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Q8C863

- ITCH_MOUSE

UniProt

Q8C863 - ITCH_MOUSE

Protein

E3 ubiquitin-protein ligase Itchy

Gene

Itch

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 124 (01 Oct 2014)
      Sequence version 2 (03 Oct 2003)
      Previous versions | rss
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    Functioni

    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 By similarity. Ubiquitinates RIPK2 by 'Lys-63'-linked conjugation and influences NOD2-dependent signal transduction pathways By similarity. Regulates the transcriptional activity of several transcription factors involved in immune response. Critical regulator of T-helper (TH2) cytokine development through its ability to induce JUNB ubiquitination and degradation. Ubiquitinates SNX9 By similarity. Ubiquitinates CXCR4 and HGS/HRS and regulates sorting of CXCR4 to the degradative pathway By similarity. 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 By similarity. Involved in the regulation of apoptosis and reactive oxygen species levels through the ubiquitination and proteasomal degradation of TXNIP By similarity. 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 By similarity.By similarity

    Enzyme regulationi

    Activated by NDFIP1- and NDFIP2-binding.By similarity

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei832 – 8321Glycyl thioester intermediatePROSITE-ProRule annotation

    GO - Molecular functioni

    1. ligase activity Source: BHF-UCL
    2. protein binding Source: IntAct
    3. ribonucleoprotein complex binding Source: Ensembl
    4. ubiquitin-protein transferase activity Source: UniProtKB

    GO - Biological processi

    1. apoptotic process Source: UniProtKB-KW
    2. defense response to virus Source: UniProtKB-KW
    3. innate immune response Source: UniProtKB-KW
    4. negative regulation of alpha-beta T cell proliferation Source: MGI
    5. negative regulation of apoptotic process Source: UniProtKB
    6. negative regulation of defense response to virus Source: UniProtKB
    7. negative regulation of JNK cascade Source: BHF-UCL
    8. negative regulation of NF-kappaB transcription factor activity Source: BHF-UCL
    9. positive regulation of protein catabolic process Source: MGI
    10. positive regulation of T cell anergy Source: MGI
    11. protein K29-linked ubiquitination Source: UniProtKB
    12. protein K48-linked ubiquitination Source: UniProtKB
    13. protein K63-linked ubiquitination Source: UniProtKB
    14. protein polyubiquitination Source: MGI
    15. protein ubiquitination Source: UniProtKB
    16. protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: MGI
    17. regulation of protein deubiquitination Source: BHF-UCL
    18. ubiquitin-dependent protein catabolic process Source: MGI

    Keywords - Molecular functioni

    Ligase

    Keywords - Biological processi

    Antiviral defense, Apoptosis, Immunity, Innate immunity, Ubl conjugation pathway

    Enzyme and pathway databases

    ReactomeiREACT_198532. Negative regulators of RIG-I/MDA5 signaling.
    REACT_199100. Downregulation of ERBB4 signaling.
    REACT_199115. Antigen processing: Ubiquitination & Proteasome degradation.
    REACT_199384. Activated NOTCH1 Transmits Signal to the Nucleus.
    REACT_211125. NOD1/2 Signaling Pathway.
    UniPathwayiUPA00143.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    E3 ubiquitin-protein ligase Itchy (EC:6.3.2.-)
    Gene namesi
    Name:Itch
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 2

    Organism-specific databases

    MGIiMGI:1202301. Itch.

    Subcellular locationi

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

    GO - Cellular componenti

    1. cell cortex Source: MGI
    2. cytoplasm Source: MGI
    3. cytoplasmic vesicle Source: MGI
    4. cytosol Source: Reactome
    5. membrane Source: MGI
    6. nucleus Source: MGI
    7. plasma membrane Source: UniProtKB-SubCell
    8. ubiquitin ligase complex Source: MGI

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Defects in Itch are the cause of the itchy phenotype which is an inflammatory and immunological condition characterized by inflammation in the lung and stomach, hyperplasia in lymphoid and hematopoietic cells and constant itching in the skin.1 Publication

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi199 – 1991S → A: No loss of MAPK8-mediated phosphorylation and no effect on ligase activity. Almost complete inactivation of ligase activity; when associated with A-232. Greatly reduced MAPK8-mediated phosphorylation; when associated with A-222 or A-232. Completely abolishes MAPK8-mediated phosphorylation; when associated with A-222 and A-232. 1 Publication
    Mutagenesisi199 – 1991S → D: More sensitive to in vitro proteolysis. 1 Publication
    Mutagenesisi222 – 2221T → A: No loss of MAPK8-mediated phosphorylation. Greatly reduced MAPK8-mediated phosphorylation; when associated with A-199 or A-232. Completely abolishes MAPK8-mediated phosphorylation; when associated with A-199 and A-232. 1 Publication
    Mutagenesisi222 – 2221T → D: Inhibits in vitro interaction between ITCH HECT domain and PRR/WW motifs. More sensitive to in vitro proteolysis. 1 Publication
    Mutagenesisi232 – 2321S → A: No loss of MAPK8-mediated phosphorylation and no effect on ligase activity. Almost complete inactivation of ligase activity; when associated with A-199. Greatly reduced MAPK8-mediated phosphorylation; when associated with A-199 or A-222. Completely abolishes MAPK8-mediated phosphorylation; when associated with A-199 and A-222. 1 Publication
    Mutagenesisi232 – 2321S → D: More sensitive to in vitro proteolysis. 1 Publication
    Mutagenesisi535 – 5406RRRLWV → AAALWA: Abolishes interaction with MAPK8.
    Mutagenesisi535 – 5373RRR → AAA: Almost complete loss of interaction with MAPK8.
    Mutagenesisi535 – 5362RR → AA: Greatly decreased interaction with MAPK8 and ligase activity.
    Mutagenesisi832 – 8321C → A: Loss of ubiquitin protein ligase activity. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 864863E3 ubiquitin-protein ligase ItchyPRO_0000120318Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylserineBy similarity
    Modified residuei199 – 1991Phosphoserine; by MAPK82 Publications
    Modified residuei222 – 2221Phosphothreonine; by MAPK82 Publications
    Modified residuei232 – 2321Phosphoserine; by MAPK82 Publications
    Modified residuei346 – 3461Phosphothreonine; by SGK3By similarity
    Modified residuei381 – 3811Phosphotyrosine; by FYNBy similarity
    Modified residuei411 – 4111Phosphoserine; by SGK3By similarity

    Post-translational modificationi

    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. Phosphorylation by FYN reduces interaction with JUNB and negatively controls JUN ubiquitination and degradation.4 Publications
    Ubiquitinated; autopolyubiquitination with 'Lys-63' linkages which does not lead to protein degradation.By similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiQ8C863.
    PaxDbiQ8C863.
    PRIDEiQ8C863.

    PTM databases

    PhosphoSiteiQ8C863.

    Expressioni

    Tissue specificityi

    Widely expressed.

    Gene expression databases

    ArrayExpressiQ8C863.
    BgeeiQ8C863.
    CleanExiMM_ITCH.
    GenevestigatoriQ8C863.

    Interactioni

    Subunit structurei

    Monomer By similarity. Interacts with (via its WW domains) with ATN1. Interacts with ARHGEF7 and 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 (via WW domain 2) with N4BP1; leading to inhibits its E3 ubiquitin-protein ligase activity. 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 with FYN; the interaction phosphorylates ITCH on Tyr-381 decreasing binding of JUNB. Interacts (via WW domains) with TXNIP (via C-terminus). Interacts with ERBB4, DTX1, SPG20, SNX9 and SNX18. Interacts with OTUD7B By similarity. Interacts (via its WW domains) with OCNL, NOTCH1, JUN and JUNB. Interacts with p15 BID and MAPK8. Interacts with NDFIP1 and NDFIP2; the interaction with NDFIP proteins activates the E3 ubiquitin-protein ligase and may induce its recruitment to exosomes. Interacts (via WW domain 2) with N4BP1; the interaction inhibits the E3 ubiquitin-protein ligase activity. Interacts (via WW domains) with SGK3.By similarity9 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CyldQ80TQ22EBI-851782,EBI-943859

    Protein-protein interaction databases

    BioGridi200813. 16 interactions.
    DIPiDIP-29318N.
    IntActiQ8C863. 10 interactions.
    MINTiMINT-142559.
    STRINGi10090.ENSMUSP00000105307.

    Structurei

    Secondary structure

    1
    864
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi399 – 4013
    Beta strandi407 – 4093
    Beta strandi411 – 4133
    Beta strandi415 – 4195
    Turni420 – 4234
    Beta strandi424 – 4263

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1YIUNMR-A399-432[»]
    2JO9NMR-A399-432[»]
    2JOCNMR-A399-432[»]
    ProteinModelPortaliQ8C863.
    SMRiQ8C863. Positions 13-145, 287-861.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ8C863.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini5 – 9995C2PROSITE-ProRule annotationAdd
    BLAST
    Domaini287 – 32034WW 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini319 – 35234WW 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini399 – 43234WW 3PROSITE-ProRule annotationAdd
    BLAST
    Domaini439 – 47234WW 4PROSITE-ProRule annotationAdd
    BLAST
    Domaini530 – 864335HECTPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni356 – 43277Required for interaction with FYNBy similarityAdd
    BLAST
    Regioni535 – 54410MAP kinase docking site

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi211 – 22616Arg/Pro-rich (PRR domain)Add
    BLAST

    Sequence similaritiesi

    Contains 1 C2 domain.PROSITE-ProRule annotation
    Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain.PROSITE-ProRule annotation
    Contains 4 WW domains.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiCOG5021.
    GeneTreeiENSGT00570000078756.
    HOVERGENiHBG004134.
    InParanoidiQ8C863.
    KOiK05632.
    OMAiGETTCSE.
    OrthoDBiEOG7RFTGT.
    PhylomeDBiQ8C863.
    TreeFamiTF323658.

    Family and domain databases

    Gene3Di2.60.40.150. 1 hit.
    InterProiIPR000008. C2_dom.
    IPR024928. E3_ub_ligase_SMURF1.
    IPR000569. HECT.
    IPR001202. WW_dom.
    [Graphical view]
    PfamiPF00168. C2. 1 hit.
    PF00632. HECT. 1 hit.
    PF00397. WW. 4 hits.
    [Graphical view]
    PIRSFiPIRSF001569. E3_ub_ligase_SMURF1. 1 hit.
    SMARTiSM00239. C2. 1 hit.
    SM00119. HECTc. 1 hit.
    SM00456. WW. 4 hits.
    [Graphical view]
    SUPFAMiSSF49562. SSF49562. 1 hit.
    SSF51045. SSF51045. 4 hits.
    SSF56204. SSF56204. 1 hit.
    PROSITEiPS50004. C2. 1 hit.
    PS50237. HECT. 1 hit.
    PS01159. WW_DOMAIN_1. 4 hits.
    PS50020. WW_DOMAIN_2. 4 hits.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q8C863-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MSDSGPQLDS MGSLTMKSQL QITVISAKLK ENKKNWFGPS PYVEVTVDGQ    50
    SKKTEKCNNT NSPKWKQPLT VIVTPTSKLC FRVWSHQTLK SDVLLGTAGL 100
    DIYETLKSNN MKLEEVVMTL QLVGDKEPTE TMGDLSVCLD GLQVEAEVVT 150
    NGETSCSEST TQNDDGCRTR DDTRVSTNGS EDPEVAASGE NKRANGNNSP 200
    SLSNGGFKPS RPPRPSRPPP PTPRRPASVN GSPSTNSDSD GSSTGSLPPT 250
    NTNVNTSTSE GATSGLIIPL TISGGSGPRP LNTVSQAPLP PGWEQRVDQH 300
    GRVYYVDHVE KRTTWDRPEP LPPGWERRVD NMGRIYYVDH FTRTTTWQRP 350
    TLESVRNYEQ WQLQRSQLQG AMQQFNQRFI YGNQDLFATS QNKEFDPLGP 400
    LPPGWEKRTD SNGRVYFVNH NTRITQWEDP RSQGQLNEKP LPEGWEMRFT 450
    VDGIPYFVDH NRRATTYIDP RTGKSALDNG PQIAYVRDFK AKVQYFRFWC 500
    QQLAMPQHIK ITVTRKTLFE DSFQQIMSFS PQDLRRRLWV IFPGEEGLDY 550
    GGVAREWFFL LSHEVLNPMY CLFEYAGKDN YCLQINPASY INPDHLKYFR 600
    FIGRFIAMAL FHGKFIDTGF SLPFYKRILN KPVGLKDLES IDPEFYNSLI 650
    WVKENNIEEC GLEMYFSVDK EILGEIKSHD LKPNGGNILV TEENKEEYIR 700
    MVAEWRLSRG VEEQTQAFFE GFNEILPQQY LQYFDAKELE VLLCGMQEID 750
    LNDWQRHAIY RHYTRTSKQI MWFWQFVKEI DNEKRMRLLQ FVTGTCRLPV 800
    GGFADLMGSN GPQKFCIEKV GKENWLPRSH TCFNRLDLPP YKSYEQLKEK 850
    LLFAIEETEG FGQE 864

    Note: Major form.

    Length:864
    Mass (Da):98,994
    Last modified:October 3, 2003 - v2
    Checksum:i905FDBE00A1EA7EA
    GO
    Isoform 2 (identifier: Q8C863-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         742-759: LLCGMQEIDLNDWQRHAI → MNFYLLKHTSKYSFRYLF
         760-864: Missing.

    Show »
    Length:759
    Mass (Da):86,702
    Checksum:iB1820795111F666B
    GO

    Sequence cautioni

    The sequence AAB99764.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei742 – 75918LLCGM…QRHAI → MNFYLLKHTSKYSFRYLF in isoform 2. 1 PublicationVSP_008452Add
    BLAST
    Alternative sequencei760 – 864105Missing in isoform 2. 1 PublicationVSP_008453Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF037454 mRNA. Translation: AAB99764.1. Different initiation.
    AK048303 mRNA. Translation: BAC33298.1.
    BC062934 mRNA. Translation: AAH62934.1.
    CCDSiCCDS38293.1. [Q8C863-1]
    RefSeqiNP_001230641.1. NM_001243712.1. [Q8C863-1]
    NP_032421.2. NM_008395.3. [Q8C863-1]
    UniGeneiMm.208286.
    Mm.490088.

    Genome annotation databases

    EnsembliENSMUST00000029126; ENSMUSP00000029126; ENSMUSG00000027598. [Q8C863-1]
    ENSMUST00000109685; ENSMUSP00000105307; ENSMUSG00000027598. [Q8C863-1]
    GeneIDi16396.
    KEGGimmu:16396.
    UCSCiuc008nkd.1. mouse. [Q8C863-2]
    uc008nke.2. mouse. [Q8C863-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF037454 mRNA. Translation: AAB99764.1 . Different initiation.
    AK048303 mRNA. Translation: BAC33298.1 .
    BC062934 mRNA. Translation: AAH62934.1 .
    CCDSi CCDS38293.1. [Q8C863-1 ]
    RefSeqi NP_001230641.1. NM_001243712.1. [Q8C863-1 ]
    NP_032421.2. NM_008395.3. [Q8C863-1 ]
    UniGenei Mm.208286.
    Mm.490088.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1YIU NMR - A 399-432 [» ]
    2JO9 NMR - A 399-432 [» ]
    2JOC NMR - A 399-432 [» ]
    ProteinModelPortali Q8C863.
    SMRi Q8C863. Positions 13-145, 287-861.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 200813. 16 interactions.
    DIPi DIP-29318N.
    IntActi Q8C863. 10 interactions.
    MINTi MINT-142559.
    STRINGi 10090.ENSMUSP00000105307.

    PTM databases

    PhosphoSitei Q8C863.

    Proteomic databases

    MaxQBi Q8C863.
    PaxDbi Q8C863.
    PRIDEi Q8C863.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000029126 ; ENSMUSP00000029126 ; ENSMUSG00000027598 . [Q8C863-1 ]
    ENSMUST00000109685 ; ENSMUSP00000105307 ; ENSMUSG00000027598 . [Q8C863-1 ]
    GeneIDi 16396.
    KEGGi mmu:16396.
    UCSCi uc008nkd.1. mouse. [Q8C863-2 ]
    uc008nke.2. mouse. [Q8C863-1 ]

    Organism-specific databases

    CTDi 83737.
    MGIi MGI:1202301. Itch.

    Phylogenomic databases

    eggNOGi COG5021.
    GeneTreei ENSGT00570000078756.
    HOVERGENi HBG004134.
    InParanoidi Q8C863.
    KOi K05632.
    OMAi GETTCSE.
    OrthoDBi EOG7RFTGT.
    PhylomeDBi Q8C863.
    TreeFami TF323658.

    Enzyme and pathway databases

    UniPathwayi UPA00143 .
    Reactomei REACT_198532. Negative regulators of RIG-I/MDA5 signaling.
    REACT_199100. Downregulation of ERBB4 signaling.
    REACT_199115. Antigen processing: Ubiquitination & Proteasome degradation.
    REACT_199384. Activated NOTCH1 Transmits Signal to the Nucleus.
    REACT_211125. NOD1/2 Signaling Pathway.

    Miscellaneous databases

    ChiTaRSi ITCH. mouse.
    EvolutionaryTracei Q8C863.
    NextBioi 289541.
    PROi Q8C863.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q8C863.
    Bgeei Q8C863.
    CleanExi MM_ITCH.
    Genevestigatori Q8C863.

    Family and domain databases

    Gene3Di 2.60.40.150. 1 hit.
    InterProi IPR000008. C2_dom.
    IPR024928. E3_ub_ligase_SMURF1.
    IPR000569. HECT.
    IPR001202. WW_dom.
    [Graphical view ]
    Pfami PF00168. C2. 1 hit.
    PF00632. HECT. 1 hit.
    PF00397. WW. 4 hits.
    [Graphical view ]
    PIRSFi PIRSF001569. E3_ub_ligase_SMURF1. 1 hit.
    SMARTi SM00239. C2. 1 hit.
    SM00119. HECTc. 1 hit.
    SM00456. WW. 4 hits.
    [Graphical view ]
    SUPFAMi SSF49562. SSF49562. 1 hit.
    SSF51045. SSF51045. 4 hits.
    SSF56204. SSF56204. 1 hit.
    PROSITEi PS50004. C2. 1 hit.
    PS50237. HECT. 1 hit.
    PS01159. WW_DOMAIN_1. 4 hits.
    PS50020. WW_DOMAIN_2. 4 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The itchy locus encodes a novel ubiquitin protein ligase that is disrupted in a18H mice."
      Perry W.L., Hustad C.M., Swing D.A., O'Sullivan T.N., Jenkins N.A., Copeland N.G.
      Nat. Genet. 18:143-146(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), DISEASE.
      Strain: C3H/HeJ.
      Tissue: Kidney.
    2. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Strain: C57BL/6J.
      Tissue: Head.
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Strain: C57BL/6.
      Tissue: Brain.
    4. "N4WBP5, a potential target for ubiquitination by the Nedd4 family of proteins, is a novel Golgi-associated protein."
      Harvey K.F., Shearwin-Whyatt L.M., Fotia A., Parton R.G., Kumar S.
      J. Biol. Chem. 277:9307-9317(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NDFIP1.
    5. "Dysregulation of T lymphocyte function in itchy mice: a role for Itch in TH2 differentiation."
      Fang D., Elly C., Gao B., Fang N., Altman Y., Joazeiro C., Hunter T., Copeland N.G., Jenkins N.A., Liu Y.C.
      Nat. Immunol. 3:281-287(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH JUN AND JUNB.
    6. "Recognition and ubiquitination of Notch by Itch, a hect-type E3 ubiquitin ligase."
      Qiu L., Joazeiro C., Fang N., Wang H.-Y., Elly C., Altman Y., Fang D., Hunter T., Liu Y.-C.
      J. Biol. Chem. 275:35734-35737(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NOTCH1, MUTAGENESIS OF CYS-832.
    7. "The tight junction-specific protein occludin is a functional target of the E3 ubiquitin-protein ligase itch."
      Traweger A., Fang D., Liu Y.-C., Stelzhammer W., Krizbai I.A., Fresser F., Bauer H.-C., Bauer H.
      J. Biol. Chem. 277:10201-10208(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH OCNL.
    8. "Jun turnover is controlled through JNK-dependent phosphorylation of the E3 ligase Itch."
      Gao M., Labuda T., Xia Y., Gallagher E., Fang D., Liu Y.C., Karin M.
      Science 306:271-275(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION, FUNCTION, AUTOUBIQUITINATION.
    9. "Ndfip1 protein promotes the function of itch ubiquitin ligase to prevent T cell activation and T helper 2 cell-mediated inflammation."
      Oliver P.M., Cao X., Worthen G.S., Shi P., Briones N., MacLeod M., White J., Kirby P., Kappler J., Marrack P., Yang B.
      Immunity 25:929-940(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NDFIP1.
    10. "Activation of the E3 ubiquitin ligase Itch through a phosphorylation-induced conformational change."
      Gallagher E., Gao M., Liu Y.C., Karin M.
      Proc. Natl. Acad. Sci. U.S.A. 103:1717-1722(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-199; THR-222 AND SER-232, INTERACTION WITH MAPK8, AUTOUBIQUITINATION, SUBUNIT, MUTAGENESIS OF SER-199; THR-222; SER-232 AND 535-ARG--VAL-540.
    11. Cited for: FUNCTION, INTERACTION WITH N4BP1.
    12. "AIP4/Itch regulates Notch receptor degradation in the absence of ligand."
      Chastagner P., Israel A., Brou C.
      PLoS ONE 3:E2735-E2735(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, UBIQUITINATION OF NOTCH1.
    13. "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."
      Azakir B.A., Desrochers G., Angers A.
      FEBS J. 277:1319-1330(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH P15 BID, UBIQUITINATION OF P15 BID.
    14. "Phosphorylation of either Ser16 or Thr30 does not disrupt the structure of the Itch E3 ubiquitin ligase third WW domain."
      Shaw A.Z., Martin-Malpartida P., Morales B., Yraola F., Royo M., Macias M.J.
      Proteins 60:558-560(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 399-432 OF WILD TYPE AND IN VITRO WW3-PHOSPHORYLATED FORMS.
    15. "NMR structural studies of the ItchWW3 domain reveal that phosphorylation at T30 inhibits the interaction with PPxY-containing ligands."
      Morales B., Ramirez-Espain X., Shaw A.Z., Martin-Malpartida P., Yraola F., Sanchez-Tillo E., Farrera C., Celada A., Royo M., Macias M.J.
      Structure 15:473-483(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 399-432 OF WILD TYPE AND IN VITRO PHOSPHORYLATED FORMS IN COMPLEX WITH PPXY MOTIFS OF EPSTEIN-BARR VIRUS LMP2A.

    Entry informationi

    Entry nameiITCH_MOUSE
    AccessioniPrimary (citable) accession number: Q8C863
    Secondary accession number(s): O54971
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 3, 2003
    Last sequence update: October 3, 2003
    Last modified: October 1, 2014
    This is version 124 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3