Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
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-medaited APP cleavage and amyloid-beta formation (PubMed:27302062).5 Publications

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ 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

  • cadherin binding Source: BHF-UCL
  • cysteine-type endopeptidase activity Source: ProtInc
  • SH3 domain binding Source: UniProtKB-KW
  • thiol-dependent ubiquitin-specific protease activity Source: UniProtKB

GO - Biological processi

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

Molecular 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

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

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_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
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_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:USP8Imported
Synonyms:KIAA0055, UBPY
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 15

Organism-specific databases

Eukaryotic Pathogen 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; 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.
See also OMIM:219090
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_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>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

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.<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_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

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

Encyclopedia of Proteome Dynamics

More...
EPDi
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 human proteome resource

More...
ProteomicsDBi
55380

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
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 220 organ(s), highest expression level in corpus callosum

CleanEx database of gene expression profiles

More...
CleanExi
HS_USP8

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
HPA050215

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

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

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

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

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...
BioGridi
114555, 83 interactors

Database of interacting proteins

More...
DIPi
DIP-40365N

Protein interaction database and analysis system

More...
IntActi
P40818, 27 interactors

Molecular INTeraction database

More...
MINTi
P40818

STRING: functional protein association networks

More...
STRINGi
9606.ENSP00000302239

Chemistry databases

BindingDB database of measured binding affinities

More...
BindingDBi
P40818

<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

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

More...
ProteinModelPortali
P40818

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

More...
SMRi
P40818

Database of comparative protein structure models

More...
ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
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_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>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
ENOG410XP8T LUCA

Ensembl GeneTree

More...
GeneTreei
ENSGT00940000157542

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...
HOGENOMi
HOG000231497

The HOVERGEN Database of Homologous Vertebrate Genes

More...
HOVERGENi
HBG012631

InParanoid: Eukaryotic Ortholog Groups

More...
InParanoidi
P40818

KEGG Orthology (KO)

More...
KOi
K11839

Identification of Orthologs from Complete Genome Data

More...
OMAi
VIMKALW

Database of Orthologous Groups

More...
OrthoDBi
EOG091G0120

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_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)i

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

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

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 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« 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.

Note: No experimental confirmation available.
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>
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>
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>
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. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.<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]

UniGene gene-oriented nucleotide sequence clusters

More...
UniGenei
Hs.443731

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]
UniGeneiHs.443731

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[»]
ProteinModelPortaliP40818
SMRiP40818
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114555, 83 interactors
DIPiDIP-40365N
IntActiP40818, 27 interactors
MINTiP40818
STRINGi9606.ENSP00000302239

Chemistry databases

BindingDBiP40818
ChEMBLiCHEMBL2157854

Protein family/group databases

MEROPSiC19.011

PTM databases

iPTMnetiP40818
PhosphoSitePlusiP40818

Polymorphism and mutation databases

BioMutaiUSP8
DMDMi731046

Proteomic databases

EPDiP40818
MaxQBiP40818
PaxDbiP40818
PeptideAtlasiP40818
PRIDEiP40818
ProteomicsDBi55380

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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

H-Invitational Database, human transcriptome db

More...
H-InvDBi
HIX0172812
HGNCiHGNC:12631 USP8
HPAiHPA050215
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
ENOG410XP8T LUCA
GeneTreeiENSGT00940000157542
HOGENOMiHOG000231497
HOVERGENiHBG012631
InParanoidiP40818
KOiK11839
OMAiVIMKALW
OrthoDBiEOG091G0120
PhylomeDBiP40818
TreeFamiTF106277

Enzyme and pathway databases

BRENDAi3.4.19.12 2681
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

Miscellaneous databases

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

Protein Ontology

More...
PROi
PR:P40818

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000138592 Expressed in 220 organ(s), highest expression level in corpus callosum
CleanExiHS_USP8
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...

<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_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: December 5, 2018
This is version 203 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, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again