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Aliases for USP8 Gene

Aliases for USP8 Gene

  • Ubiquitin Specific Peptidase 8 2 3 5
  • Ubiquitin-Specific-Processing Protease 8 3 4
  • Deubiquitinating Enzyme 8 3 4
  • Ubiquitin Isopeptidase Y 3 4
  • UBPY 3 4
  • Ubiquitin Specific Protease 8 2
  • Ubiquitin Thiolesterase 8 3
  • Ubiquitin Thioesterase 8 4
  • EC 3.4.19.12 4
  • EC 3.1.2.15 63
  • KIAA0055 4
  • HumORF8 3
  • SPG59 3
  • HUBPy 4

External Ids for USP8 Gene

Previous GeneCards Identifiers for USP8 Gene

  • GC15P046273
  • GC15P043762
  • GC15P048295
  • GC15P048432
  • GC15P048503
  • GC15P050716
  • GC15P027548

Summaries for USP8 Gene

Entrez Gene Summary for USP8 Gene

  • This gene encodes a protein that belongs to the ubiquitin-specific processing protease family of proteins. The encoded protein is thought to regulate the morphology of the endosome by ubiquitination of proteins on this organelle and is involved in cargo sorting and membrane trafficking at the early endosome stage. This protein is required for the cell to enter the S phase of the cell cycle and also functions as a positive regulator in the Hedgehog signaling pathway in development. Pseudogenes of this gene are present on chromosomes 2 and 6. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

GeneCards Summary for USP8 Gene

USP8 (Ubiquitin Specific Peptidase 8) is a Protein Coding gene. Diseases associated with USP8 include Autosomal Recessive Spastic Paraplegia Type 59 and Pituitary Adenoma, Acth-Secreting. Among its related pathways are Signaling by Wnt and Regulation of FZD by ubiquitination. GO annotations related to this gene include SH3 domain binding and thiol-dependent ubiquitin-specific protease activity. An important paralog of this gene is USP50.

UniProtKB/Swiss-Prot for USP8 Gene

  • 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.

Gene Wiki entry for USP8 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for USP8 Gene

Genomics for USP8 Gene

Regulatory Elements for USP8 Gene

Enhancers for USP8 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around USP8 on UCSC Golden Path with GeneCards custom track

Promoters for USP8 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around USP8 on UCSC Golden Path with GeneCards custom track

Genomic Location for USP8 Gene

Chromosome:
15
Start:
50,424,377 bp from pter
End:
50,514,419 bp from pter
Size:
90,043 bases
Orientation:
Plus strand

Genomic View for USP8 Gene

Genes around USP8 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
USP8 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for USP8 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for USP8 Gene

Proteins for USP8 Gene

  • Protein details for USP8 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P40818-UBP8_HUMAN
    Recommended name:
    Ubiquitin carboxyl-terminal hydrolase 8
    Protein Accession:
    P40818
    Secondary Accessions:
    • B4DKA8
    • Q2TB31
    • Q7Z3U2
    • Q86VA0
    • Q8IWI7

    Protein attributes for USP8 Gene

    Size:
    1118 amino acids
    Molecular mass:
    127523 Da
    Quaternary structure:
    • 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.
    SequenceCaution:
    • Sequence=AAH38801.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=AAH51345.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for USP8 Gene

    Alternative splice isoforms for USP8 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for USP8 Gene

Proteomics data for USP8 Gene at MOPED

Selected DME Specific Peptides for USP8 Gene

Post-translational modifications for USP8 Gene

  • 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.
  • 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).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for USP8 (USP8)

Domains & Families for USP8 Gene

Gene Families for USP8 Gene

Graphical View of Domain Structure for InterPro Entry

P40818

UniProtKB/Swiss-Prot:

UBP8_HUMAN :
  • The MIT domain is required for endosomal localization, CHMP1B-binding, maintenance of ESCRT-0 stability and EGFR degradation.
  • Belongs to the peptidase C19 family.
Domain:
  • The MIT domain is required for endosomal localization, CHMP1B-binding, maintenance of ESCRT-0 stability and EGFR degradation.
  • The rhodanese domain is sufficent for RNF41-binding.
  • Contains 1 MIT domain.
  • Contains 1 rhodanese domain.
  • Contains 1 USP domain.
Family:
  • Belongs to the peptidase C19 family.
genes like me logo Genes that share domains with USP8: view

Function for USP8 Gene

Molecular function for USP8 Gene

GENATLAS Biochemistry:
ubiquitin specific protease 8,similar to the tre oncogene,with homology to ubiquitin carboxy-terminal hydrolase,deubiquitin enzyme family
UniProtKB/Swiss-Prot CatalyticActivity:
Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).
UniProtKB/Swiss-Prot Function:
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.
UniProtKB/Swiss-Prot Induction:
Upon growth stimulation in starved human fibroblasts. Decreases in response to growth arrest induced by cell-cell contact.

Enzyme Numbers (IUBMB) for USP8 Gene

Gene Ontology (GO) - Molecular Function for USP8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0017124 SH3 domain binding IEA --
genes like me logo Genes that share ontologies with USP8: view
genes like me logo Genes that share phenotypes with USP8: view

Human Phenotype Ontology for USP8 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for USP8 Gene

MGI Knock Outs for USP8:

Animal Model Products

  • Taconic Biosciences Mouse Models for USP8

No data available for Transcription Factor Targets and HOMER Transcription for USP8 Gene

Localization for USP8 Gene

Subcellular locations from UniProtKB/Swiss-Prot for USP8 Gene

Cytoplasm. Nucleus. Endosome membrane; Peripheral membrane protein. Cell membrane; Peripheral membrane protein.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for USP8 Gene COMPARTMENTS Subcellular localization image for USP8 gene
Compartment Confidence
cytosol 5
endosome 5
golgi apparatus 5
nucleus 5
plasma membrane 5
lysosome 2
vacuole 2

Gene Ontology (GO) - Cellular Components for USP8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA 18388320
GO:0030496 midbody IDA 18388320
GO:0031313 extrinsic component of endosome membrane IBA --
genes like me logo Genes that share ontologies with USP8: view

Pathways & Interactions for USP8 Gene

genes like me logo Genes that share pathways with USP8: view

Pathways by source for USP8 Gene

1 KEGG pathway for USP8 Gene
1 Qiagen pathway for USP8 Gene

Gene Ontology (GO) - Biological Process for USP8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000281 mitotic cytokinesis IMP 18388320
GO:0071108 protein K48-linked deubiquitination IDA 16520378
genes like me logo Genes that share ontologies with USP8: view

No data available for SIGNOR curated interactions for USP8 Gene

Drugs & Compounds for USP8 Gene

(1) Drugs for USP8 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(1) Additional Compounds for USP8 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Water
  • Dihydrogen oxide
  • Steam
7732-18-5
genes like me logo Genes that share compounds with USP8: view

Transcripts for USP8 Gene

Unigene Clusters for USP8 Gene

Ubiquitin specific peptidase 8:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for USP8 Gene

ExUns: 1a · 1b · 1c · 1d · 1e ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17a · 17b ^ 18a · 18b ^ 19 ^ 20 ^
SP1: - - -
SP2: - -
SP3: - - -
SP4:
SP5: - - - - -
SP6: -
SP7: - - -
SP8:
SP9:

ExUns: 21a · 21b ^ 22a · 22b · 22c
SP1: -
SP2: -
SP3:
SP4: -
SP5:
SP6:
SP7:
SP8:
SP9:

Relevant External Links for USP8 Gene

GeneLoc Exon Structure for
USP8
ECgene alternative splicing isoforms for
USP8

Expression for USP8 Gene

mRNA expression in normal human tissues for USP8 Gene

Protein differential expression in normal tissues from HIPED for USP8 Gene

This gene is overexpressed in Heart (34.7) and Fetal heart (6.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for USP8 Gene



SOURCE GeneReport for Unigene cluster for USP8 Gene Hs.443731

genes like me logo Genes that share expression patterns with USP8: view

Protein tissue co-expression partners for USP8 Gene

- Elite partner

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for USP8 Gene

Orthologs for USP8 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for USP8 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia USP8 35
  • 92.07 (n)
  • 91.34 (a)
USP8 36
  • 91 (a)
OneToOne
dog
(Canis familiaris)
Mammalia USP8 35
  • 92.77 (n)
  • 92.03 (a)
USP8 36
  • 92 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Usp8 35
  • 84.63 (n)
  • 84.63 (a)
Usp8 16
Usp8 36
  • 84 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia USP8 35
  • 99.76 (n)
  • 99.55 (a)
USP8 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Usp8 35
  • 84.18 (n)
  • 84.27 (a)
oppossum
(Monodelphis domestica)
Mammalia USP8 36
  • 82 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia USP8 36
  • 76 (a)
OneToOne
chicken
(Gallus gallus)
Aves USP8 35
  • 76.17 (n)
  • 75.39 (a)
USP8 36
  • 75 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia USP8 36
  • 70 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia usp8 35
  • 66.86 (n)
  • 64.01 (a)
African clawed frog
(Xenopus laevis)
Amphibia usp8-prov 35
zebrafish
(Danio rerio)
Actinopterygii usp8 35
  • 59.13 (n)
  • 61.3 (a)
usp8 36
  • 55 (a)
OneToOne
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.13120 35
fruit fly
(Drosophila melanogaster)
Insecta CG5798 37
  • 44 (a)
Ubpy 35
  • 46.67 (n)
  • 38.87 (a)
Ubpy 36
  • 35 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP002900 35
  • 44.83 (n)
  • 36.65 (a)
worm
(Caenorhabditis elegans)
Secernentea Y59A8B.2 37
  • 32 (a)
E01B7.1 35
  • 42.84 (n)
  • 32.52 (a)
E01B7.1 36
  • 28 (a)
ManyToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes DOA4 36
  • 21 (a)
ManyToMany
UBP5 36
  • 22 (a)
ManyToMany
DOA4 38
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 36 (a)
OneToOne
Species with no ortholog for USP8:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for USP8 Gene

ENSEMBL:
Gene Tree for USP8 (if available)
TreeFam:
Gene Tree for USP8 (if available)

Paralogs for USP8 Gene

Paralogs for USP8 Gene

genes like me logo Genes that share paralogs with USP8: view

Variants for USP8 Gene

Sequence variations from dbSNP and Humsavar for USP8 Gene

SNP ID Clin Chr 15 pos Sequence Context AA Info Type
rs3743044 - 50,481,590(+) TCCTG(A/G)TCGTT intron-variant, reference, missense
VAR_017797 -
rs11638390 - 50,490,506(+) CTCCA(A/G)CAGTT reference, missense
rs5029514 -- 50,459,997(+) CCCCC(C/T)ttttt intron-variant
rs5812516 -- 50,426,961(+) TTTTT(-/T)GAGAT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for USP8 Gene

Variant ID Type Subtype PubMed ID
nsv524613 CNV Loss 19592680
nsv904210 CNV Loss 21882294
esv1049679 CNV Deletion 17803354
esv2749681 CNV Deletion 23290073
esv2677885 CNV Deletion 23128226
nsv471242 CNV Gain 18288195
dgv317n27 CNV Gain 19166990
esv2749682 CNV Deletion 23290073
esv2416237 CNV Deletion 18987734
esv2749683 CNV Deletion 23290073
esv2749684 CNV Deletion 23290073
esv1047910 CNV Deletion 17803354
esv994715 CNV Deletion 20482838

Variation tolerance for USP8 Gene

Residual Variation Intolerance Score: 63.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.59; 72.41% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for USP8 Gene

Human Gene Mutation Database (HGMD)
USP8

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for USP8 Gene

Disorders for USP8 Gene

MalaCards: The human disease database

(3) MalaCards diseases for USP8 Gene - From: ClinVar, Orphanet, and DISEASES

Disorder Aliases PubMed IDs
autosomal recessive spastic paraplegia type 59
  • spg59
pituitary adenoma, acth-secreting
  • pituitary-dependent cushing's disease
cushing's syndrome
  • cushing syndrome
- elite association - COSMIC cancer census association via MalaCards
Search USP8 in MalaCards View complete list of genes associated with diseases

Relevant External Links for USP8

Human Genome Epidemiology (HuGE) Navigator
USP8
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
USP8
genes like me logo Genes that share disorders with USP8: view

No data available for UniProtKB/Swiss-Prot and Genatlas for USP8 Gene

Publications for USP8 Gene

  1. Amino-terminal dimerization, NRDP1-rhodanese interaction, and inhibited catalytic domain conformation of the ubiquitin-specific protease 8 (USP8). (PMID: 17035239) Avvakumov G.V. … Dhe-Paganon S. (J. Biol. Chem. 2006) 3 4 23 67
  2. Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. (PMID: 24482476) Novarino G. … Gleeson J.G. (Science 2014) 2 3
  3. 14-3-3-dependent inhibition of the deubiquitinating activity of UBPY and its cancellation in the M phase. (PMID: 17720156) Mizuno E. … Komada M. (Exp. Cell Res. 2007) 3 23
  4. Stabilization of the E3 ubiquitin ligase Nrdp1 by the deubiquitinating enzyme USP8. (PMID: 15314180) Wu X. … Carraway K.L. III (Mol. Cell. Biol. 2004) 3 23
  5. Human and mouse proteases: a comparative genomic approach. (PMID: 12838346) Puente X.S. … Lopez-Otin C. (Nat. Rev. Genet. 2003) 2 3

Products for USP8 Gene

  • Addgene plasmids for USP8

Sources for USP8 Gene

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