identical protein binding | Binding to an identical protein or proteins. |
| phospholipase binding | Binding to a phospholipase. |
| protein kinase binding | Binding to a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate. |
| SH3 domain binding | Binding to a SH3 domain (Src homology 3) of a protein, small protein modules containing approximately 50 amino acid residues found in a great variety of intracellular or membrane-associated proteins. |
| small GTPase binding | Binding to a small monomeric GTPase. |
17 GO annotations of biological process
| Name | Definition |
|---|---|
| actin filament polymerization | Assembly of actin filaments by the addition of actin monomers to a filament. |
| actin filament-based movement | Movement of organelles or other particles along actin filaments, or sliding of actin filaments past each other, mediated by motor proteins. |
| actin polymerization or depolymerization | Assembly or disassembly of actin filaments by the addition or removal of actin monomers from a filament. |
| Cdc42 protein signal transduction | The series of molecular signals within the cell that are mediated by the Cdc42 protein switching to a GTP-bound active state. |
| cellular response to interferon-gamma | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interferon-gamma stimulus. Interferon gamma is the only member of the type II interferon found so far. |
| endosomal transport | The directed movement of substances mediated by an endosome, a membrane-bounded organelle that carries materials enclosed in the lumen or located in the endosomal membrane. |
| immune response | Any immune system process that functions in the calibrated response of an organism to a potential internal or invasive threat. |
| negative regulation of cell motility | Any process that stops, prevents, or reduces the frequency, rate or extent of cell motility. |
| negative regulation of stress fiber assembly | Any process that stops, prevents, or reduces the frequency, rate or extent of the assembly a stress fiber, a bundle of microfilaments and other proteins found in fibroblasts. |
| positive regulation of Arp2/3 complex-mediated actin nucleation | Any process that activates or increases the frequency, rate or extent of Arp2/3 complex-mediated actin nucleation. |
| positive regulation of double-strand break repair via homologous recombination | Any process that activates or increases the frequency, rate or extent of double-strand break repair via homologous recombination. |
| positive regulation of transcription by RNA polymerase II | Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter. |
| regulation of actin polymerization or depolymerization | Any process that modulates the frequency, rate or extent of the assembly or disassembly of actin filaments by the addition or removal of actin monomers from a filament. |
| regulation of lamellipodium assembly | Any process that modulates the rate, frequency or extent of the formation of a lamellipodium, a thin sheetlike extension of the surface of a migrating cell. |
| regulation of stress fiber assembly | Any process that modulates the frequency, rate or extent of the assembly of a stress fiber, a bundle of microfilaments and other proteins found in fibroblasts. |
| regulation of T cell antigen processing and presentation | Any process that modulates the frequency, rate, or extent of T cell antigen processing and presentation. |
| T cell activation | The change in morphology and behavior of a mature or immature T cell resulting from exposure to a mitogen, cytokine, chemokine, cellular ligand, or an antigen for which it is specific. |
5 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q95107 | WASL | Actin nucleation-promoting factor WASL | Bos taurus (Bovine) | SS |
| O00401 | WASL | Actin nucleation-promoting factor WASL | Homo sapiens (Human) | EV |
| P42768 | WAS | Wiskott-Aldrich syndrome protein | Homo sapiens (Human) | EV |
| Q91YD9 | Wasl | Actin nucleation-promoting factor WASL | Mus musculus (Mouse) | SS |
| O08816 | Wasl | Actin nucleation-promoting factor WASL | Rattus norvegicus (Rat) | EV |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MNSGPGPVGG | RPGGRGGPAV | QQNIPSNLLQ | DHENQRLFEL | LGRKCWTLAT | TVVQLYLALP |
| 70 | 80 | 90 | 100 | 110 | 120 |
| PGAEHWTMEH | CGAVCFVKDN | PQKSYFIRLY | GLQAGRLLWE | QELYSQLVYL | TPTPFFHTFA |
| 130 | 140 | 150 | 160 | 170 | 180 |
| GDDCQVGLNF | ADESEAQAFR | ALVQEKIQKR | NQRQSGERRQ | LPPPPAPINE | ERRGGLPPVP |
| 190 | 200 | 210 | 220 | 230 | 240 |
| PHPGGDHGGP | SGGPLSLGLV | TVDIQNPDIT | SSRYRGLPAP | GPGPTDKKRS | GKKKISKADI |
| 250 | 260 | 270 | 280 | 290 | 300 |
| GAPSGFKHVS | HVGWDPQNGF | DVNNLDPDLR | SLFSRAGISE | AQLTDAETSK | LIYDFIEDQG |
| 310 | 320 | 330 | 340 | 350 | 360 |
| GLEAVRQEMR | RQEPLPPPPP | PCRGGGGGGG | GGGGGGGGGG | GQPLRPPVVG | SNKGRSGPLP |
| 370 | 380 | 390 | 400 | 410 | 420 |
| PVPMGGAPPP | PTPRGPPPPG | RGGPPPPPPP | ATGRSGPPPP | PLPGAGGPPA | PPPPPPPPPP |
| 430 | 440 | 450 | 460 | 470 | 480 |
| PPCPGSGPAP | PPLPPTPVSG | GSPAPGGGRG | ALLDQIRQGI | QLNKTPGALE | NSVQQPPAQQ |
| 490 | 500 | 510 | |||
| SEGLVGALMH | VMQKRSRVIH | SSDEGEDQTG | EDEEDDEWDD |