Itch itchy, E3 ubiquitin protein ligase [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Itchprovided by MGI
Official Full Name: itchy, E3 ubiquitin protein ligaseprovided by MGI
Primary source: MGI:MGI:1202301
See related: Ensembl:ENSMUSG00000027598 AllianceGenome:MGI:1202301
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: AIP4; A130065M08; 6720481N21Rik; 8030492O04Rik; C230047C07Rik
Summary: Enables ligase activity. Involved in several processes, including negative regulation of JNK cascade; negative regulation of NF-kappaB transcription factor activity; and protein K48-linked ubiquitination. Acts upstream of or within several processes, including cellular protein metabolic process; negative regulation of alpha-beta T cell proliferation; and positive regulation of T cell anergy. Located in several cellular components, including cell cortex; cytoplasmic vesicle; and nucleus. Is expressed in several structures, including cardiovascular system; central nervous system; genitourinary system; gut; and sensory organ. Orthologous to human ITCH (itchy E3 ubiquitin protein ligase). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in limb E14.5 (RPKM 9.0), CNS E11.5 (RPKM 8.0) and 28 other tissues See more
Orthologs: human all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 2 H1; 2 76.94 cM

Exon count:: 27

Annotation release	Status	Assembly	Chr	Location
109	current	GRCm39 (GCF_000001635.27)	2	NC_000068.8 (154975401..155068775)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	2	NC_000068.7 (155133481..155226855)

Chromosome 2 - NC_000068.8 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

PRMT5 epigenetically regulates the E3 ubiquitin ligase ITCH to influence lipid accumulation during mycobacterial infection.
Title: PRMT5 epigenetically regulates the E3 ubiquitin ligase ITCH to influence lipid accumulation during mycobacterial infection.
ITCH E3 ubiquitin ligase downregulation compromises hepatic degradation of branched-chain amino acids.
Title: ITCH E3 ubiquitin ligase downregulation compromises hepatic degradation of branched-chain amino acids.
HECT (Homologous to the E6-AP Carboxyl Terminus)-Type Ubiquitin E3 Ligase ITCH Attenuates Cardiac Hypertrophy by Suppressing the Wnt/beta-Catenin Signaling Pathway.
Title: HECT (Homologous to the E6-AP Carboxyl Terminus)-Type Ubiquitin E3 Ligase ITCH Attenuates Cardiac Hypertrophy by Suppressing the Wnt/β-Catenin Signaling Pathway.
The E3 ubiquitin ligase Itch deficiency promotes antigen-driven B-cell responses in mice.
Title: The E3 ubiquitin ligase Itch deficiency promotes antigen-driven B-cell responses in mice.
Ubiquitination of interleukin-1alpha is associated with increased pro-inflammatory polarization of murine macrophages deficient in the E3 ligase ITCH.
Title: Ubiquitination of interleukin-1α is associated with increased pro-inflammatory polarization of murine macrophages deficient in the E3 ligase ITCH.
Gut Microbiota Contributes to Spontaneous Colitis in E3 Ligase Itch-Deficient Mice.
Title: Gut Microbiota Contributes to Spontaneous Colitis in E3 Ligase Itch-Deficient Mice.
miR-34b/c regulates doxorubicin-induced myocardial cell injury through ITCH.
Title: miR-34b/c regulates doxorubicin-induced myocardial cell injury through ITCH.
identified a novel regulatory axis between Itch and Foxo1 in B cells, suggesting that Itch is essential for B-cell development.
Title: The E3 ubiquitin ligase Itch is required for B-cell development.
These results support a novel role for Itch in limiting B cell metabolism and proliferation to suppress antigen-driven B cell responses.
Title: The E3 ubiquitin ligase Itch restricts antigen-driven B cell responses.
Itch and WWP2 cooperate to regulate TH2 differentiation by enhancing the strength of the TCR signal via inducing atypical ubiquitination of the phosphatase SHP-1.
Title: The E3 ligases Itch and WWP2 cooperate to limit T(H)2 differentiation by enhancing signaling through the TCR.

Submit: New GeneRIF Correction See all GeneRIFs (50)

Variation

Go to the top of the page Help

Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (4) 1 citation
Chemically induced (ENU) (1)
Endonuclease-mediated (1)

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Homology

Homologs of the Itch gene: The Itch gene is conserved in human, Rhesus monkey, dog, cow, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 452 organisms have orthologs with human gene Itch
Orthologs

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables CXCR chemokine receptor binding	ISO Inferred from Sequence Orthology more info
enables arrestin family protein binding	ISO Inferred from Sequence Orthology more info
enables ligase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables ribonucleoprotein complex binding	ISO Inferred from Sequence Orthology more info
enables transferase activity	IEA Inferred from Electronic Annotation more info
enables ubiquitin protein ligase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables ubiquitin protein ligase activity	ISA Inferred from Sequence Alignment more info	PubMed
enables ubiquitin protein ligase activity	ISO Inferred from Sequence Orthology more info	PubMed
enables ubiquitin-like protein ligase binding	ISO Inferred from Sequence Orthology more info
enables ubiquitin-protein transferase activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of CD4-positive, alpha-beta T cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of T cell anergy	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within apoptotic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within defense response to virus	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within immune system process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within innate immune response	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of CD4-positive, alpha-beta T cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of JNK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of NF-kappaB transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of defense response to virus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of defense response to virus	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of T cell anergy	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of receptor catabolic process	ISO Inferred from Sequence Orthology more info
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in protein K29-linked ubiquitination	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in protein K29-linked ubiquitination	ISO Inferred from Sequence Orthology more info
involved_in protein K48-linked ubiquitination	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in protein K48-linked ubiquitination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein K48-linked ubiquitination	ISO Inferred from Sequence Orthology more info
involved_in protein K63-linked ubiquitination	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in protein K63-linked ubiquitination	ISO Inferred from Sequence Orthology more info
involved_in protein autoubiquitination	ISO Inferred from Sequence Orthology more info
acts_upstream_of protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein monoubiquitination	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within protein polyubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in protein ubiquitination	ISO Inferred from Sequence Orthology more info
involved_in receptor internalization	ISO Inferred from Sequence Orthology more info
involved_in regulation of protein deubiquitination	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within ubiquitin-dependent protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within ubiquitin-dependent protein catabolic process	ISA Inferred from Sequence Alignment more info	PubMed
acts_upstream_of_or_within ubiquitin-dependent protein catabolic process	ISO Inferred from Sequence Orthology more info	PubMed
involved_in ubiquitin-dependent protein catabolic process	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in cell cortex	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic vesicle	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic vesicle	ISO Inferred from Sequence Orthology more info
located_in cytosol	TAS Traceable Author Statement more info
colocalizes_with early endosome	ISO Inferred from Sequence Orthology more info
located_in endosome	IEA Inferred from Electronic Annotation more info
located_in intracellular membrane-bounded organelle	ISO Inferred from Sequence Orthology more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	ISO Inferred from Sequence Orthology more info
part_of protein-containing complex	ISO Inferred from Sequence Orthology more info
part_of ubiquitin ligase complex	ISA Inferred from Sequence Alignment more info	PubMed

General protein information

Go to the top of the page Help

Preferred Names: E3 ubiquitin-protein ligase Itchy

Names: HECT-type E3 ubiquitin transferase Itchy homolog

NP_001230641.1

EC 2.3.2.26

NP_032421.2

EC 2.3.2.26

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001243712.1 → NP_001230641.1 E3 ubiquitin-protein ligase Itchy

See identical proteins and their annotated locations for NP_001230641.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 encode the same protein.

Source sequence(s)

AL845429, AL929588

Consensus CDS

CCDS38293.1

UniProtKB/Swiss-Prot

O54971, Q8C863

Related

ENSMUSP00000105307.2, ENSMUST00000109685.8

Conserved Domains (5) summary

cd04021
Location:17 → 140

C2_E3_ubiquitin_ligase; C2 domain present in E3 ubiquitin ligase

smart00456
Location:440 → 471

WW; Domain with 2 conserved Trp (W) residues

smart00119
Location:533 → 861

HECTc; Domain Homologous to E6-AP Carboxyl Terminus with

cd00078
Location:509 → 862

HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...

pfam00397
Location:401 → 430

WW; WW domain
NM_008395.3 → NP_032421.2 E3 ubiquitin-protein ligase Itchy

See identical proteins and their annotated locations for NP_032421.2

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the shorter transcript. Variants 1 and 2 encode the same protein.

Source sequence(s)

BC062934, BF453521, CJ122836

Consensus CDS

CCDS38293.1

UniProtKB/Swiss-Prot

O54971, Q8C863

Related

ENSMUSP00000029126.9, ENSMUST00000029126.15

Conserved Domains (5) summary

cd04021
Location:17 → 140

C2_E3_ubiquitin_ligase; C2 domain present in E3 ubiquitin ligase

smart00456
Location:440 → 471

WW; Domain with 2 conserved Trp (W) residues

smart00119
Location:533 → 861

HECTc; Domain Homologous to E6-AP Carboxyl Terminus with

cd00078
Location:509 → 862

HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...

pfam00397
Location:401 → 430

WW; WW domain