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    USP5 ubiquitin specific peptidase 5 (isopeptidase T) [ Homo sapiens ]

    Gene ID: 8078, updated on 11-May-2012
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    Summary

    Official Symbol
    USP5provided by HGNC
    Official Full Name
    ubiquitin specific peptidase 5 (isopeptidase T)provided by HGNC
    Primary source
    HGNC:12628
    See related
    Ensembl:ENSG00000111667; HPRD:03265; MIM:601447; Vega:OTTHUMG00000169233
    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
    Also known as
    ISOT
    Summary
    Ubiquitin (see MIM 191339)-dependent proteolysis is a complex pathway of protein metabolism implicated in such diverse cellular functions as maintenance of chromatin structure, receptor function, and degradation of abnormal proteins. A late step of the process involves disassembly of the polyubiquitin chains on degraded proteins into ubiquitin monomers. USP5 disassembles branched polyubiquitin chains by a sequential exo mechanism, starting at the proximal end of the chain (Wilkinson et al., 1995 [PubMed 7578059]).[supplied by OMIM, Mar 2010]
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    Genomic context

    Location :
    12p13
    Sequence :
    Chromosome: 12; NC_000012.11 (6961285..6975796)
    See USP5 in Epigenomics, MapViewer

    Chromosome 12 - NC_000012.11Genomic Context describing neighboring genes Neighboring gene guanine nucleotide binding protein (G protein), beta polypeptide 3 Neighboring gene cell division cycle associated 3 Neighboring gene triosephosphate isomerase 1 Neighboring gene splA/ryanodine receptor domain and SOCS box containing 2 Neighboring gene ribosomal protein L13 pseudogene 5

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. Two ZnF-UBP domains in isopeptidase T (USP5). Avvakumov GV, et al. Biochemistry, 2012 Feb 14. PMID 22283393.
    2. Domain analysis reveals that a deubiquitinating enzyme USP13 performs non-activating catalysis for Lys63-linked polyubiquitin. Zhang YH, et al. PLoS One, 2011. PMID 22216260.
    3. Activity-based chemical proteomics accelerates inhibitor development for deubiquitylating enzymes. Altun M, et al. Chem Biol, 2011 Nov 23. PMID 22118674.
    4. Proteomic analysis of the 20S proteasome (PSMA3)-interacting proteins reveals a functional link between the proteasome and mRNA metabolism. Fedorova OA, et al. Biochem Biophys Res Commun, 2011 Dec 16. PMID 22079093.
    5. Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels. Lee KA, et al. J Biol Chem, 2011 Dec 2. PMID 21987572.

    See all (42) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. USP5 uses multiple zinc fluoride (ZnF)-ubiquitin binding protein (UBP) domains for substrate targeting and core catalytic function.
      Title: Two ZnF-UBP domains in isopeptidase T (USP5).
    2. p53 is selectively stabilized because the unanchored polyubiquitin that accumulates after USP5 knockdown is able to compete with ubiquitinated p53 but not with Mdm2 for proteasomal recognition
      Title: Suppression of the deubiquitinating enzyme USP5 causes the accumulation of unanchored polyubiquitin and the activation of p53.
    3. We report the crystal structures of the zinc-finger ubiquitin binding domain (ZnF UBP) from the deubiquitinating enzyme isopeptidase T (IsoT, or USP5) alone and in complex with ubiquitin. This domain is required for optimal catalytic activation of IsoT.
      Title: The ubiquitin binding domain ZnF UBP recognizes the C-terminal diglycine motif of unanchored ubiquitin.
    4. identification of catalytic site
      Title: Further characterization of the putative human isopeptidase T catalytic site.
    5. Selective upregulation of the ubiquitin-proteasome proteolytic pathway proteins, proteasome zeta chain and isopeptidase T in fetal Down syndrome.
      Title: Selective upregulation of the ubiquitin-proteasome proteolytic pathway proteins, proteasome zeta chain and isopeptidase T in fetal Down syndrome.
    Submit: New GeneRIF Correction
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    P45974 O14641 DVL2    HPRD  PubMed  
    P45974 Q9Y3C5 RNF11    HPRD  PubMed  
    P45974 O75528 TADA3    HPRD  PubMed  
    BioGRID:113751 BioGRID:108189 DVL2    BioGRID  PubMed Two-hybrid 
    BioGRID:113751 BioGRID:111337 PLA2G2A    BioGRID  PubMed Biochemical Activity 
    BioGRID:113751 BioGRID:111391 PMS1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:113751 BioGRID:111657 PSMA3    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:113751 BioGRID:112497 SUMO2    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:113751 BioGRID:115737 TADA3    BioGRID  PubMed Affinity Capture-Western; Two-hybrid 
    BioGRID:113751 BioGRID:113041 TRAF6    BioGRID  PubMed Biochemical Activity 
    BioGRID:113751 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS; Biochemical Activity; Reconstituted Complex 
    BioGRID:113751 BioGRID:118150 UBE2S    BioGRID  PubMed Biochemical Activity 
    BioGRID:113751 BioGRID:31215 UBI4    BioGRID  PubMed Reconstituted Complex 
    BioGRID:113751 BioGRID:114465 USP13    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:113751 BioGRID:128649 USP32P2    BioGRID  PubMed Affinity Capture-MS 
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    General gene information

    Markers

    Genotypes

    Homology

    • Homologs of the USP5 gene: The USP5 gene is conserved in chimpanzee, , dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, S.cerevisiae, K.lactis, , S.pombe, , N.crassa, A.thaliana, and rice.
    • Map Viewer (Mouse, Rat)

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    cysteine-type endopeptidase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    omega peptidase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    peptidase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    ubiquitin thiolesterase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    zinc ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    positive regulation of proteasomal ubiquitin-dependent protein catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    protein K48-linked deubiquitination IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    proteolysis IEA
    Inferred from Electronic Annotation
    more info
    		  
    ubiquitin-dependent protein catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    lysosome TAS
    Traceable Author Statement
    more info
    		 PubMed 
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    General protein information

    Preferred Names
    ubiquitin carboxyl-terminal hydrolase 5
    Names
    ubiquitin carboxyl-terminal hydrolase 5
    isopeptidase T
    ubiquitin isopeptidase T
    ubiquitin thioesterase 5
    deubiquitinating enzyme 5
    ubiquitin thiolesterase 5
    ubiquitin-specific-processing protease 5
    ubiquitin specific protease 5 (isopeptidase T)
    ubiquitin-specific protease-5 (ubiquitin isopeptidase T)
    NP_001092006.1
    NP_003472.2
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    NCBI Reference Sequences (RefSeq)

    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_001098536.1 → NP_001092006.1  ubiquitin carboxyl-terminal hydrolase 5 isoform 1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and it encodes the longer protein (isoform 1).
      Source sequence(s)
      AU099996, BC005139, U47927
      Consensus CDS
      CCDS41743.1
      UniProtKB/Swiss-Prot
      P45974
      Related
      ENSP00000229268, OTTHUMP00000240481, ENST00000229268, OTTHUMT00000402982
      Conserved Domains (5) summary
      cd00194
      Location:728 – 761
      Blast Score: 133
      UBA; Ubiquitin Associated domain. The UBA domain is a commonly occurring sequence motif in some members of the ubiquitination pathway, UV excision repair proteins, and certain protein kinases. Although its specific role is so far unknown, it has been ...
      COG5207
      Location:18 – 855
      Blast Score: 942
      UBP14; Isopeptidase T [Posttranslational modification, protein turnover, chaperones]
      cd02658
      Location:327 – 598
      Blast Score: 850
      Peptidase_C19B; 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:797 – 854
      Blast Score: 280
      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 ...
      cl09957
      Location:199 – 272
      Blast Score: 226
      zf-UBP; Zn-finger in ubiquitin-hydrolases and other protein

    2. NM_003481.2 → NP_003472.2  ubiquitin carboxyl-terminal hydrolase 5 isoform 2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1, resulting in a shorter protein (isoform 2).
      Source sequence(s)
      AI289395, BC004889, CN276110
      Consensus CDS
      CCDS31733.1
      UniProtKB/Swiss-Prot
      P45974
      Related
      ENSP00000373883, OTTHUMP00000240482, ENST00000389231, OTTHUMT00000402983
      Conserved Domains (5) summary
      cd00194
      Location:705 – 738
      Blast Score: 132
      UBA; Ubiquitin Associated domain. The UBA domain is a commonly occurring sequence motif in some members of the ubiquitination pathway, UV excision repair proteins, and certain protein kinases. Although its specific role is so far unknown, it has been ...
      COG5207
      Location:18 – 832
      Blast Score: 971
      UBP14; Isopeptidase T [Posttranslational modification, protein turnover, chaperones]
      cd02658
      Location:327 – 598
      Blast Score: 851
      Peptidase_C19B; 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:774 – 831
      Blast Score: 280
      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 ...
      cl09957
      Location:199 – 272
      Blast Score: 227
      zf-UBP; Zn-finger in ubiquitin-hydrolases and other protein

    RefSeqs of Annotated Genomes: Build 37.3

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

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000012.11 Reference GRCh37.p5 Primary Assembly

      Range
      6961285..6975796
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000144.1 Alternate HuRef

      Range
      6815013..6829524
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic CH471116.2 EAW88724.1
      EAW88725.1
      EAW88726.1
      EAW88727.1
    genomic U47924.1 AAB51314.1
      AAB51315.1
    mRNA AI289395.1 None
    mRNA AK308021.1 None
    mRNA AU099996.1 None
    mRNA BC004889.2 AAH04889.1
    mRNA BC005139.2 AAH05139.1
    mRNA CN276110.1 None
    mRNA U35116.1 AAA78934.1
    mRNA U47927.1 AAC50465.1
    mRNA X91349.1 CAA62690.1
    other-genetic DQ893030.2 ABM83956.1
    other-genetic DQ896274.2 ABM87273.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    P45974.2 GenPept UniProtKB/Swiss-Prot:P45974
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    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
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