Usp15 ubiquitin specific peptidase 15 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Usp15provided by MGI
Official Full Name: ubiquitin specific peptidase 15provided by MGI
Primary source: MGI:MGI:101857
See related: Ensembl:ENSMUSG00000020124 AllianceGenome:MGI:101857
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Gcap18; 4921514G19Rik; E430033I05Rik
Summary: The protein encoded by this gene is a member of the large ubiquitin specific protease (Usp) family of proteins. These proteins are known to cleave ubiquitin, and contain a conserved cysteine residue (Cys box) and two conserved histidine residues (His box) that are thought to form part of the active site of the protease. This protein has been shown to cleave both the ubiquitin-proline and the ubiquitin-methionine bonds in vitro. This protein is thought to regulate many cellular processes through its deubiquitination activity, including the transforming growth factor beta (TGF-beta) pathway. Cardiac-specific overexpression of the human ortholog of this gene in mice causes enlargement of the heart that is more pronounced in the atrium than in the ventricle. This gene has two pseudogenes on chromosome 14. Alternative splicing results in multiple transcript variants that encode multiple protein isoforms.[provided by RefSeq, Aug 2014]
Expression: Ubiquitous expression in testis adult (RPKM 9.0), placenta adult (RPKM 8.8) and 26 other tissues See more
Orthologs: human all
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Genomic context

Location:: 10 D2; 10 72.31 cM

Exon count:: 25

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	10	NC_000076.7 (122940911..123032924, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	10	NC_000076.6 (123105006..123197281, complement)

Chromosome 10 - NC_000076.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Downregulation of Ubiquitin-Specific Protease 15 (USP15) Does Not Provide Therapeutic Benefit in Experimental Mesial Temporal Lobe Epilepsy.
Title: Downregulation of Ubiquitin-Specific Protease 15 (USP15) Does Not Provide Therapeutic Benefit in Experimental Mesial Temporal Lobe Epilepsy.
USP15 promotes pulmonary vascular remodeling in pulmonary hypertension in a YAP1/TAZ-dependent manner.
Title: USP15 promotes pulmonary vascular remodeling in pulmonary hypertension in a YAP1/TAZ-dependent manner.
SRA Suppresses Antiviral Innate Immune Response in Macrophages by Limiting TBK1 K63 Ubiquitination via Deubiquitinase USP15.
Title: SRA Suppresses Antiviral Innate Immune Response in Macrophages by Limiting TBK1 K63 Ubiquitination via Deubiquitinase USP15.
USP15 regulates p66Shc stability associated with Drp1 activation in liver ischemia/reperfusion.
Title: USP15 regulates p66Shc stability associated with Drp1 activation in liver ischemia/reperfusion.
USP15 Deubiquitinase Safeguards Hematopoiesis and Genome Integrity in Hematopoietic Stem Cells and Leukemia Cells.
Title: USP15 Deubiquitinase Safeguards Hematopoiesis and Genome Integrity in Hematopoietic Stem Cells and Leukemia Cells.
Inhibition of USP15 Prevent Glutamate-Induced Oxidative Damage by Activating Nrf2/HO-1 Signaling Pathway in HT22 Cells.
Title: Inhibition of USP15 Prevent Glutamate-Induced Oxidative Damage by Activating Nrf2/HO-1 Signaling Pathway in HT22 Cells.
USP15 Deubiquitinates TUT1 Associated with RNA Metabolism and Maintains Cerebellar Homeostasis.
Title: USP15 Deubiquitinates TUT1 Associated with RNA Metabolism and Maintains Cerebellar Homeostasis.
Deficiency in macrophages protects mice against lipopolysaccharide-induced septic shock, and knockdown of Usp15 in Hrd1-knockout macrophages restores the reduced IL-6 production.
Title: ER-localized Hrd1 ubiquitinates and inactivates Usp15 to promote TLR4-induced inflammation during bacterial infection.
USP15 inhibited multiple myeloma cell apoptosis through activating a feedback loop with NF-kappaBp65. USP15 silencing inhibited multiple myeloma tumor growth.
Title: USP15 inhibits multiple myeloma cell apoptosis through activating a feedback loop with the transcription factor NF-κBp65.
Study reports that USP15 affects cancer cell response to PARP inhibitors by regulating homologous recombination repair. USP15 is recruited to DNA double-strand breaks (DSBs) by MDC1. USP15 deubiquitinates BARD1 BRCT domain, and promotes BARD1-HP1gamma interaction, resulting in BRCA1/BARD1 retention at DSBs. Cancer-associated USP15 mutations, with decreased USP15-BARD1 interaction, increases PARP inhibitor sensitivity.
Title: The deubiquitylating enzyme USP15 regulates homologous recombination repair and cancer cell response to PARP inhibitors.

Submit: New GeneRIF Correction See all GeneRIFs (13)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Chemically induced (ENU) (3) 1 citation
Endonuclease-mediated (7) 1 citation
Gene trapped (1)
Targeted (4) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AI327321 (e-PCR)
- UniSTS:160038

AI451661 (e-PCR)
- UniSTS:208619

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables K48-linked deubiquitinase activity	IEA Inferred from Electronic Annotation more info
enables K48-linked deubiquitinase activity	ISO Inferred from Sequence Orthology more info
enables SMAD binding	IEA Inferred from Electronic Annotation more info
enables SMAD binding	ISO Inferred from Sequence Orthology more info
enables cysteine-type deubiquitinase activity	IDA Inferred from Direct Assay more info	PubMed
enables cysteine-type deubiquitinase activity	ISO Inferred from Sequence Orthology more info
enables cysteine-type deubiquitinase activity	ISS Inferred from Sequence or Structural Similarity more info
enables cysteine-type endopeptidase activity	ISO Inferred from Sequence Orthology more info
enables cysteine-type endopeptidase activity	ISS Inferred from Sequence or Structural Similarity more info
enables deubiquitinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables deubiquitinase activity	ISO Inferred from Sequence Orthology more info
enables identical protein binding	IEA Inferred from Electronic Annotation more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables transforming growth factor beta receptor binding	IEA Inferred from Electronic Annotation more info
enables transforming growth factor beta receptor binding	ISO Inferred from Sequence Orthology more info
enables ubiquitin-modified histone reader activity	IEA Inferred from Electronic Annotation more info
enables ubiquitin-modified histone reader activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in BMP signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in BMP signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in monoubiquitinated protein deubiquitination	ISO Inferred from Sequence Orthology more info
involved_in monoubiquitinated protein deubiquitination	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of antifungal innate immune response	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of antifungal innate immune response	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of transforming growth factor beta receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of transforming growth factor beta receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of RIG-I signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of RIG-I signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in protein K27-linked deubiquitination	ISO Inferred from Sequence Orthology more info
involved_in protein K27-linked deubiquitination	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein deubiquitination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein deubiquitination	ISO Inferred from Sequence Orthology more info
involved_in protein deubiquitination	ISS Inferred from Sequence or Structural Similarity more info
involved_in proteolysis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of intrinsic apoptotic signaling pathway in response to osmotic stress by p53 class mediator	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in transcription elongation-coupled chromatin remodeling	IBA Inferred from Biological aspect of Ancestor more info
involved_in transcription elongation-coupled chromatin remodeling	ISO Inferred from Sequence Orthology more info
involved_in transcription elongation-coupled chromatin remodeling	ISS Inferred from Sequence or Structural Similarity more info
involved_in transforming growth factor beta receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in transforming growth factor beta receptor signaling pathway	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in mitochondrion	IEA Inferred from Electronic Annotation more info
located_in nuclear body	IEA Inferred from Electronic Annotation more info
located_in nuclear body	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	ISO Inferred from Sequence Orthology more info
located_in nucleus	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: ubiquitin carboxyl-terminal hydrolase 15

Names: deubiquitinating enzyme 15; granule cell antiserum positive 18; ubiquitin thioesterase 15; ubiquitin thiolesterase 15; ubiquitin-specific-processing protease 15

NP_001288557.1

EC 3.4.19.12

NP_081880.2

EC 3.4.19.12

XP_006513288.1

EC 3.4.19.12

XP_006513289.1

EC 3.4.19.12

XP_006513290.1

EC 3.4.19.12

XP_006513291.1

EC 3.4.19.12

XP_036011508.1

EC 3.4.19.12

XP_036011509.1

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.

mRNA and Protein(s)

NM_001301628.2 → NP_001288557.1 ubiquitin carboxyl-terminal hydrolase 15 isoform 2

See identical proteins and their annotated locations for NP_001288557.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame exon compared to variant 1. It encodes isoform 2 which is shorter than isoform 1.

Source sequence(s)

AC153021, AC158802

Consensus CDS

CCDS88095.1

UniProtKB/Swiss-Prot

Q8R5H1

Related

ENSMUSP00000020334.9, ENSMUST00000020334.9

Conserved Domains (6) summary

smart00695
Location:24 → 121

DUSP; Domain in ubiquitin-specific proteases

COG5560
Location:12 → 903

UBP12; Ubiquitin C-terminal hydrolase [Posttranslational modification, protein turnover, chaperones]

cd02674
Location:755 → 902

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 ...

cl02553
Location:261 → 446

Peptidase_C19; Peptidase C19 contains ubiquitinyl hydrolases. They are intracellular peptidases that remove ubiquitin molecules from polyubiquinated peptides by cleavage of isopeptide bonds. They hydrolyse bonds involving the carboxyl group of the C-terminal Gly ...

pfam14533
Location:462 → 568

USP7_C2; Ubiquitin-specific protease C-terminal

pfam14836
Location:135 → 222

Ubiquitin_3; Ubiquitin-like domain
NM_001428484.1 → NP_001415413.1 ubiquitin carboxyl-terminal hydrolase 15 isoform 3

Status: REVIEWED

Source sequence(s)

AC153021, AC158802
NM_001428485.1 → NP_001415414.1 ubiquitin carboxyl-terminal hydrolase 15 isoform 4

Status: REVIEWED

Source sequence(s)

AC153021, AC158802
NM_001428486.1 → NP_001415415.1 ubiquitin carboxyl-terminal hydrolase 15 isoform 5

Status: REVIEWED

Source sequence(s)

AC153021, AC158802
NM_001428487.1 → NP_001415416.1 ubiquitin carboxyl-terminal hydrolase 15 isoform 6

Status: REVIEWED

Source sequence(s)

AC153021, AC158802
NM_027604.5 → NP_081880.2 ubiquitin carboxyl-terminal hydrolase 15 isoform 1

See identical proteins and their annotated locations for NP_081880.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

AC153021, AC158802

Consensus CDS

CCDS24217.1

UniProtKB/Swiss-Prot

Q3TGF5, Q3TTB2, Q3UL25, Q3UZH0, Q80TY6, Q80UK9, Q8R5H1

Related

ENSMUSP00000151244.2, ENSMUST00000220377.2

Conserved Domains (6) summary

smart00695
Location:24 → 121

DUSP; Domain in ubiquitin-specific proteases

COG5560
Location:12 → 932

UBP12; Ubiquitin C-terminal hydrolase [Posttranslational modification, protein turnover, chaperones]

cd02674
Location:784 → 931

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 ...

cl02553
Location:290 → 475

Peptidase_C19; Peptidase C19 contains ubiquitinyl hydrolases. They are intracellular peptidases that remove ubiquitin molecules from polyubiquinated peptides by cleavage of isopeptide bonds. They hydrolyse bonds involving the carboxyl group of the C-terminal Gly ...

pfam14533
Location:491 → 597

USP7_C2; Ubiquitin-specific protease C-terminal

pfam14836
Location:135 → 222

Ubiquitin_3; Ubiquitin-like domain

RNA

NR_190377.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC153021, AC158802
NR_190378.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC153021, AC158802
NR_190379.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC158802

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000076.7 Reference GRCm39 C57BL/6J

Range

122940911..123032924 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_036155616.1 → XP_036011509.1 ubiquitin carboxyl-terminal hydrolase 15 isoform X3

Conserved Domains (1) summary

COG5560
Location:34 → 683

UBP12; Ubiquitin C-terminal hydrolase [Posttranslational modification, protein turnover, chaperones]
XM_036155615.1 → XP_036011508.1 ubiquitin carboxyl-terminal hydrolase 15 isoform X1

Conserved Domains (1) summary

COG5560
Location:63 → 712

UBP12; Ubiquitin C-terminal hydrolase [Posttranslational modification, protein turnover, chaperones]
XM_006513227.5 → XP_006513290.1 ubiquitin carboxyl-terminal hydrolase 15 isoform X5

Conserved Domains (1) summary

COG5560
Location:1 → 633

UBP12; Ubiquitin C-terminal hydrolase [Posttranslational modification, protein turnover, chaperones]
XM_006513226.5 → XP_006513289.1 ubiquitin carboxyl-terminal hydrolase 15 isoform X4

Conserved Domains (1) summary

COG5560
Location:32 → 681

UBP12; Ubiquitin C-terminal hydrolase [Posttranslational modification, protein turnover, chaperones]
XM_006513225.5 → XP_006513288.1 ubiquitin carboxyl-terminal hydrolase 15 isoform X2

Conserved Domains (1) summary

COG5560
Location:41 → 690

UBP12; Ubiquitin C-terminal hydrolase [Posttranslational modification, protein turnover, chaperones]
XM_006513228.5 → XP_006513291.1 ubiquitin carboxyl-terminal hydrolase 15 isoform X6

UniProtKB/TrEMBL

Q3TPH3

Conserved Domains (2) summary

smart00695
Location:24 → 121

DUSP; Domain in ubiquitin-specific proteases

pfam14836
Location:135 → 222

Ubiquitin_3; Ubiquitin-like domain