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UniProtKB - Q13107 (UBP4_HUMAN)

Entry version 191 (10 Feb 2021)
Sequence version 3 (17 Oct 2006)
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Protein

Ubiquitin carboxyl-terminal hydrolase 4

Gene

USP4

Organism
Homo sapiens (Human)
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

Deubiquitinating enzyme that removes conjugated ubiquitin from target proteins (PubMed:16316627, PubMed:16472766, PubMed:16339847, PubMed:20595234, PubMed:22347420, PubMed:25404403). Deubiquitinates PDPK1 (PubMed:22347420). Deubiquitinates TRIM21 (PubMed:16316627). Deubiquitinates receptor ADORA2A which increases the amount of functional receptor at the cell surface (PubMed:16339847). May regulate mRNA splicing through deubiquitination of the U4 spliceosomal protein PRPF3 (PubMed:20595234). This may prevent its recognition by the U5 component PRPF8 thereby destabilizing interactions within the U4/U6.U5 snRNP (PubMed:20595234). May also play a role in the regulation of quality control in the ER (PubMed:16339847).6 Publications

Caution

The ubiquitin-like domain 2 was thought to interact with the catalytic domain competing with the ubiquitin substrate and thus partially inhibiting USP4 activity (PubMed:21415856). As the results could not be reproduced this work was later retracted (PubMed:24398133). The cristal structure in the paper was correct and was republished later (PubMed:25404403).3 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">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%5Fsection">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

The completion of the deubiquitinase reaction is mediated by the DUSP and ubiquitin-like 1 domains which promotes the release of ubiquitin from the catalytic site enabling subsequent reactions to occur.1 Publication

<p>This subsection of the 'Function' section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

  1. KM=0.15 µM for ubiquitin-rhodamine1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">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 sitei311NucleophilePROSITE-ProRule annotation1
    <p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the 'Description' field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi461ZincCombined sources1 Publication1
    Metal bindingi464ZincCombined sources1 Publication1
    Metal bindingi799ZincCombined sources1 Publication1
    Metal bindingi802ZincCombined sources1 Publication1
    Active sitei881Proton acceptorPROSITE-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

    Complete GO annotation on QuickGO ...

    GO - Biological processi

    Complete GO annotation on QuickGO ...

    <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 functionHydrolase, Protease, Thiol protease
    Biological processUbl conjugation pathway
    LigandMetal-binding, Zinc

    Enzyme and pathway databases

    Pathway Commons web resource for biological pathway data

    More...    PathwayCommonsi    		Q13107

    Reactome - a knowledgebase of biological pathways and processes

    More...    Reactomei    		R-HSA-5357786, TNFR1-induced proapoptotic signaling
    R-HSA-5357905, Regulation of TNFR1 signaling
    R-HSA-5357956, TNFR1-induced NFkappaB signaling pathway
    R-HSA-5689880, Ub-specific processing proteases

    Protein family/group databases

    MEROPS protease database

    More...    MEROPSi    		C19.010

    <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%5Fand%5Ftaxonomy%5Fsection">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:
    Ubiquitin carboxyl-terminal hydrolase 4 (EC:3.4.19.126 Publications)
    Alternative name(s):
    Deubiquitinating enzyme 4
    Ubiquitin thioesterase 4
    Ubiquitin-specific-processing protease 4
    Ubiquitous nuclear protein homolog
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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:USP4
    Synonyms:UNP, UNPH
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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>OrganismiHomo sapiens (Human)
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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 identifieri9606 [NCBI]
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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
    • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">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 3

    Organism-specific databases

    Human Gene Nomenclature Database

    More...    HGNCi    		HGNC:12627, USP4

    Online Mendelian Inheritance in Man (OMIM)

    More...    MIMi    		603486, gene

    neXtProt; the human protein knowledge platform

    More...    neXtProti    		NX_Q13107

    Eukaryotic Pathogen, Vector and Host Database Resources

    More...    VEuPathDBi    		HostDB:ENSG00000114316.12

    <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

    Cytoplasm, 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

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'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>Mutagenesisi24M → D: Moderate reduction in catalytic activity. 1 Publication1
    Mutagenesisi40R → E: Moderate reduction in catalytic activity. 1 Publication1
    Mutagenesisi51F → D: Moderate reduction in catalytic activity. 1 Publication1
    Mutagenesisi88I → P: Severe reduction in catalytic activity. 1 Publication1
    Mutagenesisi88I → R: Moderate reduction in catalytic activity. 1 Publication1
    Mutagenesisi89D → G: Severe reduction in catalytic activity. 1 Publication1
    Mutagenesisi90E → A: Moderate reduction in catalytic activity. 1 Publication1
    Mutagenesisi91L → E: Moderate reduction in catalytic activity. 1 Publication1
    Mutagenesisi92D → R: Severe reduction in catalytic activity. 1 Publication1
    Mutagenesisi134E → A: Severe reduction in catalytic activity. 1 Publication1
    Mutagenesisi136Y → A: Severe reduction in catalytic activity. 1 Publication1
    Mutagenesisi311C → A: Loss of activity. Its ubiquitination by TRIM21 is enhanced. 2 Publications1
    Mutagenesisi384 – 385PQ → AV: Severe reduction in catalytic activity. 1 Publication2
    Mutagenesisi386F → G: Lowers affinity for ubiquitin characterized by a 10-fold increase in ubiquitin release and a slight reduction in ubiquitin binding. 1 Publication1
    Mutagenesisi459 – 463LVCPE → AVRPH: Reduces the interaction with RB1. 1 Publication5
    Mutagenesisi463E → Q: Reduces the interaction with RB1. 1 Publication1

    Keywords - Diseasei

    Proto-oncogene

    Organism-specific databases

    DisGeNET

    More...    DisGeNETi    		7375

    Open Targets

    More...    OpenTargetsi    		ENSG00000114316

    The Pharmacogenetics and Pharmacogenomics Knowledge Base

    More...    PharmGKBi    		PA37252

    Miscellaneous databases

    Pharos NIH Druggable Genome Knowledgebase

    More...    Pharosi    		Q13107, Tbio

    Chemistry databases

    ChEMBL database of bioactive drug-like small molecules

    More...    ChEMBLi    		CHEMBL2406900

    Genetic variation databases

    BioMuta curated single-nucleotide variation and disease association database

    More...    BioMutai    		USP4

    Domain mapping of disease mutations (DMDM)

    More...    DMDMi    		116242839

    <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 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000806211 – 963Ubiquitin carboxyl-terminal hydrolase 4Add BLAST963

    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 residuei655PhosphoserineBy similarity1
    Modified residuei675PhosphoserineBy similarity1
    Modified residuei680PhosphoserineBy similarity1

    <p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">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

    Monoubiquitinated by TRIM21. Ubiquitination does not lead to its proteasomal degradation. Autodeubiquitinated.2 Publications

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    Encyclopedia of Proteome Dynamics

    More...    EPDi    		Q13107

    jPOST - Japan Proteome Standard Repository/Database

    More...    jPOSTi    		Q13107

    MassIVE - Mass Spectrometry Interactive Virtual Environment

    More...    MassIVEi    		Q13107

    MaxQB - The MaxQuant DataBase

    More...    MaxQBi    		Q13107

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

    More...    PaxDbi    		Q13107

    PeptideAtlas

    More...    PeptideAtlasi    		Q13107

    PRoteomics IDEntifications database

    More...    PRIDEi    		Q13107

    ProteomicsDB: a multi-organism proteome resource

    More...    ProteomicsDBi    		59158 [Q13107-1]
    59159 [Q13107-2]
    7631

    PTM databases

    iPTMnet integrated resource for PTMs in systems biology context

    More...    iPTMneti    		Q13107

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

    More...    PhosphoSitePlusi    		Q13107

    <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

    Overexpressed in small cell tumors and adenocarcinomas of the lung compared to wild-type lung (at protein level). Expressed in the hippocampal neurons.2 Publications

    Gene expression databases

    Bgee dataBase for Gene Expression Evolution

    More...    Bgeei    		ENSG00000114316, Expressed in sural nerve and 236 other tissues

    ExpressionAtlas, Differential and Baseline Expression

    More...    ExpressionAtlasi    		Q13107, baseline and differential

    Genevisible search portal to normalized and curated expression data from Genevestigator

    More...    Genevisiblei    		Q13107, HS

    Organism-specific databases

    Human Protein Atlas

    More...    HPAi    		ENSG00000114316, Low tissue specificity

    <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%5Fsection">'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%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

    Interacts with RB1 (both dephosphorylated and hypophosphorylated forms) (PubMed:11571652).

    Interacts with RBL1 and RBL2 (By similarity).

    Interacts with ADORA2A (via cytoplasmic C-terminus); the interaction is direct (PubMed:16339847).

    Interacts with SART3; recruits USP4 to its substrate PRPF3 (PubMed:20595234).

    By similarity3 Publications

    <p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">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="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

    Hide details

    GO - Molecular functioni

    Complete GO annotation on QuickGO ...

    Protein-protein interaction databases

    The Biological General Repository for Interaction Datasets (BioGRID)

    More...    BioGRIDi    		113221, 128 interactors

    Protein interaction database and analysis system

    More...    IntActi    		Q13107, 56 interactors

    Molecular INTeraction database

    More...    MINTi    		Q13107

    STRING: functional protein association networks

    More...    STRINGi    		9606.ENSP00000265560

    Chemistry databases

    BindingDB database of measured binding affinities

    More...    BindingDBi    		Q13107

    Miscellaneous databases

    RNAct, Protein-RNA interaction predictions for model organisms.

    More...    RNActi    		Q13107, protein

    <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

    1963
    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

    More...    SMRi    		Q13107

    Database of comparative protein structure models

    More...    ModBasei    		Search...

    Protein Data Bank in Europe - Knowledge Base

    More...    PDBe-KBi    		Search...

    Miscellaneous databases

    Relative evolutionary importance of amino acids within a protein sequence

    More...    EvolutionaryTracei    		Q13107

    <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%5Fand%5Fdomains%5Fsection">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>Domaini11 – 122DUSPPROSITE-ProRule annotationAdd BLAST112
    Domaini142 – 226Ubiquitin-like 1Sequence analysisAdd BLAST85
    Domaini302 – 923USPPROSITE-ProRule annotationAdd BLAST622
    Domaini483 – 571Ubiquitin-like 2Sequence analysisAdd BLAST89

    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>Regioni27 – 216Necessary for interaction with SART31 PublicationAdd BLAST190
    Regioni229 – 295Required for USP4 activation by providing conformational flexibility between the DUSP and catalytic domains1 PublicationAdd BLAST67
    Regioni384 – 386Regulates ubiquitin dissociation1 Publication3
    Regioni405 – 407Necessary for interaction with RBL2By similarity3
    Regioni459 – 463Necessary for interaction with RB1 and RBL2By similarity1 Publication5
    Regioni485 – 775Interacts with DUSP and ubiquitin-like 1 domains and is required for USP4 activation1 PublicationAdd BLAST291

    Motif

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the 'Family and Domains' section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi133 – 141Nuclear export signalBy similarity9
    Motifi767 – 772Nuclear localization signalBy similarity6

    <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 DUSP and ubiquitin-like 1 domains promote ubiquitin release and thus enhance USB4 catalytic activity. However, these domains do not bind ubiquitin.1 Publication

    <p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

    Belongs to the peptidase C19 family. USP4 subfamily.Curated

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    evolutionary genealogy of genes: Non-supervised Orthologous Groups

    More...    eggNOGi    		KOG1870, Eukaryota

    Ensembl GeneTree

    More...    GeneTreei    		ENSGT00940000156645

    The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

    More...    HOGENOMi    		CLU_001060_7_1_1

    InParanoid: Eukaryotic Ortholog Groups

    More...    InParanoidi    		Q13107

    Identification of Orthologs from Complete Genome Data

    More...    OMAi    		LQRGAQX

    Database for complete collections of gene phylogenies

    More...    PhylomeDBi    		Q13107

    TreeFam database of animal gene trees

    More...    TreeFami    		TF106276

    Family and domain databases

    Integrated resource of protein families, domains and functional sites

    More...    InterProi    		View protein in InterPro
    IPR035927, DUSP-like_sf
    IPR038765, Papain-like_cys_pep_sf
    IPR006615, Pept_C19_DUSP
    IPR001394, Peptidase_C19_UCH
    IPR028135, Ub_USP-typ
    IPR018200, USP_CS
    IPR028889, USP_dom

    Pfam protein domain database

    More...    Pfami    		View protein in Pfam
    PF06337, DUSP, 1 hit
    PF14836, Ubiquitin_3, 1 hit
    PF00443, UCH, 1 hit

    Simple Modular Architecture Research Tool; a protein domain database

    More...    SMARTi    		View protein in SMART
    SM00695, DUSP, 1 hit

    Superfamily database of structural and functional annotation

    More...    SUPFAMi    		SSF143791, SSF143791, 1 hit
    SSF54001, SSF54001, 1 hit

    PROSITE; a protein domain and family database

    More...    PROSITEi    		View protein in PROSITE
    PS51283, DUSP, 1 hit
    PS00972, USP_1, 1 hit
    PS00973, USP_2, 1 hit
    PS50235, USP_3, 1 hit

    <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%5Flength">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 (3+)i

    <p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">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.

    This entry describes 3 <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. This section is only present in reviewed entries, i.e. in UniProtKB/Swiss-Prot.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

    This entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

    Isoform 1 (identifier: Q13107-1) [UniParc]FASTAAdd to basket
    Also known as: UnpEL

    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.

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            10         20         30         40         50
    MAEGGGCRER PDAETQKSEL GPLMRTTLQR GAQWYLIDSR WFKQWKKYVG 
            60         70         80         90        100
    FDSWDMYNVG EHNLFPGPID NSGLFSDPES QTLKEHLIDE LDYVLVPTEA 
           110        120        130        140        150
    WNKLLNWYGC VEGQQPIVRK VVEHGLFVKH CKVEVYLLEL KLCENSDPTN 
           160        170        180        190        200
    VLSCHFSKAD TIATIEKEMR KLFNIPAERE TRLWNKYMSN TYEQLSKLDN 
           210        220        230        240        250
    TVQDAGLYQG QVLVIEPQNE DGTWPRQTLQ SKSSTAPSRN FTTSPKSSAS 
           260        270        280        290        300
    PYSSVSASLI ANGDSTSTCG MHSSGVSRGG SGFSASYNCQ EPPSSHIQPG 
           310        320        330        340        350
    LCGLGNLGNT CFMNSALQCL SNTAPLTDYF LKDEYEAEIN RDNPLGMKGE 
           360        370        380        390        400
    IAEAYAELIK QMWSGRDAHV APRMFKTQVG RFAPQFSGYQ QQDSQELLAF 
           410        420        430        440        450
    LLDGLHEDLN RVKKKPYLEL KDANGRPDAV VAKEAWENHR LRNDSVIVDT 
           460        470        480        490        500
    FHGLFKSTLV CPECAKVSVT FDPFCYLTLP LPLKKDRVME VFLVPADPHC 
           510        520        530        540        550
    RPTQYRVTVP LMGAVSDLCE ALSRLSGIAA ENMVVADVYN HRFHKIFQMD 
           560        570        580        590        600
    EGLNHIMPRD DIFVYEVCST SVDGSECVTL PVYFRERKSR PSSTSSASAL 
           610        620        630        640        650
    YGQPLLLSVP KHKLTLESLY QAVCDRISRY VKQPLPDEFG SSPLEPGACN 
           660        670        680        690        700
    GSRNSCEGED EEEMEHQEEG KEQLSETEGS GEDEPGNDPS ETTQKKIKGQ 
           710        720        730        740        750
    PCPKRLFTFS LVNSYGTADI NSLAADGKLL KLNSRSTLAM DWDSETRRLY 
           760        770        780        790        800
    YDEQESEAYE KHVSMLQPQK KKKTTVALRD CIELFTTMET LGEHDPWYCP 
           810        820        830        840        850
    NCKKHQQATK KFDLWSLPKI LVVHLKRFSY NRYWRDKLDT VVEFPIRGLN 
           860        870        880        890        900
    MSEFVCNLSA RPYVYDLIAV SNHYGAMGVG HYTAYAKNKL NGKWYYFDDS 
           910        920        930        940        950
    NVSLASEDQI VTKAAYVLFY QRRDDEFYKT PSLSSSGSSD GGTRPSSSQQ 
           960 
    GFGDDEACSM DTN
    Length:963
    Mass (Da):108,565
    Last modified:October 17, 2006 - v3
    <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:i63055C9ADFE36713
    GO
    Isoform 2 (identifier: Q13107-2) [UniParc]FASTAAdd to basket
    Also known as: UnpES

    The sequence of this isoform differs from the canonical sequence as follows:
         232-279: KSSTAPSRNFTTSPKSSASPYSSVSASLIANGDSTSTCGMHSSGVSRG → N

    Show »
    Length:916
    Mass (Da):103,958
    Checksum:i86CBBDE6AA2AB04E
    GO
    Isoform 3 (identifier: Q13107-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         233-313: SSTAPSRNFT...LGNLGNTCFM → VSFFLPRLEC...LLPQPPEWLG
         314-963: Missing.

    Show »
    Length:313
    Mass (Da):35,661
    Checksum:i7B2258A3A64AC0EB
    GO

    <p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

    There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    		Gene namesLengthAnnotation
    H7C189H7C189_HUMAN
    Ubiquitin carboxyl-terminal hydrola...
    USP4
    		621Annotation score:

    Annotation score:3 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>
    C9JNU9C9JNU9_HUMAN
    Ubiquitin carboxyl-terminal hydrola...
    USP4
    		363Annotation score:

    Annotation score:2 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 Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti373R → S in AAB72237 (PubMed:7784062).Curated1
    Sequence conflicti744S → R in AAB72237 (PubMed:7784062).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_028180620Y → C. Corresponds to variant dbSNP:rs9311440EnsemblClinVar.1

    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_005258232 – 279KSSTA…GVSRG → N in isoform 2. 1 PublicationAdd BLAST48
    Alternative sequenceiVSP_044814233 – 313SSTAP…NTCFM → VSFFLPRLECNGAILAHCNF CLPGSSNSPASASRVAPSHL ANFFFFEMESHSVTKLECGG AVSAYSRVQVMLLPQPPEWL G in isoform 3. 1 PublicationAdd BLAST81
    Alternative sequenceiVSP_044815314 – 963Missing in isoform 3. 1 PublicationAdd BLAST650

    Sequence databases

    Select the link destinations:

    EMBL nucleotide sequence database

    More...    EMBLi

    GenBank nucleotide sequence database

    More...    GenBanki

    DNA Data Bank of Japan; a nucleotide sequence database

    More...    DDBJi
    Links Updated
    		U20657 mRNA Translation: AAB72237.1
    AF017305 mRNA Translation: AAC27355.1
    AF017306 mRNA Translation: AAC27356.1
    AK291795 mRNA Translation: BAF84484.1
    AC121247 Genomic DNA No translation available.
    BC068017 mRNA No translation available.
    BC125130 mRNA Translation: AAI25131.1

    The Consensus CDS (CCDS) project

    More...    CCDSi    		CCDS2793.1 [Q13107-1]
    CCDS2794.1 [Q13107-2]
    CCDS58832.1 [Q13107-3]

    Protein sequence database of the Protein Information Resource

    More...    PIRi    		T09478

    NCBI Reference Sequences

    More...    RefSeqi    		NP_001238806.1, NM_001251877.1 [Q13107-3]
    NP_003354.2, NM_003363.3 [Q13107-1]
    NP_955475.1, NM_199443.2 [Q13107-2]

    Genome annotation databases

    Ensembl eukaryotic genome annotation project

    More...    Ensembli    		ENST00000265560; ENSP00000265560; ENSG00000114316 [Q13107-1]
    ENST00000351842; ENSP00000341028; ENSG00000114316 [Q13107-2]
    ENST00000416417; ENSP00000400623; ENSG00000114316 [Q13107-3]

    Database of genes from NCBI RefSeq genomes

    More...    GeneIDi    		7375

    KEGG: Kyoto Encyclopedia of Genes and Genomes

    More...    KEGGi    		hsa:7375

    UCSC genome browser

    More...    UCSCi    		uc003cwq.3, human [Q13107-1]

    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
    		U20657 mRNA Translation: AAB72237.1
    AF017305 mRNA Translation: AAC27355.1
    AF017306 mRNA Translation: AAC27356.1
    AK291795 mRNA Translation: BAF84484.1
    AC121247 Genomic DNA No translation available.
    BC068017 mRNA No translation available.
    BC125130 mRNA Translation: AAI25131.1
    CCDSiCCDS2793.1 [Q13107-1]
    CCDS2794.1 [Q13107-2]
    CCDS58832.1 [Q13107-3]
    PIRiT09478
    RefSeqiNP_001238806.1, NM_001251877.1 [Q13107-3]
    NP_003354.2, NM_003363.3 [Q13107-1]
    NP_955475.1, NM_199443.2 [Q13107-2]

    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
    2Y6EX-ray2.40A/B/C/D/E/F296-490[»]
    A/B/C/D/E/F765-932[»]
    5CTRX-ray3.01C/D1-230[»]
    SMRiQ13107
    ModBaseiSearch...
    PDBe-KBiSearch...

    Protein-protein interaction databases

    BioGRIDi113221, 128 interactors
    IntActiQ13107, 56 interactors
    MINTiQ13107
    STRINGi9606.ENSP00000265560

    Chemistry databases

    BindingDBiQ13107
    ChEMBLiCHEMBL2406900

    Protein family/group databases

    MEROPSiC19.010

    PTM databases

    iPTMnetiQ13107
    PhosphoSitePlusiQ13107

    Genetic variation databases

    BioMutaiUSP4
    DMDMi116242839

    Proteomic databases

    EPDiQ13107
    jPOSTiQ13107
    MassIVEiQ13107
    MaxQBiQ13107
    PaxDbiQ13107
    PeptideAtlasiQ13107
    PRIDEiQ13107
    ProteomicsDBi59158 [Q13107-1]
    59159 [Q13107-2]
    7631

    Protocols and materials databases

    Antibodypedia a portal for validated antibodies

    More...    Antibodypediai    		13556, 364 antibodies

    Genome annotation databases

    EnsembliENST00000265560; ENSP00000265560; ENSG00000114316 [Q13107-1]
    ENST00000351842; ENSP00000341028; ENSG00000114316 [Q13107-2]
    ENST00000416417; ENSP00000400623; ENSG00000114316 [Q13107-3]
    GeneIDi7375
    KEGGihsa:7375
    UCSCiuc003cwq.3, human [Q13107-1]

    Organism-specific databases

    Comparative Toxicogenomics Database

    More...    CTDi    		7375
    DisGeNETi7375

    GeneCards: human genes, protein and diseases

    More...    GeneCardsi    		USP4
    HGNCiHGNC:12627, USP4
    HPAiENSG00000114316, Low tissue specificity
    MIMi603486, gene
    neXtProtiNX_Q13107
    OpenTargetsiENSG00000114316
    PharmGKBiPA37252
    VEuPathDBiHostDB:ENSG00000114316.12

    GenAtlas: human gene database

    More...    GenAtlasi    		Search...

    Phylogenomic databases

    eggNOGiKOG1870, Eukaryota
    GeneTreeiENSGT00940000156645
    HOGENOMiCLU_001060_7_1_1
    InParanoidiQ13107
    OMAiLQRGAQX
    PhylomeDBiQ13107
    TreeFamiTF106276

    Enzyme and pathway databases

    PathwayCommonsiQ13107
    ReactomeiR-HSA-5357786, TNFR1-induced proapoptotic signaling
    R-HSA-5357905, Regulation of TNFR1 signaling
    R-HSA-5357956, TNFR1-induced NFkappaB signaling pathway
    R-HSA-5689880, Ub-specific processing proteases

    Miscellaneous databases

    BioGRID ORCS database of CRISPR phenotype screens

    More...    BioGRID-ORCSi    		7375, 6 hits in 883 CRISPR screens

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

    More...    ChiTaRSi    		USP4, human
    EvolutionaryTraceiQ13107

    The Gene Wiki collection of pages on human genes and proteins

    More...    GeneWikii    		USP4

    Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

    More...    GenomeRNAii    		7375
    PharosiQ13107, Tbio

    Protein Ontology

    More...    PROi    		PR:Q13107
    RNActiQ13107, protein

    The Stanford Online Universal Resource for Clones and ESTs

    More...    SOURCEi    		Search...

    Gene expression databases

    BgeeiENSG00000114316, Expressed in sural nerve and 236 other tissues
    ExpressionAtlasiQ13107, baseline and differential
    GenevisibleiQ13107, HS

    Family and domain databases

    InterProiView protein in InterPro
    IPR035927, DUSP-like_sf
    IPR038765, Papain-like_cys_pep_sf
    IPR006615, Pept_C19_DUSP
    IPR001394, Peptidase_C19_UCH
    IPR028135, Ub_USP-typ
    IPR018200, USP_CS
    IPR028889, USP_dom
    PfamiView protein in Pfam
    PF06337, DUSP, 1 hit
    PF14836, Ubiquitin_3, 1 hit
    PF00443, UCH, 1 hit
    SMARTiView protein in SMART
    SM00695, DUSP, 1 hit
    SUPFAMiSSF143791, SSF143791, 1 hit
    SSF54001, SSF54001, 1 hit
    PROSITEiView protein in PROSITE
    PS51283, DUSP, 1 hit
    PS00972, USP_1, 1 hit
    PS00973, USP_2, 1 hit
    PS50235, USP_3, 1 hit

    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 nameiUBP4_HUMAN
    <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: Q13107
    Secondary accession number(s): A8K6Y0
    , C9IY91, O43452, O43453, Q08AK8
    <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%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: October 17, 2006
    Last modified: February 10, 2021
    This is version 191 of the entry and version 3 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
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    <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, Reference proteome

    Documents

    1. Peptidase families
      Classification of peptidase families and list of entries
    2. Human chromosome 3
      Human chromosome 3: entries, gene names and cross-references to MIM
    3. Human entries with genetic variants
      List of human entries with genetic variants
    4. Human variants curated from literature reports
      Index of human variants curated from literature reports
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families
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