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

    Gene ID: 64854, updated on 10-Dec-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
    mouse all
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    Genomic context

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    See USP46 in Genome Data Viewer
    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_000004.12Genomic 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. The USP46 complex deubiquitylates LRP6 to promote Wnt/β-catenin signaling. Ng VH, et al. Nat Commun, 2023 Oct 5. PMID 37798301, Free PMC Article
    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. Ubiquitin-specific peptidase 46 (USP46) suppresses renal cell carcinoma tumorigenesis through AKT pathway inactivation. Gui D, et al. Biochem Biophys Res Commun, 2019 Nov 19. PMID 31542232

    See all (57) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. WDR20 prevents hepatocellular carcinoma senescence by orchestrating the simultaneous USP12/46-mediated deubiquitination of c-Myc.
      Title: WDR20 prevents hepatocellular carcinoma senescence by orchestrating the simultaneous USP12/46-mediated deubiquitination of c-Myc.
    2. The USP46 complex deubiquitylates LRP6 to promote Wnt/beta-catenin signaling.
      Title: The USP46 complex deubiquitylates LRP6 to promote Wnt/β-catenin signaling.
    3. 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.
    4. 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.
    5. 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.
    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)

    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 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
    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_2024_08

    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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