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THOP1 thimet oligopeptidase 1 [ Homo sapiens (human) ]

Gene ID: 7064, updated on 3-Apr-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
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Genomic context

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Location:
19p13.3
Exon count:
15
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (2785503..2815807)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (2760790..2791094)
105.20220307 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: 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. Thimet Oligopeptidase Biochemical and Biological Significances: Past, Present, and Future Directions. Ferro ES, et al. Biomolecules, 2020 Aug 24. PMID 32847123, Free PMC Article
  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. Expression analysis of THOP1 in background liver, a prognostic predictive factor in hepatocellular carcinoma, extracted by multiarray analysis. Nomoto S, et al. Ann Surg Oncol, 2014 Jun. PMID 24604581
  4. 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
  5. 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

See all (61) 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)

Genotypes

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_2023_10

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

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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