Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Nedd4. (This text reflects annotations as of Wednesday, January 23, 2013.) MGI curation of this mouse gene is considered complete, including annotations derived from the biomedical literature as of July 25, 2012. If you know of any additional information regarding this mouse gene please let us know. Please supply mouse gene symbol and a PubMed ID.

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Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Nedd4
  • participates in the following biological processes:
    • negative regulation of sodium ion transport ^[5]
    • negative regulation of vascular endothelial growth factor receptor signaling pathway ^[13]
    • positive regulation of protein catabolic process ^[4]
    • protein monoubiquitination ^[16]
    • protein ubiquitination ^[6]
  • performs the following molecular functions:
    • phosphoserine binding ^[11]
    • phosphothreonine binding ^[11]
    • sodium channel inhibitor activity ^[5]
    • ubiquitin-protein ligase activity ^{[6, 14]}
  • is located in the following cellular components:
    • cytoplasm ^[7]
    • cytosol ^{[1, 6]}
    • membrane ^[7]
• The gene product of Nedd4 has been shown to bind to the gene products of Adrbk1, Bean1, Dlg3, Grb10, N4bp1, N4bp3, Ndfip1, Rap2a, Scnn1b, Tnik. ^{[8, 9, 12, 13, 14, 15, 16]} Researchers have inferred, based on physical interactions, that the gene product of Nedd4
  • performs the following molecular functions:
    • proline-rich region binding ^{[3, 4]}
  • is located in the following cellular components:
    • ubiquitin ligase complex ^[8]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Nedd4
  • participates in the following biological processes:
    • adaptive immune response ^[17]
    • blood vessel morphogenesis ^[2]
    • endocardial cushion development ^[2]
    • negative regulation of transcription from RNA polymerase II promoter ^[2]
    • neuromuscular junction development ^[10]
    • outflow tract morphogenesis ^[2]
    • protein ubiquitination involved in ubiquitin-dependent protein catabolic process ^[17]
    • regulation of dendrite morphogenesis ^[9]
    • regulation of synapse organization ^[10]
    • T cell activation ^[17]
• Researchers have inferred, based on genetic interactions, that the gene product of Nedd4
  • participates in the following biological processes:
    • blood vessel morphogenesis based on interactions with Thbs1 ^[2]
    • endocardial cushion development based on interactions with Thbs1 ^[2]
    • outflow tract morphogenesis based on interactions with Thbs1 ^[2]

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Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Nedd4:
  • participates in the following biological processes:
    • cellular response to UV
    • development involved in symbiotic interaction
    • glucocorticoid receptor signaling pathway
    • lysosomal transport
    • negative regulation of sodium ion transport
    • negative regulation of transcription from RNA polymerase II promoter in response to UV-induced DNA damage
    • positive regulation of nucleocytoplasmic transport
    • positive regulation of phosphatidylinositol 3-kinase cascade
    • positive regulation of protein catabolic process
    • progesterone receptor signaling pathway
    • protein K63-linked ubiquitination
    • protein targeting to lysosome
    • protein ubiquitination involved in ubiquitin-dependent protein catabolic process
    • receptor catabolic process
    • receptor internalization
    • regulation of dendrite morphogenesis
    • regulation of ion transmembrane transport
    • regulation of membrane potential
    • regulation of potassium ion transmembrane transporter activity
    • transmission of virus
    • ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
  • performs the following molecular functions:
    • beta-2 adrenergic receptor binding
    • proline-rich region binding
    • protein C-terminus binding
    • protein domain specific binding
    • RNA polymerase binding
    • sodium channel inhibitor activity
    • ubiquitin binding
    • ubiquitin-protein ligase activity
  • is located in the following cellular components:
    • cell cortex
    • chromatin
    • cytoplasm
    • Golgi apparatus
    • membrane raft
    • microvillus
    • nucleus
    • perinuclear region of cytoplasm
    • plasma membrane

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Summary text based on GO annotations supported by structural data

• Nedd4 encodes a protein or proteins that contain the following InterPro domains: C2 calcium-dependent membrane targeting, C2 calcium/lipid-binding domain, CaLB, C2 domain, C2 membrane targeting protein, E3 ubiquitin-protein ligase, SMURF1 type, HECT, WW/Rsp5/WWP, indicating that the gene product:
  • participates in the following biological processes:
    • cellular protein modification process
  • is located in the following cellular components:
    • intracellular

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Nedd4 indicates that it:
  • participates in the following biological processes:
    • nervous system development
  • performs the following molecular functions:
    • ligase activity

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References

1. Aitken JF et al. (2010) Tetracycline treatment retards the onset and slows the progression of diabetes in human amylin/islet amyloid polypeptide transgenic mice. Diabetes, 59:161-71. (PubMed:19794060)
2. Fouladkou F et al. (2010) The ubiquitin ligase Nedd4-1 is required for heart development and is a suppressor of thrombospondin-1. J Biol Chem, 285:6770-80. (PubMed:20026598)
3. 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:9305852)
4. Harvey KF et al. (2002) N4WBP5, a potential target for ubiquitination by the Nedd4 family of proteins, is a novel Golgi-associated protein. J Biol Chem, 277:9307-17. (PubMed:11748237)
5. Harvey KF et al. (1999) All three WW domains of murine Nedd4 are involved in the regulation of epithelial sodium channels by intracellular Na+. J Biol Chem, 274:12525-30. (PubMed:10212229)
6. 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:9182527)
7. Heissmeyer V et al. (2004) Calcineurin imposes T cell unresponsiveness through targeted proteolysis of signaling proteins. Nat Immunol, 5:255-65. (PubMed:14973438)
8. 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:11042109)
9. Kawabe H et al. (2010) Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development. Neuron, 65:358-72. (PubMed:20159449)
10. Liu Y et al. (2009) Abnormal development of the neuromuscular junction in Nedd4-deficient mice. Dev Biol, 330:153-66. (PubMed:19345204)
11. Lu PJ et al. (1999) Function of WW domains as phosphoserine- or phosphothreonine-binding modules. Science, 283:1325-8. (PubMed:10037602)
12. Morrione A et al. (1999) mGrb10 interacts with Nedd4. J Biol Chem, 274:24094-9. (PubMed:10446181)
13. Murdaca J et al. (2004) Grb10 prevents Nedd4-mediated vascular endothelial growth factor receptor-2 degradation. J Biol Chem, 279:26754-61. (PubMed:15060076)
14. Murillas R et al. (2002) Identification of developmentally expressed proteins that functionally interact with Nedd4 ubiquitin ligase. J Biol Chem, 277:2897-907. (PubMed:11717310)
15. Sanchez-Perez A et al. (2007) GRK2 interacts with and phosphorylates Nedd4 and Nedd4-2. Biochem Biophys Res Commun, 359:611-5. (PubMed:17544362)
16. Van Campenhout CA et al. (2011) Dlg3 trafficking and apical tight junction formation is regulated by nedd4 and nedd4-2 e3 ubiquitin ligases. Dev Cell, 21:479-91. (PubMed:21920314)
17. Yang B et al. (2008) Nedd4 augments the adaptive immune response by promoting ubiquitin-mediated degradation of Cbl-b in activated T cells. Nat Immunol, 9:1356-63. (PubMed:18931680)

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Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

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