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Protein

E3 ubiquitin-protein ligase Itchy

Gene

Itch

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 similarity5 Publications

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. CXCR chemokine receptor binding Source: MGI
  2. ligase activity Source: BHF-UCL
  3. ribonucleoprotein complex binding Source: MGI
  4. ubiquitin protein ligase activity Source: MGI
  5. 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
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

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

Enzyme and pathway databases

BRENDAi6.3.2.19. 3474.
ReactomeiREACT_286692. Activated NOTCH1 Transmits Signal to the Nucleus.
REACT_289760. Negative regulators of RIG-I/MDA5 signaling.
REACT_301153. NOD1/2 Signaling Pathway.
REACT_309591. Downregulation of ERBB4 signaling.
REACT_324511. Degradation of GLI1 by the proteasome.
REACT_343568. Antigen processing: Ubiquitination & Proteasome degradation.
REACT_351311. Hedgehog 'on' state.
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 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1202301. Itch.

Subcellular locationi

  1. Cell membrane By similarity
  2. Cytoplasm
  3. Nucleus

  4. 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. extracellular vesicular exosome Source: MGI
  6. membrane Source: MGI
  7. nucleus Source: MGI
  8. plasma membrane Source: MGI
  9. ubiquitin ligase complex Source: MGI
Complete GO annotation...

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.

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. 1 Publication
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 MAPK81 Publication
Modified residuei222 – 2221Phosphothreonine; by MAPK81 Publication
Modified residuei232 – 2321Phosphoserine; by MAPK81 Publication
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

Detected in uterus (at protein level) (PubMed:23146885). Widely expressed (PubMed:9462742).2 Publications

Gene expression databases

BgeeiQ8C863.
CleanExiMM_ITCH.
ExpressionAtlasiQ8C863. baseline and differential.
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 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 (via WW domain 2) with N4BP1; the interaction inhibits the E3 ubiquitin-protein ligase activity. 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 domains) with SGK3. Interacts with PI4K2A (PubMed:23146885).By similarity10 Publications

Binary interactionsi

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

Protein-protein interaction databases

BioGridi200813. 18 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 – 4013Combined sources
Beta strandi407 – 4093Combined sources
Beta strandi411 – 4133Combined sources
Beta strandi415 – 4195Combined sources
Turni420 – 4234Combined sources
Beta strandi424 – 4263Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
GeneTreeiENSGT00760000118966.
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. AlignAdd to basket

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

        10         20         30         40         50
MSDSGPQLDS MGSLTMKSQL QITVISAKLK ENKKNWFGPS PYVEVTVDGQ
60 70 80 90 100
SKKTEKCNNT NSPKWKQPLT VIVTPTSKLC FRVWSHQTLK SDVLLGTAGL
110 120 130 140 150
DIYETLKSNN MKLEEVVMTL QLVGDKEPTE TMGDLSVCLD GLQVEAEVVT
160 170 180 190 200
NGETSCSEST TQNDDGCRTR DDTRVSTNGS EDPEVAASGE NKRANGNNSP
210 220 230 240 250
SLSNGGFKPS RPPRPSRPPP PTPRRPASVN GSPSTNSDSD GSSTGSLPPT
260 270 280 290 300
NTNVNTSTSE GATSGLIIPL TISGGSGPRP LNTVSQAPLP PGWEQRVDQH
310 320 330 340 350
GRVYYVDHVE KRTTWDRPEP LPPGWERRVD NMGRIYYVDH FTRTTTWQRP
360 370 380 390 400
TLESVRNYEQ WQLQRSQLQG AMQQFNQRFI YGNQDLFATS QNKEFDPLGP
410 420 430 440 450
LPPGWEKRTD SNGRVYFVNH NTRITQWEDP RSQGQLNEKP LPEGWEMRFT
460 470 480 490 500
VDGIPYFVDH NRRATTYIDP RTGKSALDNG PQIAYVRDFK AKVQYFRFWC
510 520 530 540 550
QQLAMPQHIK ITVTRKTLFE DSFQQIMSFS PQDLRRRLWV IFPGEEGLDY
560 570 580 590 600
GGVAREWFFL LSHEVLNPMY CLFEYAGKDN YCLQINPASY INPDHLKYFR
610 620 630 640 650
FIGRFIAMAL FHGKFIDTGF SLPFYKRILN KPVGLKDLES IDPEFYNSLI
660 670 680 690 700
WVKENNIEEC GLEMYFSVDK EILGEIKSHD LKPNGGNILV TEENKEEYIR
710 720 730 740 750
MVAEWRLSRG VEEQTQAFFE GFNEILPQQY LQYFDAKELE VLLCGMQEID
760 770 780 790 800
LNDWQRHAIY RHYTRTSKQI MWFWQFVKEI DNEKRMRLLQ FVTGTCRLPV
810 820 830 840 850
GGFADLMGSN GPQKFCIEKV GKENWLPRSH TCFNRLDLPP YKSYEQLKEK
860
LLFAIEETEG FGQE

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.Curated

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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

BioGridi200813. 18 interactions.
DIPiDIP-29318N.
IntActiQ8C863. 10 interactions.
MINTiMINT-142559.
STRINGi10090.ENSMUSP00000105307.

PTM databases

PhosphoSiteiQ8C863.

Proteomic databases

MaxQBiQ8C863.
PaxDbiQ8C863.
PRIDEiQ8C863.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi83737.
MGIiMGI:1202301. Itch.

Phylogenomic databases

eggNOGiCOG5021.
GeneTreeiENSGT00760000118966.
HOVERGENiHBG004134.
InParanoidiQ8C863.
KOiK05632.
OMAiGETTCSE.
OrthoDBiEOG7RFTGT.
PhylomeDBiQ8C863.
TreeFamiTF323658.

Enzyme and pathway databases

UniPathwayiUPA00143.
BRENDAi6.3.2.19. 3474.
ReactomeiREACT_286692. Activated NOTCH1 Transmits Signal to the Nucleus.
REACT_289760. Negative regulators of RIG-I/MDA5 signaling.
REACT_301153. NOD1/2 Signaling Pathway.
REACT_309591. Downregulation of ERBB4 signaling.
REACT_324511. Degradation of GLI1 by the proteasome.
REACT_343568. Antigen processing: Ubiquitination & Proteasome degradation.
REACT_351311. Hedgehog 'on' state.

Miscellaneous databases

ChiTaRSiItch. mouse.
EvolutionaryTraceiQ8C863.
NextBioi289541.
PROiQ8C863.
SOURCEiSearch...

Gene expression databases

BgeeiQ8C863.
CleanExiMM_ITCH.
ExpressionAtlasiQ8C863. baseline and differential.
GenevestigatoriQ8C863.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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, FUNCTION, TISSUE SPECIFICITY.
    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.
  16. "Phosphatidylinositol 4-kinase IIalpha function at endosomes is regulated by the ubiquitin ligase Itch."
    Mossinger J., Wieffer M., Krause E., Freund C., Gerth F., Krauss M., Haucke V.
    EMBO Rep. 13:1087-1094(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PI4K2A, TISSUE SPECIFICITY.

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: April 29, 2015
This is version 131 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

It is uncertain whether Met-1 or Met-11 is the initiator.Curated

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.