UBE1L2, a novel E1 enzyme specific for ubiquitin.
UBE1 is known as the human ubiquitin-activating enzyme (E1), which activates ubiquitin in an ATP-dependent manner. Here, we identified a novel human ubiquitin-activating enzyme referred to as UBE1L2, which also shows specificity for ubiquitin. The UBE1L2 sequence displays a 40% identity to UBE1 and also contains an ATP-binding domain and an active site cysteine conserved among E1 family proteins. UBE1L2 forms a covalent link with ubiquitin in vitro and in vivo, which is sensitive to reducing conditions. In an in vitro polyubiquitylation assay, recombinant UBE1L2 could activate ubiquitin and transfer it onto the ubiquitin-conjugating enzyme UbcH5b. Ubiquitin activated by UBE1L2 could be used for ubiquitylation of p53 by MDM2 and supported the autoubiquitylation of the E3 ubiquitin ligases HectH9 and E6-AP. The UBE1L2 mRNA is most abundantly expressed in the testis, suggesting an organ-specific regulation of ubiquitin activation.
Pelzer
Christiane
C
Division of Immunology, Department of Biology, University of Constance, 78457 Konstanz, Germany.
Kassner
Ingrid
I
Matentzoglu
Konstantin
K
Singh
Rajesh K
RK
Wollscheid
Hans-Peter
HP
Scheffner
Martin
M
Schmidtke
Gunter
G
Groettrup
Marcus
M
D000255:Adenosine Triphosphate / Q000737:chemistry; D000595:Amino Acid Sequence; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025801:Ubiquitin / Q000737:chemistry*; D044764:Ubiquitin-Activating Enzymes / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D044763:Ubiquitin-Conjugating Enzymes / Q000737:chemistry
D012333:RNA, Messenger; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; C521757:UBA6 protein, human; D025801:Ubiquitin; D000255:Adenosine Triphosphate; C097309:UBE2D2 protein, human; D044763:Ubiquitin-Conjugating Enzymes; D044764:Ubiquitin-Activating Enzymes