RefGenome Electronic Jamboree 2008-10 NEDD4

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Orthoset

Ortholog set at PPOD

Participants

NEDD4

Notes

NEDD4

SGD: receptor-mediated endocytosis vs. ubiquitin-mediated endocytosis Should these be two different processes in GO? Are they different enough? The definition of RME in GO refers to ligand binding, but this doesn't always happen.

Action Item: SGD will submit a new term request to SourceForge for ubiquitin- mediated endocytosis.

SGD: RSP5/NEDD4, a ubiquitin ligase, directly ubiquitinates many targets that are involved in many different processes. Should RSP5 be annotated, then, to regulation of each of these processes?

For example, ergosterol biosynthesis. If a mutation in RSP5 results in loss of ergosterol biosynthesis, then it seems reasonable to annotate RSP5 to regulation of ergosterol biosynthesis with an IMP evidence code.

High throughput experiments show many proteins ubiquitinated by RSP5. Without other experiments, is it appropriate to annotate RSP5 to regulation of any of the processes in which the target proteins are involved?

Consensus seemed to be no; in the absence of other experimental data (i.e. mutant phenotypes) making this type of annotation wouldn't be appropriate.

GOA: If NEDD4 ubiquitinates a protein, is it appropriate to annotate to protein binding to capture the target?

Some groups capture targets in comments, but should targets be captured more explicitly with the MF annotation?

An analogous situation would be capturing enzyme and substrate interactions with a binding term.

In the past, there's been an understanding that if a physical interaction was transient, for example, an enzyme substrate interaction, then we haven't captured that binding interaction in GO.

However, how does this differ from a kinases being annotated to ATP binding, an annotation that *is* made in GO? (see InterPro2GO mappings, also)

Couldn't the relationship between kinase activity and ATP binding be captured in the ontology, i.e. kinase activity would be a child term of ATP binding?

Since not all kinases bind ATP, such a relationship would violate the true path rule.

But if we are going to annotate kinases that bind ATP to that MF term, we need to be consistent with other binding annotations.

Action Item: Put the issue of consistently annotating to binding terms on the agenda for the Montreal meeting.

Human and yeast NEDD4 proteins were annotated to many different BP terms. What are the appropriate terms for other groups to consider making ISS annotations?

Generally, MF and CC terms are more easily transferred for ISS annotations, but curators need to use discretion when making ISS annotations to BP terms. For example, it would be approrpiate to annotate a kinase to the BP term phosphorylation, but other processes would need to be assessed in the context of each organism and its biology.

The issue of automatic ISS annotations was raised. What is really meant by 'automatic ISS' and are these annotations ever appropriate?

The October 2008 electronic jamboree also annotated PFKL.

References

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1. ↑ ^{1.0 1.1 1.2 1.3 1.4 1.5 1.6} Anindya R et al. (2007) Damage-induced ubiquitylation of human RNA polymerase II by the ubiquitin ligase Nedd4, but not Cockayne syndrome proteins or BRCA1. Mol Cell 28: 386-97 PubMed GONUTS page
2. ↑ ^{2.0 2.1} Imhof MO & McDonnell DP (1996) Yeast RSP5 and its human homolog hRPF1 potentiate hormone-dependent activation of transcription by human progesterone and glucocorticoid receptors. Mol Cell Biol 16: 2594-605 PubMed GONUTS page
3. ↑ ^{3.0 3.1 3.2 3.3 3.4} Anan T et al. (1998) Human ubiquitin-protein ligase Nedd4: expression, subcellular localization and selective interaction with ubiquitin-conjugating enzymes. Genes Cells 3: 751-63 PubMed GONUTS page
4. ↑ ^{4.0 4.1} Wang X et al. (2007) NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN. Cell 128: 129-39 PubMed GONUTS page
5. ↑ Trotman LC et al. (2007) Ubiquitination regulates PTEN nuclear import and tumor suppression. Cell 128: 141-56 PubMed GONUTS page
6. ↑ ^{6.0 6.1 6.2 6.3} Shenoy SK et al. (2008) Nedd4 mediates agonist-dependent ubiquitination, lysosomal targeting, and degradation of the beta2-adrenergic receptor. J Biol Chem 283: 22166-76 PubMed GONUTS page
7. ↑ Pak Y et al. (2006) Transport of LAPTM5 to lysosomes requires association with the ubiquitin ligase Nedd4, but not LAPTM5 ubiquitination. J Cell Biol 175: 631-45 PubMed GONUTS page
8. ↑ ^{8.0 8.1 8.2 8.3 8.4} Farr TJ et al. (2000) Human Nedd4 interacts with the human epithelial Na+ channel: WW3 but not WW1 binds to Na+-channel subunits. Biochem J 345 Pt 3: 503-9 PubMed GONUTS page
9. ↑ ^{9.0 9.1 9.2 9.3} Ing B et al. (2007) Regulation of Commissureless by the ubiquitin ligase DNedd4 is required for neuromuscular synaptogenesis in Drosophila melanogaster. Mol Cell Biol 27: 481-96 PubMed GONUTS page
10. ↑ Gavva NR et al. (1997) Interaction of WW domains with hematopoietic transcription factor p45/NF-E2 and RNA polymerase II. J Biol Chem 272: 24105-8 PubMed GONUTS page
11. ↑ ^{11.0 11.1} Cristillo AD et al. (2003) Cloning and characterization of N4WBP5A, an inducible, cyclosporine-sensitive, Nedd4-binding protein in human T lymphocytes. J Biol Chem 278: 34587-97 PubMed GONUTS page
12. ↑ Kanelis V et al. (2006) Structural determinants for high-affinity binding in a Nedd4 WW3* domain-Comm PY motif complex. Structure 14: 543-53 PubMed GONUTS page
13. ↑ ^{13.0 13.1 13.2 13.3 13.4} Blot V et al. (2004) Nedd4.1-mediated ubiquitination and subsequent recruitment of Tsg101 ensure HTLV-1 Gag trafficking towards the multivesicular body pathway prior to virus budding. J Cell Sci 117: 2357-67 PubMed GONUTS page
14. ↑ Xu LL et al. (2003) PMEPA1, an androgen-regulated NEDD4-binding protein, exhibits cell growth inhibitory function and decreased expression during prostate cancer progression. Cancer Res 63: 4299-304 PubMed GONUTS page
15. ↑ Hamilton MH et al. (2001) Nuclear import/export of hRPF1/Nedd4 regulates the ubiquitin-dependent degradation of its nuclear substrates. J Biol Chem 276: 26324-31 PubMed GONUTS page
16. ↑ ^{16.0 16.1 16.2 16.3 16.4} Sakata T et al. (2004) Drosophila Nedd4 regulates endocytosis of notch and suppresses its ligand-independent activation. Curr Biol 14: 2228-36 PubMed GONUTS page
17. ↑ ^{17.0 17.1} 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: 3656-61 PubMed GONUTS page
18. ↑ ^{18.0 18.1 18.2} 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: 135-44 PubMed GONUTS page
19. ↑ Stamenova SD et al. (2004) The Rsp5 ubiquitin ligase binds to and ubiquitinates members of the yeast CIN85-endophilin complex, Sla1-Rvs167. J Biol Chem 279: 16017-25 PubMed GONUTS page
20. ↑ Springael JY & André B (1998) Nitrogen-regulated ubiquitination of the Gap1 permease of Saccharomyces cerevisiae. Mol Biol Cell 9: 1253-63 PubMed GONUTS page
21. ↑ Kim Y et al. (2007) GGA2- and ubiquitin-dependent trafficking of Arn1, the ferrichrome transporter of Saccharomyces cerevisiae. Mol Biol Cell 18: 1790-802 PubMed GONUTS page
22. ↑ Gwizdek C et al. (2005) The mRNA nuclear export factor Hpr1 is regulated by Rsp5-mediated ubiquitylation. J Biol Chem 280: 13401-5 PubMed GONUTS page
23. ↑ Oestreich AJ et al. (2007) Characterization of multiple multivesicular body sorting determinants within Sna3: a role for the ubiquitin ligase Rsp5. Mol Biol Cell 18: 707-20 PubMed GONUTS page
24. ↑ Shcherbik N et al. (2003) Rsp5p is required for ER bound Mga2p120 polyubiquitination and release of the processed/tethered transactivator Mga2p90. Curr Biol 13: 1227-33 PubMed GONUTS page
25. ↑ Dunn R & Hicke L (2001) Domains of the Rsp5 ubiquitin-protein ligase required for receptor-mediated and fluid-phase endocytosis. Mol Biol Cell 12: 421-35 PubMed GONUTS page
26. ↑ Davies BA et al. (2003) Vps9p CUE domain ubiquitin binding is required for efficient endocytic protein traffic. J Biol Chem 278: 19826-33 PubMed GONUTS page
27. ↑ Hoppe T et al. (2000) Activation of a membrane-bound transcription factor by regulated ubiquitin/proteasome-dependent processing. Cell 102: 577-86 PubMed GONUTS page
28. ↑ Harkness TA et al. (2002) The ubiquitin-dependent targeting pathway in Saccharomyces cerevisiae plays a critical role in multiple chromatin assembly regulatory steps. Genetics 162: 615-32 PubMed GONUTS page
29. ↑ Kraft C & Peter M (2008) Is the Rsp5 ubiquitin ligase involved in the regulation of ribophagy? Autophagy 4: 838-40 PubMed GONUTS page
30. ↑ ^{30.0 30.1 30.2 30.3 30.4 30.5} Neumann S et al. (2003) Formation and nuclear export of tRNA, rRNA and mRNA is regulated by the ubiquitin ligase Rsp5p. EMBO Rep 4: 1156-62 PubMed GONUTS page
31. ↑ Beaudenon SL et al. (1999) Rsp5 ubiquitin-protein ligase mediates DNA damage-induced degradation of the large subunit of RNA polymerase II in Saccharomyces cerevisiae. Mol Cell Biol 19: 6972-9 PubMed GONUTS page
32. ↑ Andoh T et al. (2002) PY motifs of Rod1 are required for binding to Rsp5 and for drug resistance. FEBS Lett 525: 131-4 PubMed GONUTS page
33. ↑ Fisk HA & Yaffe MP (1999) A role for ubiquitination in mitochondrial inheritance in Saccharomyces cerevisiae. J Cell Biol 145: 1199-208 PubMed GONUTS page
34. ↑ Kaliszewski P et al. (2008) Rsp5p ubiquitin ligase and the transcriptional activators Spt23p and Mga2p are involved in co-regulation of biosynthesis of end products of the mevalonate pathway and triacylglycerol in yeast Saccharomyces cerevisiae. Biochim Biophys Acta PubMed GONUTS page
35. ↑ Gourlay CW & Ayscough KR (2005) Identification of an upstream regulatory pathway controlling actin-mediated apoptosis in yeast. J Cell Sci 118: 2119-32 PubMed GONUTS page
36. ↑ Crespo JL et al. (2004) NPR1 kinase and RSP5-BUL1/2 ubiquitin ligase control GLN3-dependent transcription in Saccharomyces cerevisiae. J Biol Chem 279: 37512-7 PubMed GONUTS page
37. ↑ Estrella LA et al. (2008) The Rsp5 E3 ligase mediates turnover of low affinity phosphate transporters in Saccharomyces cerevisiae. J Biol Chem 283: 5327-34 PubMed GONUTS page
38. ↑ Yashiroda H et al. (1998) The PY-motif of Bul1 protein is essential for growth of Saccharomyces cerevisiae under various stress conditions. Gene 225: 39-46 PubMed GONUTS page
39. ↑ Reinders J et al. (2006) Toward the complete yeast mitochondrial proteome: multidimensional separation techniques for mitochondrial proteomics. J Proteome Res 5: 1543-54 PubMed GONUTS page
40. ↑ Sickmann A et al. (2003) The proteome of Saccharomyces cerevisiae mitochondria. Proc Natl Acad Sci U S A 100: 13207-12 PubMed GONUTS page
41. ↑ ^{41.0 41.1 41.2} 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: 468-80 PubMed GONUTS page
42. ↑ Wilkin MB et al. (2004) Regulation of notch endosomal sorting and signaling by Drosophila Nedd4 family proteins. Curr Biol 14: 2237-44 PubMed GONUTS page
43. ↑ ^{43.0 43.1 43.2 43.3} Myat A et al. (2002) Drosophila Nedd4, a ubiquitin ligase, is recruited by Commissureless to control cell surface levels of the roundabout receptor. Neuron 35: 447-59 PubMed GONUTS page
44. ↑ Keleman K et al. (2005) Comm function in commissural axon guidance: cell-autonomous sorting of Robo in vivo. Nat Neurosci 8: 156-63 PubMed GONUTS page
45. ↑ Morrione A et al. (1999) mGrb10 interacts with Nedd4. J Biol Chem 274: 24094-9 PubMed GONUTS page
46. ↑ ^{46.0 46.1} Hatakeyama S et al. (1997) Subcellular localization and ubiquitin-conjugating enzyme (E2) interactions of mammalian HECT family ubiquitin protein ligases. J Biol Chem 272: 15085-92 PubMed GONUTS page
47. ↑ Jolliffe CN et al. (2000) Identification of multiple proteins expressed in murine embryos as binding partners for the WW domains of the ubiquitin-protein ligase Nedd4. Biochem J 351 Pt 3: 557-65 PubMed GONUTS page