| Primary Identifier | IPR043969 | Type | Domain |
| Short Name | MAP3K_PH |
| description | Apoptosis signal-regulating kinases (ASK1/2/3 or MAP3K5/6/15) are mitogen-activated protein kinase kinase kinases (MAP3Ks) that mediate cellular responses to redox stress and inflammatory cytokines and play a key role in innate immunity and viral infection. This kind of signalling kinases are regulated by oligomerization and regulatory domains. In its N-terminal there is a thioredoxin-binding domain that negatively regulates activity and a TNF receptor-associated factors (TRAFs)-binding domain which triggers ASK activation and kinase activity. TRAFs-binding domain is composed by 14 helices, which form seven tetratricopeptide repeats (TPRs), followed by a PH-like domain to complete de central regulatory domain of ASK. The central regulatory region promotes ASK1 activity via its PH domain but also facilitates ASK1 autoinhibition by bringing the thioredoxin-binding and kinase domains into close proximity. The PH-like domain, adjacent to the kinase domain, is required together with an intact TPR region for ASK1 activity.The major role of the central regulatory region is to bring the thioredoxin-binding domain into close proximity to the kinase domain to inhibit its activity [].This PH-like domain is found in the regulatory region of ASK1/2/3 (also known as MAP3K5/6/15). The central regulatory region of ASK1 mediates a compact arrangement of the kinase and thioredoxin-binding domains which allows the binding of substrates for phosphorylation. This PH-like domain adopts the typical form of two antiparallel β-sheets followed by a C-terminal amphipathic helix []. |
