PMID:7708685

Citation	Huibregtse, JM, Scheffner, M, Beaudenon, S and Howley, PM (1995) A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase. Proc. Natl. Acad. Sci. U.S.A. 92:2563-7
Abstract	E6-AP is a 100-kDa cellular protein that interacts with the E6 protein of the cancer-associated human papillomavirus types 16 and 18. The E6/E6-AP complex binds to and targets the p53 tumor-suppressor protein for ubiquitin-mediated proteolysis. E6-AP is an 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. The amino acid sequence of E6-AP shows similarity to a number of protein sequences over an approximately 350-aa region corresponding to the carboxyl termini of both E6-AP and the E6-AP-related proteins. Of particular note is a conserved cysteine residue within the last 32-34 aa, which in E6-AP is likely to be the site of ubiquitin thioester formation. Two of the E6-AP-related proteins, a rat 100-kDa protein and a yeast 95-kDa protein (RSP5), both of previously unknown function, are shown here to form thioesters with ubiquitin. Mutation of the conserved cysteine residue of these proteins destroys their ability to accept ubiquitin. These data strongly suggest that the rat 100-kDa protein and RSP5, as well as the other E6-AP-related proteins, belong to a class of functionally related E3 ubiquitin-protein ligases, defined by a domain homologous to the E6-AP carboxyl terminus (hect domain).
Links	PubMed PMC42258
Keywords	Amino Acid Sequence; Animals; Conserved Sequence; Cysteine; Endosomal Sorting Complexes Required for Transport; Humans; Ligases/chemistry; Ligases/metabolism; Mice; Molecular Sequence Data; Mutagenesis; Papillomaviridae/metabolism; Rabbits; Rats; Reticulocytes/metabolism; Saccharomyces cerevisiae/enzymology; Saccharomyces cerevisiae Proteins; Sequence Homology, Amino Acid; Ubiquitin-Protein Ligase Complexes; Ubiquitin-Protein Ligases; Viral Proteins/chemistry; Viral Proteins/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:UBE3A	enables	GO:0061630: ubiquitin protein ligase activity	ECO:0000315: mutant phenotype evidence used in manual assertion		F		Seeded From UniProt	complete
HUMAN:UBE3A		GO:0061630: ubiquitin protein ligase activity	ECO:0000315:		F		Fig4; panel A shows E3 ubiquitin-protein ligase activity.	complete CACAO 10253
YEAST:RSP5	enables	GO:0061630: ubiquitin protein ligase activity	ECO:0000315: mutant phenotype evidence used in manual assertion		F		Seeded From UniProt	complete
YEAST:RSP5		GO:0061630: ubiquitin protein ligase activity	ECO:0000247:	UniProtKB:Q05086	F		Fig 1B shows sequence alignment, including highly conserved cysteine residue necessary for Ubiquitin thioester formation.	complete CACAO 10316
YEAST:RSP5		GO:0061630: ubiquitin protein ligase activity	ECO:0000315:		F		Fig3 shows evidence for E3 Ubiquitin-protein ligase activty	complete CACAO 10317
RAT:UBR5	enables	GO:0061630: ubiquitin protein ligase activity	ECO:0000315: mutant phenotype evidence used in manual assertion		F		Seeded From UniProt	complete
RAT:UBR5		GO:0061630: ubiquitin protein ligase activity	ECO:0000315:		F		See Figure 2 for evidence of E3 ubiquitin-protein ligase activity. Note that Genbank PIR S22659 has been replaced with PIR Q62671.3 since the publication of this paper.	complete CACAO 10254
RAT:UBR5		GO:0061630: ubiquitin protein ligase activity	ECO:0000247:	UniProtKB:Q05086	F		Fig 1B shows sequence alignment, including highly conserved cysteine residue necessary for Ubiquitin thioester formation.	complete CACAO 10302
DROME:HYD		GO:0061630: ubiquitin protein ligase activity	ECO:0000247:	UniProtKB:Q05086	F		Fig 1B shows sequence alignment, including highly conserved cysteine residue necessary for Ubiquitin thioester formation.	complete CACAO 10328

References

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