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ITCH Gene

protein-coding   GIFtS: 66
GCID: GC20P032951

Itchy E3 Ubiquitin Protein Ligase

(Previous names: itchy (mouse homolog) E3 ubiquitin protein ligase, itchy...)
  See ITCH-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Itchy E3 Ubiquitin Protein Ligase1 2     dJ468O1.12
AIP42 3 5     DJ468O1.1 (Atrophin 1 Interacting Protein 4 (AIP4))2
NAPP12 3 5     E3 Ubiquitin-Protein Ligase Itchy Homolog2
NFE2-Associated Polypeptide 12 3     Itchy E3 Ubiquitin Protein Ligase Homolog2
Itchy (Mouse Homolog) E3 Ubiquitin Protein Ligase1     EC 6.3.2.-3
Itchy E3 Ubiquitin Protein Ligase Homolog (Mouse)1     Itch3
AIF42     Atrophin-1-Interacting Protein 43
Atrophin-1 Interacting Protein 42     EC 6.3.28

External Ids:    HGNC: 138901   Entrez Gene: 837372   Ensembl: ENSG000000787477   OMIM: 6064095   UniProtKB: Q96J023   

Export aliases for ITCH gene to outside databases

Previous GC identifers: GC20P032709 GC20P033619 GC20P033666 GC20P032414 GC20P029732


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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 itch e3 ubiquitin ligase deficiency, and familial hemiplegic migraine. GO annotations related to this gene include ubiquitin-protein ligase activity and CXCR chemokine receptor binding. An important paralog of this gene is NEDD4L.

UniProtKB/Swiss-Prot: ITCH_HUMAN, Q96J02
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




(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000020.11  NT_011362.11  NC_018931.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the ITCH gene promoter:
         COUP-TF1   p53   COUP   HNF-4alpha2   HNF-4alpha1   E47   C/EBPalpha   COUP-TF   HFH-1   HOXA5   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidITCH promoter sequence
   Search Chromatin IP Primers for ITCH

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat ITCH


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 20q11.22   Ensembl cytogenetic band:  20q11.22   HGNC cytogenetic band: 20q11.22

ITCH Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
ITCH gene location

GeneLoc information about chromosome 20         GeneLoc Exon Structure

GeneLoc location for GC20P032951:  view genomic region     (about GC identifiers)

Start:
32,951,041 bp from pter      End:
33,099,198 bp from pter
Size:
148,158 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: ITCH_HUMAN, Q96J02 (See protein sequence)
Recommended Name: E3 ubiquitin-protein ligase Itchy homolog  
Size: 903 amino acids; 102803 Da
Subunit: 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. 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
6 PDB 3D structures from and Proteopedia for ITCH:
2DMV (3D)        2KYK (3D)        2NQ3 (3D)        2P4R (3D)        2YSF (3D)        3TUG (3D)    
Secondary accessions: A6NEW4 B4E234 E1P5P3 F5H217 O43584 Q5QP37 Q5TEL0 Q96F66 Q9BY75 Q9H451
Q9H4U5
Alternative splicing: 3 isoforms:  Q96J02-1   Q96J02-2   Q96J02-3   (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for ITCH: NX_Q96J02

Explore proteomics data for ITCH at MOPED

Post-translational modifications: 

  • 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 degradation1
  • Ubiquitinated; autopolyubiquitination with 'Lys-63' linkages which does not lead to protein degradation1
  • Ubiquitination2 at Lys34, Lys66, Lys432, Lys446, Lys478, Lys513, Lys665, Lys861, Lys881
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for ITCH (Q96J02) (see all 13)
     LQINPAS  PLPPGWE  TQWEDPR  RLLQFVTG 


    See ITCH Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (3 alternative transcripts): 
    NP_001244066.1  NP_001244067.1  NP_113671.3  

    ENSEMBL proteins: 
     ENSP00000363998   ENSP00000262650   ENSP00000445608  
    Reactome Protein details: Q96J02

    ITCH Human Recombinant Protein Products:

    Browse Purified and Recombinant Proteins at EMD Millipore
    R&D Systems Recombinant & Natural Proteins for ITCH (ITCH/AIP4)
    Browse recombinant and purified proteins available from Enzo Life Sciences
    Browse OriGene full length recombinant human proteins expressed in human HEK293 cells
    OriGene Protein Over-expression Lysate for ITCH
    OriGene Custom MassSpec
    OriGene Custom Protein Services for ITCH
    GenScript Custom Purified and Recombinant Proteins Services for ITCH
    Novus Biologicals ITCH Protein
    Novus Biologicals ITCH Lysates
    Sino Biological Recombinant Protein for ITCH
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for ITCH

     
    Search eBioscience for Proteins for ITCH 

    ITCH Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of ITCH
    Browse R&D Systems for Antibodies
    Cell Signaling Technology (CST) Antibodies for ITCH 
    OriGene Antibodies for ITCH
    OriGene Custom Antibody Services for ITCH
    Novus Biologicals ITCH Antibodies
    Abcam antibodies for ITCH
    Cloud-Clone Corp. Antibodies for ITCH
    ThermoFisher Antibodies for ITCH
    LSBio Antibodies in human, mouse, rat for ITCH

    ITCH Assay Products:

    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for ITCH
    R&D Systems Ubiquitin Proteasome Pathway (UPP) Assay Kits & Reagents for ITCH (ITCH/AIP4)
    GenScript Custom Assay Services for ITCH
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for ITCH
    Cloud-Clone Corp. CLIAs for ITCH
    Search eBioscience for ELISAs for ITCH 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    4 InterPro protein domains:
     IPR024928 E3_ub_ligase_SMURF1
     IPR000569 HECT
     IPR001202 WW_dom
     IPR000008 C2_dom

    Graphical View of Domain Structure for InterPro Entry Q96J02

    ProtoNet protein and cluster: Q96J02

    3 Blocks protein domains:
    IPB000008 C2 domain
    IPB000569 HECT domain (Ubiquitin-protein ligase)
    IPB002349 WW domain signature


    UniProtKB/Swiss-Prot: ITCH_HUMAN, Q96J02
    Similarity: Contains 1 C2 domain
    Similarity: Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain
    Similarity: Contains 4 WW domains


    Find genes that share domains with ITCH           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: ITCH_HUMAN, Q96J02
    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 regulation: Activated by NDFIP1- and NDFIP2-binding (By similarity)

         Enzyme Numbers (IUBMB): EC 6.3.2.-1 EC 6.3.22

         Gene Ontology (GO): 5 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004842ubiquitin-protein ligase activity TAS--
    GO:0005515protein binding IPI15678106
    GO:0016874ligase activity ----
    GO:0043021ribonucleoprotein complex binding IPI19881509
    GO:0045236CXCR chemokine receptor binding IPI19116316
         
    Find genes that share ontologies with ITCH           About GenesLikeMe


    Phenotypes:
         2 GenomeRNAi human phenotypes for ITCH:
     Increased cell death HMECs cel  Synthetic lethal with imatinib 

         9 MGI mutant phenotypes (inferred from 1 allele(MGI details for Itch):
     behavior/neurological  digestive/alimentary  hematopoietic system  homeostasis/metabolism  immune system 
     integument  mortality/aging  pigmentation  respiratory system 

    Find genes that share phenotypes with ITCH           About GenesLikeMe

    Animal Models:
       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for ITCH
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for ITCH

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for ITCH
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for ITCH

    miRNA
    Products:
        
    miRTarBase miRNAs that target ITCH:
    hsa-mir-324-3p (MIRT042842), hsa-mir-106b-5p (MIRT000372)

    Block miRNA regulation of human, mouse, rat ITCH using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate ITCH (see all 82):
    hsa-miR-576-3p hsa-miR-100* hsa-miR-26a-2* hsa-miR-607 hsa-miR-300 hsa-miR-106a hsa-miR-128 hsa-miR-138-2*
    SwitchGear 3'UTR luciferase reporter plasmidITCH 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for ITCH
    Predesigned siRNA for gene silencing in human, mouse, rat ITCH

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for ITCH

    Clone
    Products:
         
    OriGene clones in human, mouse for ITCH (see all 6)
    OriGene ORF clones in mouse, rat for ITCH
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: ITCH (NM_031483)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for ITCH
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat ITCH
    Addgene plasmids for ITCH 

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for ITCH
    Browse ESI BIO Cell Lines and PureStem Progenitors for ITCH 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for ITCH


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    ITCH_HUMAN, Q96J02: Cell membrane. Cytoplasm (By similarity). Nucleus. Note=Associates with endocytic vesicles.
    May be recruited to exosomes by NDFIP1
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    nucleus5
    plasma membrane5
    cytosol4
    cytoskeleton1
    extracellular1

    Gene Ontology (GO): Selected cellular component terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IDA--
    GO:0005737cytoplasm IDA--
    GO:0005829cytosol TAS--
    GO:0005886plasma membrane IDA14602072
    GO:0005938cell cortex IEA--

    Find genes that share ontologies with ITCH           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for ITCH About   (see all 24)  
    See pathways by source

    SuperPathContained pathways About
    1Class I MHC mediated antigen processing and presentation
    Class I MHC mediated antigen processing and presentation0.84
    Adaptive Immune System0.41
    Antigen processing- Ubiquitination and Proteasome degradation0.84
    Ubiquitin mediated proteolysis0.35
    2Signaling by NOTCH1 PEST Domain Mutants in Cancer
    Signaling by NOTCH1 PEST Domain Mutants in Cancer0.79
    Signaling by NOTCH1 t(7;9)(NOTCH1-M1580 K2555) Translocation Mutant0.79
    Signaling by NOTCH1 HD Domain Mutants in Cancer0.79
    FBXW7 Mutants and NOTCH1 in Cancer0.79
    Signaling by NOTCH1 in Cancer0.79
    Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer0.79
    Signaling by NOTCH10.79
    Signaling by NOTCH0.64
    3Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
    Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways0.68
    NOD1/2 Signaling Pathway0.68
    4PI-3K cascade
    Signaling by ERBB40.66
    Downregulation of ERBB4 signaling0.00
    5RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
    RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways0.47
    Negative regulators of RIG-I/MDA5 signaling0.42


    Find genes that share SuperPaths with ITCH           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    2 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for ITCH
        SMAD Signaling Network
    Ubiquitin-Proteasome Dependent Proteolysis

    3 Cell Signaling Technology (CST) Pathways for ITCH
        Wnt / Hedgehog / Notch
    Lymphocyte Signaling
    Protein Stability

    Selected BioSystems Pathways for ITCH (see all 7)
        EGFR1 Signaling Pathway
    Delta-Notch Signaling Pathway
    ErbB4 signaling events
    Calcineurin-regulated NFAT-dependent transcription in lymphocytes
    TGF-beta receptor signaling


    5 Reactome Pathways for ITCH
        Antigen processing: Ubiquitination & Proteasome degradation
    Negative regulators of RIG-I/MDA5 signaling
    NOD1/2 Signaling Pathway
    Downregulation of ERBB4 signaling
    Activated NOTCH1 Transmits Signal to the Nucleus


    4 Kegg Pathways  (Kegg details for ITCH):
        Ubiquitin mediated proteolysis
    Endocytosis
    TNF signaling pathway
    Non-alcoholic fatty liver disease (NAFLD)

    UniProtKB/Swiss-Prot: ITCH_HUMAN, Q96J02
    Pathway: Protein modification; protein ubiquitination

        Pathway & Disease-focused RT2 Profiler PCR Arrays including ITCH: 

              Ubiquitination (Ubiquitylation) Pathway in human mouse rat
              T-Cell Anergy & Immune Tolerance in human mouse rat
              Ubiquitin Ligases in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for ITCH

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for ITCH (Q96J021, 2, 3 ENSP000003639984) via UniProtKB, MINT, STRING, and/or I2D (see all 235)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    TP73O153502, 3, ENSP000003675454MINT-3389196 MINT-3389321 MINT-3389044 MINT-3389118 MINT-3389173 MINT-3389070 MINT-3389148 MINT-3389300 I2D: score=4 STRING: ENSP00000367545
    SNX9Q9Y5X11, 2, 3, ENSP000003760244EBI-1564678,EBI-77848 MINT-7889571 MINT-7890033 MINT-7889610 MINT-7889689 MINT-7889591 MINT-7889673 MINT-7889619 I2D: score=2 STRING: ENSP00000376024
    SGK3Q96BR11, 2, 3EBI-1564678,EBI-2801236 MINT-2881316 MINT-2881371 MINT-2879884 MINT-2881283 MINT-2881346 I2D: score=1 
    CBLCQ9ULV82, 3, ENSP000002702794MINT-58330 MINT-58329 MINT-58340 MINT-58341 MINT-58290 I2D: score=2 STRING: ENSP00000270279
    PI4K2AQ9BTU61, 2EBI-1564678,EBI-3239392 MINT-8427834 MINT-8427868 MINT-8427783 MINT-8427854 MINT-8427799
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 26):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000209protein polyubiquitination ----
    GO:0001558regulation of cell growth NAS9462742
    GO:0002669positive regulation of T cell anergy IEA--
    GO:0006511ubiquitin-dependent protein catabolic process NAS9462742
    GO:0006915apoptotic process IEA--

    Find genes that share ontologies with ITCH           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
    About This Section

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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for ITCH

    4 HMDB Compounds for ITCH    About this table
    CompoundSynonyms CAS #PubMed Ids
    Adenosine monophosphate5'-AMP (see all 28)61-19-8--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--
    Phosphoric acidacide phosphorique (FRENCH) (see all 20)7664-38-2--
    Pyrophosphate(4-)Diphosphoric acid ion (see all 10)14000-31-8--

    1 Novoseek inferred chemical compound relationship for ITCH gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    tyrosine 20.9 1 17652093 (1)



    Find genes that share compounds with ITCH           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for ITCH gene (3 alternative transcripts): 
    NM_001257137.1  NM_001257138.1  NM_031483.5  

    Unigene Cluster for ITCH:

    Itchy E3 ubiquitin protein ligase
    Hs.632272  [show with all ESTs]
    Unigene Representative Sequence: NM_001257137
    7 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000374864(uc002xak.2 uc010geu.1 uc010zuj.1) ENST00000486883
    ENST00000479215 ENST00000262650 ENST00000483727 ENST00000461661 ENST00000535650

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    hsa-miR-576-3p hsa-miR-100* hsa-miR-26a-2* hsa-miR-607 hsa-miR-300 hsa-miR-106a hsa-miR-128 hsa-miR-138-2*
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    Additional mRNA sequence: 

    AB056663.2 AB209747.1 AF038564.1 AF095745.1 AJ308022.1 AK297809.1 AK304090.1 AK315212.1 
    BC006848.1 BC011571.1 

    16 DOTS entries:

    DT.456331  DT.97842535  DT.456332  DT.86853079  DT.91763117  DT.95376436  DT.86846116  DT.314309 
    DT.100716533  DT.40111191  DT.95376440  DT.120838501  DT.91763114  DT.95078691  DT.120838522  DT.91744978 

    1 AceView cDNA sequence:

    BF813768 

    GeneLoc Exon Structure

    4 Alternative Splicing Database (ASD) splice patterns (SP) for ITCH    About this scheme

    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:                        


    ECgene alternative splicing isoforms for ITCH

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    ITCH expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: AATGGGCAAG
    ITCH Expression
    About this image


    ITCH expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 8) fully expand
     
     Brain (Nervous System)    fully expand to see all 5 entries
             Cerebral Cortex
     
     Ovary (Reproductive System)    fully expand to see all 2 entries
             Ovarian Mesenchymal Stroma Cells Ovary Interstitium
             Oviduct
     
     Neural Tube (Nervous System)    fully expand to see all 2 entries
             Metencephalon
     
     Bone (Muscoskeletal System)
             Bone Marrow
     
     Trophoblast (Extraembryonic Tissues)
             Trophoblast Cells Trophoblast
    ITCH Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    ITCH Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.632272

    UniProtKB/Swiss-Prot: ITCH_HUMAN, Q96J02
    Tissue specificity: Widely expressed

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

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

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

    Orthologs for ITCH gene from Selected species (see all 15)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Itch1 , 5 itchy, E3 ubiquitin protein ligase1, 5 91.3(n)1
    95.94(a)1
      2 (76.94 cM)5
    163961  NM_001243712.11  NP_001230641.11 
     1551335095 
    chicken
    (Gallus gallus)
    Aves ITCH1 itchy E3 ubiquitin protein ligase 80.95(n)
    86.61(a)
      419145  XM_417330.3  XP_417330.2 
    lizard
    (Anolis carolinensis)
    Reptilia ITCH6
    itchy E3 ubiquitin protein ligase
    78(a)
    1 ↔ 1
    4(138101190-138167461)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia BX709797.12   -- 76.62(n)    BX709797.1 
    zebrafish
    (Danio rerio)
    Actinopterygii itch1 itchy E3 ubiquitin protein ligase homolog (mouse) 68.56(n)
    77.46(a)
      100331274  XM_002667532.3  XP_002667578.2 
    fruit fly
    (Drosophila melanogaster)
    Insecta Su(dx)3 N receptor signaling pathway
    ubiquitin-protein more
    64(a)   2 22C1   --
    worm
    (Caenorhabditis elegans)
    Secernentea Y65B4BR.4a3   -- 61(a)
    (best of 2)
      I(537141-541634)   --
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes RSP56
    E3 ubiquitin ligase of the NEDD4 family; involved ...
    40(a)
    1 → many
    V(410189-412618) YER125W


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for ITCH gene
    NEDD4L2  HECW22  AREL12  UBR52  WWP22  HECW12  SMURF22  SMURF12  
    HUWE12  NEDD42  WWP12  
    11 SIMAP similar genes for ITCH using alignment to 1 protein entry:     ITCH_HUMAN:
    WWP1    WWP2    HUWE1    NEDD4    PIN1P1    SMURF2
    SMURF1    HECW1    NEDL1    HECW2    NEDD4L

    Find genes that share paralogs with ITCH           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for ITCH (see all 2958)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 20 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1139485931,2
    F--32952586(+) CAGCTG/ACTAGG 3 -- int11Minor allele frequency- A:0.50CSA 2
    rs1865119451,2
    --32952623(+) AATGGC/TGTGAT 3 -- us2k10--------
    rs1914031051,2
    C--32952673(+) TTATCA/GTGCTT 3 -- us2k10--------
    rs1168391091,2
    F--32952755(+) AAGGGG/ATTTCA 3 -- us2k11Minor allele frequency- A:0.09WA 118
    rs1147484661,2
    F--32953273(+) TGCACC/TGCTGC 3 -- us2k11Minor allele frequency- T:0.03WA 118
    rs1829783411,2
    --32953292(+) TTGGGA/TGACAG 3 -- us2k10--------
    rs1857977721,2
    --32953425(+) CTAAGG/TATTGA 3 -- us2k10--------
    rs1454633731,2
    C--32953470(+) AGCCTA/GTTATT 3 -- us2k10--------
    rs1909446521,2
    --32953715(+) AAAGGC/TAGAAA 3 -- us2k10--------
    rs60597791,2
    C,F,H--32953903(+) aggagT/Ctggag 3 -- us2k111Minor allele frequency- C:0.45NA WA CSA EA 373

    HapMap Linkage Disequilibrium report for ITCH (32951041 - 33099198 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 7 variations for ITCH:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2675421CNV Deletion23128226
    nsv912859CNV Loss21882294
    nsv912858CNV Loss21882294
    dgv4566n71CNV Loss21882294
    nsv912857CNV Loss21882294
    nsv912856CNV Loss21882294
    dgv4567n71CNV Loss21882294

    Human Gene Mutation Database (HGMD): ITCH
    Site Specific Mutation Identification with PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section

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    OMIM gene information: 606409   
    OMIM disorders: 613385  
    UniProtKB/Swiss-Prot: ITCH_HUMAN, Q96J02
  • Syndromic multisystem autoimmune disease (SMAD) [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. Note=The disease is caused by mutations affecting the gene represented in this entry

  • 3 diseases for ITCH:    
    About MalaCards
    itch e3 ubiquitin ligase deficiency    familial hemiplegic migraine    hemiplegic migraine


    Find genes that share disorders with ITCH           About GenesLikeMe

    2 Novoseek inferred disease relationships for ITCH gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    tumors 3.27 2 17592138 (1), 19016753 (1)
    cancer 0.799 2 17592138 (1), 20395198 (1)

    Genetic Association Database (GAD): ITCH

    Export disorders for ITCH gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for ITCH gene, integrated from 10 sources (see all 160):
    (articles sorted by number of sources associating them with ITCH)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Human ITCH is a co-regulator of the hematopoietic transcription factor NF-E2. (PubMed id 11318614)1, 2, 3, 9 Chen X.... Shen C.K.J. (Genomics 2001)
    2. The E3 ubiquitin ligase atrophin interacting protein 4 binds directly to the chemokine receptor CXCR4 via a novel WW domain-mediated interaction. (PubMed id 19116316)1, 2, 9 Bhandari D.... Marchese A. (Mol. Biol. Cell 2009)
    3. The ubiquitin ligase itch regulates apoptosis by targeting thioredoxin-interacting protein for ubiquitin-dependent degradation. (PubMed id 20068034)1, 2, 9 Zhang P.... Yu L. (J. Biol. Chem. 2010)
    4. Endogenous spartin (SPG20) is recruited to endosomes and lipid droplets and interacts with the ubiquitin E3 ligases AIP4 and AIP5. (PubMed id 19580544)1, 2, 9 Edwards T.L.... Reid E. (Biochem. J. 2009)
    5. A novel interaction between atrophin-interacting protein 4 and beta- p21-activated kinase-interactive exchange factor is mediated by an SH3 domain. (PubMed id 17652093)1, 2, 9 Janz J.M.... Min K.C. (J. Biol. Chem. 2007)
    6. The E3 ubiquitin ligase AIP4 mediates ubiquitination and sorting of the G protein-coupled receptor CXCR4. (PubMed id 14602072)1, 2, 9 Marchese A....Benovic J.L. (Dev. Cell 2003)
    7. Interaction between two ubiquitin-protein isopeptide ligases of different classes, CBLC and AIP4/ITCH. (PubMed id 12226085)1, 2, 9 Courbard J.-R....Ollendorff V. (J. Biol. Chem. 2002)
    8. Human ITCH E3 ubiquitin ligase deficiency causes syndromic multisystem autoimmune disease. (PubMed id 20170897)1, 2 Lohr N.J.... Puffenberger E.G. (Am. J. Hum. Genet. 2010)
    9. The ubiquitin ligase Itch mediates the antiapoptotic activity of epidermal growth factor by promoting the ubiquitylation and degradation of the truncated C-terminal portion of Bid. (PubMed id 20392206)1, 2 Azakir B.A.... Angers A. (FEBS J. 2010)
    10. The E3 ubiquitin ligase Itch regulates sorting nexin 9 through an unconventional substrate recognition domain. (PubMed id 20491914)1, 2 Baumann C.... Levy F. (FEBS J. 2010)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 83737 HGNC: 13890 AceView: ITCH.2 Ensembl:ENSG00000078747 euGenes: HUgn83737
    ECgene: ITCH Kegg: 83737 H-InvDB: ITCH

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for ITCH Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section

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    Patent Information for ITCH gene:
    Search GeneIP for patents involving ITCH

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, eBioscience, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
    Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory, genOway)
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