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    THOP1 thimet oligopeptidase 1 [ Homo sapiens (human) ]

    Gene ID: 7064, updated on 10-Dec-2024

    Summary

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    Official Symbol
    THOP1provided by HGNC
    Official Full Name
    thimet oligopeptidase 1provided by HGNC
    Primary source
    HGNC:HGNC:11793
    See related
    Ensembl:ENSG00000172009 MIM:601117; AllianceGenome:HGNC:11793
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    TOP; MP78; EP24.15; MEPD_HUMAN
    Summary
    The protein encoded by this gene is a kininase that uses zinc as a cofactor. The encoded oligopeptidase cleaves cytosolic peptides, making them unavailable for display on antigen-presenting cells. This protein also cleaves neuropeptides under 20 aa in length and can degrade beta-amyloid precursor protein to amyloidogenic peptides. [provided by RefSeq, Nov 2015]
    Expression
    Broad expression in testis (RPKM 14.1), brain (RPKM 6.4) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See THOP1 in Genome Data Viewer
    Location:
    19p13.3
    Exon count:
    15
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (2785503..2815807)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (2760790..2791094)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (2785501..2815805)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:2734868-2735368 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:2735369-2735869 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:2739111-2739378 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13716 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9805 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13717 Neighboring gene solute carrier family 39 member 3 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9806 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9807 Neighboring gene small glutamine rich tetratricopeptide repeat co-chaperone alpha Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:2768763-2769263 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13718 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9808 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13719 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9810 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9809 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:2786765-2787291 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:2787292-2787818 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13720 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:2796022-2796522 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:2820277-2820970 Neighboring gene MPRA-validated peak3238 silencer Neighboring gene zinc finger protein 554 Neighboring gene MPRA-validated peak3239 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9812 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9813 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9814 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9815 Neighboring gene zinc finger protein 555

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. Thimet oligopeptidase EC 3.4.24.15 is a major liver kininase. Molina HM, et al. Life Sci, 2000 Jun 23. PMID 10993116
    2. Expression of THOP1 and its relationship to prognosis in non-small cell lung cancer. Qi L, et al. PLoS One, 2014. PMID 25180910, Free PMC Article
    3. Recycling of the high valence States of heme proteins by cysteine residues of THIMET-oligopeptidase. Ferreira JC, et al. PLoS One, 2013. PMID 24223886, Free PMC Article
    4. Inhibition of thimet oligopeptidase by siRNA alters specific intracellular peptides and potentiates isoproterenol signal transduction. Russo LC, et al. FEBS Lett, 2012 Sep 21. PMID 22796113
    5. Analysis of intracellular substrates and products of thimet oligopeptidase in human embryonic kidney 293 cells. Berti DA, et al. J Biol Chem, 2009 May 22. PMID 19282285, Free PMC Article

    See all (68) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Expression of thimet oligopeptidase (THOP) modulated by oxidative stress in human multidrug resistant (MDR) leukemia cells.
      Title: Expression of thimet oligopeptidase (THOP) modulated by oxidative stress in human multidrug resistant (MDR) leukemia cells.
    2. Data suggest that three new candidate genes involved in the development of rheumatoid arthritis (RA): ERBB2, TP53 and THOP1.
      Title: Discovery of new candidate genes for rheumatoid arthritis through integration of genetic association data with expression pathway analysis.
    3. THOP1 may have clinical potentials to be employed as a promising biomarker to identify individuals with better prognosis and a novel antitumor agent for therapy of patients with NSCLC
      Title: Expression of THOP1 and its relationship to prognosis in non-small cell lung cancer.
    4. Low THOP1 expression levels are associated with recurrence of hepatocellular carcinoma.
      Title: Expression analysis of THOP1 in background liver, a prognostic predictive factor in hepatocellular carcinoma, extracted by multiarray analysis.
    5. TCEP. Data indicate that THIMET-oligopeptidase (TOP) oxidation by H2O2 and high valence states of hemeproteins does not lead to enzyme oligomerization.
      Title: Recycling of the high valence States of heme proteins by cysteine residues of THIMET-oligopeptidase.
    6. shear-dependent TOP induction down-regulates MHC1 levels, pointing to a role for TOP in the flow-mediated regulation of endothelial immunogenicity
      Title: Shear stress is a positive regulator of thimet oligopeptidase (EC3.4.24.15) in vascular endothelial cells: consequences for MHC1 levels.
    7. The semi-quantitative intracellular peptidome analyses of siRNA-transfected HEK293 cells shows that the levels of specific intracellular peptides are either increased or decreased upon EP24.15 inhibition.
      Title: Inhibition of thimet oligopeptidase by siRNA alters specific intracellular peptides and potentiates isoproterenol signal transduction.
    8. mediates antigen processing that generates cytotoxic T cell epitopes
      Title: Antigen processing by nardilysin and thimet oligopeptidase generates cytotoxic T cell epitopes.
    9. interaction between EP24.15 and calmodulin is regulated within cells and is important for the stimulated secretion of EP24.15 from HEK293 cells.
      Title: Interaction with calmodulin is important for the secretion of thimet oligopeptidase following stimulation.
    10. Over 100 peptides were identified in human embryonic kidney 293 (HEK293) cells that are derived from intracellular proteins; many but not all of these peptides are substrates or products of EP24.15.
      Title: Analysis of intracellular substrates and products of thimet oligopeptidase in human embryonic kidney 293 cells.
    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

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metalloendopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables metalloendopeptidase activity TAS
    Traceable Author Statement
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in peptide metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein polyubiquitination TAS
    Traceable Author Statement
    more info
    		  
    involved_in proteolysis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    is_active_in mitochondrial intermembrane space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    thimet oligopeptidase
    Names
    endopeptidase 24.15
    NP_003240.1
    XP_011526530.1
    XP_047295255.1
    XP_054177873.1
    XP_054177874.1

    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_003249.5 → NP_003240.1  thimet oligopeptidase

      See identical proteins and their annotated locations for NP_003240.1

      Status: REVIEWED

      Source sequence(s)
      AC006538, BC002391, BU741442, BU849088
      Consensus CDS
      CCDS12095.1
      UniProtKB/Swiss-Prot
      B3KSE2, P52888, Q9UCB3
      UniProtKB/TrEMBL
      Q96CV8
      Related
      ENSP00000304467.5, ENST00000307741.11
      Conserved Domains (2) summary
      cd06455
      Location:34 → 675
      M3A_TOP; Peptidase M3 Thimet oligopeptidase (TOP) also includes neurolysin
      COG0339
      Location:39 → 679
      Dcp; Zn-dependent oligopeptidase [Posttranslational modification, protein turnover, chaperones]

    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_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      2785503..2815807
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047439299.1 → XP_047295255.1  thimet oligopeptidase isoform X2

    2. XM_011528228.3 → XP_011526530.1  thimet oligopeptidase isoform X1

      UniProtKB/TrEMBL
      K7EP46
      Conserved Domains (1) summary
      cd06455
      Location:2 → 466
      M3A_TOP; Peptidase M3 Thimet oligopeptidase (TOP) also includes neurolysin

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      2760790..2791094
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054321899.1 → XP_054177874.1  thimet oligopeptidase isoform X2

    2. XM_054321898.1 → XP_054177873.1  thimet oligopeptidase isoform X1

      UniProtKB/TrEMBL
      K7EP46
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P52888.2 GenPept UniProtKB/Swiss-Prot:P52888

    Gene LinkOut

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