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Entry version 170 (18 Sep 2019)
Sequence version 2 (03 Oct 2003)
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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

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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 (PubMed:15358865, PubMed:16446428, PubMed:17592138, PubMed:18628966, PubMed:20392206, PubMed:25632008). It catalyzes 'Lys-29'-, 'Lys-48'- and 'Lys-63'-linked ubiquitin conjugation (By similarity). Involved in the control of inflammatory signaling pathways (By similarity). 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 (By similarity). Promotes the association of the complex after TNF stimulation (By similarity). Once the complex is formed, TNFAIP3 deubiquitinates 'Lys-63' polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains (By similarity). 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 (PubMed:15358865, PubMed:11828324). Ubiquitinates NFE2 by 'Lys-63' linkages and is implicated in the control of the development of hematopoietic lineages (By similarity). Mediates JUN ubiquitination and degradation (PubMed:15358865). Mediates JUNB ubiquitination and degradation (PubMed:11828324, PubMed:15358865). Critical regulator of type 2 helper T (Th2) cell cytokine production by inducing JUNB ubiquitination and degradation (PubMed:11828324). Involved in the negative regulation of MAVS-dependent cellular antiviral responses (By similarity). Ubiquitinates MAVS through 'Lys-48'-linked conjugation resulting in MAVS proteasomal degradation (By similarity). Following ligand stimulation, regulates sorting of Wnt receptor FZD4 to the degradative endocytic pathway probably by modulating PI42KA activity (By similarity). Ubiquitinates PI4K2A and negatively regulates its catalytic activity (By similarity). Ubiquitinates chemokine receptor CXCR4 and regulates sorting of CXCR4 to the degradative endocytic pathway following ligand stimulation by ubiquitinating endosomal sorting complex required for transport ESCRT-0 components HGS and STAM (By similarity). Targets DTX1 for lysosomal degradation and controls NOTCH1 degradation, in the absence of ligand, through 'Lys-29'-linked polyubiquitination (PubMed:18628966). Ubiquitinates SNX9 (By similarity). Ubiquitinates MAP3K7 through 'Lys-48'-linked conjugation (PubMed:25632008). 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 (PubMed:20392206). Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (By similarity).By similarity6 Publications

Caution

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

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Activated by NDFIP1- and NDFIP2-binding (PubMed:25632008). Activated by PI4K2A-binding (By similarity). Inhibited by DTX3L-binding (By similarity). Inhibited by N4BP1 binding (PubMed:17592138).By similarity2 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.6 Publications
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei832Glycyl thioester intermediatePROSITE-ProRule annotation1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionTransferase
Biological processAntiviral defense, Apoptosis, Immunity, Innate immunity, Ubl conjugation pathway

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

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BRENDAi
6.3.2.19 3474

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-MMU-1253288 Downregulation of ERBB4 signaling
R-MMU-168638 NOD1/2 Signaling Pathway
R-MMU-2122948 Activated NOTCH1 Transmits Signal to the Nucleus
R-MMU-5610780 Degradation of GLI1 by the proteasome
R-MMU-5632684 Hedgehog 'on' state
R-MMU-8939236 RUNX1 regulates transcription of genes involved in differentiation of HSCs
R-MMU-983168 Antigen processing: Ubiquitination & Proteasome degradation

UniPathway: a resource for the exploration and annotation of metabolic pathways

More...
UniPathwayi
UPA00143

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
E3 ubiquitin-protein ligase Itchy (EC:2.3.2.266 Publications)
Alternative name(s):
HECT-type E3 ubiquitin transferase Itchy homolog
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:Itch
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiMus musculus (Mouse)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri10090 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000000589 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 2

Organism-specific databases

Mouse genome database (MGD) from Mouse Genome Informatics (MGI)

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MGIi
MGI:1202301 Itch

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endosome, Membrane, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>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)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi199S → 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 Publication1
Mutagenesisi199S → D: More sensitive to in vitro proteolysis. 1 Publication1
Mutagenesisi222T → 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 Publication1
Mutagenesisi222T → D: Inhibits in vitro interaction between ITCH HECT domain and PRR/WW motifs. More sensitive to in vitro proteolysis. 1 Publication1
Mutagenesisi232S → 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 Publication1
Mutagenesisi232S → D: More sensitive to in vitro proteolysis. 1 Publication1
Mutagenesisi535 – 540RRRLWV → AAALWA: Abolishes interaction with MAPK8. 1 Publication6
Mutagenesisi535 – 537RRR → AAA: Almost complete loss of interaction with MAPK8. 3
Mutagenesisi535 – 536RR → AA: Greatly decreased interaction with MAPK8 and ligase activity. 2
Mutagenesisi832C → A: Loss of ubiquitin protein ligase activity. 1 Publication1

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section indicates that the initiator methionine is cleaved from the mature protein.<p><a href='/help/init_met' target='_top'>More...</a></p>Initiator methionineiRemovedBy similarity
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001203182 – 864E3 ubiquitin-protein ligase ItchyAdd BLAST863

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei2N-acetylserineBy similarity1
Modified residuei199Phosphoserine; by MAPK81 Publication1
Modified residuei222Phosphothreonine; by MAPK81 Publication1
Modified residuei232Phosphoserine; by MAPK81 Publication1
Modified residuei346Phosphothreonine; by SGK3By similarity1
Modified residuei381Phosphotyrosine; by FYNBy similarity1
Modified residuei411Phosphoserine; by SGK3By similarity1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>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
Monoubiquitinated. Autopolyubiquitinated with 'Lys-63' linkages which does not lead to protein degradation.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
Q8C863

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
Q8C863

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
Q8C863

PeptideAtlas

More...
PeptideAtlasi
Q8C863

PRoteomics IDEntifications database

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PRIDEi
Q8C863

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
Q8C863

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
Q8C863

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

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

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSMUSG00000027598 Expressed in 288 organ(s), highest expression level in rostral migratory stream

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q8C863 MM

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Monomer.

Interacts (via WW domains) with OCNL (PubMed:11782481).

Interacts (via WW domains) with NOTCH1 (PubMed:10940313, PubMed:18628966).

Interacts (via WW domains) JUN (PubMed:11828324). Interacts with JUNB; the interaction promotes ITCH-mediated ubiquitination and degradation of JUNB (PubMed:11828324).

Interacts with FYN; the interaction phosphorylates ITCH on Tyr-381 decreasing binding of JUNB (By similarity).

Interacts (via WW domain 2) with N4BP1; the interaction inhibits the E3 ubiquitin-protein ligase activity (PubMed:17592138).

Interacts with NDFIP1 and NDFIP2; the interaction with NDFIP proteins activates the E3 ubiquitin-protein ligase and may induce its recruitment to exosomes (PubMed:11748237, PubMed:17137798, PubMed:25632008).

Interacts with ARHGEF7 (By similarity).

Interacts with RNF11 (By similarity).

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 (By similarity).

Interacts (via WW domains) with CXCR4 (via C-terminus); the interaction depends on CXCR4 phosphorylation (By similarity).

Found in a complex with E3 ligase DTX3L and ESCRT-0 components HGS and STAM (By similarity).

Interacts with DTX3L (via C-terminus); the interaction is increased upon CXCL12 stimulation and inhibits ITCH catalytic activity (the interaction is direct) (By similarity).

Interacts with HGS (By similarity).

Interacts (via WW domains) with PCBP2 within a complex containing ITCH, MAVS and PCBP2 (By similarity).

Interacts (via WW domains) with TXNIP (via C-terminus) (By similarity).

Interacts with p15 BID (PubMed:20392206).

Interacts with ERBB4 (By similarity).

Interacts with DTX1 (By similarity).

Interacts with SPART (By similarity).

Interacts with SNX9 and SNX18 (By similarity).

Interacts (via its WW domains) with ATN1 (By similarity).

Interacts (via WW domains) with SGK3 (By similarity).

Interacts with CBLC (By similarity).

Interacts with OTUD7B (By similarity).

Interacts (via WW domain 1,2 and 3) with PI4K2A; the interaction inhibits PI4K2A catalytic activity and promotes ITCH catalytic activity (PubMed:23146885).

Interacts with ARRDC4 (By similarity).

Part of a complex containing ITCH, NDFIP1 and MAP3K7 (PubMed:25632008).

Interacts with UBE2L3; the interaction is mediated by NDFIP1 (PubMed:25632008).

Interacts with MAPK8/JNK1 (PubMed:16446428).

Interacts (via WW domains) with ARRDC1 (via PPxY motifs); the interaction is direct and participates to the recruitment of the ubiquitin-protein ligase ITCH to the NOTCH1 receptor (By similarity).

Interacts (via WW domains) with ARRDC2 (By similarity).

Interacts (via WW domains) with ARRDC3 (By similarity).

By similarity10 Publications

(Microbial infection)

Interacts with Epstein-Barr virus LMP2A.

1 Publication

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
200813, 35 interactors

Database of interacting proteins

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DIPi
DIP-29318N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

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ELMi
Q8C863

Protein interaction database and analysis system

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IntActi
Q8C863, 13 interactors

Molecular INTeraction database

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MINTi
Q8C863

STRING: functional protein association networks

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STRINGi
10090.ENSMUSP00000105307

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1864
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
Q8C863

Database of comparative protein structure models

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ModBasei
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
Q8C863

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini5 – 99C2PROSITE-ProRule annotationAdd BLAST95
Domaini287 – 320WW 1PROSITE-ProRule annotationAdd BLAST34
Domaini319 – 352WW 2PROSITE-ProRule annotationAdd BLAST34
Domaini399 – 432WW 3PROSITE-ProRule annotationAdd BLAST34
Domaini439 – 472WW 4PROSITE-ProRule annotationAdd BLAST34
Domaini530 – 864HECTPROSITE-ProRule annotationAdd BLAST335

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni356 – 432Required for interaction with FYNBy similarityAdd BLAST77
Regioni535 – 544MAP kinase docking site10

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes the position of regions of compositional bias within the protein and the particular amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi211 – 226Arg/Pro-rich (PRR domain)Add BLAST16

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The WW domains mediate interaction with PPxY motif-containing proteins.By similarity

Keywords - Domaini

Repeat

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG0940 Eukaryota
COG5021 LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000157014

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
Q8C863

KEGG Orthology (KO)

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KOi
K05632

Identification of Orthologs from Complete Genome Data

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OMAi
QHLTVIV

Database of Orthologous Groups

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OrthoDBi
167687at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
Q8C863

TreeFam database of animal gene trees

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TreeFami
TF323658

Family and domain databases

Conserved Domains Database

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CDDi
cd00078 HECTc, 1 hit
cd00201 WW, 4 hits

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
2.60.40.150, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR024928 E3_ub_ligase_SMURF1
IPR000569 HECT_dom
IPR035983 Hect_E3_ubiquitin_ligase
IPR001202 WW_dom
IPR036020 WW_dom_sf

Pfam protein domain database

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Pfami
View protein in Pfam
PF00168 C2, 1 hit
PF00632 HECT, 1 hit
PF00397 WW, 3 hits

PIRSF; a whole-protein classification database

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PIRSFi
PIRSF001569 E3_ub_ligase_SMURF1, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00239 C2, 1 hit
SM00119 HECTc, 1 hit
SM00456 WW, 4 hits

Superfamily database of structural and functional annotation

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SUPFAMi
SSF51045 SSF51045, 4 hits
SSF56204 SSF56204, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS50004 C2, 1 hit
PS50237 HECT, 1 hit
PS01159 WW_DOMAIN_1, 4 hits
PS50020 WW_DOMAIN_2, 4 hits

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q8C863-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali 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
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> 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

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

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

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_008452742 – 759LLCGM…QRHAI → MNFYLLKHTSKYSFRYLF in isoform 2. 1 PublicationAdd BLAST18
Alternative sequenceiVSP_008453760 – 864Missing in isoform 2. 1 PublicationAdd BLAST105

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
AF037454 mRNA Translation: AAB99764.1 Different initiation.
AK048303 mRNA Translation: BAC33298.1
BC062934 mRNA Translation: AAH62934.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS38293.1 [Q8C863-1]

NCBI Reference Sequences

More...
RefSeqi
NP_001230641.1, NM_001243712.1 [Q8C863-1]
NP_032421.2, NM_008395.3 [Q8C863-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENSMUST00000029126; ENSMUSP00000029126; ENSMUSG00000027598 [Q8C863-1]
ENSMUST00000109685; ENSMUSP00000105307; ENSMUSG00000027598 [Q8C863-1]

Database of genes from NCBI RefSeq genomes

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GeneIDi
16396

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
mmu:16396

UCSC genome browser

More...
UCSCi
uc008nkd.1 mouse [Q8C863-2]
uc008nke.2 mouse [Q8C863-1]

Keywords - Coding sequence diversityi

Alternative splicing

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>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]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...
PDBei

Protein Data Bank RCSB

More...
RCSB PDBi

Protein Data Bank Japan

More...
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1YIUNMR-A399-432[»]
2JO9NMR-A399-432[»]
2JOCNMR-A399-432[»]
5XMCX-ray2.60A143-864[»]
SMRiQ8C863
ModBaseiSearch...

Protein-protein interaction databases

BioGridi200813, 35 interactors
DIPiDIP-29318N
ELMiQ8C863
IntActiQ8C863, 13 interactors
MINTiQ8C863
STRINGi10090.ENSMUSP00000105307

PTM databases

iPTMnetiQ8C863
PhosphoSitePlusiQ8C863

Proteomic databases

EPDiQ8C863
jPOSTiQ8C863
PaxDbiQ8C863
PeptideAtlasiQ8C863
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

Comparative Toxicogenomics Database

More...
CTDi
83737
MGIiMGI:1202301 Itch

Phylogenomic databases

eggNOGiKOG0940 Eukaryota
COG5021 LUCA
GeneTreeiENSGT00940000157014
InParanoidiQ8C863
KOiK05632
OMAiQHLTVIV
OrthoDBi167687at2759
PhylomeDBiQ8C863
TreeFamiTF323658

Enzyme and pathway databases

UniPathwayiUPA00143
BRENDAi6.3.2.19 3474
ReactomeiR-MMU-1253288 Downregulation of ERBB4 signaling
R-MMU-168638 NOD1/2 Signaling Pathway
R-MMU-2122948 Activated NOTCH1 Transmits Signal to the Nucleus
R-MMU-5610780 Degradation of GLI1 by the proteasome
R-MMU-5632684 Hedgehog 'on' state
R-MMU-8939236 RUNX1 regulates transcription of genes involved in differentiation of HSCs
R-MMU-983168 Antigen processing: Ubiquitination & Proteasome degradation

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
Itch mouse
EvolutionaryTraceiQ8C863

Protein Ontology

More...
PROi
PR:Q8C863

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSMUSG00000027598 Expressed in 288 organ(s), highest expression level in rostral migratory stream
GenevisibleiQ8C863 MM

Family and domain databases

CDDicd00078 HECTc, 1 hit
cd00201 WW, 4 hits
Gene3Di2.60.40.150, 1 hit
InterProiView protein in InterPro
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR024928 E3_ub_ligase_SMURF1
IPR000569 HECT_dom
IPR035983 Hect_E3_ubiquitin_ligase
IPR001202 WW_dom
IPR036020 WW_dom_sf
PfamiView protein in Pfam
PF00168 C2, 1 hit
PF00632 HECT, 1 hit
PF00397 WW, 3 hits
PIRSFiPIRSF001569 E3_ub_ligase_SMURF1, 1 hit
SMARTiView protein in SMART
SM00239 C2, 1 hit
SM00119 HECTc, 1 hit
SM00456 WW, 4 hits
SUPFAMiSSF51045 SSF51045, 4 hits
SSF56204 SSF56204, 1 hit
PROSITEiView protein in PROSITE
PS50004 C2, 1 hit
PS50237 HECT, 1 hit
PS01159 WW_DOMAIN_1, 4 hits
PS50020 WW_DOMAIN_2, 4 hits

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiITCH_MOUSE
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q8C863
Secondary accession number(s): O54971
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 3, 2003
Last sequence update: October 3, 2003
Last modified: September 18, 2019
This is version 170 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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