| Tbio | Wiskott-Aldrich syndrome protein |
Effector protein for Rho-type GTPases. Regulates actin filament reorganization via its interaction with the Arp2/3 complex. Important for efficient actin polymerization. Possible regulator of lymphocyte and platelet function. Mediates actin filament reorganization and the formation of actin pedestals upon infection by pathogenic bacteria.
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. [provided by RefSeq, Jul 2008]
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. [provided by RefSeq, Jul 2008]
Comments
| Disease | Target Count |
|---|---|
| THROMBOCYTOPENIA 1 (disorder) | 1 |
| Thrombocytopenia, X-Linked, Intermittent | 1 |
| Disease | Target Count | P-value |
|---|---|---|
| osteosarcoma | 7933 | 1.01028141012077E-6 |
| malignant mesothelioma | 3163 | 3.46043493989563E-6 |
| psoriasis | 6685 | 1.72497462308529E-5 |
| cutaneous lupus erythematosus | 1056 | 0.00222670305781282 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Severe congenital neutropenia | 10 | 0.0 | 5.0 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Thrombocytopenia | 105 | 5.678 | 2.8 |
| Dermatitis | 141 | 5.1 | 2.6 |
| Primary immunodeficiency disease | 52 | 4.561 | 2.3 |
| Neutropenia | 78 | 3.496 | 1.7 |
| Allergic hypersensitivity disease | 123 | 3.352 | 1.7 |
| Toxic optic neuropathy | 2 | 3.181 | 1.6 |
| Disease | Target Count |
|---|---|
| Thrombocytopenia 1 | 1 |
| Disease | log2 FC | p |
|---|---|---|
| malignant mesothelioma | 2.100 | 0.000 |
| cutaneous lupus erythematosus | 1.700 | 0.002 |
| psoriasis | 2.700 | 0.000 |
| osteosarcoma | -3.511 | 0.000 |
| Species | Source |
|---|---|
| Macaque | OMA Inparanoid |
| Mouse | OMA Inparanoid |
| Rat | OMA Inparanoid |
| Dog | OMA EggNOG Inparanoid |
| Opossum | OMA Inparanoid |
| Anole lizard | OMA Inparanoid |
| Zebrafish | OMA EggNOG Inparanoid |
| S.cerevisiae | OMA Inparanoid |
| PMID | Text |
|---|---|
| 26463123 | This suggests that N-WASP's failure to compensate for WASP in rescuing chemotaxis could be due to the absence of this I30 region. |
| 26368308 | The introduction of functional WASp by GT corrected the alterations of both central and peripheral B cell tolerance checkpoints. WASp plays an important role in the establishment and maintenance of B cell tolerance in humans. |
| 26277674 | We describe two Malay patients with classical Wiskott-Aldrich Syndrome with two different mutations in the WASP gene |
| 26261240 | we identify small ubiquitin-related modifier (SUMO)ylation as a novel posttranslational modification of WASp |
| 26175287 | WASP, RUNX1, and ANKRD26 genes are important for normal TPO signaling and the network underlying thrombopoiesis. |
| 26159751 | Studies indicate that mutations in the Wiskott-Aldrich syndrome protein (WASp) gene cause a continuum of clinical symptoms ranging from intermittent X-linked thrombocytopenia to full classical Wiskott-Aldrich syndrome (WAS). |
| 26028144 | Platelet actin nodule formation is dependent on WASp and the ARP2/3 complex. |
| 25931402 | A total of 60 unique WAS mutations were identified in Chinese patients, including 20 novel mutations and 8 hotspots, from 75 unrelated families with a total of 81 affected members. |
| 25413351 | conclude that tyrosine phosphorylation of WIP is a crucial regulator of WASP stability and function as an actin-nucleation-promoting factor |
| 25388447 | retrospectively investigated the outcome of hematopoietic stem cell transplantation in a cohort of 24 patients with the X-linked thrombocytopenia phenotype and mutations in the WAS gene |
| More... |
MSGGPMGGRPGGRGAPAVQQNIPSTLLQDHENQRLFEMLGRKCLTLATAVVQLYLALPPGAEHWTKEHCG 1 - 70 AVCFVKDNPQKSYFIRLYGLQAGRLLWEQELYSQLVYSTPTPFFHTFAGDDCQAGLNFADEDEAQAFRAL 71 - 140 VQEKIQKRNQRQSGDRRQLPPPPTPANEERRGGLPPLPLHPGGDQGGPPVGPLSLGLATVDIQNPDITSS 141 - 210 RYRGLPAPGPSPADKKRSGKKKISKADIGAPSGFKHVSHVGWDPQNGFDVNNLDPDLRSLFSRAGISEAQ 211 - 280 LTDAETSKLIYDFIEDQGGLEAVRQEMRRQEPLPPPPPPSRGGNQLPRPPIVGGNKGRSGPLPPVPLGIA 281 - 350 PPPPTPRGPPPPGRGGPPPPPPPATGRSGPLPPPPPGAGGPPMPPPPPPPPPPPSSGNGPAPPPLPPALV 351 - 420 PAGGLAPGGGRGALLDQIRQGIQLNKTPGAPESSALQPPPQSSEGLVGALMHVMQKRSRAIHSSDEGEDQ 421 - 490 AGDEDEDDEWDD 491 - 502 //
| PMID | Year | Title |
|---|---|---|
| 26566883 | 2016 | Homozygous missense mutation in the LMAN2L gene segregates with intellectual disability in a large consanguineous Pakistani family. |
| 26463123 | 2015 | Molecular difference between WASP and N-WASP critical for chemotaxis of T-cells towards SDF-1?. |
| 26368308 | 2015 | Lentiviral-mediated gene therapy restores B cell tolerance in Wiskott-Aldrich syndrome patients. |
| 26277674 | 2015 | Molecular characterization of two Malaysian patients with Wiskott-Aldrich syndrome. |
| 26261240 | 2015 | SUMOylation-disrupting WAS mutation converts WASp from a transcriptional activator to a repressor of NF-?B response genes in T cells. |
| 26175287 | 2015 | Analyses of Genetic and Clinical Parameters for Screening Patients With Inherited Thrombocytopenia with Small or Normal-Sized Platelets. |
| 26159751 | 2015 | Current and emerging treatment options for Wiskott-Aldrich syndrome. |
| 26028144 | 2015 | Platelet actin nodules are podosome-like structures dependent on Wiskott-Aldrich syndrome protein and ARP2/3 complex. |
| 25944712 | 2015 | N-terminome analysis of the human mitochondrial proteome. |
| 25931402 | 2015 | Wiskott-Aldrich syndrome/X-linked thrombocytopenia in China: Clinical characteristic and genotype-phenotype correlation. |
| More... |
