ITCH - E3 ubiquitin-protein ligase Itchy homolog - human protein (Function)
 
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References

 
ITCH »  E3 ubiquitin-protein ligase Itchy homolog   [ EC 6.3.2.- ]  (Itch)
 
Protein also known as:  Atrophin-1-interacting protein 4 (AIP4).
Gene name:  ITCH
Entry whose protein(s) existence is based on evidence at protein level
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1 116 3
GENE REF ISO

Function

 show evidences
Overview 
Acts as an E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. It catalyzes 'Lys-29'-, 'Lys-48'- and 'Lys-63'-linked ubiquitin conjugation. It is involved in the control of inflammatory signaling pathways. Is an essential component of a ubiquitin-editing protein complex, comprising also TNFAIP3, TAX1BP1 and RNF11, that ensures the transient nature of inflammatory signaling pathways. Promotes the association of the complex after TNF stimulation. Once the complex is formed, TNFAIP3 deubiquitinates 'Lys-63' polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains. This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NFKB1. Ubiquitinates RIPK2 by 'Lys-63'-linked conjugation and influences NOD2-dependent signal transduction pathways. Regulates the transcriptional activity of several transcription factors, and probably plays an important role in the regulation of immune response. Ubiquitinates NFE2 by 'Lys-63' linkages and is implicated in the control of the development of hematopoietic lineages. Critical regulator of T-helper (TH2) cytokine development through its ability to induce JUNB ubiquitination and degradation (By similarity). Ubiquitinates SNX9. Ubiquitinates CXCR4 and HGS/HRS and regulates sorting of CXCR4 to the degradative pathway. It is involved in the negative regulation of MAVS-dependent cellular antiviral responses. Ubiquitinates MAVS through 'Lys-48'-linked conjugation resulting in MAVS proteasomal degradation. Involved in the regulation of apoptosis and reactive oxygen species levels through the ubiquitination and proteasomal degradation of TXNIP. Mediates the antiapoptotic activity of epidermal growth factor through the ubiquitination and proteasomal degradation of p15 BID. Targets DTX1 for lysosomal degradation and controls NOTCH1 degradation, in the absence of ligand, through 'Lys-29'-linked polyubiquitination.  
11
  • CuratedUniProtKB
GO molecular function 
CXCR chemokine receptor bindingdefinition[GO:0045236]  
1
  • IPIUniProtKB
Ligase activitydefinition[GO:0016874] silver  
  • IEAOrtholog Compara
Protein bindingdefinition[GO:0005515]  
15
  • IPIIntAct
  • IPIUniProtKB
Ribonucleoprotein complex bindingdefinition[GO:0043021]  
1
  • IPIUniProtKB
Ubiquitin-protein transferase activitydefinition[GO:0004842]  
3
  • IDAUniProtKB
  • IDAMGI
GO biological process 
Apoptotic processdefinition[GO:0006915]  
  • IEAUniProtKB KW
Defense response to virusdefinition[GO:0051607]  
  • IEAUniProtKB KW
Inflammatory responsedefinition[GO:0006954]  
1
  • NASUniProtKB
Negative regulation of alpha-beta T cell proliferationdefinition[GO:0046642] silver  
  • IEAOrtholog Compara
Negative regulation of apoptotic processdefinition[GO:0043066]  
1
  • IMPUniProtKB
Negative regulation of defense response to virusdefinition[GO:0050687]  
1
  • IMPUniProtKB
Negative regulation of JNK cascadedefinition[GO:0046329]  
  • ISSOrtholog Curator
Negative regulation of NF-kappaB transcription factor activitydefinition[GO:0032088]  
  • ISSOrtholog Curator
Positive regulation of protein catabolic processdefinition[GO:0045732] silver  
  • IEAOrtholog Compara
Positive regulation of T cell anergydefinition[GO:0002669] silver  
  • IEAOrtholog Compara
Protein K29-linked ubiquitinationdefinition[GO:0035519]  
2
  • IDAUniProtKB
Protein K48-linked ubiquitinationdefinition[GO:0070936]  
1
  • IDAUniProtKB
Protein K63-linked ubiquitinationdefinition[GO:0070534]  
2
  • IDAUniProtKB
Protein ubiquitinationdefinition[GO:0016567]  
1
  • IDAUniProtKB
Protein ubiquitination involved in ubiquitin-dependent protein catabolic processdefinition[GO:0042787] silver  
  • IBARefGenome
Regulation of cell growthdefinition[GO:0001558]  
1
  • NASUniProtKB
Regulation of protein deubiquitinationdefinition[GO:0090085]  
  • ISSOrtholog Curator
Ubiquitin-dependent protein catabolic processdefinition[GO:0006511]  
2
  • IDAMGI
  • NASUniProtKB
Viral entry into host celldefinition[GO:0046718]  
1
  • TASUniProtKB
Enzymatic activity 
It is regulated in the following manner
Activated by NDFIP1- and NDFIP2-binding (By similarity).  
  • CuratedUniProtKB
Pathways 
This protein is involved in the following pathway
According to Reactome, this protein belongs to the following pathways:
Activated NOTCH1 Transmits Signal to the Nucleus  REACT_118614  
Antigen processing: Ubiquitination & Proteasome degradation  REACT_75842  
Downregulation of ERBB4 signaling  REACT_115828  
Negative regulators of RIG-I/MDA5 signaling  REACT_25271  
NOD1/2 Signaling Pathway  REACT_75776  
 

Keywords

Biological process 
Antiviral defense  definition   [KW-0051]
Apoptosis  definition   [KW-0053]
Host-virus interaction  definition   [KW-0945]
Immunity  definition   [KW-0391]
Innate immunity  definition   [KW-0399]
Ubl conjugation pathway  definition   [KW-0833]
Molecular function 
Ligase  definition   [KW-0436]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GenomeRNAi: 83737
PRO: PR:Q96J02