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)

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

More general terms

• E3 ubiquitin ligase
• nuclear protein
• phosphoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=7337
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:7337
• OMIM: https://mirror.omim.org/entry/105830
• OMIM: https://mirror.omim.org/entry/601623
• UniProt: http://www.uniprot.org/uniprot/Q05086.html