Reviewed,
UniProtKB/Swiss-Prot Q8C863 (ITCH_MOUSE)
Last modified
November 24, 2009.
Version 74.
History...
Clusters with 100%,
90%,
50% identity |
Documents (4) |
Third-party data |
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Names and origin
| Protein names | Recommended name: E3 ubiquitin-protein ligase Itchy EC=6.3.2.- | ||
| Gene names |
| ||
| Organism | Mus musculus (Mouse) | ||
| Taxonomic identifier | 10090 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus |
Protein attributes
| Sequence length | 864 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | 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 proteosomal degradation and consequently termination of the TNF- or LPS-mediated activation of NF-kappa-B By similarity. 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. Regulates the transcriptional activity of several transcription factors, and probably plays an important role in the regulation of immune response. |
| Pathway | |
| Subunit structure | Interacts via its WW domains with OCLN, NOTCH1, JUN and JUNB. Interacts with DRPLA and NFE2. Interacts with ARHGEF7 By similarity. Interacts with NDFIP1 in vitro. Interacts with RNF11 By similarity. |
| Subcellular location | |
| Tissue specificity | Widely expressed. |
| Post-translational modification | Phosphorylated on tyrosine residues By similarity. |
| 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. |
Ontologies
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 key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||||||||
Molecule processing | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 864 | 864 | E3 ubiquitin-protein ligase Itchy | PRO_0000120318 | |||||||||||||
Regions | |||||||||||||||||
| Domain | 5 – 99 | 95 | C2 | ||||||||||||||
| Domain | 287 – 320 | 34 | WW 1 | ||||||||||||||
| Domain | 319 – 352 | 34 | WW 2 | ||||||||||||||
| Domain | 399 – 432 | 34 | WW 3 | ||||||||||||||
| Domain | 439 – 472 | 34 | WW 4 | ||||||||||||||
| Domain | 530 – 864 | 335 | HECT | ||||||||||||||
| Compositional bias | 218 – 223 | 6 | Poly-Pro | ||||||||||||||
Sites | |||||||||||||||||
| Active site | 832 | 1 | Glycyl thioester intermediate By similarity | ||||||||||||||
Amino acid modifications | |||||||||||||||||
| Modified residue | 304 | 1 | Phosphotyrosine By similarity | ||||||||||||||
| Modified residue | 381 | 1 | Phosphotyrosine By similarity | ||||||||||||||
Natural variations | |||||||||||||||||
| Alternative sequence | 742 – 759 | 18 | LLCGM…QRHAI → MNFYLLKHTSKYSFRYLF in isoform 2. | VSP_008452 | |||||||||||||
| Alternative sequence | 760 – 864 | 105 | Missing in isoform 2. | VSP_008453 | |||||||||||||
Experimental info | |||||||||||||||||
| Mutagenesis | 832 | 1 | C → A: Loss of ubiquitin protein ligase activity. Ref.6 | ||||||||||||||
Secondary structure | |||||||||||||||||
Helix Strand Turn | |||||||||||||||||
| Beta strand | 407 – 409 | 3 | |||||||||||||||
| Beta strand | 411 – 413 | 3 | |||||||||||||||
| Beta strand | 415 – 419 | 5 | |||||||||||||||
| Turn | 420 – 423 | 4 | |||||||||||||||
| Beta strand | 424 – 426 | 3 | |||||||||||||||
Sequences
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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: 9462742] [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. Hayashizaki Y.Science 309:1559-1563(2005) [PubMed: 16141072] [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: 15489334] [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: 11748237] [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: 11828324] [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: 10940313] [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: 11782481] [Abstract] Cited for: INTERACTION WITH OCNL. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| AF037454 mRNA. Translation: AAB99764.1. Different initiation. AK048303 mRNA. Translation: BAC33298.1. BC062934 mRNA. Translation: AAH62934.1. | |||||||||||||||||||||||||
| IPI | IPI00380162. IPI00380163. | ||||||||||||||||||||||||
| RefSeq | NP_032421.2. | ||||||||||||||||||||||||
| UniGene | Mm.208286 Mm.462050 | ||||||||||||||||||||||||
3D structure databases | |||||||||||||||||||||||||
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| SMR | Q8C863. Positions 13-145. | ||||||||||||||||||||||||
| ModBase | Search... | ||||||||||||||||||||||||
Protein-protein interaction databases | |||||||||||||||||||||||||
| IntAct | Q8C863. 2 interactions. | ||||||||||||||||||||||||
| STRING | Q8C863. | ||||||||||||||||||||||||
PTM databases | |||||||||||||||||||||||||
| PhosphoSite | Q8C863. | ||||||||||||||||||||||||
Proteomic databases | |||||||||||||||||||||||||
| PRIDE | Q8C863. | ||||||||||||||||||||||||
Genome annotation databases | |||||||||||||||||||||||||
| Ensembl | ENSMUST00000029126; ENSMUSP00000029126; ENSMUSG00000027598; Mus musculus. [Genome view] ENSMUST00000109685; ENSMUSP00000105307; ENSMUSG00000027598; Mus musculus. [Genome view] | ||||||||||||||||||||||||
| GeneID | 16396. | ||||||||||||||||||||||||
| KEGG | mmu:16396. | ||||||||||||||||||||||||
| UCSC | uc008nkd.1. mouse. uc008nke.1. mouse. | ||||||||||||||||||||||||
Organism-specific databases | |||||||||||||||||||||||||
| CTD | 16396. | ||||||||||||||||||||||||
| MGI | MGI:1202301. Itch. | ||||||||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||||||||
| HOVERGEN | Q8C863. | ||||||||||||||||||||||||
| OMA | NSNTSEG | ||||||||||||||||||||||||
| OrthoDB | EOG9RBT45 | ||||||||||||||||||||||||
Gene expression databases | |||||||||||||||||||||||||
| ArrayExpress | Q8C863. | ||||||||||||||||||||||||
| Bgee | Q8C863. | ||||||||||||||||||||||||
| CleanEx | MM_ITCH. | ||||||||||||||||||||||||
| Genevestigator | Q8C863. | ||||||||||||||||||||||||
| GermOnline | ENSMUSG00000027598. Mus musculus. | ||||||||||||||||||||||||
Family and domain databases | |||||||||||||||||||||||||
| InterPro | IPR000008. C2_Ca-dep. IPR008973. C2_Ca/lipid-bd_reg_CaLB. IPR018029. C2_membr_targeting. IPR000569. HECT. IPR001202. WW_Rsp5_WWP. [Graphical view] | ||||||||||||||||||||||||
| Pfam | PF00168. C2. 1 hit. PF00632. HECT. 1 hit. PF00397. WW. 4 hits. [Graphical view] | ||||||||||||||||||||||||
| SMART | SM00239. C2. 1 hit. SM00119. HECTc. 1 hit. SM00456. WW. 4 hits. [Graphical view] | ||||||||||||||||||||||||
| PROSITE | PS50004. C2. 1 hit. PS50237. HECT. 1 hit. PS01159. WW_DOMAIN_1. 4 hits. PS50020. WW_DOMAIN_2. 4 hits. [Graphical view] | ||||||||||||||||||||||||
| ProtoNet | Search... | ||||||||||||||||||||||||
Other Resources | |||||||||||||||||||||||||
| NextBio | 289541. | ||||||||||||||||||||||||
| SOURCE | Search... | ||||||||||||||||||||||||
Entry information
| Entry name | ITCH_MOUSE | ||||||||
| Accession | Primary (citable) accession number: Q8C863 Secondary accession number(s): O54971 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| MGD cross-references Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot |
| PATHWAY comments Index of metabolic and biosynthesis pathways |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with


