NEDD4-like E3 ubiquitin-protein ligase WWP2; atrophin-1-interacting protein 2; AIP2; WW domain-containing protein 2 (WWP2)

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: nucleus 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

General

nuclear protein phosphoprotein E3 ubiquitin ligase; ubiquitin-ligating enzyme E3; N end-recognizing protein

Properties

SIZE: entity length = 870 aa MW = 99 kD COMPARTMENT: cell nucleus MOTIF: C2 domain {20-100} MOTIF: binding site FOR-BINDING-OF: phospholipid Ca+2-binding site Ser phosphorylation site {S211} WW domain (W/rsp5/WWP domain) {300-333} WW domain (W/rsp5/WWP domain) {330-363} WW domain (W/rsp5/WWP domain) {405-437} WW domain (W/rsp5/WWP domain) {444-477} HECT domain {536-870} MOTIF: cysteine residue {C838}

Database Correlations

OMIM 602308 UniProt O00308 PFAM correlations Entrez Gene 11060 Kegg hsa:11060 ENZYME EC=6.3.2.-

References

UniProt :accession O00308