USP46 ubiquitin specific peptidase 46 [Homo sapiens (human)] - Gene

Summary

Official Symbol: USP46provided by HGNC
Official Full Name: ubiquitin specific peptidase 46provided by HGNC
Primary source: HGNC:HGNC:20075
See related: Ensembl:ENSG00000109189 MIM:612849; AllianceGenome:HGNC:20075
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary: Modification of cellular proteins by ubiquitin is an essential regulatory mechanism controlled by the coordinated action of multiple ubiquitin-conjugating and deubiquitinating enzymes. USP46 belongs to a large family of cysteine proteases that function as deubiquitinating enzymes (Quesada et al., 2004 [PubMed 14715245]).[supplied by OMIM, Jun 2009]
Expression: Ubiquitous expression in brain (RPKM 11.8), heart (RPKM 7.4) and 23 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 4q12

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (52590960..52659301, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (56077847..56146196, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (53457126..53525468, complement)

Chromosome 4 - NC_000004.12 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 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?

The USP46 complex deubiquitylates LRP6 to promote Wnt/beta-catenin signaling.
Title: The USP46 complex deubiquitylates LRP6 to promote Wnt/β-catenin signaling.
Ubiquitin specific protease 46 potentiates triple negative breast cancer development by stabilizing PGAM1-mediated glycolysis.
Title: Ubiquitin specific protease 46 potentiates triple negative breast cancer development by stabilizing PGAM1-mediated glycolysis.
MiR-27a-3p targets USP46 to inhibit the cell proliferation of hepatocellular carcinoma.
Title: MiR-27a-3p targets USP46 to inhibit the cell proliferation of hepatocellular carcinoma.
Deubiquitinating enzyme USP46 suppresses the progression of hepatocellular carcinoma by stabilizing MST1.
Title: Deubiquitinating enzyme USP46 suppresses the progression of hepatocellular carcinoma by stabilizing MST1.
USP46 Inhibits Cell Proliferation in Lung Cancer through PHLPP1/AKT Pathway.
Title: USP46 Inhibits Cell Proliferation in Lung Cancer through PHLPP1/AKT Pathway.
Data indicate a mechanism of USP46 regulation in renal cell carcinoma (RCC), and that USP46 is a tumor suppressor in RCC via proto-oncogene protein Akt (AKT) signaling pathway inactivation.
Title: Ubiquitin-specific peptidase 46 (USP46) suppresses renal cell carcinoma tumorigenesis through AKT pathway inactivation.
The deubiquitinase USP46 is essential for proliferation and tumor growth of HPV-transformed cancers.
Title: The Deubiquitinase USP46 Is Essential for Proliferation and Tumor Growth of HPV-Transformed Cancers.
Results suggest role for USP46/USP12 in Epstein-Barr virus induced growth transformation.
Title: The EBNA3 family of Epstein-Barr virus nuclear proteins associates with the USP46/USP12 deubiquitination complexes to regulate lymphoblastoid cell line growth.
USP46-mediated stabilization of PHLPP and the subsequent inhibition of Akt.
Title: The deubiquitination enzyme USP46 functions as a tumor suppressor by controlling PHLPP-dependent attenuation of Akt signaling in colon cancer.
results suggest that the USP46 gene might play a role in the pathophysiology of major depressive disorder in the Japanese population.
Title: Possible association between ubiquitin-specific peptidase 46 gene and major depressive disorders in the Japanese population.

Submit: New GeneRIF Correction See all GeneRIFs (14)

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

EBI GWAS Catalog

Description
Genome-wide association study of biochemical traits in Korcula Island, Croatia. EBI GWAS Catalog EBI GWAS CatalogPubMed

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

SHGC-107185 (e-PCR)
- UniSTS:170272

G19858 (e-PCR)
- UniSTS:40257

A002A30 (e-PCR)
- UniSTS:40258

D7S2067E (e-PCR)
- UniSTS:151120

SHGC-8627 (e-PCR)
- UniSTS:93040

D1S1423 (e-PCR)
- UniSTS:149619

G11823 (e-PCR)
- UniSTS:7323

STS-N90897 (e-PCR)
- UniSTS:71087

SHGC-50294 (e-PCR)
- UniSTS:68299

STS-T67163 (e-PCR)
- UniSTS:15342

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
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 metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in adult feeding behavior	IEA Inferred from Electronic Annotation more info
involved_in behavioral fear response	IEA Inferred from Electronic Annotation more info
involved_in behavioral response to ethanol	IEA Inferred from Electronic Annotation more info
involved_in protein deubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in proteolysis	IEA Inferred from Electronic Annotation more info
involved_in regulation of protein stability	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of synaptic transmission, GABAergic	ISS Inferred from Sequence or Structural Similarity more info
involved_in righting reflex	IEA Inferred from Electronic Annotation more info

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 nucleus	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: ubiquitin carboxyl-terminal hydrolase 46

Names: deubiquitinating enzyme 46; ubiquitin thioesterase 46; ubiquitin thiolesterase 46; ubiquitin-specific-processing protease 46

NP_001127695.1

EC 3.4.19.12

NP_001273696.1

EC 3.4.19.12

NP_001273697.1

EC 3.4.19.12

NP_073743.2

EC 3.4.19.12

XP_047272044.1

EC 3.4.19.12

XP_054206707.1

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_001134223.2 → NP_001127695.1 ubiquitin carboxyl-terminal hydrolase 46 isoform 2

See identical proteins and their annotated locations for NP_001127695.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) contains an alternate 5'-terminal exon and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (2) has a shorter and distinct N-terminus, compared isoform 1.

Source sequence(s)

AC026448, BC037574, BP371221, BU620990

Consensus CDS

CCDS47054.1

UniProtKB/Swiss-Prot

P62068

Related

ENSP00000423244.1, ENST00000508499.5

Conserved Domains (1) summary

cd02663
Location:29 → 356

Peptidase_C19G; 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 ...
NM_001286767.2 → NP_001273696.1 ubiquitin carboxyl-terminal hydrolase 46 isoform 3

See identical proteins and their annotated locations for NP_001273696.1

Status: VALIDATED

Description

Transcript Variant: This variant (3) uses an alternate in-frame splice site in the central coding region, compared to variant 1. The encoded isoform (3) is shorter, compared to isoform 1.

Source sequence(s)

AC026448, AK299883, BC037574, CN483539

UniProtKB/Swiss-Prot

P62068

Conserved Domains (1) summary

cd02663
Location:62 → 351

Peptidase_C19G; 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 ...
NM_001286768.2 → NP_001273697.1 ubiquitin carboxyl-terminal hydrolase 46 isoform 4

See identical proteins and their annotated locations for NP_001273697.1

Status: VALIDATED

Description

Transcript Variant: This variant (4) differs in its 5' UTR and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (4) has a shorter N-terminus, compared to isoform 1.

Source sequence(s)

AC026448, AK296493, CN483539

UniProtKB/Swiss-Prot

P62068

Conserved Domains (2) summary

cl02553
Location:1 → 217

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 ...

pfam00443
Location:1 → 218

UCH; Ubiquitin carboxyl-terminal hydrolase
NM_022832.4 → NP_073743.2 ubiquitin carboxyl-terminal hydrolase 46 isoform 1

See identical proteins and their annotated locations for NP_073743.2

Status: VALIDATED

Description

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

Source sequence(s)

AC026448, BC037574, BU620990, CN483539

Consensus CDS

CCDS47053.1

UniProtKB/Swiss-Prot

B7Z3Y7, B7Z675, B7Z7S3, G8ACC7, P62068, Q80V95, Q9H7U4, Q9H9T8

Related

ENSP00000407818.2, ENST00000441222.8

Conserved Domains (1) summary

cd02663
Location:36 → 363

Peptidase_C19G; 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 ...