THOP1 thimet oligopeptidase 1 [Homo sapiens (human)] - Gene

Summary

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

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_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
mediates antigen processing that generates cytotoxic T cell epitopes
Title: Antigen processing by nardilysin and thimet oligopeptidase generates cytotoxic T cell epitopes.
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.
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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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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

EC 3.4.24.15

XP_011526530.1

EC 3.4.24.15

XP_047295255.1

EC 3.4.24.15

XP_054177873.1

EC 3.4.24.15

XP_054177874.1

EC 3.4.24.15

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)

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

NC_000019.10 Reference GRCh38.p14 Primary Assembly

Range

2785503..2815807

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047439299.1 → XP_047295255.1 thimet oligopeptidase isoform X2
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

NC_060943.1 Alternate T2T-CHM13v2.0

Range

2760790..2791094

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054321899.1 → XP_054177874.1 thimet oligopeptidase isoform X2
XM_054321898.1 → XP_054177873.1 thimet oligopeptidase isoform X1

UniProtKB/TrEMBL

K7EP46