NEDD4-like E3 ubiquitin-protein ligase WWP2; atrophin-1-interacting protein 2; AIP2; WW domain-containing protein 2 (WWP2)
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Function
- E3 ubiquitin-protein ligase
- accepts ubiquitin froman E2 ubiquitin-conjugating enzyme in the form of a thioester & then directly transfers the ubiquitin to targeted substrates
- polyubiquitinates POU5F1 by Lys-63-linked conjugation & promotes it to proteasomal degradation
- in embryonic stem cells, ubiquitination may regulate POU5F1 protein level
- ubiquitinates EGR2 & promotes its proteasomal degradation; in T-cells the ubiquitination inhibits activation-induced cell death
- ubiquitinates SLC11A2; ubiquitination is enhanced in the presence of NDFIP1 & NDFIP2
- ubiquitinates RPB1 & promotes its proteasomal degradation
- activated by NDFIP1- & NDFIP2-binding
- protein modification; protein ubiquitination
- autoubiquitinated
- binds SCNN1A, SCNN1B, SCNN1G, WBP1, WBP2, DRPLA & adenovirus type 2 PIII
- interacts with NDFIP1
- interacts with NDFIP2 (probable)
- interacts with POU5F1 & EGR2
- interacts with SLC11A2 (putative)
Structure
- the C2 domain is involved in autoinhibition of the catalytic activity by interacting with the HECT domain
- contains 1 C2 domain
- contains 1 HECT domain
- contains 4 WW domains
- a Cys is required for ubiquitin-thioester formation
Compartment
Expression
- detected in heart, throughout the brain, placenta, lung, liver, muscle, kidney & pancreas
- also detected in spleen & peripheral blood leukocytes
- highly expressed in undifferentiated embryonic stem cells
- expression is reduced after embryoid body formation
- not detectable at day 13 o fembryoid body formation
- low levels are again detected at day 18 of embryoid body formation