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

Gene ID: 64854, updated on 5-Mar-2024

Summary

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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
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Genomic context

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Location:
4q12
Exon count:
11
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (52590960..52659301, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (56077847..56146196, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (53457126..53525468, complement)

Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene RNA, U6 small nuclear 1252, pseudogene Neighboring gene small nucleolar RNA U13 Neighboring gene ReSE screen-validated silencer GRCh37_chr4:53427991-53428218 Neighboring gene NANOG hESC enhancer GRCh37_chr4:53434310-53435021 Neighboring gene ReSE screen-validated silencer GRCh37_chr4:53505773-53506003 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21554 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21555 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15423 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15424 Neighboring gene USP46 divergent transcript Neighboring gene ReSE screen-validated silencer GRCh37_chr4:53578367-53579200 Neighboring gene microRNA 4449 Neighboring gene differentiation antagonizing non-protein coding RNA

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. Ubiquitin specific protease 46 potentiates triple negative breast cancer development by stabilizing PGAM1-mediated glycolysis. Ke L, et al. Cell Biol Int, 2023 Jan. PMID 36335636
  2. The Deubiquitinase USP46 Is Essential for Proliferation and Tumor Growth of HPV-Transformed Cancers. Kiran S, et al. Mol Cell, 2018 Dec 6. PMID 30415951, Free PMC Article
  3. Possible association between ubiquitin-specific peptidase 46 gene and major depressive disorders in the Japanese population. Fukuo Y, et al. J Affect Disord, 2011 Sep. PMID 21663972
  4. Association study of ubiquitin-specific peptidase 46 (USP46) with bipolar disorder and schizophrenia in a Japanese population. Kushima I, et al. J Hum Genet, 2010 Mar. PMID 20111060
  5. MiR-27a-3p targets USP46 to inhibit the cell proliferation of hepatocellular carcinoma. Wen M, et al. Chem Biol Drug Des, 2022 Aug. PMID 35637630

See all (53) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. The USP46 complex deubiquitylates LRP6 to promote Wnt/beta-catenin signaling.
    Title: The USP46 complex deubiquitylates LRP6 to promote Wnt/β-catenin signaling.
  2. 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.
  3. 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.
  4. 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.
  5. Downregulated expression levels of USP46 promote the resistance of ovarian cancer to cisplatin and are regulated by PUM2.
    Title: Downregulated expression levels of USP46 promote the resistance of ovarian cancer to cisplatin and are regulated by PUM2.
  6. USP46 Inhibits Cell Proliferation in Lung Cancer through PHLPP1/AKT Pathway.
    Title: USP46 Inhibits Cell Proliferation in Lung Cancer through PHLPP1/AKT Pathway.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
Submit: New GeneRIF Correction See all GeneRIFs (15)

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ11850, FLJ12552, FLJ14283, FLJ39393

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 IBA
Inferred from Biological aspect of Ancestor
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 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
NP_001273696.1
NP_001273697.1
NP_073743.2
XP_047272044.1
XP_054206707.1

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)

  1. 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 ...

  2. 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 ...

  3. 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

  4. 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 ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000004.12 Reference GRCh38.p14 Primary Assembly

    Range
    52590960..52659301 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047416088.1 → XP_047272044.1  ubiquitin carboxyl-terminal hydrolase 46 isoform X1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060928.1 Alternate T2T-CHM13v2.0

    Range
    56077847..56146196 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054350732.1 → XP_054206707.1  ubiquitin carboxyl-terminal hydrolase 46 isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P62068.1 GenPept UniProtKB/Swiss-Prot:P62068

Gene LinkOut

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