ITCH

Itch
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 1YIU, 2JO9, 2JOC
Identifiers
Aliases	6720481N21Rik8030492O04RikA130065M08AIP4C230047C07RikitchyE3 ubiquitin protein ligase
External IDs	HomoloGene: 88442; GeneCards: [1]; OMA:- orthologs
Gene location (Human) Chr. Chromosome 2 (human) Band 2 H1|2 76.94 cM Start 154,975,429 bp End 155,068,775 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Rostral migratory stream genital tubercle mesenteric lymph nodes calvaria hand jejunum tail of embryo lacrimal gland epithelium of small intestine right kidney n/a More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding ubiquitin-protein transferase activity transferase activity ligase activity ribonucleoprotein complex binding CXCR chemokine receptor binding ubiquitin protein ligase activity ubiquitin-like protein ligase binding arrestin family protein binding Cellular component cytosol ubiquitin ligase complex plasma membrane cell cortex cytoplasmic vesicle nucleus cytoplasm nucleoplasm early endosome endosome endosome membrane early endosome membrane membrane intracellular membrane-bounded organelle protein-containing complex Biological process positive regulation of protein catabolic process immune system process protein polyubiquitination regulation of protein deubiquitination negative regulation of JNK cascade negative regulation of alpha-beta T cell proliferation positive regulation of T cell anergy defense response to virus protein ubiquitination innate immune response negative regulation of NF-kappaB transcription factor activity apoptotic process negative regulation of apoptotic process negative regulation of defense response to virus protein K48-linked ubiquitination ubiquitin-dependent protein catabolic process protein K29-linked ubiquitination proteasome-mediated ubiquitin-dependent protein catabolic process protein K63-linked ubiquitination protein autoubiquitination positive regulation of receptor catabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 16396 n/a Ensembl ENSMUSG00000027598 n/a UniProt Q8C863 Q8C863 RefSeq (mRNA) NM_001243712 NM_008395 n/a RefSeq (protein) NP_001230641 NP_032421 NP_001230641 NP_032421 Location (UCSC) Chr 2: 154.98 – 155.07 Mb n/a PubMed search [1] n/a
Wikidata
View/Edit Human

ITCH is a HECT domain–containing E3 ubiquitin ligase that is ablated in non-agouti-lethal 18H (aka Itchy) mice.^[2][3] Itchy mice develop a severe immunological phenotype after birth that includes hyperplasia of lymphoid and hematopoietic cells, and stomach and lung inflammation.^[4][5] In humans ITCH deficiency causes altered physical growth, craniofacial morphology defects, defective muscle development, and aberrant immune system function.^[6] The ITCH gene is located on chromosome 20 in humans.^[7] ITCH contains a C2 domain, proline-rich region, WW domains, HECT domain, and multiple amino acids that are phosphorylated and ubiquitinated.^[8]

ITCH is regulated by MAPK8.^[9] MAPK8 regulates JUNB protein turnover by MAPK8-dependent phosphorylation of ITCH and a subsequent conformational change in ITCH. This mechanism is discrete from the direct activation of Jun family transcription factors by direct phosphorylation. ITCH serves as a paradigm for our understanding of the regulation of the ubiquitylation machinery by direct protein phosphorylation of its components. Importantly, this regulatory process controls the balance of Th2 cytokine secretion by negatively regulating JUNB levels and Interleukin 4 transcription.^[10]

Itch has been shown to interact with a number of proteins,^[11] including:

• CXCR4,^[12]
• c-Jun,^[13]
• MAP2K4,^[14]
• MAP3K1,^[15]
• MAP3K7,^[16]
• MAPK8,^[17]
• N4BP1,^[18]
• NOTCH1,^[19]
• TP63,^[20] and
• TP73.^[21]

• ITCH+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)