ITCH

ITCH

itchy E3 ubiquitin protein ligase | AIP4

This gene encodes a member of the Nedd4 family of HECT domain E3 ubiquitin ligases. HECT domain E3 ubiquitin ligases transfer ubiquitin from E2 ubiquitin-conjugating enzymes to protein substrates, thus targeting specific proteins for lysosomal degradation. The encoded protein plays a role in multiple cellular processes including erythroid and lymphoid cell differentiation and the regulation of immune responses. Mutations in this gene are a cause of syndromic multisystem autoimmune disease. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

Member of: DE-2 DE-2.1

Biological processes 79 terms

CXCR chemokine receptor binding (GO:0045236)arrestin family protein binding (GO:1990763)cell cortex (GO:0005938)cell periphery (GO:0071944)cytoplasm (GO:0005737)cytoplasm (GO:0005737)cytoplasmic vesicle (GO:0031410)cytoplasmic vesicle (GO:0031410)cytosol (GO:0005829)cytosol (GO:0005829)early endosome (GO:0005769)early endosome membrane (GO:0031901)endosome membrane (GO:0010008)extracellular exosome (GO:0070062)inflammatory response (GO:0006954)ligase activity (GO:0016874)membrane (GO:0016020)membrane (GO:0016020)mitochondrion (GO:0005739)negative regulation of JNK cascade (GO:0046329)negative regulation of JNK cascade (GO:0046329)negative regulation of apoptotic process (GO:0043066)negative regulation of canonical NF-kappaB signal transduction (GO:0043124)negative regulation of canonical NF-kappaB signal transduction (GO:0043124)negative regulation of cytoplasmic pattern recognition receptor signaling pathway (GO:0039532)negative regulation of defense response to virus (GO:0050687)negative regulation of defense response to virus (GO:0050687)negative regulation of immune system process (GO:0002683)negative regulation of intracellular signal transduction (GO:1902532)negative regulation of multicellular organismal process (GO:0051241)negative regulation of type I interferon production (GO:0032480)nucleoplasm (GO:0005654)nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway (GO:0035872)nucleus (GO:0005634)plasma membrane (GO:0005886)plasma membrane (GO:0005886)plasma membrane (GO:0005886)positive regulation of catabolic process (GO:0009896)positive regulation of immune system process (GO:0002684)positive regulation of receptor catabolic process (GO:2000646)proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161)proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161)proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161)protein K29-linked ubiquitination (GO:0035519)protein K48-linked ubiquitination (GO:0070936)protein K48-linked ubiquitination (GO:0070936)protein K63-linked ubiquitination (GO:0070534)protein autoubiquitination (GO:0051865)protein binding (GO:0005515)protein branched polyubiquitination (GO:0141198)protein monoubiquitination (GO:0006513)protein ubiquitination (GO:0016567)protein ubiquitination (GO:0016567)protein ubiquitination (GO:0016567)protein-containing complex (GO:0032991)receptor internalization (GO:0031623)regulation of cell growth (GO:0001558)regulation of hematopoietic stem cell differentiation (GO:1902036)regulation of necroptotic process (GO:0060544)regulation of protein deubiquitination (GO:0090085)regulation of protein deubiquitination (GO:0090085)ribonucleoprotein complex binding (GO:0043021)symbiont entry into host cell (GO:0046718)symbiont entry into host cell (GO:0046718)ubiquitin protein ligase activity (GO:0061630)ubiquitin protein ligase activity (GO:0061630)ubiquitin protein ligase activity (GO:0061630)ubiquitin protein ligase activity (GO:0061630)ubiquitin protein ligase activity (GO:0061630)ubiquitin protein ligase activity (GO:0061630)ubiquitin-dependent protein catabolic process (GO:0006511)ubiquitin-dependent protein catabolic process (GO:0006511)ubiquitin-dependent protein catabolic process (GO:0006511)ubiquitin-dependent protein catabolic process (GO:0006511)ubiquitin-like protein ligase binding (GO:0044389)ubiquitin-like protein transferase activity (GO:0019787)ubiquitin-protein transferase activity (GO:0004842)ubiquitin-protein transferase activity (GO:0004842)ubiquitin-ubiquitin ligase activity (GO:0034450)

Expression (TPM)

TFs regulating ITCH 0 TFs

Transcription factors with Perturb-seq knockdown data for ITCH. The Binding column indicates whether any binding evidence exists for this TF–gene pair (ChIP-seq or motif footprint peaks). The Mean coef is the average Perturb-seq regression coefficient across active gRNAs (positive = ITCH upregulated upon KD; negative = downregulated). The Outlier column indicates whether this gene is in the top or bottom 5% of all TF knockdown effects.

TF	Mean coef	Binding	Outlier	TF→Gene link

Rows:

Elements linked to ITCH

Open chromatin peaks (ATAC-seq) in the genomic neighbourhood of ITCH, linked by TSS proximity or chromatin conformation (Multiome / HiCAR). Each element overlaps at least one TF ChIP-seq binding site — the TFs column shows how many distinct TFs bind that element.

Accessibility	Element	Dist. to TSS	Link type	TFs
	chr20:34,111,659–34,113,028	251.0 kb	Distal (>10kb) Multiome	1069
	chr20:34,302,649–34,303,619	60.1 kb	Distal (>10kb) Multiome	1055
	chr20:34,311,332–34,311,914	51.8 kb	Distal (>10kb) Multiome	577
	chr20:34,312,547–34,313,008	50.4 kb	Distal (>10kb) Multiome	740
	chr20:34,345,865–34,346,371	17.1 kb	Distal (>10kb) Multiome	61
	chr20:34,362,888–34,363,977	at TSS	At TSS Multiome	858
	chr20:34,515,293–34,516,855	152.2 kb	Distal (>10kb) Multiome	1003
	chr20:34,549,322–34,549,906	186.4 kb	Distal (>10kb) Multiome	216
	chr20:34,558,287–34,559,412	195.4 kb	Distal (>10kb) Multiome	380

Genome Browser

Genomic view of the ITCH locus showing ATAC-seq accessibility and RNA-seq expression across the ESC → DE time course, together with TF binding peaks and element-to-TSS loop connections.