Summary

Name ITCH
Full Name E3 ubiquitin-protein ligase Itchy homolog
Synonyms Itch, Atrophin-1-interacting protein 4, AIP4, HECT-type E3 ubiquitin transferase Itchy homolog, NFE2-associated polypeptide 1, NAPP1
Primary ID Q96J02
Links - -
Type protein
Relations 39
Pathways NF-KB Canonical
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).

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Modifications Tables

Relations

Regulator Mechanism target score
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination MAVS 0.628
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png polyubiquitination H1-2 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation ITCH 0.643
Publications: 5 Organism: Homo Sapiens, Mus Musculus
+ up-regulates quantity img/direct-activation.png phosphorylation ITCH 0.327
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation ITCH 0.374
Publications: 1 Organism: Mus Musculus
+ down-regulates img/direct_inhibition.png ubiquitination NOTCH1 0.625
Publications: 1 Organism: Homo Sapiens
Tissue: Skin
+ up-regulates activity img/direct-activation.png binding ITCH 0.596
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png ubiquitination GLI1 0.554
Publications: 2 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination BCL10 0.282
Publications: 2 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation ITCH 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination, polyubiquitination ERBB4 0.586
Publications: 2 Organism: Chlorocebus Aethiops, Homo Sapiens
+ up-regulates activity img/direct-activation.png binding SPART 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding ITCH 0.575
Publications: 1 Organism: Homo Sapiens
Pathways:IL1 Signaling , NF-KB Canonical
+ down-regulates activity img/direct_inhibition.png ubiquitination TRPC4 0.357
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png ubiquitination ITCH 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding ITCH 0.595
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png ubiquitination SMAD7 0.521
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png ubiquitination NOTCH 0.625
Publications: 1 Organism: Homo Sapiens
Tissue: Skin
+ down-regulates img/direct_inhibition.png ubiquitination DTX1 0.686
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity img/direct_inhibition.png ubiquitination CFLAR 0.598
Publications: 1 Organism: Mus Musculus
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination LAPTM5 0.422
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png ubiquitination TRPV4 0.386
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding ITCH 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination JUNB 0.418
Publications: 1 Organism: Mus Musculus
+ up-regulates img/direct-activation.png phosphorylation ITCH 0.643
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png ubiquitination SMAD2 0.465
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination BID 0.359
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png ubiquitination NFE2 0.425
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination EGFR 0.469
Publications: 1 Organism: Chlorocebus Aethiops
+ down-regulates img/direct_inhibition.png ubiquitination TNIP2 0.274
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding TNFAIP3 0.287
Publications: 1 Organism: Homo Sapiens
Pathways:IL1 Signaling , NF-KB Canonical