WWP2
Developmental stage
Highly expressed in undifferentiated embryonic stem cells and expression is reduced after embryoid body (EB) formation. Not detectable at day 13 of EB formation; low levels are again detected at day 18 of EB formation.
Domain
The C2 domain is involved in autoinhibition of the catalytic activity by interacting with the HECT domain.
The WW domains mediate interaction with PPxY motif-containing proteins.
Function
E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Polyubiquitinates POU5F1 by 'Lys-63'-linked conjugation and promotes it to proteasomal degradation; in embryonic stem cells (ESCs) the ubiquitination is proposed to regulate POU5F1 protein level. Ubiquitinates EGR2 and promotes it to proteasomal degradation; in T-cells the ubiquitination inhibits activation-induced cell death. Ubiquitinates SLC11A2; the ubiquitination is enhanced by presence of NDFIP1 and NDFIP2. Ubiquitinates RPB1 and promotes it to proteasomal degradation.
Pathway
Protein modification; protein ubiquitination.
Post-translational modifications
Autoubiquitinated. Ubiquitinated by the SCF(FBXL15) complex, leading to its degradation by the proteasome.
Tissue Specificity
Detected in heart, throughout the brain, placenta, lung, liver, muscle, kidney and pancreas. Also detected in spleen and peripheral blood leukocytes.
Cellular localization
- Nucleus
Alternative names
NEDD4-like E3 ubiquitin-protein ligase WWP2, Atrophin-1-interacting protein 2, HECT-type E3 ubiquitin transferase WWP2, WW domain-containing protein 2, AIP2, WWP2