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USP8 ubiquitin specific peptidase 8 [ Homo sapiens (human) ]

Gene ID: 9101, updated on 27-Nov-2024

Summary

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Official Symbol
USP8provided by HGNC
Official Full Name
ubiquitin specific peptidase 8provided by HGNC
Primary source
HGNC:HGNC:12631
See related
Ensembl:ENSG00000138592 MIM:603158; AllianceGenome:HGNC:12631
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
UBPY; PITA4; SPG59; HumORF8
Summary
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]
Expression
Ubiquitous expression in testis (RPKM 16.5), thyroid (RPKM 12.8) and 25 other tissues See more
Orthologs
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Genomic context

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See USP8 in Genome Data Viewer
Location:
15q21.2
Exon count:
20
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (50424405..50514421)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (48232513..48322500)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (50716602..50806618)

Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene ReSE screen-validated silencer GRCh37_chr15:50674110-50674285 Neighboring gene microRNA 4712 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:50676534-50676699 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:50715425-50716421 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9393 Neighboring gene adenosylhomocysteinase pseudogene 7 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9394 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9395 Neighboring gene RNA, 5S ribosomal pseudogene 395 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:50776274-50776376 Neighboring gene ribosomal protein S20 pseudogene 34 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:50801331-50801565 Neighboring gene ubiquitin specific peptidase 50 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr15:50843324-50843838 Neighboring gene transient receptor potential cation channel subfamily M member 7 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr15:50884350-50885549 Neighboring gene uncharacterized LOC128092252 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:50969254-50969754 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:50969755-50970255 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:50978082-50978946 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6429 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9397 Neighboring gene RNA, 7SL, cytoplasmic 354, pseudogene

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. The USP8 mutational status may predict drug susceptibility in corticotroph adenomas of Cushing's disease. Hayashi K, et al. Eur J Endocrinol, 2016 Feb. PMID 26578638
  2. Ubiquitin-specific Protease 8 Gene Expression in Sporadic Pituitary Adenomas. Hatipoglu E, et al. Neuro Endocrinol Lett, 2022 Jun 5. PMID 35981231
  3. Cushing's disease due to somatic USP8 mutations: a systematic review and meta-analysis. Wanichi IQ, et al. Pituitary, 2019 Aug. PMID 31273566
  4. Ubiquitin-Specific Protease 8 Mutant Corticotrope Adenomas Present Unique Secretory and Molecular Features and Shed Light on the Role of Ubiquitylation on ACTH Processing. Sesta A, et al. Neuroendocrinology, 2020. PMID 31280266, Free PMC Article
  5. [Study on the association of USP8 gene polymorphisms with male infertility in ethnic Han Chinese from Sichuan]. Ding M, et al. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 2015 Apr. PMID 25863102

See all (201) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Autoinhibition of ubiquitin-specific protease 8: Insights into domain interactions and mechanisms of regulation.
    Title: Autoinhibition of ubiquitin-specific protease 8: Insights into domain interactions and mechanisms of regulation.
  2. A long-term prognosis study of human USP8-mutated ACTH-secreting pituitary neuroendocrine tumours.
    Title: A long-term prognosis study of human USP8-mutated ACTH-secreting pituitary neuroendocrine tumours.
  3. Polymorphic USP8 allele promotes Parkinson's disease by inducing the accumulation of alpha-synuclein through deubiquitination.
    Title: Polymorphic USP8 allele promotes Parkinson's disease by inducing the accumulation of α-synuclein through deubiquitination.
  4. USP8 prevents aberrant NF-kappaB and Nrf2 activation by counteracting ubiquitin signals from endosomes.
    Title: USP8 prevents aberrant NF-κB and Nrf2 activation by counteracting ubiquitin signals from endosomes.
  5. Clinical Spectrum of USP8 Pathogenic Variants in Cushing's Disease.
    Title: Clinical Spectrum of USP8 Pathogenic Variants in Cushing's Disease.
  6. Central role of ubiquitin-specific protease 8 in leptin signaling pathway in pulmonary arterial hypertension.
    Title: Central role of ubiquitin-specific protease 8 in leptin signaling pathway in pulmonary arterial hypertension.
  7. USP8 targeted by Mir-874-3p promotes trophoblastic cell invasion by stabilizing the expression of ENaC on trophoblast membrane.
    Title: USP8 targeted by Mir-874-3p promotes trophoblastic cell invasion by stabilizing the expression of ENaC on trophoblast membrane.
  8. USP8 promotes gemcitabine resistance of pancreatic cancer via deubiquitinating and stabilizing Nrf2.
    Title: USP8 promotes gemcitabine resistance of pancreatic cancer via deubiquitinating and stabilizing Nrf2.
  9. piRNA-1742 promotes renal cell carcinoma malignancy by regulating USP8 stability through binding to hnRNPU and thereby inhibiting MUC12 ubiquitination.
    Title: piRNA-1742 promotes renal cell carcinoma malignancy by regulating USP8 stability through binding to hnRNPU and thereby inhibiting MUC12 ubiquitination.
  10. USP8 Down-Regulation Promotes Parkin-Independent Mitophagy in the Drosophila Brain and in Human Neurons.
    Title: USP8 Down-Regulation Promotes Parkin-Independent Mitophagy in the Drosophila Brain and in Human Neurons.
Submit: New GeneRIF Correction See all GeneRIFs (86)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Pituitary dependent hypercortisolism
MedGen: C0221406 OMIM: 219090 GeneReviews: Not available
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Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ34456, KIAA0055, MGC129718

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables K48-linked deubiquitinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables K63-linked deubiquitinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables SH3 domain binding IEA
Inferred from Electronic Annotation
more info
  
enables cadherin binding HDA PubMed 
enables cysteine-type deubiquitinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables cysteine-type deubiquitinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables cysteine-type deubiquitinase activity TAS
Traceable Author Statement
more info
  
enables cysteine-type endopeptidase activity TAS
Traceable Author Statement
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in Ras protein signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in cellular response to dexamethasone stimulus IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to nerve growth factor stimulus IEA
Inferred from Electronic Annotation
more info
  
involved_in endosome organization IBA
Inferred from Biological aspect of Ancestor
more info
  
acts_upstream_of_or_within mitotic cytokinesis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of lysosomal protein catabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of amyloid fibril formation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of canonical Wnt signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein K48-linked deubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein K63-linked deubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of_or_within protein deubiquitination IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein deubiquitination IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in proteolysis IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of protein catabolic process at postsynapse, modulating synaptic transmission IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of protein localization IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of protein stability IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in cytosol IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
is_active_in dendritic spine IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in early endosome IDA
Inferred from Direct Assay
more info
 PubMed 
located_in endosome membrane IEA
Inferred from Electronic Annotation
more info
  
located_in glutamatergic synapse IEA
Inferred from Electronic Annotation
more info
  
is_active_in midbody IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in midbody IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleus IEA
Inferred from Electronic Annotation
more info
  
located_in plasma membrane IEA
Inferred from Electronic Annotation
more info
  
is_active_in postsynaptic density IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
ubiquitin carboxyl-terminal hydrolase 8
Names
deubiquitinating enzyme 8
ubiquitin isopeptidase Y
ubiquitin thiolesterase 8
ubiquitin-specific-processing protease 8
NP_001122082.1
NP_001269978.1
NP_005145.3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_047101.2 RefSeqGene

    Range
    5002..95018
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001128610.3 → NP_001122082.1  ubiquitin carboxyl-terminal hydrolase 8 isoform a

    See identical proteins and their annotated locations for NP_001122082.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 encode the same protein (isoform a).
    Source sequence(s)
    AA399951, AA399952, AC012170, AI276208, BM751645, D29956
    Consensus CDS
    CCDS10137.1
    UniProtKB/Swiss-Prot
    B4DKA8, P40818, Q2TB31, Q7Z3U2, Q86VA0, Q8IWI7
    UniProtKB/TrEMBL
    A8K8N5
    Related
    ENSP00000379721.3, ENST00000396444.7
    Conserved Domains (5) summary
    smart00450
    Location:199 → 310
    RHOD; Rhodanese Homology Domain
    TIGR02794
    Location:375 → 547
    tolA_full; TolA protein
    pfam00443
    Location:777 → 1106
    UCH; Ubiquitin carboxyl-terminal hydrolase
    pfam08969
    Location:8 → 115
    USP8_dimer; USP8 dimerisation domain
    pfam10243
    Location:474 → 646
    MIP-T3; Microtubule-binding protein MIP-T3

  2. NM_001283049.2 → NP_001269978.1  ubiquitin carboxyl-terminal hydrolase 8 isoform b

    See identical proteins and their annotated locations for NP_001269978.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks three in-frame exons in the coding region compared to variant 1. The encoded isoform (b) is shorter than isoform a.
    Source sequence(s)
    AA399951, AA399952, AC012170, AI276208, AK296480, BM751645, D29956
    Consensus CDS
    CCDS61632.1
    UniProtKB/TrEMBL
    A8K8N5
    Related
    ENSP00000412682.3, ENST00000425032.7
    Conserved Domains (6) summary
    smart00450
    Location:122 → 233
    RHOD; Rhodanese Homology Domain
    cd02674
    Location:672 → 1001
    Peptidase_C19R; A subfamily of peptidase C19. Peptidase C19 contains ubiquitinyl hydrolases. They are intracellular peptidases that remove ubiquitin molecules from polyubiquinated peptides by cleavage of isopeptide bonds. They hydrolyze bonds involving the carboxyl ...
    TIGR02794
    Location:298 → 470
    tolA_full; TolA protein
    pfam00443
    Location:670 → 1000
    UCH; Ubiquitin carboxyl-terminal hydrolase
    pfam08969
    Location:6 → 53
    USP8_dimer; USP8 dimerization domain
    pfam10211
    Location:393 → 442
    Ax_dynein_light; Axonemal dynein light chain

  3. NM_005154.5 → NP_005145.3  ubiquitin carboxyl-terminal hydrolase 8 isoform a

    See identical proteins and their annotated locations for NP_005145.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longer isoform (a). Variants 1 and 2 encode the same protein.
    Source sequence(s)
    AA399951, AA399952, AC012170, AI276208, AK292400, BM751645, D29956, KF459553
    Consensus CDS
    CCDS10137.1
    UniProtKB/Swiss-Prot
    B4DKA8, P40818, Q2TB31, Q7Z3U2, Q86VA0, Q8IWI7
    UniProtKB/TrEMBL
    A8K8N5
    Related
    ENSP00000302239.4, ENST00000307179.9
    Conserved Domains (5) summary
    smart00450
    Location:199 → 310
    RHOD; Rhodanese Homology Domain
    TIGR02794
    Location:375 → 547
    tolA_full; TolA protein
    pfam00443
    Location:777 → 1106
    UCH; Ubiquitin carboxyl-terminal hydrolase
    pfam08969
    Location:8 → 115
    USP8_dimer; USP8 dimerisation domain
    pfam10243
    Location:474 → 646
    MIP-T3; Microtubule-binding protein MIP-T3

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000015.10 Reference GRCh38.p14 Primary Assembly

    Range
    50424405..50514421
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060939.1 Alternate T2T-CHM13v2.0

    Range
    48232513..48322500
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_001128611.1: Suppressed sequence

    Description
    NM_001128611.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P40818.1 GenPept UniProtKB/Swiss-Prot:P40818

Gene LinkOut

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