Q95107
SS
Gene name |
WASL |
Protein name |
Actin nucleation-promoting factor WASL |
Names |
Neural Wiskott-Aldrich syndrome protein , N-WASP |
Species |
Bos taurus (Bovine) |
KEGG Pathway |
bta:281577 |
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 |
466-485 (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
1 structures for Q95107
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-Q95107-F1 | Predicted | AlphaFoldDB |
68 variants for Q95107
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs471375396 | 2 | S>C | No | EVA | |
| rs471375396 | 2 | S>G | No | EVA | |
| rs453156464 | 3 | S>A | No | EVA | |
| rs453156464 | 3 | S>P | No | EVA | |
| rs441108618 | 5 | Q>* | No | EVA | |
| rs455353312 | 5 | Q>H | No | EVA | |
| rs474162332 | 5 | Q>P | No | EVA | |
| rs437007947 | 6 | Q>R | No | EVA | |
| rs469301189 | 7 | Q>E | No | EVA | |
| rs457282254 | 7 | Q>R | No | EVA | |
| rs432328348 | 8 | P>A | No | EVA | |
| rs432328348 | 8 | P>T | No | EVA | |
| rs480149560 | 12 | R>G | No | EVA | |
| rs449488862 | 14 | V>G | No | EVA | |
| rs463400509 | 16 | N>I | No | EVA | |
| rs438508798 | 17 | V>G | No | EVA | |
| rs459265140 | 19 | S>A | No | EVA | |
| rs461920734 | 23 | T>N | No | EVA | |
| rs473903082 | 23 | T>P | No | EVA | |
| rs457400262 | 28 | E>D | No | EVA | |
| rs471942173 | 32 | T>A | No | EVA | |
| rs471942173 | 32 | T>P | No | EVA | |
| rs471942173 | 32 | T>S | No | EVA | |
| rs453233239 | 36 | K>* | No | EVA | |
| rs434816000 | 36 | K>N | No | EVA | |
| rs468026389 | 37 | K>T | No | EVA | |
| rs449603783 | 38 | C>R | No | EVA | |
| rs437363588 | 38 | C>Y | No | EVA | |
| rs470394984 | 39 | V>G | No | EVA | |
| rs462653534 | 40 | T>N | No | EVA | |
| rs444016575 | 43 | S>P | No | EVA | |
| rs458565673 | 44 | A>G | No | EVA | |
| rs470597691 | 44 | A>T | No | EVA | |
| rs458565673 | 44 | A>V | No | EVA | |
| rs473377769 | 45 | V>L | No | EVA | |
| rs465037743 | 88 | L>R | No | EVA | |
| rs446516465 | 97 | N>K | No | EVA | |
| rs438830293 | 145 | S>Y | No | EVA | |
| rs478503974 | 146 | E>Q | No | EVA | |
| rs438219741 | 198 | L>S | No | EVA | |
| rs448058847 | 246 | L>H | No | EVA | |
| rs466688310 | 246 | L>V | No | EVA | |
| rs440905012 | 277 | P>T | No | EVA | |
| rs455372710 | 281 | P>Q | No | EVA | |
| rs473592867 | 281 | P>T | No | EVA | |
| rs437033375 | 282 | P>A | No | EVA | |
| rs432992003 | 288 | P>R | No | EVA | |
| rs449270406 | 291 | P>H | No | EVA | |
| rs467766025 | 291 | P>T | No | EVA | |
| rs478196470 | 295 | H>P | No | EVA | |
| rs459818532 | 296 | S>N | No | EVA | |
| rs440864314 | 297 | S>P | No | EVA | |
| rs461672852 | 298 | G>D | No | EVA | |
| rs476486378 | 299 | P>L | No | EVA | |
| rs433083069 | 300 | P>S | No | EVA | |
| rs434823303 | 303 | P>A | No | EVA | |
| rs455627288 | 304 | A>P | No | EVA | |
| rs478357950 | 308 | G>R | No | EVA | |
| rs466156176 | 309 | A>G | No | EVA | |
| rs457702220 | 315 | S>* | No | EVA | |
| rs472487540 | 316 | R>I | No | EVA | |
| rs441864501 | 320 | A>G | No | EVA | |
| rs470194198 | 325 | P>R | No | EVA | |
| rs451600196 | 333 | G>E | No | EVA | |
| rs381146131 | 342 | M>V | No | EVA | |
| rs480829212 | 369 | G>R | No | EVA | |
| rs382069383 | 392 | P>L | No | EVA | |
| rs526406844 | 493 | D>E | No | EVA |
No associated diseases with Q95107
5 regional properties for Q95107
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | CRIB domain | 202 - 260 | IPR000095 |
| domain | WH1/EVH1 domain | 32 - 141 | IPR000697 |
| domain | WH2 domain | 402 - 427 | IPR003124-1 |
| domain | WH2 domain | 431 - 454 | IPR003124-2 |
| domain | WASP family, EVH1 domain | 40 - 138 | IPR033927 |
Functions
4 GO annotations of cellular component
| Name | Definition |
|---|---|
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| cytoskeleton | A cellular structure that forms the internal framework of eukaryotic and prokaryotic cells. The cytoskeleton includes intermediate filaments, microfilaments, microtubules, the microtrabecular lattice, and other structures characterized by a polymeric filamentous nature and long-range order within the cell. The various elements of the cytoskeleton not only serve in the maintenance of cellular shape but also have roles in other cellular functions, including cellular movement, cell division, endocytosis, and movement of organelles. |
| endoplasmic reticulum membrane | The lipid bilayer surrounding the endoplasmic reticulum. |
| 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. |
3 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. |
| microtubule binding | Binding to a microtubule, a filament composed of tubulin monomers. |
5 GO annotations of biological process
| Name | Definition |
|---|---|
| actin filament polymerization | Assembly of actin filaments by the addition of actin monomers to a filament. |
| cell cycle | The progression of biochemical and morphological phases and events that occur in a cell during successive cell replication or nuclear replication events. Canonically, the cell cycle comprises the replication and segregation of genetic material followed by the division of the cell, but in endocycles or syncytial cells nuclear replication or nuclear division may not be followed by cell division. |
| 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. |
| 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. |
5 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| P42768 | WAS | Wiskott-Aldrich syndrome protein | Homo sapiens (Human) | EV |
| O00401 | WASL | Actin nucleation-promoting factor WASL | Homo sapiens (Human) | EV |
| P70315 | Was | Wiskott-Aldrich syndrome protein homolog | Mus musculus (Mouse) | SS |
| 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 |
| MSSGQQQPPP | PRRVTNVGSL | LLTPQENESL | FTFLGKKCVT | MSSAVVQLYA | ADRNCMWSKK |
| 70 | 80 | 90 | 100 | 110 | 120 |
| CSGVACLVKD | NPQRSYFLRI | FDIKDGKLLW | EQELYNNFVY | NSPRGYFHTF | AGDTCQVALN |
| 130 | 140 | 150 | 160 | 170 | 180 |
| FANEEEAKKF | RKAVTDLLGR | RQRKSEKRRD | PPNGPNLPMA | TVDIKNPEIT | TNRFYGPQIN |
| 190 | 200 | 210 | 220 | 230 | 240 |
| NISHTKEKKK | GKAKKKRLTK | ADIGTPSNFQ | HIGHVGWDPN | TGFDLNNLDP | ELKNLFDMCG |
| 250 | 260 | 270 | 280 | 290 | 300 |
| ISEAQLKDRE | TSKVIYDFIE | KTGGVEAVKN | ELRRQAPPPP | PPSRGGPPPP | PPPPHSSGPP |
| 310 | 320 | 330 | 340 | 350 | 360 |
| PPPARGRGAP | PPPPSRAPTA | APPPPPPSRP | GVGAPPPPPN | RMYPPPLPAL | PSSAPSGPPP |
| 370 | 380 | 390 | 400 | 410 | 420 |
| PPPPLSVSGS | VAPPPPPPPP | PPPGPPPPPG | LPSDGDHQVP | TPAGSKAALL | DQIREGAQLK |
| 430 | 440 | 450 | 460 | 470 | 480 |
| KVEQNSRPVS | CSGRDALLDQ | IRQGIQLKSV | TDAPESTPPA | PAPTSGIVGA | LMEVMQKRSK |
| 490 | 500 | ||||
| AIHSSDEDED | EDDDEDFEDD | DEWED |