Contents

Search

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 a) RAD23A & RAD23B, MCM7 (involved in DNA replication) b) annexin A1 c) the PML tumor suppressor d) 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: - UBE3A gene mutation

Related

UBE3A gene UBE3A gene mutation

General

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

Properties

SIZE: entity length = 875 aa MW = 101 kD COMPARTMENT: cell nucleus MOTIF: Ser phosphorylation site {S218} acidic region {394-399} MOTIF: acidic residue (SEVERAL) binding site SITE: 401-418 FOR-BINDING-OF: papillomavirus oncoprotein E6 active site HCV core protein interaction {418-517} HECT domain {776-875} MOTIF: cysteine residue {C843}

Database Correlations

OMIM correlations MORBIDMAP 601623 UniProt Q05086 Pfam PF00632 Entrez Gene 7337 Kegg hsa:7337

References

  1. UniProt :accession Q05086
  2. Scheffner M et al Protein ubiquitination involving an E1-E2-E3 enzyme ubiquitin thioester cascade. Nature 373:81-3, 1995 PMID: 7800044