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

GO curators for mouse genes have assigned the following annotations to the gene product of Itch. (This text reflects annotations as of Wednesday, January 23, 2013.)

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the Nedd4 family of HECT domain E3 ubiquitin ligases. HECT domain E3 ubiquitin ligases transfer ubiquitin from E2 ubiquitin-conjugating enzymes to protein substrates, thus targeting specific proteins for lysosomal degradation. The encoded protein plays a role in multiple cellular processes including erythroid and lymphoid cell differentiation and the regulation of immune responses. Mutations in this gene are a cause of syndromic multisystem autoimmune disease. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

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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 Itch
  • participates in the following biological processes:
    • positive regulation of protein catabolic process ^[1]
    • protein polyubiquitination ^[1]
    • protein ubiquitination involved in ubiquitin-dependent protein catabolic process ^[1]
    • ubiquitin-dependent protein catabolic process ^[3]
  • is located in the following cellular components:
    • cell cortex ^[2]
    • cytoplasm ^[1]
    • cytoplasmic vesicle ^[2]
    • membrane ^[1]
    • nucleus ^[5]
• The gene product of Itch has been shown to bind to the gene products of Tax1bp1. ^[4]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Itch
  • participates in the following biological processes:
    • negative regulation of alpha-beta T cell proliferation ^[1]
    • negative regulation of defense response to virus ^[6]
    • negative regulation of JNK cascade ^[4]
    • negative regulation of NF-kappaB transcription factor activity ^[4]
    • positive regulation of protein catabolic process ^[1]
    • positive regulation of T cell anergy ^[1]
    • protein K48-linked ubiquitination ^[4]
    • regulation of protein deubiquitination ^[4]
  • performs the following molecular functions:
    • ligase activity ^[4]

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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 Itch:
  • participates in the following biological processes:
    • negative regulation of apoptotic process
    • negative regulation of defense response to virus
    • protein K29-linked ubiquitination
    • protein K48-linked ubiquitination
    • protein K63-linked ubiquitination
    • protein ubiquitination
    • ubiquitin-dependent protein catabolic process
  • performs the following molecular functions:
    • CXCR chemokine receptor binding
    • ribonucleoprotein complex binding
    • ubiquitin-protein ligase activity
  • is located in the following cellular components:
    • cytoplasm
    • plasma membrane
    • ubiquitin ligase complex

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Summary text based on GO annotations supported by structural data

• Itch encodes a protein or proteins that contain the following InterPro domains: C2 calcium-dependent membrane targeting, C2 calcium/lipid-binding domain, CaLB, 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 Itch indicates that it:
  • participates in the following biological processes:
    • apoptotic process
    • defense response to virus
    • innate immune response

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References

1. Heissmeyer V et al. (2004) Calcineurin imposes T cell unresponsiveness through targeted proteolysis of signaling proteins. Nat Immunol, 5:255-65. (PubMed:14973438)
2. Oliver PM et al. (2006) Ndfip1 protein promotes the function of itch ubiquitin ligase to prevent T cell activation and T helper 2 cell-mediated inflammation. Immunity, 25:929-40. (PubMed:17137798)
3. Rossi M et al. (2005) The ubiquitin-protein ligase Itch regulates p73 stability. EMBO J, 24:836-48. (PubMed:15678106)
4. Shembade N et al. (2008) The E3 ligase Itch negatively regulates inflammatory signaling pathways by controlling the function of the ubiquitin-editing enzyme A20. Nat Immunol, 9:254-62. (PubMed:18246070)
5. Sutherland HG et al. (2001) Large-scale identification of mammalian proteins localized to nuclear sub-compartments. Hum Mol Genet, 10:1995-2011. (PubMed:11555636)
6. You F et al. (2009) PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin ligase AIP4. Nat Immunol, 10:1300-8. (PubMed:19881509)

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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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