Q91YD9
SS
Gene name |
Wasl |
Protein name |
Actin nucleation-promoting factor WASL |
Names |
Neural Wiskott-Aldrich syndrome protein , N-WASP |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:73178 |
EC number |
|
Protein Class |
|
Descriptions
Members of the Wiskott-Aldrich syndrome protein (WASP) family link Rho GTPase signaling pathways to the cytoskeleton through a multiprotein assembly called Arp2/3 complex. The family includes WASP, the widely expressed neuronal-WASP (N-WASP), and several Scar/WAVE proteins. The C-terminal VCA regions (verprolin-homology, central hydrophobic, and acidic regions) of WASP and its relatives stimulate Arp2/3 complex to nucleate actin filament branches. In the autoinhibition model, the C (central) region of the VCA is sequestered by the Rho GTPase-binding Cdc42/Rac-interactive binding (CRIB) domain. Destabilization of the CRIB-VCA contact by Cdc42 binding increases the exposure of the C region, which enhances its interaction with the Arp2/3 complex and induces its activation.
Autoinhibitory domains (AIDs)
Target domain |
462-481 (Central region in the C-terminal VCA domain) |
Relief mechanism |
Partner binding |
Assay |
|
Accessory elements
No accessory elements
References
- Peterson JR et al. (2004) "Autoinhibited proteins as promising drug targets", Journal of cellular biochemistry, 93, 68-73
- 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
- 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
- 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
- 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
Autoinhibited structure
Activated structure
3 structures for Q91YD9
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| 3M3N | X-ray | 700 A | W | 397-474 | PDB |
| 6UHC | EM | 390 A | H/I | 1-501 | PDB |
| AF-Q91YD9-F1 | Predicted | AlphaFoldDB |
19 variants for Q91YD9
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3388818702 | 53 | M>E | No | EVA | |
| rs3388797955 | 106 | T>I | No | EVA | |
| rs3388824934 | 132 | T>K | No | EVA | |
| rs3544110938 | 155 | P>L | No | EVA | |
| rs3388817369 | 174 | S>P | No | EVA | |
| rs3388785406 | 214 | W>R | No | EVA | |
| rs3388817361 | 218 | T>I | No | EVA | |
| rs3544122672 | 268 | E>K | No | EVA | |
| rs3544073229 | 298 | P>T | No | EVA | |
| rs3544102286 | 376 | P>L | No | EVA | |
| rs217795354 | 391 | G>D | No | EVA | |
| rs241019471 | 391 | G>S | No | EVA | |
| rs3388806334 | 395 | V>A | No | EVA | |
| rs3388817344 | 403 | A>T | No | EVA | |
| rs260885695 | 453 | T>S | No | EVA | |
| rs236060608 | 454 | P>A | No | EVA | |
| rs3396541534 | 456 | T>S | No | EVA | |
| rs212804173 | 461 | S>A | No | EVA | |
| rs37549990 | 490 | E>D | No | EVA |
No associated diseases with Q91YD9
4 regional properties for Q91YD9
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Protein kinase domain | 1332 - 1590 | IPR000719 |
| active_site | Serine/threonine-protein kinase, active site | 1448 - 1460 | IPR008271 |
| binding_site | Protein kinase, ATP binding site | 1338 - 1361 | IPR017441 |
| domain | Mitogen-activated protein kinase kinase kinase, N-terminal | 44 - 1257 | IPR045801 |
Functions
10 GO annotations of cellular component
| Name | Definition |
|---|---|
| actin cap | Polarized accumulation of cytoskeletal proteins (including F-actin) and regulatory proteins in a cell. An example of this is the actin cap found in Saccharomyces cerevisiae. |
| cell leading edge | The area of a motile cell closest to the direction of movement. |
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| cytoplasmic vesicle | A vesicle found in the cytoplasm of a cell. |
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| glutamatergic synapse | A synapse that uses glutamate as a neurotransmitter. |
| Golgi membrane | The lipid bilayer surrounding any of the compartments of the Golgi apparatus. |
| lamellipodium | A thin sheetlike process extended by the leading edge of a migrating cell or extending cell process; contains a dense meshwork of actin filaments. |
| 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. |
| postsynapse | The part of a synapse that is part of the post-synaptic cell. |
3 GO annotations of molecular function
| Name | Definition |
|---|---|
| actin binding | Binding to monomeric or multimeric forms of actin, including actin filaments. |
| cytoskeletal protein binding | Binding to a protein component of a cytoskeleton (actin, microtubule, or intermediate filament cytoskeleton). |
| identical protein binding | Binding to an identical protein or proteins. |
24 GO annotations of biological process
| Name | Definition |
|---|---|
| actin cytoskeleton organization | A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising actin filaments and their associated proteins. |
| actin filament polymerization | Assembly of actin filaments by the addition of actin monomers to a filament. |
| actin nucleation | The initial step in the formation of an actin filament, in which actin monomers combine to form a new filament. Nucleation is slow relative to the subsequent addition of more monomers to extend the filament. |
| cell division | The process resulting in division and partitioning of components of a cell to form more cells; may or may not be accompanied by the physical separation of a cell into distinct, individually membrane-bounded daughter cells. |
| dendritic spine morphogenesis | The process in which the anatomical structures of a dendritic spine are generated and organized. A dendritic spine is a protrusion from a dendrite and a specialized subcellular compartment involved in synaptic transmission. |
| membrane invagination | The infolding of a membrane. |
| negative regulation of lymphocyte migration | Any process that stops, prevents or reduces the frequency, rate or extent of lymphocyte migration. |
| negative regulation of membrane tubulation | Any process that stops, prevents or reduces the frequency, rate or extent of membrane tubulation. |
| plasma membrane tubulation | A membrane tubulation process occurring in a plasma membrane. |
| positive regulation of chemotaxis | Any process that activates or increases the frequency, rate or extent of the directed movement of a motile cell or organism in response to a specific chemical concentration gradient. |
| positive regulation of clathrin-dependent endocytosis | Any process that activates or increases the frequency, rate or extent of clathrin-mediated endocytosis. |
| positive regulation of filopodium assembly | Any process that activates or increases the frequency, rate or extent of the assembly of a filopodium, a thin, stiff protrusion extended by the leading edge of a motile cell such as a crawling fibroblast or amoeba, or an axonal growth cone. |
| 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. |
| postsynapse organization | A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of a postsynapse. |
| postsynaptic actin cytoskeleton organization | A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising actin filaments and their associated proteins in the postsynaptic actin cytoskeleton. |
| protein-containing complex localization | A localization process that acts on a protein complex; the complex is transported to, or maintained in, a specific location. |
| regulation of cell projection assembly | Any process that modulates the rate, frequency, or extent of cell projection assembly. |
| regulation of postsynapse organization | Any process that modulates the physical form of a postsynapse. |
| regulation of protein localization | Any process that modulates the frequency, rate or extent of any process in which a protein is transported to, or maintained in, a specific location. |
| response to bacterium | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a bacterium. |
| spindle localization | Any process in which is the spindle is transported to, and/or maintained in, a specific location. |
| vesicle budding from membrane | The evagination of a membrane, resulting in formation of a vesicle. |
| vesicle organization | A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of a vesicle. |
| vesicle transport along actin filament | Movement of a vesicle along an actin filament, mediated by motor proteins. |
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 |
| P70315 | Was | Wiskott-Aldrich syndrome protein homolog | Mus musculus (Mouse) | SS |
| O08816 | Wasl | Actin nucleation-promoting factor WASL | Rattus norvegicus (Rat) | EV |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MSSGQQPPRR | VTNVGSLLLT | PQENESLFSF | LGKKCVTMSS | AVVQLYAADR | NCMWAKKCSG |
| 70 | 80 | 90 | 100 | 110 | 120 |
| VACLVKDNPQ | RSYFLRIFDI | KDGKLLWEQE | LYNNFVYNSP | RGYFHTFAGD | TCQVALNFAN |
| 130 | 140 | 150 | 160 | 170 | 180 |
| EEEAKKFRKA | VTDLLGRRQR | KSEKRRDAPN | GPNLPMATVD | IKNPEITTNR | FYGSQVNNIS |
| 190 | 200 | 210 | 220 | 230 | 240 |
| HTKEKKKGKA | KKKRLTKADI | GTPSNFQHIG | HVGWDPNTGF | DLNNLDPELK | NLFDMCGISE |
| 250 | 260 | 270 | 280 | 290 | 300 |
| AQLKDRETSK | VIYDFIEKTG | GVEAVKNELR | RQAPPPPPPS | RGGPPPPPPP | PHSSGPPPPP |
| 310 | 320 | 330 | 340 | 350 | 360 |
| ARGRGAPPPP | PSRAPTAAPP | PPPPSRPGVV | VPPPPPNRMY | PPPPPALPSS | APSGPPPPPP |
| 370 | 380 | 390 | 400 | 410 | 420 |
| PSMAGSTAPP | PPPPPPPPPG | PPPPPGLPSD | GDHQVPAPSG | NKAALLDQIR | EGAQLKKVEQ |
| 430 | 440 | 450 | 460 | 470 | 480 |
| NSRPVSCSGR | DALLDQIRQG | IQLKSVSDGQ | ESTPPTPAPT | SGIVGALMEV | MQKRSKAIHS |
| 490 | 500 | ||||
| SDEDEDDDDE | EDFEDDDEWE | D |