PRE4/YFR050C Summary Help

Standard Name PRE4 1
Systematic Name YFR050C
Feature Type ORF, Verified
Description Beta 7 subunit of the 20S proteasome (2, 3 and see Summary Paragraph)
Name Description PRoteinase yscE 1
Chromosomal Location
ChrVI:249866 to 249066 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gene Ontology Annotations All PRE4 GO evidence and references
  View Computational GO annotations for PRE4
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 6 genes
Classical genetics
Large-scale survey
reduction of function
170 total interaction(s) for 75 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 59
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 11
  • Co-crystal Structure: 5
  • Co-fractionation: 1
  • Co-purification: 1
  • Two-hybrid: 8

Genetic Interactions
  • Dosage Lethality: 4
  • Dosage Rescue: 1
  • Negative Genetic: 41
  • Phenotypic Enhancement: 3
  • Positive Genetic: 31
  • Synthetic Growth Defect: 1
  • Synthetic Lethality: 2
  • Synthetic Rescue: 1

Expression Summary
Length (a.a.) 266
Molecular Weight (Da) 29,443
Isoelectric Point (pI) 5.81
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrVI:249866 to 249066 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..801 249866..249066 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000001946

The 26S proteasome, comprised of a 19S regulatory particle and a 20S catalytic core particle, is a protease that is the responsible for the non-vacuolar degradation of cellular proteins (4, 5). Classic substrates of the proteasome are polyubiquitinated proteins, including damaged proteins, aberrant or misfolded proteins, and proteins that are essential to the regulation of a pathway (4, 6, 7, 8, 9, 10, 11). In addition, non-ubiquitinated proteins and proteins with unconventional polyubiquitin linkages have been identified as substrates of the 26S proteasome (12, 13, 14). The 19S regulatory particle recognizes, unfolds, and translocates ubiquitinated proteins into the catalytic core particle (4). The 20S catalytic core degrades the protein into fragments ranging from 3 to 25 amino acids (15, 16).

The 20S catalytic core contains 7 alpha-type and 7 beta-type subunits (17). The 7 alpha-type subunits form a ring, as do the 7 beta-type subunits. The 20S catalytic core is a cylinder of four stacked rings: two beta-type rings in the center and two alpha-type rings at the ends (18). Each beta-type ring contains 3 catalytically active subunits: Pre3p (also known as B1), Pup1p (also known as B2), and Pre2p (also known as B5), which provide the postacidic/post-glutamic-like, the trypsin-like, and the chymotrypsin-like activities, respectively (19, 20, 21). Five of the beta-type subunits are synthesized with N-terminal propeptides that are removed (2). The three catalytically active subunits are activated by autocatalytic removal of their propeptides during assembly and maturation of the proteasome (22, 19, 23).

The 20S catalytic core is first assembled to form "half-proteasome precursor complexes" containing an alpha-type ring, a beta-type ring, and the maturation factor Ump1p (24, 25, 26). The dimerization of these two halves results in the degradation of Ump1p and activation of the catalytic subunits (19, 24). In addition to Ump1p, the propeptides of Pre2p and Pup1p and proteasomal subunits Pre1p and Pre4p contribute to efficient assembly of the 20S proteasome core (19, 23, 3, 25, 26). Additional 20S proteasome assembly factors include the Poc1p-Poc2p, Poc3p-Poc4p, and Pba3p-Pba4p heterodimers (27, 28). Once assembled, the catalytic core is opened and stabilized by the 19S regulatory particle and Blm10p (29, 30).

Transcription of proteasomal subunit genes is regulated by Rpn4p (31, 32). The catalytic activity of the proteasome can be inactivated by N-acetylation of Pre1p, Pre2p, and Pup1p as well as S-glutathionylation (23, 3, 33, 34). Additional post-translational modification of the proteasomal subunits have been identified (35).

The subunit composition and structure of the proteasome are conserved in various organisms, including Archaea, plants, and mammals (17, 36, 37). In mammals, the protein fragments resulting from degradation are loaded onto MHC class I molecules for antigen presentation (6). Because the 20S proteasome is essential in the proper regulation of multiple cellular process and antigen generation, it is a target for many drugs (38, 39).

Last updated: 2010-06-29 Contact SGD

References cited on this page View Complete Literature Guide for PRE4
1) Hilt W, et al.  (1993) The PRE4 gene codes for a subunit of the yeast proteasome necessary for peptidylglutamyl-peptide-hydrolyzing activity. Mutations link the proteasome to stress- and ubiquitin-dependent proteolysis. J Biol Chem 268(5):3479-86
2) Groll M, et al.  (1999) The catalytic sites of 20S proteasomes and their role in subunit maturation: a mutational and crystallographic study. Proc Natl Acad Sci U S A 96(20):10976-83
3) Jager S, et al.  (1999) Proteasome beta-type subunits: unequal roles of propeptides in core particle maturation and a hierarchy of active site function. J Mol Biol 291(4):997-1013
4) Hochstrasser M  (1996) Ubiquitin-dependent protein degradation. Annu Rev Genet 30:405-39
5) Fischer M, et al.  (1994) The 26S proteasome of the yeast Saccharomyces cerevisiae. FEBS Lett 355(1):69-75
6) Hilt W and Wolf DH  (1996) Proteasomes: destruction as a programme. Trends Biochem Sci 21(3):96-102
7) Werner ED, et al.  (1996) Proteasome-dependent endoplasmic reticulum-associated protein degradation: an unconventional route to a familiar fate. Proc Natl Acad Sci U S A 93(24):13797-801
8) Loayza D and Michaelis S  (1998) Role for the ubiquitin-proteasome system in the vacuolar degradation of Ste6p, the a-factor transporter in Saccharomyces cerevisiae. Mol Cell Biol 18(2):779-89
9) Wilson M, et al.  (2007) A genomic screen in yeast reveals novel aspects of nonstop mRNA metabolism. Genetics 177(2):773-84
10) Verma R, et al.  (2001) Selective degradation of ubiquitinated Sic1 by purified 26S proteasome yields active S phase cyclin-Cdk. Mol Cell 8(2):439-48
11) Cohen MM, et al.  (2008) Ubiquitin-Proteasome-dependent Degradation of a Mitofusin, a Critical Regulator of Mitochondrial Fusion. Mol Biol Cell 19(6):2457-64
12) Voges D, et al.  (1999) The 26S proteasome: a molecular machine designed for controlled proteolysis. Annu Rev Biochem 68:1015-68
13) Baugh JM, et al.  (2009) Proteasomes can degrade a significant proportion of cellular proteins independent of ubiquitination. J Mol Biol 386(3):814-27
14) Xu P, et al.  (2009) Quantitative proteomics reveals the function of unconventional ubiquitin chains in proteasomal degradation. Cell 137(1):133-45
15) Nussbaum AK, et al.  (1998) Cleavage motifs of the yeast 20S proteasome beta subunits deduced from digests of enolase 1. Proc Natl Acad Sci U S A 95(21):12504-9
16) Dick TP, et al.  (1998) Contribution of proteasomal beta-subunits to the cleavage of peptide substrates analyzed with yeast mutants. J Biol Chem 273(40):25637-46
17) Heinemeyer W, et al.  (1994) PRE5 and PRE6, the last missing genes encoding 20S proteasome subunits from yeast? Indication for a set of 14 different subunits in the eukaryotic proteasome core. Biochemistry 33(40):12229-37
18) Groll M, et al.  (1997) Structure of 20S proteasome from yeast at 2.4 A resolution. Nature 386(6624):463-71
19) Chen P and Hochstrasser M  (1996) Autocatalytic subunit processing couples active site formation in the 20S proteasome to completion of assembly. Cell 86(6):961-72
20) Arendt CS and Hochstrasser M  (1997) Identification of the yeast 20S proteasome catalytic centers and subunit interactions required for active-site formation. Proc Natl Acad Sci U S A 94(14):7156-61
21) Heinemeyer W, et al.  (1997) The active sites of the eukaryotic 20 S proteasome and their involvement in subunit precursor processing. J Biol Chem 272(40):25200-9
22) Chen P and Hochstrasser M  (1995) Biogenesis, structure and function of the yeast 20S proteasome. EMBO J 14(11):2620-30
23) Arendt CS and Hochstrasser M  (1999) Eukaryotic 20S proteasome catalytic subunit propeptides prevent active site inactivation by N-terminal acetylation and promote particle assembly. EMBO J 18(13):3575-85
24) Ramos PC, et al.  (1998) Ump1p is required for proper maturation of the 20S proteasome and becomes its substrate upon completion of the assembly. Cell 92(4):489-99
25) Ramos PC, et al.  (2004) Role of C-terminal extensions of subunits beta2 and beta7 in assembly and activity of eukaryotic proteasomes. J Biol Chem 279(14):14323-30
26) Li X, et al.  (2007) beta-Subunit appendages promote 20S proteasome assembly by overcoming an Ump1-dependent checkpoint. EMBO J 26(9):2339-49
27) Le Tallec B, et al.  (2007) 20S proteasome assembly is orchestrated by two distinct pairs of chaperones in yeast and in mammals. Mol Cell 27(4):660-74
28) Kusmierczyk AR, et al.  (2008) A multimeric assembly factor controls the formation of alternative 20S proteasomes. Nat Struct Mol Biol 15(3):237-44
29) Marques AJ, et al.  (2007) The C-terminal Extension of the 7 Subunit and Activator Complexes Stabilize Nascent 20 S Proteasomes and Promote Their Maturation. J Biol Chem 282(48):34869-76
30) Bech-Otschir D, et al.  (2009) Polyubiquitin substrates allosterically activate their own degradation by the 26S proteasome. Nat Struct Mol Biol 16(2):219-25
31) London MK, et al.  (2004) Regulatory mechanisms controlling biogenesis of ubiquitin and the proteasome. FEBS Lett 567(2-3):259-64
32) Wang X, et al.  (2008) Disruption of Rpn4-Induced Proteasome Expression in Saccharomyces cerevisiae Reduces Cell Viability Under Stressed Conditions. Genetics 180(4):1945-53
33) Demasi M, et al.  (2003) 20 S proteasome from Saccharomyces cerevisiae is responsive to redox modifications and is S-glutathionylated. J Biol Chem 278(1):679-85
34) Silva GM, et al.  (2008) Role of glutaredoxin 2 and cytosolic thioredoxins in cysteinyl-based redox modification of the 20S proteasome. FEBS J 275(11):2942-55
35) Kikuchi J, et al.  (2010) Co- and post-translational modifications of the 26S proteasome in yeast. Proteomics 10(15):2769-79
36) Fu H, et al.  (1998) Molecular organization of the 20S proteasome gene family from Arabidopsis thaliana. Genetics 149(2):677-92
37) Dahlmann B, et al.  (1999) Identical subunit topographies of human and yeast 20S proteasomes. Arch Biochem Biophys 363(2):296-300
38) Groll M, et al.  (2006) Crystal structure of the boronic acid-based proteasome inhibitor bortezomib in complex with the yeast 20S proteasome. Structure 14(3):451-6
39) Groll M, et al.  (2006) Inhibitor-binding mode of homobelactosin C to proteasomes: new insights into class I MHC ligand generation. Proc Natl Acad Sci U S A 103(12):4576-9