RSP5/YER125W Summary Help

Standard Name RSP5 1
Systematic Name YER125W
Alias MDP1 , MUT2 , NPI1 , UBY1 , SMM1
Feature Type ORF, Verified
Description E3 ubiquitin ligase of NEDD4 family; regulates many cellular processes including MVB sorting, heat shock response, transcription, endocytosis, ribosome stability; mutant tolerates aneuploidy; autoubiquitinates; ubiquitinates Sec23p and Sna3p; deubiquitinated by Ubp2p; activity regulated by SUMO ligase Siz1p, in turn regulates Siz1p SUMO ligase activity; required for efficient Golgi-to-ER trafficking in COPI mutants; human homolog implicated in Liddle syndrome (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and see Summary Paragraph)
Name Description Reverses Spt- Phenotype 15
Chromosomal Location
ChrV:410189 to 412618 | ORF Map | GBrowse
Gene Ontology Annotations All RSP5 GO evidence and references
  View Computational GO annotations for RSP5
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 6 genes
Classical genetics
reduction of function
Large-scale survey
reduction of function
714 total interaction(s) for 395 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 84
  • Affinity Capture-RNA: 3
  • Affinity Capture-Western: 67
  • Biochemical Activity: 100
  • Co-crystal Structure: 2
  • Co-fractionation: 2
  • Co-localization: 1
  • Co-purification: 1
  • Far Western: 2
  • PCA: 1
  • Protein-peptide: 120
  • Reconstituted Complex: 96
  • Two-hybrid: 33

Genetic Interactions
  • Dosage Growth Defect: 6
  • Dosage Lethality: 17
  • Dosage Rescue: 25
  • Negative Genetic: 79
  • Phenotypic Enhancement: 24
  • Phenotypic Suppression: 11
  • Positive Genetic: 14
  • Synthetic Growth Defect: 10
  • Synthetic Lethality: 4
  • Synthetic Rescue: 12

Expression Summary
Length (a.a.) 809
Molecular Weight (Da) 91,816
Isoelectric Point (pI) 6.67
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrV:410189 to 412618 | ORF Map | GBrowse
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..2430 410189..412618 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 SGDIDS000000927

RSP5 encodes an essential protein that is the only S. cerevisiae member of the NEDD4 family of E3 ubiquitin ligases (16 and reviewed in 17 and 18). NEDD4 ubiquitin ligases are structurally similar and are comprised of an N-terminal C2 domain, a series of WW domains, and a C-terminal catalytic HECT domain (reviewed in 19). For Rsp5p, the C2 domain binds phosphoinositides, the C2 and WW domains mediate substrate recognition, the C2 and HECT domains are important for proper cellular localization, and the HECT domain contains two ubiquitin binding sites (20 and reviewed in 19 and 21). One of these ubiquitin binding sites is the active site and forms a covalent thioester intermediate with ubiquitin and the other is a non-covalent ubiquitin binding site that may regulate the length of polyubiquitin chains formed on subtrates (22 and references therein). Rsp5p is a multifunctional enzyme that is able to both mono- and polyubquitinate target proteins thereby regulating many cellular processes including endocytosis, multivesicular body (MVB) sorting, RNA export, transcription, lipid biosynthesis, mitochondrial inheritance, and protein catabolism (reviewed in 17 and 18). While Rsp5p is able directly interact with some of its targets, in other cases substrate interaction is mediated by adapter proteins (reviewed in 18, 21).

Human NEDD4 is associated with a hereditary form of hypertension known as Liddle syndrome (5).

Last updated: 2010-02-01 Contact SGD

References cited on this page View Complete Literature Guide for RSP5
1) Winston, F.  (1993) RSP5 alleles can suppress SPT3 mutations. Personal Communication
2) Huibregtse JM, et al.  (1997) The large subunit of RNA polymerase II is a substrate of the Rsp5 ubiquitin-protein ligase. Proc Natl Acad Sci U S A 94(8):3656-61
3) Dunn R and Hicke L  (2001) Domains of the Rsp5 ubiquitin-protein ligase required for receptor-mediated and fluid-phase endocytosis. Mol Biol Cell 12(2):421-35
4) Kaida D, et al.  (2003) Rsp5-Bul1/2 complex is necessary for the HSE-mediated gene expression in budding yeast. Biochem Biophys Res Commun 306(4):1037-41
5) Gajewska B, et al.  (2003) Functional analysis of the human orthologue of the RSP5-encoded ubiquitin protein ligase, hNedd4, in yeast. Curr Genet 43(1):1-10
6) Katzmann DJ, et al.  (2004) Multivesicular body sorting: ubiquitin ligase Rsp5 is required for the modification and sorting of carboxypeptidase S. Mol Biol Cell 15(2):468-80
7) Somesh BP, et al.  (2005) Multiple mechanisms confining RNA polymerase II ubiquitylation to polymerases undergoing transcriptional arrest. Cell 121(6):913-23
8) McNatt MW, et al.  (2007) Direct binding to Rsp5 mediates ubiquitin-independent sorting of Sna3 via the multivesicular body pathway. Mol Biol Cell 18(2):697-706
9) Torres EM, et al.  (2010) Identification of aneuploidy-tolerating mutations. Cell 143(1):71-83
10) Ossareh-Nazari B, et al.  (2010) The Rsp5 ubiquitin ligase and the AAA-ATPase Cdc48 control the ubiquitin-mediated degradation of the COPII component Sec23. Exp Cell Res 316(20):3351-7
11) Shcherbik N and Pestov DG  (2011) The ubiquitin ligase Rsp5 is required for ribosome stability in Saccharomyces cerevisiae. RNA 17(8):1422-8
12) Jarmoszewicz K, et al.  (2012) Rsp5 Ubiquitin Ligase Is Required for Protein Trafficking in Saccharomyces cerevisiae COPI Mutants. PLoS One 7(6):e39582
13) Novoselova TV, et al.  (2013) SUMOylation regulates the homologous to E6-AP carboxyl terminus (HECT) ubiquitin ligase Rsp5p. J Biol Chem 288(15):10308-17
14) Lam MH and Emili A  (2013) Ubp2 regulates rsp5 ubiquitination activity in vivo and in vitro. PLoS One 8(9):e75372
15) Eisenmann DM, et al.  (1992) SPT3 interacts with TFIID to allow normal transcription in Saccharomyces cerevisiae. Genes Dev 6(7):1319-31
16) Huibregtse JM, et al.  (1995) A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase. Proc Natl Acad Sci U S A 92(7):2563-7
17) Kaliszewski P and Zoladek T  (2008) The role of Rsp5 ubiquitin ligase in regulation of diverse processes in yeast cells. Acta Biochim Pol 55(4):649-62
18) Belgareh-Touze N, et al.  (2008) Versatile role of the yeast ubiquitin ligase Rsp5p in intracellular trafficking. Biochem Soc Trans 36(Pt 5):791-6
19) Ingham RJ, et al.  (2004) The Nedd4 family of E3 ubiquitin ligases: functional diversity within a common modular architecture. Oncogene 23(11):1972-84
20) Dunn R, et al.  (2004) The C2 domain of the Rsp5 ubiquitin ligase binds membrane phosphoinositides and directs ubiquitination of endosomal cargo. J Cell Biol 165(1):135-44
21) Shearwin-Whyatt L, et al.  (2006) Regulation of functional diversity within the Nedd4 family by accessory and adaptor proteins. Bioessays 28(6):617-28
22) French ME, et al.  (2009) Regulation of the RSP5 Ubiquitin Ligase by an Intrinsic Ubiquitin-binding Site. J Biol Chem 284(18):12071-9