| Primary Identifier | IPR037771 | Type | Domain |
| Short Name | C2_WWC |
| description | The WWC (WW-and-C2-domain-containing protein) family negatively regulates cell proliferation and organ growth by suppressing the transcriptional activityof YAP, a major effector of the Hippo pathway. They activate large tumour suppressor 1 and 2 kinases (LATS1/2), which in turn phosphorylates the transcriptional co-activator YAP [, ]. Their two amino terminal WW domains mediate binding to target proteins, whereas the internal C2 domain is required for membrane association. WWC family members include WWC1 (also known as KIBRA), WWC2 and WWC3 [].C2 domains fold into an 8-standed β-sandwich that can adopt 2 structural arrangements: type I and type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Whereas the majority of known C2 domains have a role in Ca2+-dependent vesicle membrane association, these protein modules are also involved in Ca2+-insensitive membrane targeting as well as in intracellular protein-protein interactions. The C2 domain of KIBRA has been shown to have Ca2+-dependent-binding specificity for monophosphorylated phosphatidylinositols []. |
