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Aliases for ITCH Gene

Aliases for ITCH Gene

  • Itchy E3 Ubiquitin Protein Ligase 2 3
  • NAPP1 3 4 6
  • AIP4 3 4 6
  • NFE2-Associated Polypeptide 1 3 4
  • DJ468O1.1 (Atrophin 1 Interacting Protein 4 (AIP4)) 3
  • Itchy (Mouse Homolog) E3 Ubiquitin Protein Ligase 2
  • Itchy E3 Ubiquitin Protein Ligase Homolog (Mouse) 2
  • E3 Ubiquitin-Protein Ligase Itchy Homolog 3
  • Itchy E3 Ubiquitin Protein Ligase Homolog 3
  • Atrophin-1 Interacting Protein 4 3
  • Atrophin-1-Interacting Protein 4 4
  • EC 6.3.2.- 4
  • DJ468O1.1 3
  • EC 6.3.2 63
  • ADMFD 3
  • AIF4 3
  • Itch 4

External Ids for ITCH Gene

Previous GeneCards Identifiers for ITCH Gene

  • GC20P032709
  • GC20P033619
  • GC20P033666
  • GC20P032414
  • GC20P032951
  • GC20P029732

Summaries for ITCH Gene

Entrez Gene Summary for ITCH Gene

  • 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]

GeneCards Summary for ITCH Gene

ITCH (Itchy E3 Ubiquitin Protein Ligase) is a Protein Coding gene. Diseases associated with ITCH include autoimmune disease, multisystem, with facial dysmorphism and syndromic multisystem autoimmune disease due to itch deficiency. Among its related pathways are PI-3K cascade and Signaling by GPCR. GO annotations related to this gene include ubiquitin-protein transferase activity and CXCR chemokine receptor binding. An important paralog of this gene is AREL1.

UniProtKB/Swiss-Prot for ITCH Gene

  • 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. It catalyzes Lys-29-, Lys-48- and Lys-63-linked ubiquitin conjugation. It is involved in the control of inflammatory signaling pathways. Is an essential component of a ubiquitin-editing protein complex, comprising also TNFAIP3, TAX1BP1 and RNF11, that ensures the transient nature of inflammatory signaling pathways. Promotes the association of the complex after TNF stimulation. Once the complex is formed, TNFAIP3 deubiquitinates Lys-63 polyubiquitin chains on RIPK1 and catalyzes the formation of Lys-48-polyubiquitin chains. This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NFKB1. Ubiquitinates RIPK2 by Lys-63-linked conjugation and influences NOD2-dependent signal transduction pathways. Regulates the transcriptional activity of several transcription factors, and probably plays an important role in the regulation of immune response. Ubiquitinates NFE2 by Lys-63 linkages and is implicated in the control of the development of hematopoietic lineages. Critical regulator of T-helper (TH2) cytokine development through its ability to induce JUNB ubiquitination and degradation (By similarity). Ubiquitinates SNX9. Ubiquitinates CXCR4 and HGS/HRS and regulates sorting of CXCR4 to the degradative pathway. It is involved in the negative regulation of MAVS-dependent cellular antiviral responses. Ubiquitinates MAVS through Lys-48-linked conjugation resulting in MAVS proteasomal degradation. Involved in the regulation of apoptosis and reactive oxygen species levels through the ubiquitination and proteasomal degradation of TXNIP. Mediates the antiapoptotic activity of epidermal growth factor through the ubiquitination and proteasomal degradation of p15 BID. Targets DTX1 for lysosomal degradation and controls NOTCH1 degradation, in the absence of ligand, through Lys-29-linked polyubiquitination.

No data available for Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for ITCH Gene

Genomics for ITCH Gene

Regulatory Elements for ITCH Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for ITCH Gene

Start:
34,363,235 bp from pter
End:
34,515,451 bp from pter
Size:
152,217 bases
Orientation:
Plus strand

Genomic View for ITCH Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for ITCH Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ITCH Gene

Proteins for ITCH Gene

  • Protein details for ITCH Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96J02-ITCH_HUMAN
    Recommended name:
    E3 ubiquitin-protein ligase Itchy homolog
    Protein Accession:
    Q96J02
    Secondary Accessions:
    • A6NEW4
    • B4E234
    • E1P5P3
    • F5H217
    • O43584
    • Q5QP37
    • Q5TEL0
    • Q96F66
    • Q9BY75
    • Q9H451
    • Q9H4U5

    Protein attributes for ITCH Gene

    Size:
    903 amino acids
    Molecular mass:
    102803 Da
    Quaternary structure:
    • Monomer (By similarity). Interacts (via its WW domains) with OCNL, NOTCH1 AND JUN. Interacts (via WW domain 2) with N4BP1; leading to inhibiting its E3 ubiquitin-protein ligase activity. Interacts with JUNB; the interaction promotes ITCH-mediated ubiquitination and degradation of JUNB. Interacts with NDFIP1 and NDFIP2; this interaction activates the E3 ubiquitin-protein ligase and may induce its recruitment to exosomes (By similarity). Interacts with ARHGEF7 (PubMed:17652093). Interacts with RNF11. Interacts (via the WW 1 domain) with NFE2 (via the PXY motif 1); the interaction promotes Lys-63-linked ubiquitination of NFE2, retains it in the cytoplasm and prevents its transactivation activity. Interacts with FYN; the interaction phosphorylates ITCH on Tyr-420 decreasing binding of JUNB. Interacts (via WW domains) with CXCR4 (via C-terminus); the interaction depends on CXCR4 phosphorylation. Interacts (via WW domains) with PCBP2 within a complex containing ITCH, MAVS and PCBP2. Interacts (via WW domains) with TXNIP (via C-terminus). Interacts with p15 BID. Interacts with ERBB4, DTX1, SPG20, SNX9 and SNX18. Interacts (via its WW domains) with ATN1. Interacts with Epstein-Barr virus LMP2A. Interacts (via WW domains) with SGK3. Interacts with OTUD7B. Interacts with PI4K2A (PubMed:23146885).

    Three dimensional structures from OCA and Proteopedia for ITCH Gene

    Alternative splice isoforms for ITCH Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ITCH Gene

Proteomics data for ITCH Gene at MOPED

Post-translational modifications for ITCH Gene

  • On T-cell activation, phosphorylation by the JNK cascade on serine and threonine residues surrounding the PRR domain accelerates the ubiquitination and degradation of JUN and JUNB. The increased ITCH catalytic activity due to phosphorylation by JNK1 may occur due to a conformational change disrupting the interaction between the PRR/WW motifs domain and the HECT domain and, thus exposing the HECT domain (By similarity). Phosphorylation by FYN reduces interaction with JUNB and negatively controls JUN ubiquitination and degradation.
  • Ubiquitinated; autopolyubiquitination with Lys-63 linkages which does not lead to protein degradation.
  • Ubiquitination at Lys34, Lys66, Lys432, Lys446, Lys478, Lys513, Lys665, Lys861, and Lys881
  • Modification sites at PhosphoSitePlus

Other Protein References for ITCH Gene

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for ITCH (ITCH)

Domains for ITCH Gene

Protein Domains for ITCH Gene

Graphical View of Domain Structure for InterPro Entry

Q96J02

UniProtKB/Swiss-Prot:

ITCH_HUMAN :
  • Q96J02
Domain:
  • Contains 1 C2 domain.
  • Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain.
  • Contains 4 WW domains.
genes like me logo Genes that share domains with ITCH: view

No data available for Gene Families for ITCH Gene

Function for ITCH Gene

Molecular function for ITCH Gene

UniProtKB/Swiss-Prot EnzymeRegulation: Activated by NDFIP1- and NDFIP2-binding.
UniProtKB/Swiss-Prot Function: 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. It catalyzes Lys-29-, Lys-48- and Lys-63-linked ubiquitin conjugation. It is involved in the control of inflammatory signaling pathways. Is an essential component of a ubiquitin-editing protein complex, comprising also TNFAIP3, TAX1BP1 and RNF11, that ensures the transient nature of inflammatory signaling pathways. Promotes the association of the complex after TNF stimulation. Once the complex is formed, TNFAIP3 deubiquitinates Lys-63 polyubiquitin chains on RIPK1 and catalyzes the formation of Lys-48-polyubiquitin chains. This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NFKB1. Ubiquitinates RIPK2 by Lys-63-linked conjugation and influences NOD2-dependent signal transduction pathways. Regulates the transcriptional activity of several transcription factors, and probably plays an important role in the regulation of immune response. Ubiquitinates NFE2 by Lys-63 linkages and is implicated in the control of the development of hematopoietic lineages. Critical regulator of T-helper (TH2) cytokine development through its ability to induce JUNB ubiquitination and degradation (By similarity). Ubiquitinates SNX9. Ubiquitinates CXCR4 and HGS/HRS and regulates sorting of CXCR4 to the degradative pathway. It is involved in the negative regulation of MAVS-dependent cellular antiviral responses. Ubiquitinates MAVS through Lys-48-linked conjugation resulting in MAVS proteasomal degradation. Involved in the regulation of apoptosis and reactive oxygen species levels through the ubiquitination and proteasomal degradation of TXNIP. Mediates the antiapoptotic activity of epidermal growth factor through the ubiquitination and proteasomal degradation of p15 BID. Targets DTX1 for lysosomal degradation and controls NOTCH1 degradation, in the absence of ligand, through Lys-29-linked polyubiquitination.

Enzyme Numbers (IUBMB) for ITCH Gene

Gene Ontology (GO) - Molecular Function for ITCH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004842 ubiquitin-protein transferase activity TAS --
GO:0005515 protein binding IPI 15678106
GO:0016874 ligase activity IEA --
GO:0043021 ribonucleoprotein complex binding IPI 19881509
GO:0045236 CXCR chemokine receptor binding IPI 19116316
genes like me logo Genes that share ontologies with ITCH: view
genes like me logo Genes that share phenotypes with ITCH: view

Animal Model Products

CRISPR Products

miRNA for ITCH Gene

miRTarBase miRNAs that target ITCH

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for ITCH

In Situ Assay Products

Flow Cytometry Products

No data available for Animal Models , Transcription Factor Targeting and HOMER Transcription for ITCH Gene

Localization for ITCH Gene

Subcellular locations from UniProtKB/Swiss-Prot for ITCH Gene

Cell membrane. Cytoplasm. Nucleus. Note=Associates with endocytic vesicles. May be recruited to exosomes by NDFIP1.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for ITCH Gene COMPARTMENTS Subcellular localization image for ITCH gene
Compartment Confidence
nucleus 5
plasma membrane 5
cytosol 4
cytoskeleton 1
extracellular 1

Gene Ontology (GO) - Cellular Components for ITCH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA --
GO:0005737 cytoplasm IDA --
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane IDA 14602072
GO:0005938 cell cortex IEA --
genes like me logo Genes that share ontologies with ITCH: view

Pathways for ITCH Gene

genes like me logo Genes that share pathways with ITCH: view

PCR Array Products

  • Pathway & Disease-focused RT² Profiler PCR Arrays
    • T-Cell Anergy & Immune Tolerance in human,mouse,rat
    • Ubiquitin Ligases in human,mouse,rat
    • Ubiquitination (Ubiquitylation) Pathway in human,mouse,rat

UniProtKB/Swiss-Prot Q96J02-ITCH_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

Gene Ontology (GO) - Biological Process for ITCH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000209 protein polyubiquitination --
GO:0001558 regulation of cell growth NAS 9462742
GO:0002669 positive regulation of T cell anergy IEA --
GO:0006511 ubiquitin-dependent protein catabolic process NAS 9462742
GO:0006915 apoptotic process IEA --
genes like me logo Genes that share ontologies with ITCH: view

Compounds for ITCH Gene

(4) HMDB Compounds for ITCH Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine monophosphate
  • 5'-AMP
61-19-8
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
Phosphoric acid
  • acide phosphorique (FRENCH)
7664-38-2
Pyrophosphate
  • (4-)Diphosphoric acid ion
14000-31-8

(1) Novoseek inferred chemical compound relationships for ITCH Gene

Compound -log(P) Hits PubMed IDs
tyrosine 20.9 1
genes like me logo Genes that share compounds with ITCH: view

Transcripts for ITCH Gene

mRNA/cDNA for ITCH Gene

(7) REFSEQ mRNAs :
(10) Additional mRNA sequences :
(1) Selected AceView cDNA sequences:
(9) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for ITCH Gene

Itchy E3 ubiquitin protein ligase:
Representative Sequences:

CRISPR Products

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for ITCH

Primer Products

  • OriGene qSTAR qPCR primer pairs in human,mouse,rat for ITCH

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for ITCH Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17a · 17b ^ 18 ^ 19 ^ 20 ^ 21 ^ 22 ^ 23 ^
SP1: - -
SP2: - - -
SP3:
SP4:

ExUns: 24 ^ 25 ^ 26a · 26b
SP1:
SP2:
SP3:
SP4:

Relevant External Links for ITCH Gene

GeneLoc Exon Structure for
ITCH
ECgene alternative splicing isoforms for
ITCH

Expression for ITCH Gene

mRNA expression in normal human tissues for ITCH Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for ITCH Gene

SOURCE GeneReport for Unigene cluster for ITCH Gene Hs.632272

mRNA Expression by UniProt/SwissProt for ITCH Gene

Q96J02-ITCH_HUMAN
Tissue specificity: Widely expressed
genes like me logo Genes that share expressions with ITCH: view

In Situ Assay Products

No data available for mRNA differential expression in normal tissues for ITCH Gene

Orthologs for ITCH Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for ITCH Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia ITCH 36
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia ITCH 35
  • 93.66 (n)
  • 96.87 (a)
ITCH 36
  • 97 (a)
OneToOne
dog
(Canis familiaris)
Mammalia ITCH 35
  • 94.43 (n)
  • 97.33 (a)
ITCH 36
  • 94 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Itch 35
  • 91.3 (n)
  • 95.94 (a)
Itch 16
Itch 36
  • 96 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia ITCH 36
  • 85 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia ITCH 36
  • 67 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Itch 35
  • 90.81 (n)
  • 95.42 (a)
chicken
(Gallus gallus)
Aves ITCH 35
  • 80.95 (n)
  • 86.61 (a)
ITCH 36
  • 82 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia ITCH 36
  • 78 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia itch 35
  • 72.43 (n)
  • 80.95 (a)
zebrafish
(Danio rerio)
Actinopterygii itch 35
  • 68.56 (n)
  • 77.46 (a)
ITCH (2 of 2) 36
  • 75 (a)
OneToMany
itcha 36
  • 76 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta Su(dx) 36
  • 48 (a)
OneToMany
Su(dx) 37
  • 64 (a)
worm
(Caenorhabditis elegans)
Secernentea wwp-1 36
  • 53 (a)
OneToMany
Y65B4BR.4a 37
  • 61 (a)
Y65B4BR.4b 37
  • 61 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes RSP5 36
  • 40 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.9326 36
  • 66 (a)
OneToMany
Species with no ortholog for ITCH:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for ITCH Gene

ENSEMBL:
Gene Tree for ITCH (if available)
TreeFam:
Gene Tree for ITCH (if available)

Paralogs for ITCH Gene

Paralogs for ITCH Gene

Selected SIMAP similar genes for ITCH Gene using alignment to 1 proteins:

genes like me logo Genes that share paralogs with ITCH: view

Variants for ITCH Gene

Sequence variations from dbSNP and Humsavar for ITCH Gene

SNP ID Clin Chr 20 pos Sequence Context AA Info Type MAF
rs945673 -- 34,376,459(-) TTTAT(G/T)TATTT intron-variant
rs945674 -- 34,376,441(-) agaca(C/G)ggtca intron-variant
rs1042199 -- 34,476,340(-) GGCGG(G/T)AGCGC intron-variant
rs1052275 -- 34,457,447(+) AATTA(C/T)ACAAT reference, missense, nc-transcript-variant
rs1061506 -- 34,409,903(+) CTCAC(A/G)CCTGT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for ITCH Gene

Variant ID Type Subtype PubMed ID
dgv4566n71 CNV Loss 21882294
dgv4567n71 CNV Loss 21882294
nsv912856 CNV Loss 21882294
nsv912857 CNV Loss 21882294
esv2675421 CNV Deletion 23128226
nsv912858 CNV Loss 21882294
nsv912859 CNV Loss 21882294

Relevant External Links for ITCH Gene

HapMap Linkage Disequilibrium report
ITCH
Human Gene Mutation Database (HGMD)
ITCH

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ITCH Gene

Disorders for ITCH Gene

(1) OMIM Diseases for ITCH Gene (606409)

UniProtKB/Swiss-Prot

ITCH_HUMAN
  • Autoimmune disease, multisystem, with facial dysmorphism (ADMFD) [MIM:613385]: A disorder characterized by organomegaly, failure to thrive, developmental delay, dysmorphic features and autoimmune inflammatory cell infiltration of the lungs, liver and gut. {ECO:0000269 PubMed:20170897}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(2) Novoseek inferred disease relationships for ITCH Gene

Disease -log(P) Hits PubMed IDs
tumors 3.27 2
cancer 0.799 2

Relevant External Links for ITCH

Genetic Association Database (GAD)
ITCH
genes like me logo Genes that share disorders with ITCH: view

Publications for ITCH Gene

  1. Human ITCH is a co-regulator of the hematopoietic transcription factor NF-E2. (PMID: 11318614) Chen X. … Shen C.K.J. (Genomics 2001) 2 3 4 23
  2. Interaction between two ubiquitin-protein isopeptide ligases of different classes, CBLC and AIP4/ITCH. (PMID: 12226085) Courbard J.-R. … Ollendorff V. (J. Biol. Chem. 2002) 3 4 23
  3. The E3 ubiquitin ligase AIP4 mediates ubiquitination and sorting of the G protein-coupled receptor CXCR4. (PMID: 14602072) Marchese A. … Benovic J.L. (Dev. Cell 2003) 3 4 23
  4. A novel interaction between atrophin-interacting protein 4 and beta- p21-activated kinase-interactive exchange factor is mediated by an SH3 domain. (PMID: 17652093) Janz J.M. … Min K.C. (J. Biol. Chem. 2007) 3 4 23
  5. The E3 ubiquitin ligase atrophin interacting protein 4 binds directly to the chemokine receptor CXCR4 via a novel WW domain-mediated interaction. (PMID: 19116316) Bhandari D. … Marchese A. (Mol. Biol. Cell 2009) 3 4 23

Products for ITCH Gene

  • Addgene plasmids for ITCH

Sources for ITCH Gene

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