Identification of a family of closely related human ubiquitin conjugating enzymes.
Two very closely related human E2 ubiquitin conjugating enzymes, UbfH5B and UbcH5C, have been identified. These enzymes are products of distinct genes and are 88-89% identical in amino acid sequence to the recently described human E2, UbcH5 (now designated UbcH5A), UbcH5A-C are homologous to a family of five ubiquitin conjugating enzymes from Arabidopsis thaliana, AtUBC8-12. They are also closely related to Saccharomyces cerevisiae ScUBC4 and ScUBC5, which are involved in the stress response, and play a central role in the targeting of short-lived regulatory proteins for degradation. mRNAs encoding UbcH5A-C were co-expressed in all cell lines and tissues evaluated, with UbcH5C transcripts generally expressed at the highest levels. Analysis of Southern blots suggests that there are likely to be other related members of this family. Both UbcH5B and UbcH5C form thiol ester adducts with ubiquitin, and have activities similar to UbcH5A and AtUBC8 in the conjugation of ubiquitin to target proteins in the presence of the human ubiquitin protein ligase E6-AP. These results establish the existence of a highly conserved, and widely expressed, family of human ubiquitin conjugating enzymes.
Laboratory of Immune Cell Biology, National Cancer Institute, Bethesda, Maryland 20892-1152, USA.
J P
JP
Jensen
P W
PW
Bates
M
M
Yang
R D
RD
Vierstra
A M
AM
Weissman
D000595:Amino Acid Sequence; D000818:Animals; D017360:Arabidopsis / Q000201:enzymology; D001483:Base Sequence; D005075:Biological Evolution; D015139:Blotting, Southern; D002460:Cell Line; D003001:Cloning, Molecular; D005260:Female; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D033862:Iron-Binding Proteins; D008025:Ligases / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D008214:Lymphocytes / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010920:Placenta / Q000201:enzymology; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D044763:Ubiquitin-Conjugating Enzymes
D033862:Iron-Binding Proteins; D011994:Recombinant Proteins; C097308:UBE2D1 protein, human; C097309:UBE2D2 protein, human; C097310:UBE2D3 protein, human; C490789:Ube2d1 protein, mouse; D044763:Ubiquitin-Conjugating Enzymes; D008025:Ligases