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Q8C863 (ITCH_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
E3 ubiquitin-protein ligase Itchy

EC=6.3.2.-
Gene names
Name:Itch
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length864 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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 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. Ref.5 Ref.8 Ref.11 Ref.12 Ref.13

Enzyme regulation

Activated by NDFIP1- and NDFIP2-binding By similarity.

Pathway

Protein modification; protein ubiquitination.

Subunit structure

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. Ref.4 Ref.5 Ref.6 Ref.7 Ref.9 Ref.10 Ref.11 Ref.13

Subcellular location

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

Tissue specificity

Widely expressed.

Post-translational modification

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.

Ubiquitinated; autopolyubiquitination with 'Lys-63' linkages which does not lead to protein degradation By similarity. Ref.8 Ref.10 Ref.12 Ref.13

Involvement in disease

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. Ref.1

Sequence similarities

Contains 1 C2 domain.

Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain.

Contains 4 WW domains.

Caution

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

Sequence caution

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

Ontologies

Keywords
   Biological processAntiviral defense
Apoptosis
Immunity
Innate immunity
Ubl conjugation pathway
   Cellular componentCell membrane
Cytoplasm
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
   DomainRepeat
   Molecular functionLigase
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

defense response to virus

Inferred from electronic annotation. Source: UniProtKB-KW

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of JNK cascade

Inferred from mutant phenotype PubMed 18246070. Source: BHF-UCL

negative regulation of NF-kappaB transcription factor activity

Inferred from mutant phenotype PubMed 18246070. Source: BHF-UCL

negative regulation of alpha-beta T cell proliferation

Inferred from mutant phenotype PubMed 14973438. Source: MGI

negative regulation of apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of defense response to virus

Inferred from mutant phenotype PubMed 19881509. Source: UniProtKB

positive regulation of T cell anergy

Inferred from mutant phenotype PubMed 14973438. Source: MGI

positive regulation of protein catabolic process

Inferred from direct assay PubMed 14973438. Source: MGI

protein K29-linked ubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

protein K48-linked ubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

protein K63-linked ubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

protein polyubiquitination

Inferred from direct assay PubMed 14973438. Source: MGI

protein ubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

protein ubiquitination involved in ubiquitin-dependent protein catabolic process

Inferred from direct assay PubMed 14973438. Source: MGI

regulation of protein deubiquitination

Inferred from mutant phenotype PubMed 18246070. Source: BHF-UCL

ubiquitin-dependent protein catabolic process

Inferred from direct assay PubMed 15678106. Source: MGI

   Cellular_componentcell cortex

Inferred from direct assay Ref.9. Source: MGI

cytoplasm

Inferred from direct assay PubMed 14973438. Source: MGI

cytoplasmic vesicle

Inferred from direct assay Ref.9. Source: MGI

cytosol

Traceable author statement. Source: Reactome

membrane

Inferred from direct assay PubMed 14973438. Source: MGI

nucleus

Inferred from direct assay PubMed 11555636. Source: MGI

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

ubiquitin ligase complex

Inferred from sequence alignment Ref.1. Source: MGI

   Molecular_functionligase activity

Inferred from mutant phenotype PubMed 18246070. Source: BHF-UCL

ribonucleoprotein complex binding

Inferred from electronic annotation. Source: Ensembl

ubiquitin-protein ligase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CyldQ80TQ22EBI-851782,EBI-943859

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8C863-1)

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.
Note: Major form.
Isoform 2 (identifier: Q8C863-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 864863E3 ubiquitin-protein ligase Itchy
PRO_0000120318

Regions

Domain5 – 9995C2
Domain287 – 32034WW 1
Domain319 – 35234WW 2
Domain399 – 43234WW 3
Domain439 – 47234WW 4
Domain530 – 864335HECT
Region356 – 43277Required for interaction with FYN By similarity
Region535 – 54410MAP kinase docking site
Compositional bias211 – 22616Arg/Pro-rich (PRR domain)

Sites

Active site8321Glycyl thioester intermediate By similarity

Amino acid modifications

Modified residue21N-acetylserine By similarity
Modified residue1991Phosphoserine; by MAPK8 Ref.10
Modified residue2221Phosphothreonine; by MAPK8 Ref.10
Modified residue2321Phosphoserine; by MAPK8 Ref.10
Modified residue3461Phosphothreonine; by SGK3 By similarity
Modified residue3811Phosphotyrosine; by FYN By similarity
Modified residue4111Phosphoserine; by SGK3 By similarity

Natural variations

Alternative sequence742 – 75918LLCGM…QRHAI → MNFYLLKHTSKYSFRYLF in isoform 2.
VSP_008452
Alternative sequence760 – 864105Missing in isoform 2.
VSP_008453

Experimental info

Mutagenesis1991S → 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. Ref.10
Mutagenesis1991S → D: More sensitive to in vitro proteolysis. Ref.10
Mutagenesis2221T → 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. Ref.10
Mutagenesis2221T → D: Inhibits in vitro interaction between ITCH HECT domain and PRR/WW motifs. More sensitive to in vitro proteolysis. Ref.10
Mutagenesis2321S → 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. Ref.10
Mutagenesis2321S → D: More sensitive to in vitro proteolysis. Ref.10
Mutagenesis535 – 5406RRRLWV → AAALWA: Abolishes interaction with MAPK8. Ref.10
Mutagenesis535 – 5373RRR → AAA: Almost complete loss of interaction with MAPK8.
Mutagenesis535 – 5362RR → AA: Greatly decreased interaction with MAPK8 and ligase activity.
Mutagenesis8321C → A: Loss of ubiquitin protein ligase activity. Ref.6

Secondary structure

........... 864
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 3, 2003. Version 2.
Checksum: 905FDBE00A1EA7EA

FASTA86498,994
        10         20         30         40         50         60 
MSDSGPQLDS MGSLTMKSQL QITVISAKLK ENKKNWFGPS PYVEVTVDGQ SKKTEKCNNT 

        70         80         90        100        110        120 
NSPKWKQPLT VIVTPTSKLC FRVWSHQTLK SDVLLGTAGL DIYETLKSNN MKLEEVVMTL 

       130        140        150        160        170        180 
QLVGDKEPTE TMGDLSVCLD GLQVEAEVVT NGETSCSEST TQNDDGCRTR DDTRVSTNGS 

       190        200        210        220        230        240 
EDPEVAASGE NKRANGNNSP SLSNGGFKPS RPPRPSRPPP PTPRRPASVN GSPSTNSDSD 

       250        260        270        280        290        300 
GSSTGSLPPT NTNVNTSTSE GATSGLIIPL TISGGSGPRP LNTVSQAPLP PGWEQRVDQH 

       310        320        330        340        350        360 
GRVYYVDHVE KRTTWDRPEP LPPGWERRVD NMGRIYYVDH FTRTTTWQRP TLESVRNYEQ 

       370        380        390        400        410        420 
WQLQRSQLQG AMQQFNQRFI YGNQDLFATS QNKEFDPLGP LPPGWEKRTD SNGRVYFVNH 

       430        440        450        460        470        480 
NTRITQWEDP RSQGQLNEKP LPEGWEMRFT VDGIPYFVDH NRRATTYIDP RTGKSALDNG 

       490        500        510        520        530        540 
PQIAYVRDFK AKVQYFRFWC QQLAMPQHIK ITVTRKTLFE DSFQQIMSFS PQDLRRRLWV 

       550        560        570        580        590        600 
IFPGEEGLDY GGVAREWFFL LSHEVLNPMY CLFEYAGKDN YCLQINPASY INPDHLKYFR 

       610        620        630        640        650        660 
FIGRFIAMAL FHGKFIDTGF SLPFYKRILN KPVGLKDLES IDPEFYNSLI WVKENNIEEC 

       670        680        690        700        710        720 
GLEMYFSVDK EILGEIKSHD LKPNGGNILV TEENKEEYIR MVAEWRLSRG VEEQTQAFFE 

       730        740        750        760        770        780 
GFNEILPQQY LQYFDAKELE VLLCGMQEID LNDWQRHAIY RHYTRTSKQI MWFWQFVKEI 

       790        800        810        820        830        840 
DNEKRMRLLQ FVTGTCRLPV GGFADLMGSN GPQKFCIEKV GKENWLPRSH TCFNRLDLPP 

       850        860 
YKSYEQLKEK LLFAIEETEG FGQE 

« Hide

Isoform 2 [UniParc].

Checksum: B1820795111F666B
Show »

FASTA75986,702

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"The Nedd4-binding partner 1 (N4BP1) protein is an inhibitor of the E3 ligase Itch."
Oberst A., Malatesta M., Aqeilan R.I., Rossi M., Salomoni P., Murillas R., Sharma P., Kuehn M.R., Oren M., Croce C.M., Bernassola F., Melino G.
Proc. Natl. Acad. Sci. U.S.A. 104:11280-11285(2007) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF037454 mRNA. Translation: AAB99764.1. Different initiation.
AK048303 mRNA. Translation: BAC33298.1.
BC062934 mRNA. Translation: AAH62934.1.
RefSeqNP_001230641.1. NM_001243712.1.
NP_032421.2. NM_008395.3.
UniGeneMm.208286.
Mm.490088.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1YIUNMR-A399-432[»]
2JO9NMR-A399-432[»]
2JOCNMR-A399-432[»]
ProteinModelPortalQ8C863.
SMRQ8C863. Positions 13-145, 287-861.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid200813. 16 interactions.
DIPDIP-29318N.
IntActQ8C863. 10 interactions.
MINTMINT-142559.
STRING10090.ENSMUSP00000105307.

PTM databases

PhosphoSiteQ8C863.

Proteomic databases

PaxDbQ8C863.
PRIDEQ8C863.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000029126; ENSMUSP00000029126; ENSMUSG00000027598. [Q8C863-1]
ENSMUST00000109685; ENSMUSP00000105307; ENSMUSG00000027598. [Q8C863-1]
GeneID16396.
KEGGmmu:16396.
UCSCuc008nkd.1. mouse. [Q8C863-2]
uc008nke.2. mouse. [Q8C863-1]

Organism-specific databases

CTD83737.
MGIMGI:1202301. Itch.

Phylogenomic databases

eggNOGCOG5021.
GeneTreeENSGT00570000078756.
HOVERGENHBG004134.
InParanoidQ8C863.
KOK05632.
OMAGETTCSE.
OrthoDBEOG7RFTGT.
PhylomeDBQ8C863.
TreeFamTF323658.

Enzyme and pathway databases

ReactomeREACT_188257. Signal Transduction.
REACT_189085. Disease.
UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ8C863.
BgeeQ8C863.
CleanExMM_ITCH.
GenevestigatorQ8C863.

Family and domain databases

Gene3D2.60.40.150. 1 hit.
InterProIPR000008. C2_dom.
IPR024928. E3_ub_ligase_SMURF1.
IPR000569. HECT.
IPR001202. WW_dom.
[Graphical view]
PfamPF00168. C2. 1 hit.
PF00632. HECT. 1 hit.
PF00397. WW. 4 hits.
[Graphical view]
PIRSFPIRSF001569. E3_ub_ligase_SMURF1. 1 hit.
SMARTSM00239. C2. 1 hit.
SM00119. HECTc. 1 hit.
SM00456. WW. 4 hits.
[Graphical view]
SUPFAMSSF49562. SSF49562. 1 hit.
SSF51045. SSF51045. 4 hits.
SSF56204. SSF56204. 1 hit.
PROSITEPS50004. C2. 1 hit.
PS50237. HECT. 1 hit.
PS01159. WW_DOMAIN_1. 4 hits.
PS50020. WW_DOMAIN_2. 4 hits.
[Graphical view]
ProtoNetSearch...

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ChiTaRSITCH. mouse.
EvolutionaryTraceQ8C863.
NextBio289541.
PROQ8C863.
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Entry information

Entry nameITCH_MOUSE
AccessionPrimary (citable) accession number: Q8C863
Secondary accession number(s): O54971
Entry history
Integrated into UniProtKB/Swiss-Prot: October 3, 2003
Last sequence update: October 3, 2003
Last modified: April 16, 2014
This is version 119 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot