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Identification
HMDB Protein ID HMDBP13430
Secondary Accession Numbers None
Name E3 ubiquitin-protein ligase Itchy homolog
Synonyms
  1. Itch
  2. Atrophin-1-interacting protein 4
  3. HECT-type E3 ubiquitin transferase Itchy homolog
  4. NFE2-associated polypeptide 1
  5. AIP4
  6. NAPP1
Gene Name ITCH
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function 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 (PubMed:14602072, PubMed:17028573, PubMed:16387660, PubMed:18718448, PubMed:18718449, PubMed:11046148, PubMed:19592251, PubMed:19116316, PubMed:19881509, PubMed:20491914, PubMed:20392206, PubMed:20068034, PubMed:23146885, PubMed:24790097, PubMed:25631046). Catalyzes 'Lys-29'-, 'Lys-48'- and 'Lys-63'-linked ubiquitin conjugation (PubMed:17028573, PubMed:18718448, PubMed:19131965, PubMed:19881509). Involved in the control of inflammatory signaling pathways (PubMed:19131965). Essential component of a ubiquitin-editing protein complex, comprising also TNFAIP3, TAX1BP1 and RNF11, that ensures the transient nature of inflammatory signaling pathways (PubMed:19131965). Promotes the association of the complex after TNF stimulation (PubMed:19131965). Once the complex is formed, TNFAIP3 deubiquitinates 'Lys-63' polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains (PubMed:19131965). This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NFKB1 (PubMed:19131965). Ubiquitinates RIPK2 by 'Lys-63'-linked conjugation and influences NOD2-dependent signal transduction pathways (PubMed:19592251). Regulates the transcriptional activity of several transcription factors, and probably plays an important role in the regulation of immune response (PubMed:18718448, PubMed:20491914). Ubiquitinates NFE2 by 'Lys-63' linkages and is implicated in the control of the development of hematopoietic lineages (PubMed:18718448). Mediates JUN ubiquitination and degradation (By similarity). Mediates JUNB ubiquitination and degradation (PubMed:16387660). Critical regulator of type 2 helper T (Th2) cell cytokine production by inducing JUNB ubiquitination and degradation (By similarity). Involved in the negative regulation of MAVS-dependent cellular antiviral responses (PubMed:19881509). Ubiquitinates MAVS through 'Lys-48'-linked conjugation resulting in MAVS proteasomal degradation (PubMed:19881509). Following ligand stimulation, regulates sorting of Wnt receptor FZD4 to the degradative endocytic pathway probably by modulating PI42KA activity (PubMed:23146885). Ubiquitinates PI4K2A and negatively regulates its catalytic activity (PubMed:23146885). Ubiquitinates chemokine receptor CXCR4 and regulates sorting of CXCR4 to the degradative endocytic pathway following ligand stimulation by ubiquitinating endosomal sorting complex required for transport ESCRT-0 components HGS and STAM (PubMed:14602072, PubMed:23146885). Targets DTX1 for lysosomal degradation and controls NOTCH1 degradation, in the absence of ligand, through 'Lys-29'-linked polyubiquitination (PubMed:17028573, PubMed:18628966, PubMed:23886940). Ubiquitinates SNX9 (PubMed:20491914). Ubiquitinates MAP3K7 through 'Lys-48'-linked conjugation (By similarity). Involved in the regulation of apoptosis and reactive oxygen species levels through the ubiquitination and proteasomal degradation of TXNIP (PubMed:20068034). Mediates the antiapoptotic activity of epidermal growth factor through the ubiquitination and proteasomal degradation of p15 BID (PubMed:20392206). Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046). Inhibits the replication of influenza A virus (IAV) via ubiquitination of IAV matrix protein 1 (M1) through 'Lys-48'-linked conjugation resulting in M1 proteasomal degradation (PubMed:30328013).
Pathways
  • Endocytosis
  • Non-alcoholic fatty liver disease
  • protein ubiquitination
  • TNF signaling pathway
  • Ubiquitin mediated proteolysis
Reactions Not Available
GO Classification
Biological Process
regulation of cell growth
positive regulation of protein catabolic process
protein polyubiquitination
viral entry into host cell
apoptotic process
negative regulation of apoptotic process
Notch signaling pathway
inflammatory response
protein K48-linked ubiquitination
ubiquitin-dependent protein catabolic process
protein K29-linked ubiquitination
protein K63-linked ubiquitination
protein autoubiquitination
nucleotide-binding oligomerization domain containing signaling pathway
negative regulation of type I interferon production
regulation of hematopoietic stem cell differentiation
defense response to virus
innate immune response
negative regulation of NF-kappaB transcription factor activity
negative regulation of JNK cascade
negative regulation of defense response to virus
positive regulation of receptor catabolic process
proteasomal ubiquitin-dependent protein catabolic process
regulation of protein deubiquitination
protein ubiquitination
Cellular Component
cytosol
protein-containing complex
cytoplasm
extracellular vesicular exosome
plasma membrane
early endosome membrane
nucleoplasm
membrane
cytoplasmic vesicle
intracellular membrane-bounded organelle
Molecular Function
ubiquitin-protein ligase activity
ubiquitin protein ligase activity
ribonucleoprotein complex binding
arrestin family protein binding
CXCR chemokine receptor binding
ubiquitin-like protein ligase binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 903
Molecular Weight 102802.11
Theoretical pI 6.306
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q96J02
UniProtKB/Swiss-Prot Entry Name ITCH_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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