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Gene Review

UBR1  -  E3 ubiquitin-protein ligase UBR1

Saccharomyces cerevisiae S288c

Synonyms: G7168, N-end-recognizing protein, N-recognin-1, PTR1, YGR184C
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High impact information on UBR1

  • RAD6 interacts physically with the UBR1 gene product in carrying out the multiubiquitination of amino-end rule proteolytic substrates [1].
  • We previously showed that UBR1 and UFD4, two E3 ligases of the yeast Saccharomyces cerevisiae, interact with specific proteasomal subunits [2].
  • These results defined the topography of the Ubc2p-Ubr1p interaction and revealed the essential function of the RING-H2 finger, a domain that is present in many otherwise dissimilar E3 proteins of the ubiquitin system [3].
  • The Ubr1p-Cup9p-Ptr2p circuit is the first example of a physiological process controlled by the N-end rule pathway [4].
  • In contrast to engineered N-end rule substrates, which are recognized by Ubr1p through their destabilizing N-terminal residues, Cup9p is targeted by Ubr1p through an internal degradation signal [4].

Biological context of UBR1

  • TYS1 was reported previously to lie on chromosome XV based on sequence overlap with the adjacent UBR1 gene [5].
  • We demonstrated, through in vivo and in vitro assays, that Rpn4 is a physiological substrate of the Ubr2 ubiquitin ligase, which was originally identified as a sequence homolog of Ubr1, the E3 component of the N-end rule pathway [6].

Anatomical context of UBR1


Associations of UBR1 with chemical compounds

  • This defect in histidine uptake, exhibited by the sln2 mutant in the absence but not in the presence of Ubr1p, was traced to the gene HIP1, which encodes the histidine transporter [8].

Physical interactions of UBR1

  • A ptr1-1 rae1-167 double mutant showed a synthetic effect on a growth defect, indicating that Ptr1p functionally interacts with an essential mRNA export factor Rae1p [9].

Other interactions of UBR1

  • Previous work demonstrated that dipeptides with destabilizing N-terminal residues allosterically activate UBR1, leading to accelerated in vivo degradation of CUP9 and the induction of PTR2 expression [10].
  • Previous studies have indicated the involvement of N-terminal and C-terminal regions of Rad6 in interactions with Ubr1 [11].
  • Yet another property of the sln2 mutant was its inviability at 37 degrees C, which could not be rescued by either UBR1 or HIS3 [8].
  • Our findings show that peptide transport and the ubiquitin pathway--two dynamic phenomena universal to eukaryotic cells--share a common component, namely UBR1/PTR1 [12].
  • The PTR system consists of three genes, PTR1, PTR2 and PTR3 [13].
  • A third substrate-binding site of UBR1 targets an internal degron of CUP9, a transcriptional repressor of peptide import [14].


  1. Specific complex formation between yeast RAD6 and RAD18 proteins: a potential mechanism for targeting RAD6 ubiquitin-conjugating activity to DNA damage sites. Bailly, V., Lamb, J., Sung, P., Prakash, S., Prakash, L. Genes Dev. (1994) [Pubmed]
  2. UFD4 lacking the proteasome-binding region catalyses ubiquitination but is impaired in proteolysis. Xie, Y., Varshavsky, A. Nat. Cell Biol. (2002) [Pubmed]
  3. The E2-E3 interaction in the N-end rule pathway: the RING-H2 finger of E3 is required for the synthesis of multiubiquitin chain. Xie, Y., Varshavsky, A. EMBO J. (1999) [Pubmed]
  4. The N-end rule pathway controls the import of peptides through degradation of a transcriptional repressor. Byrd, C., Turner, G.C., Varshavsky, A. EMBO J. (1998) [Pubmed]
  5. SSU71, encoding the largest subunit of TFIIF, is located on the right arm of chromosome VII in Saccharomyces cerevisiae. Sun, Z.W., Hampsey, M. Yeast (1995) [Pubmed]
  6. Rpn4 is a physiological substrate of the Ubr2 ubiquitin ligase. Wang, L., Mao, X., Ju, D., Xie, Y. J. Biol. Chem. (2004) [Pubmed]
  7. Construction and analysis of mouse strains lacking the ubiquitin ligase UBR1 (E3alpha) of the N-end rule pathway. Kwon, Y.T., Xia, Z., Davydov, I.V., Lecker, S.H., Varshavsky, A. Mol. Cell. Biol. (2001) [Pubmed]
  8. The N-end rule pathway is required for import of histidine in yeast lacking the kinesin-like protein Cin8p. Xie, Y., Varshavsky, A. Curr. Genet. (1999) [Pubmed]
  9. The fission yeast ptr1+ gene involved in nuclear mRNA export encodes a putative ubiquitin ligase. Andoh, T., Azad, A.K., Shigematsu, A., Ohshima, Y., Tani, T. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  10. Pairs of dipeptides synergistically activate the binding of substrate by ubiquitin ligase through dissociation of its autoinhibitory domain. Du, F., Navarro-Garcia, F., Xia, Z., Tasaki, T., Varshavsky, A. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  11. Domains required for dimerization of yeast Rad6 ubiquitin-conjugating enzyme and Rad18 DNA binding protein. Bailly, V., Prakash, S., Prakash, L. Mol. Cell. Biol. (1997) [Pubmed]
  12. A recognition component of the ubiquitin system is required for peptide transport in Saccharomyces cerevisiae. Alagramam, K., Naider, F., Becker, J.M. Mol. Microbiol. (1995) [Pubmed]
  13. Multiplicity and regulation of genes encoding peptide transporters in Saccharomyces cerevisiae. Hauser, M., Narita, V., Donhardt, A.M., Naider, F., Becker, J.M. Mol. Membr. Biol. (2001) [Pubmed]
  14. Substrate-binding sites of UBR1, the ubiquitin ligase of the N-end rule pathway. Xia, Z., Webster, A., Du, F., Piatkov, K., Ghislain, M., Varshavsky, A. J. Biol. Chem. (2008) [Pubmed]
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