Thop1 thimet oligopeptidase 1 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Thop1provided by RGD
Official Full Name: thimet oligopeptidase 1provided by RGD
Primary source: RGD:68330
See related: Ensembl:ENSRNOG00000019924 AllianceGenome:RGD:68330
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: EP24.15
Summary: Enables peptidase activity and peptide binding activity. Predicted to be involved in peptide metabolic process and proteolysis. Predicted to act upstream of or within intracellular signal transduction. Predicted to be active in mitochondrial intermembrane space. Orthologous to human THOP1 (thimet oligopeptidase 1). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in Testes (RPKM 451.0), Brain (RPKM 80.0) and 9 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 7q11

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	7	NC_086025.1 (9283617..9295957, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	7	NC_051342.1 (8632911..8645339, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	7	NC_005106.4 (11501145..11513576, complement)

Chromosome 7 - NC_086025.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Coincubation of Kiss1 and EP24.15 demonstrated multiple cleavages of the peptide in vitro. immunohistochemistry indicated coexpression of EP24.15 and Kiss1, implicating that the regulation of Kiss1 by EP24.15 could occur in vivo.
Title: EP24.15 as a Potential Regulator of Kisspeptin Within the Neuroendocrine Hypothalamus.
we show that Ang-(1-7) is the main metabolite of angiotensin I in rat hippocampi, and, strikingly, that thimet oligopeptidase is the main enzyme involved in the generation of Ang-(1-7).
Title: Angiotensin II-independent angiotensin-(1-7) formation in rat hippocampus: involvement of thimet oligopeptidase.
TOP changes in the brain could play important role in the balance of neuropeptide level correlated with cocaine effects.
Title: Acute cocaine treatment increases thimet oligopeptidase in the striatum of rat brain.
increase in THOP1 expression might be part of a compensatory defense mechanism of the brain against an increased Abeta load
Title: Increased expression of the oligopeptidase THOP1 is a neuroprotective response to Abeta toxicity.
this is the first evidence of an in vivo role for EP 24.15 in brain function, specifically in regulating alterations in microvessel permeability induced by exogenous bradykinin
Title: Metalloendopeptidases EC 3.4.24.15/16 regulate bradykinin activity in the cerebral microvasculature.
PTZ-induced seizures of the rats activates NMDA receptors, then decrease thimet oligopeptidase enzyme activity and immunoreactivity in hippocampal neurons.
Title: Pentylenetetrazol-induced seizures affect the levels of prolyl oligopeptidase, thimet oligopeptidase and glial proteins in rat brain regions, and attenuation by MK-801 pretreatment.
Analysis of transcription factors binding to promoter consensus sequences of the thimet oligopeptidase gene. Gene expression is differentially regulated in neuroendocrine and spermatid cell lines.
Title: Thimet oligopeptidase expression is differentially regulated in neuroendocrine and spermatid cell lines by transcription factor binding to SRY (sex-determining region Y), CAAT and CREB (cAMP-response-element-binding protein) promoter consensus sequences.
Data report mapping of the positions of the 224 surface residues that differ in sequence between thimet oligopeptidase and neurolysin onto the surface of the neurolysin crystal structure.
Title: Mapping sequence differences between thimet oligopeptidase and neurolysin implicates key residues in substrate recognition.
together, these data demonstrate that EP24.15/16 modulate intracellular, peptidergic signaling cascades through B2R in a physiologically relevant nociceptive system.
Title: Modulation of bradykinin signaling by EP24.15 and EP24.16 in cultured trigeminal ganglia.
data suggest that calcium may be an important modulator of ep24.15 cell function
Title: Calcium modulates endopeptidase 24.15 (EC 3.4.24.15) membrane association, secondary structure and substrate specificity.

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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

D7Wox43 (e-PCR)
- UniSTS:518694

UniSTS:236402 (e-PCR)
- UniSTS:236402

Gene Ontology Provided by RGD

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	IEA Inferred from Electronic Annotation more info
enables metalloendopeptidase activity	ISO Inferred from Sequence Orthology more info
enables metalloendopeptidase activity	TAS Traceable Author Statement more info	PubMed
enables peptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables peptide binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
acts_upstream_of_or_within intracellular signal transduction	ISO Inferred from Sequence Orthology more info
involved_in peptide catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in peptide metabolic process	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within peptide metabolic process	ISO Inferred from Sequence Orthology more info
involved_in proteolysis	IBA Inferred from Biological aspect of Ancestor more info
involved_in proteolysis	IEA Inferred from Electronic Annotation more info
involved_in proteolysis	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	IEA Inferred from Electronic Annotation 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: PZ-peptidase; endo-oligopeptidase A; endopeptidase 24.15; metalloendopeptidase; soluble metallo-endopeptidase

NP_742072.2

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_172075.2 → NP_742072.2 thimet oligopeptidase

See identical proteins and their annotated locations for NP_742072.2

Status: VALIDATED

Source sequence(s)

BC081706, CB780843

UniProtKB/Swiss-Prot

P24155, Q66HS4

UniProtKB/TrEMBL

A0A0G2KAW4, A6K8C9

Related

ENSRNOP00000027045.5, ENSRNOT00000027045.7

Conserved Domains (2) summary

cd06455
Location:35 → 675

M3A_TOP; Peptidase M3 Thimet oligopeptidase (TOP) also includes neurolysin

COG0339
Location:37 → 679

Dcp; Zn-dependent oligopeptidase [Posttranslational modification, protein turnover, chaperones]