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UniProtKB - P40818 (UBP8_HUMAN)

Entry version 218 (02 Dec 2020)
Sequence version 1 (01 Feb 1995)
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Protein

Ubiquitin carboxyl-terminal hydrolase 8

Gene

USP8

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

Hydrolase that can remove conjugated ubiquitin from proteins and therefore plays an important regulatory role at the level of protein turnover by preventing degradation. Converts both 'Lys-48' an 'Lys-63'-linked ubiquitin chains. Catalytic activity is enhanced in the M phase. Involved in cell proliferation. Required to enter into S phase in response to serum stimulation. May regulate T-cell anergy mediated by RNF128 via the formation of a complex containing RNF128 and OTUB1. Probably regulates the stability of STAM2 and RASGRF1. Regulates endosomal ubiquitin dynamics, cargo sorting, membrane traffic at early endosomes, and maintenance of ESCRT-0 stability. The level of protein ubiquitination on endosomes is essential for maintaining the morphology of the organelle. Deubiquitinates EPS15 and controles tyrosine kinase stability. Removes conjugated ubiquitin from EGFR thus regulating EGFR degradation and downstream MAPK signaling. Involved in acrosome biogenesis through interaction with the spermatid ESCRT-0 complex and microtubules. Deubiquitinates BIRC6/bruce and KIF23/MKLP1. Deubiquitinates BACE1 which inhibits BACE1 lysosomal degradation and modulates BACE-mediated APP cleavage and amyloid-beta formation (PubMed:27302062).5 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

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 sitei786NucleophilePROSITE-ProRule annotation1
Active sitei1067Proton 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 processCell cycle, Ubl conjugation pathway

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

More...BRENDAi		3.4.19.12, 2681

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		P40818

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-1358803, Downregulation of ERBB2:ERBB3 signaling
R-HSA-4641263, Regulation of FZD by ubiquitination
R-HSA-5689880, Ub-specific processing proteases
R-HSA-6807004, Negative regulation of MET activity

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...SignaLinki		P40818

SIGNOR Signaling Network Open Resource

More...SIGNORi		P40818

Protein family/group databases

MEROPS protease database

More...MEROPSi		C19.011

<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 8Curated (EC:3.4.19.121 Publication)
Alternative name(s):
Deubiquitinating enzyme 8
Ubiquitin isopeptidase Y
Short name:
hUBPy
Ubiquitin thioesterase 8
Ubiquitin-specific-processing protease 8
<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:USP8Imported
Synonyms:KIAA0055, UBPY
<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 15

Organism-specific databases

Eukaryotic Pathogen and Host Database Resources

More...EuPathDBi		HostDB:ENSG00000138592.13

Human Gene Nomenclature Database

More...HGNCi		HGNC:12631, USP8

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		603158, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_P40818

<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

Pituitary adenoma 4, ACTH-secreting (PITA4)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of pituitary adenoma, a neoplasm of the pituitary gland and one of the most common neuroendocrine tumors. Pituitary adenomas are clinically classified as functional and non-functional tumors, and manifest with a variety of features, including local invasion of surrounding structures and excessive hormone secretion. Functional pituitary adenomas are further classified by the type of hormone they secrete. PITA4 results in excessive production of adrenocorticotropic hormone. This leads to hypersecretion of cortisol by the adrenal glands and ACTH-dependent Cushing syndrome. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes.
Related information in OMIM
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_079717718 – 723Missing in PITA4; somatic mutation; unknown pathological significance. 1 Publication6
Natural variantiVAR_079718718S → C in PITA4; somatic mutation; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs672601308EnsemblClinVar.1
Natural variantiVAR_079719718S → P in PITA4; somatic mutation; unknown pathological significance; localizes to nucleus instead of cytoplasm. 1 PublicationCorresponds to variant dbSNP:rs672601307EnsemblClinVar.1
Natural variantiVAR_079720718Missing in PITA4; somatic mutation; unknown pathological significance. 1 Publication1
Natural variantiVAR_079721720P → R in PITA4; somatic mutation; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs672601311EnsemblClinVar.1

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>Mutagenesisi786C → S: Impairs deubiquitination activity and leads to endosome membrane accumulation. 1 Publication1

Keywords - Diseasei

Cushing syndrome, Disease mutation

Organism-specific databases

DisGeNET

More...DisGeNETi		9101

MalaCards human disease database

More...MalaCardsi		USP8
MIMi219090, phenotype

Open Targets

More...OpenTargetsi		ENSG00000138592

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		401795, Autosomal recessive spastic paraplegia type 59
96253, Cushing disease

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA37256

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		P40818, Tbio

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL2157854

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		USP8

Domain mapping of disease mutations (DMDM)

More...DMDMi		731046

<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_00000806271 – 1118Ubiquitin carboxyl-terminal hydrolase 8Add BLAST1118

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 residuei160PhosphoserineCombined sources1
Modified residuei392PhosphoserineCombined sources1
Modified residuei400PhosphoserineCombined sources1
Modified residuei452PhosphoserineCombined sources1
Modified residuei577PhosphothreonineCombined sources1
Modified residuei718PhosphoserineCombined sources1
Modified residuei719PhosphoserineCombined sources1
Modified residuei945PhosphothreonineBy 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

Phosphorylation of Ser-718 is essential for interaction with YWHAE and for cytosol localization. Undergoes dephosphorylation at Ser-718 in the M phase. Tyrosine-phosphorylated in its N-terminal half in an EGFR-dependent manner.By similarity
Ubiquitinated. Inactive form is mostly monoubiquitinated, but polyubiquitination happens too. Ubiquitination is increased in EGF-stimulated cells. Ubiquitination of active form is undetectable, suggesting a possibility that USP8 deubiquitinates itself, thereby regulating its own function (By similarity).By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

The CPTAC Assay portal

More...CPTACi		CPTAC-1733
CPTAC-1734

Encyclopedia of Proteome Dynamics

More...EPDi		P40818

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		P40818

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		P40818

MaxQB - The MaxQuant DataBase

More...MaxQBi		P40818

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

More...PaxDbi		P40818

PeptideAtlas

More...PeptideAtlasi		P40818

PRoteomics IDEntifications database

More...PRIDEi		P40818

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		4442
55380 [P40818-1]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		P40818

MetOSite database of methionine sulfoxide sites

More...MetOSitei		P40818

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

More...PhosphoSitePlusi		P40818

<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 reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

Upon growth stimulation in starved human fibroblasts. Decreases in response to growth arrest induced by cell-cell contact.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000138592, Expressed in sural nerve and 235 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		P40818, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		P40818, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000138592, 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

Forms a ternary complex with RNF128 and OTUB1.

Interacts (via C-terminal UCH catalytic domain) with OTUB1 isoform 1.

Interacts with STAM2 (via SH3 domain).

Interacts with DNAJB3, EGFR, EPS15, RASGRF1, RNF41, YWHAE, YWHAG and YWHAZ (By similarity).

Interacts with NBR1, RASGRF1, RNF41 and IST1. Associates with the ESCRT-0 complex and with microtubules (By similarity).

Interacts with BIRC6/bruce and KIF23/MKLP1.

By similarity5 Publications

(Microbial infection) Interacts with Zika virus non-structural protein 1.

1 Publication

<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		114555, 100 interactors

Database of interacting proteins

More...DIPi		DIP-40365N

Protein interaction database and analysis system

More...IntActi		P40818, 35 interactors

Molecular INTeraction database

More...MINTi		P40818

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000379721

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		P40818

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		P40818, 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

11118
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		P40818

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		P40818

<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>Domaini33 – 116MITAdd BLAST84
Domaini195 – 313RhodanesePROSITE-ProRule annotationAdd BLAST119
Domaini777 – 1109USPAdd BLAST333

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>Motifi405 – 413SH3-bindingBy similarity9

<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 MIT domain is required for endosomal localization, CHMP1B-binding, maintenance of ESCRT-0 stability and EGFR degradation.1 Publication
The rhodanese domain is sufficient for RNF41-binding.By similarity

<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.Curated

Keywords - Domaini

SH3-binding

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG1868, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00940000157542

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_009980_0_0_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		P40818

Identification of Orthologs from Complete Genome Data

More...OMAi		LCVPEEA

Database for complete collections of gene phylogenies

More...PhylomeDBi		P40818

TreeFam database of animal gene trees

More...TreeFami		TF106277

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		3.40.250.10, 1 hit

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR038765, Papain-like_cys_pep_sf
IPR001394, Peptidase_C19_UCH
IPR001763, Rhodanese-like_dom
IPR036873, Rhodanese-like_dom_sf
IPR015063, USP8_dimer
IPR018200, USP_CS
IPR028889, USP_dom

Pfam protein domain database

More...Pfami		View protein in Pfam
PF00581, Rhodanese, 1 hit
PF00443, UCH, 1 hit
PF08969, USP8_dimer, 1 hit

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF52821, SSF52821, 1 hit
SSF54001, SSF54001, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS50206, RHODANESE_3, 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 (2+)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 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. 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 2 described isoforms and 7 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P40818-1) [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
MPAVASVPKE LYLSSSLKDL NKKTEVKPEK ISTKSYVHSA LKIFKTAEEC 
        60         70         80         90        100
RLDRDEERAY VLYMKYVTVY NLIKKRPDFK QQQDYFHSIL GPGNIKKAVE 
       110        120        130        140        150
EAERLSESLK LRYEEAEVRK KLEEKDRQEE AQRLQQKRQE TGREDGGTLA 
       160        170        180        190        200
KGSLENVLDS KDKTQKSNGE KNEKCETKEK GAITAKELYT MMTDKNISLI 
       210        220        230        240        250
IMDARRMQDY QDSCILHSLS VPEEAISPGV TASWIEAHLP DDSKDTWKKR 
       260        270        280        290        300
GNVEYVVLLD WFSSAKDLQI GTTLRSLKDA LFKWESKTVL RNEPLVLEGG 
       310        320        330        340        350
YENWLLCYPQ YTTNAKVTPP PRRQNEEVSI SLDFTYPSLE ESIPSKPAAQ 
       360        370        380        390        400
TPPASIEVDE NIELISGQNE RMGPLNISTP VEPVAASKSD VSPIIQPVPS 
       410        420        430        440        450
IKNVPQIDRT KKPAVKLPEE HRIKSESTNH EQQSPQSGKV IPDRSTKPVV 
       460        470        480        490        500
FSPTLMLTDE EKARIHAETA LLMEKNKQEK ELRERQQEEQ KEKLRKEEQE 
       510        520        530        540        550
QKAKKKQEAE ENEITEKQQK AKEEMEKKES EQAKKEDKET SAKRGKEITG 
       560        570        580        590        600
VKRQSKSEHE TSDAKKSVED RGKRCPTPEI QKKSTGDVPH TSVTGDSGSG 
       610        620        630        640        650
KPFKIKGQPE SGILRTGTFR EDTDDTERNK AQREPLTRAR SEEMGRIVPG 
       660        670        680        690        700
LPSGWAKFLD PITGTFRYYH SPTNTVHMYP PEMAPSSAPP STPPTHKAKP 
       710        720        730        740        750
QIPAERDREP SKLKRSYSSP DITQAIQEEE KRKPTVTPTV NRENKPTCYP 
       760        770        780        790        800
KAEISRLSAS QIRNLNPVFG GSGPALTGLR NLGNTCYMNS ILQCLCNAPH 
       810        820        830        840        850
LADYFNRNCY QDDINRSNLL GHKGEVAEEF GIIMKALWTG QYRYISPKDF 
       860        870        880        890        900
KITIGKINDQ FAGYSQQDSQ ELLLFLMDGL HEDLNKADNR KRYKEENNDH 
       910        920        930        940        950
LDDFKAAEHA WQKHKQLNES IIVALFQGQF KSTVQCLTCH KKSRTFEAFM 
       960        970        980        990       1000
YLSLPLASTS KCTLQDCLRL FSKEEKLTDN NRFYCSHCRA RRDSLKKIEI 
      1010       1020       1030       1040       1050
WKLPPVLLVH LKRFSYDGRW KQKLQTSVDF PLENLDLSQY VIGPKNNLKK 
      1060       1070       1080       1090       1100
YNLFSVSNHY GGLDGGHYTA YCKNAARQRW FKFDDHEVSD ISVSSVKSSA 
      1110 
AYILFYTSLG PRVTDVAT
Length:1,118
Mass (Da):127,523
Last modified:February 1, 1995 - v1
<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:i8B884B7A842F9A9A
GO
Isoform 2 (identifier: P40818-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     35-111: Missing.
     601-629: Missing.

Show »
Length:1,012
Mass (Da):115,080
Checksum:iB31B38D37E837812
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 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A075B720A0A075B720_HUMAN
Ubiquitin carboxyl-terminal hydrola...
USP8
480Annotation score:

Annotation score:1 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>
H0YNL5H0YNL5_HUMAN
Ubiquitin carboxyl-terminal hydrola...
USP8
135Annotation score:

Annotation score:1 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>
H0YM17H0YM17_HUMAN
Ubiquitin carboxyl-terminal hydrola...
USP8
73Annotation score:

Annotation score:1 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>
H0YM47H0YM47_HUMAN
Ubiquitin carboxyl-terminal hydrola...
USP8
125Annotation score:

Annotation score:1 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>
H0YKV1H0YKV1_HUMAN
Ubiquitin carboxyl-terminal hydrola...
USP8
136Annotation score:

Annotation score:1 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>
H0YLH2H0YLH2_HUMAN
Ubiquitin carboxyl-terminal hydrola...
USP8
96Annotation score:

Annotation score:1 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>
H0YLS3H0YLS3_HUMAN
Ubiquitin carboxyl-terminal hydrola...
USP8
62Annotation score:

Annotation score:1 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>

<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 AAH38801 differs from that shown. Contaminating sequence. Potential poly-A sequence.Curated
The sequence AAH51345 differs from that shown. Contaminating sequence. Potential poly-A sequence.Curated

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 conflicti526E → G in CAD97662 (PubMed:17974005).Curated1
Sequence conflicti717Y → H in CAD97662 (PubMed:17974005).Curated1
Sequence conflicti945T → A in CAD97662 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_077850310Q → K Found in a patient with spastic paraplegia; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs587777201EnsemblClinVar.1
Natural variantiVAR_017796443D → G. Corresponds to variant dbSNP:rs3743044EnsemblClinVar.1
Natural variantiVAR_079717718 – 723Missing in PITA4; somatic mutation; unknown pathological significance. 1 Publication6
Natural variantiVAR_079718718S → C in PITA4; somatic mutation; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs672601308EnsemblClinVar.1
Natural variantiVAR_079719718S → P in PITA4; somatic mutation; unknown pathological significance; localizes to nucleus instead of cytoplasm. 1 PublicationCorresponds to variant dbSNP:rs672601307EnsemblClinVar.1
Natural variantiVAR_079720718Missing in PITA4; somatic mutation; unknown pathological significance. 1 Publication1
Natural variantiVAR_079721720P → R in PITA4; somatic mutation; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs672601311EnsemblClinVar.1
Natural variantiVAR_051525739T → A. Corresponds to variant dbSNP:rs11638390Ensembl.1
Natural variantiVAR_017797827A → G. Corresponds to variant dbSNP:rs1056577Ensembl.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_05459435 – 111Missing in isoform 2. 1 PublicationAdd BLAST77
Alternative sequenceiVSP_054595601 – 629Missing in isoform 2. 1 PublicationAdd BLAST29

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
D29956 mRNA Translation: BAA06225.2
AK296480 mRNA Translation: BAG59120.1
BX537420 mRNA Translation: CAD97662.1
AC012170 Genomic DNA No translation available.
BC038801 mRNA Translation: AAH38801.1 Sequence problems.
BC051345 mRNA Translation: AAH51345.1 Sequence problems.
BC110590 mRNA Translation: AAI10591.1

The Consensus CDS (CCDS) project

More...CCDSi		CCDS10137.1 [P40818-1]
CCDS61632.1 [P40818-2]

NCBI Reference Sequences

More...RefSeqi		NP_001122082.1, NM_001128610.2 [P40818-1]
NP_001269978.1, NM_001283049.1 [P40818-2]
NP_005145.3, NM_005154.4 [P40818-1]
XP_006720824.1, XM_006720761.3 [P40818-1]
XP_011520495.1, XM_011522193.2 [P40818-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000307179; ENSP00000302239; ENSG00000138592 [P40818-1]
ENST00000396444; ENSP00000379721; ENSG00000138592 [P40818-1]
ENST00000425032; ENSP00000412682; ENSG00000138592 [P40818-2]

Database of genes from NCBI RefSeq genomes

More...GeneIDi		9101

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:9101

UCSC genome browser

More...UCSCi		uc001zyl.6, human [P40818-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<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
D29956 mRNA Translation: BAA06225.2
AK296480 mRNA Translation: BAG59120.1
BX537420 mRNA Translation: CAD97662.1
AC012170 Genomic DNA No translation available.
BC038801 mRNA Translation: AAH38801.1 Sequence problems.
BC051345 mRNA Translation: AAH51345.1 Sequence problems.
BC110590 mRNA Translation: AAI10591.1
CCDSiCCDS10137.1 [P40818-1]
CCDS61632.1 [P40818-2]
RefSeqiNP_001122082.1, NM_001128610.2 [P40818-1]
NP_001269978.1, NM_001283049.1 [P40818-2]
NP_005145.3, NM_005154.4 [P40818-1]
XP_006720824.1, XM_006720761.3 [P40818-1]
XP_011520495.1, XM_011522193.2 [P40818-1]

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
1WHBNMR-A174-317[»]
2A9UX-ray2.10A/B1-142[»]
2GFOX-ray2.00A734-1110[»]
2GWFX-ray2.30A/C/E181-318[»]
3N3KX-ray2.60A734-1110[»]
6F09X-ray1.59A/B/C/D712-724[»]
SMRiP40818
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi114555, 100 interactors
DIPiDIP-40365N
IntActiP40818, 35 interactors
MINTiP40818
STRINGi9606.ENSP00000379721

Chemistry databases

BindingDBiP40818
ChEMBLiCHEMBL2157854

Protein family/group databases

MEROPSiC19.011

PTM databases

iPTMnetiP40818
MetOSiteiP40818
PhosphoSitePlusiP40818

Polymorphism and mutation databases

BioMutaiUSP8
DMDMi731046

Proteomic databases

CPTACiCPTAC-1733
CPTAC-1734
EPDiP40818
jPOSTiP40818
MassIVEiP40818
MaxQBiP40818
PaxDbiP40818
PeptideAtlasiP40818
PRIDEiP40818
ProteomicsDBi4442
55380 [P40818-1]

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...Antibodypediai		1385, 260 antibodies

Genome annotation databases

EnsembliENST00000307179; ENSP00000302239; ENSG00000138592 [P40818-1]
ENST00000396444; ENSP00000379721; ENSG00000138592 [P40818-1]
ENST00000425032; ENSP00000412682; ENSG00000138592 [P40818-2]
GeneIDi9101
KEGGihsa:9101
UCSCiuc001zyl.6, human [P40818-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		9101
DisGeNETi9101
EuPathDBiHostDB:ENSG00000138592.13

GeneCards: human genes, protein and diseases

More...GeneCardsi		USP8
HGNCiHGNC:12631, USP8
HPAiENSG00000138592, Low tissue specificity
MalaCardsiUSP8
MIMi219090, phenotype
603158, gene
neXtProtiNX_P40818
OpenTargetsiENSG00000138592
Orphaneti401795, Autosomal recessive spastic paraplegia type 59
96253, Cushing disease
PharmGKBiPA37256

Human Unidentified Gene-Encoded large proteins database

More...HUGEi		Search...

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG1868, Eukaryota
GeneTreeiENSGT00940000157542
HOGENOMiCLU_009980_0_0_1
InParanoidiP40818
OMAiLCVPEEA
PhylomeDBiP40818
TreeFamiTF106277

Enzyme and pathway databases

BRENDAi3.4.19.12, 2681
PathwayCommonsiP40818
ReactomeiR-HSA-1358803, Downregulation of ERBB2:ERBB3 signaling
R-HSA-4641263, Regulation of FZD by ubiquitination
R-HSA-5689880, Ub-specific processing proteases
R-HSA-6807004, Negative regulation of MET activity
SignaLinkiP40818
SIGNORiP40818

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		9101, 524 hits in 856 CRISPR screens

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

More...ChiTaRSi		USP8, human
EvolutionaryTraceiP40818

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		USP8

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

More...GenomeRNAii		9101
PharosiP40818, Tbio

Protein Ontology

More...PROi		PR:P40818
RNActiP40818, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000138592, Expressed in sural nerve and 235 other tissues
ExpressionAtlasiP40818, baseline and differential
GenevisibleiP40818, HS

Family and domain databases

Gene3Di3.40.250.10, 1 hit
InterProiView protein in InterPro
IPR038765, Papain-like_cys_pep_sf
IPR001394, Peptidase_C19_UCH
IPR001763, Rhodanese-like_dom
IPR036873, Rhodanese-like_dom_sf
IPR015063, USP8_dimer
IPR018200, USP_CS
IPR028889, USP_dom
PfamiView protein in Pfam
PF00581, Rhodanese, 1 hit
PF00443, UCH, 1 hit
PF08969, USP8_dimer, 1 hit
SUPFAMiSSF52821, SSF52821, 1 hit
SSF54001, SSF54001, 1 hit
PROSITEiView protein in PROSITE
PS50206, RHODANESE_3, 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 nameiUBP8_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: P40818
Secondary accession number(s): B4DKA8
, Q2TB31, Q7Z3U2, Q86VA0, Q8IWI7
<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: February 1, 1995
Last sequence update: February 1, 1995
Last modified: December 2, 2020
This is version 218 of the entry and version 1 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. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families
  5. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  6. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  7. Peptidase families
    Classification of peptidase families and list of entries
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