RSP5/YER125W Summary 
RSP5 BASIC INFORMATION
| Standard Name | RSP5 1 |
|---|---|
| Systematic Name | YER125W |
| Alias | MDP1 , MUT2 , NPI1 , UBY1 , SMM1 |
| Feature Type | ORF, Verified |
| Description | E3 ubiquitin ligase of the NEDD4 family; involved in regulating many cellular processes, including MVB sorting, heat shock response, transcription, and endocytosis; the human homolog is invovled in Liddle syndrome (2, 3, 4, 5, 6, 7 and see Summary Paragraph) 
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| Name Description | Reverses Spt- Phenotype 8 |
| Mutant Phenotype | All RSP5 Phenotype details and references |
|---|---|
| Classical genetics | |
| conditional |
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| overexpression | |
| reduction of function |
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| repressible | |
| unspecified | |
| Large-scale survey | |
| null | |
| overexpression | |
| reduction of function |
| Interactions | RSP5 All interactions details and references |
|---|---|
| View additional details at BioGRID | |
| 444 total interaction(s) for 256 unique genes/features. | |
| Physical Interactions |
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| Genetic Interactions |
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| Post-translational Modifications | PhosphoGRID | PhosphoPep Database |
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| External Links | All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | UniProtKB |
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| Primary SGDID | S000000927 |
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RSP5 RESOURCES
| SGD ORF map | GBrowse |
|---|---|
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Click on histogram for expression summary
Expression Summary
ADDITIONAL INFORMATION for RSP5
SUMMARY PARAGRAPH for RSP5
RSP5 encodes an essential protein that is the only S. cerevisiae member of the NEDD4 family of E3 ubiquitin ligases (9 and reviewed in 10 and 11). 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 12). 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 (13 and reviewed in 12 and 14). 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 (15 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 10 and 11). While Rsp5p is able directly interact with some of its targets, in other cases substrate interaction is mediated by adapter proteins (reviewed in 11, 14).
Human NEDD4 is associated with a hereditary form of hypertension known as Liddle syndrome (5).
Last updated: 2010-02-01
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) | Eisenmann DM, et al. (1992) SPT3 interacts with TFIID to allow normal transcription in Saccharomyces cerevisiae. Genes Dev 6(7):1319-31 |
| 9) | 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 |
| 10) | 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 |
| 11) | 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 |
| 12) | Ingham RJ, et al. (2004) The Nedd4 family of E3 ubiquitin ligases: functional diversity within a common modular architecture. Oncogene 23(11):1972-84 |
| 13) | 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 |
| 14) | Shearwin-Whyatt L, et al. (2006) Regulation of functional diversity within the Nedd4 family by accessory and adaptor proteins. Bioessays 28(6):617-28 |
| 15) | French ME, et al. (2009) Regulation of the RSP5 Ubiquitin Ligase by an Intrinsic Ubiquitin-binding Site. J Biol Chem 284(18):12071-9 |
