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

Summary

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: mouse all
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Genomic context

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_000015.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
Clinical Spectrum of USP8 Pathogenic Variants in Cushing's Disease.
Title: Clinical Spectrum of USP8 Pathogenic Variants in Cushing's Disease.
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.
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.
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.
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.
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	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH45725 (e-PCR)
- UniSTS:70725

RH25289 (e-PCR)
- UniSTS:63625

D15S1200 (e-PCR)
- UniSTS:6290

D15S712E (e-PCR)
- UniSTS:80064

RH104427 (e-PCR)
- UniSTS:98752

G07414 (e-PCR)
- UniSTS:21961

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 more info	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

EC 3.4.19.12

NP_001269978.1

EC 3.4.19.12

NP_005145.3

EC 3.4.19.12

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

NG_047101.2 RefSeqGene

Range

5002..95018

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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

NC_000015.10 Reference GRCh38.p14 Primary Assembly

Range

50424405..50514421

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060939.1 Alternate T2T-CHM13v2.0

Range

48232513..48322500

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GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_001128611.1: Suppressed sequence

Description

NM_001128611.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript.