Anti-ITCH Antibody

The Itchy E3 ubiquitin protein ligase (ITCH) is a member of the Nedd4 family of HECT domain E3 ubiquitin ligases (1) . HECT domain E3 ubiquitin ligases transfer ubiquitin from E2 ubiquitin-conjugating enzymes to protein substrates, thus targeting specific proteins for lysosomal degradation. ITCH plays a role in multiple cellular processes including erythroid and lymphoid cell differentiation and the regulation of immune responses (2) . In B cells, ITCH is thought to associate with latent membrane protein 2A (LMP2A) of Epstein-Barr virus, specifically down-regulating its activity in B cell signaling (3) . Mutations in this gene are a cause of syndromic multisystem autoimmune disease (4) .

ITCH antibody is human, mouse and rat reactive. At least three isoforms of ITCH are known to exist; this antibody only recognizes the two longest isoforms. This antibody is predicted to not cross-react with other members of the Nedd4 protein family.

ITCH antibody was raised against a 15 amino acid peptide near the amino terminus of human ITCH . The immunogen is located within amino acids 40 - 90 of ITCH.

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) .