ubiquitin-protein ligase E3A; E6AP ubiquitin-protein ligase; human papillomavirus E6-associated protein; oncogenic protein-associated protein E6-AP; renal carcinoma antigen NY-REN-54 (UBE3A, E6AP, EPVE6AP, HPVE6A)
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Function
- E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester & transfers it to its substrates
- substrates include
- RAD23A & RAD23B, MCM7 (involved in DNA replication)
- annexin A1
- the PML tumor suppressor
- the cell cycle regulator CDKN1B
- may also function as a cellular quality control ubiquitin ligase by helping degradation of cytoplasmic misfolded proteins
- UBE3A also promotes its own degradation in vivo
- protein modification; protein ubiquitination
- phosphorylated upon DNA damage, probably by ATM or ATR
- binds UBQLN1 & UBQLN2
- interacts with the 26S proteasome
- interacts with BPY2
Structure
- contains 1 HECT domain (E6AP-type E3 ubiquitin-protein ligase)
Compartment
nucleus (probable)
Alternative splicing
named isoforms=3
Pathology
- defects associated with Angelman's syndrome
- required for binding of HPV 16,18 E6 oncoprotein to p53
- associates with E6 in absence of p53.
- E6-AP/E6 complex binds to & targets p53 for ubiquitin- mediated proteolysis
- Cys at position 833 necessary for thioester formation with ubiquitin & E6-AP dependent ubiquitination
- interacts with HCV core protein & targets it to degradation
Laboratory
More general terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/Q05086.html
- ↑ Scheffner M et al Protein ubiquitination involving an E1-E2-E3 enzyme ubiquitin thioester cascade. Nature 373:81-3, 1995 PMID: https://www.ncbi.nlm.nih.gov/pubmed/7800044