ITCH

2DMV, 2KYK, 2NQ3, 2P4R, 2YSF, 3TUG, 4ROF, 5CQ2, 5DWS, 5DZD, 5C7M8373716396ENSG00000078747ENSMUSG00000027598Q96J02Q8C863NM_001257137NM_001257138NM_031483NM_001324197NM_001324198NM_001243712NM_008395NP_001244066NP_001244067NP_001311126NP_001311127NP_113671NP_001230641NP_032421ITCH is a HECT domain–containing E3 ubiquitin ligase that is ablated in non-agouti-lethal 18H (aka Itchy) mice.

[5][6] Itchy mice develop a severe immunological phenotype after birth that includes hyperplasia of lymphoid and hematopoietic cells, and stomach and lung inflammation.

[7][8] In humans ITCH deficiency causes altered physical growth, craniofacial morphology defects, defective muscle development, and aberrant immune system function.

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.

MAPK8 regulates JUNB protein turnover by the phosphorylation of ITCH and a conformational change. Importantly, this regulatory process controls the balance of T helper 2 cytokine production by negatively regulating JUNB turnover and Interleukin 4 transcription.