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Literature summary for 3.4.24.15 extracted from

  • Santos, N.B.; Franco, R.D.; Camarini, R.; Munhoz, C.D.; Eichler, R.A.S.; Gewehr, M.C.F.; Reckziegel, P.; Llanos, R.P.; Dale, C.S.; Silva, V.R.O.D.; Borges, V.F.; Lima, B.H.F.; Cunha, F.Q.; Visniauskas, B.; Chagas, J.R.; Tufik, S.; Peres, F.F.; Abilio, V.C.; Florio, J.C.; Iwai, L.K.; Rioli, V.; Presoto, B.C.; Guimaraes, A.O.; Pesquero, J.B.; Bader, M.; Castro, L.M.; Ferro, E.S.
    Thimet oligopeptidase (EC 3.4.24.15) key functions suggested by knockout mice phenotype characterization (2019), Biomolecules, 9, 382 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
gene Thop1, genotyping, enzyme expression analysis Mus musculus

Protein Variants

Protein Variants Comment Organism
additional information generation of enzyme knockout mice, phenotype, detailed overview. Wild-type and THOP1-/- mice demonstrate similar basal nociceptive sensibility in the hot plate test. Analysis of a potential depressive-like phenotype of THOP1-/-. THOP1-/- animals seem to have an impairment in their memory retention process Mus musculus

Inhibitors

Inhibitors Comment Organism Structure
Pro-Ile
-
Mus musculus

Localization

Localization Comment Organism GeneOntology No. Textmining
cell surface
-
Mus musculus 9986
-
cytosol
-
Mus musculus 5829
-
extracellular the enzyme is secreted. THOP1 secretion from cultured cells has been shown to occur through an unconventional secretory pathway, and is facilitated by interaction with 14-3-3 epsilon and/or calmodulin, the process is regulated by phosphorylation of THOP1 at Ser644 Mus musculus
-
-
additional information THOP1 can be secreted or associated to the external surface of the plasma membrane to function as a neuropeptide-degrading enzyme. The amount of THOP1 found in the nucleus is inversely correlated with that found in the cytosol and associated to the cytosolic face of organelles, suggesting that the enzyme can be mobilized from one intracellular compartment to the other. Predominant intracellular localization of THOP1 Mus musculus
-
-
nucleus
-
Mus musculus 5634
-

Metals/Ions

Metals/Ions Comment Organism Structure
Zn2+ a zinc-dependent endopeptidase Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
gonadotrophin-releasing hormone + H2O Mus musculus
-
?
-
?
gonadotrophin-releasing hormone + H2O Mus musculus C57BL/6
-
?
-
?

Organism

Organism UniProt Comment Textmining
Mus musculus Q8C1A5
-
-
Mus musculus C57BL/6 Q8C1A5
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
phosphoprotein phosphorylation of THOP1 at Ser644 regulates its secretion and interaction with 14-3-3 epsilon, as well as its catalytic activity toward gonadotrophin-releasing hormone (GnRH) Mus musculus
side-chain modification THOP1's maximal enzymatic activity is maintained by partial S-glutathionylation, a mechanism that apparently triggers protein oligomerization to dimeric and trimeric catalytically inactive complexes Mus musculus

Source Tissue

Source Tissue Comment Organism Textmining
bone marrow
-
Mus musculus
-
brain
-
Mus musculus
-
endocrine gland
-
Mus musculus
-
additional information THOP1 is ubiquitously expressed in mammalian cells and tissues, and in rodents its specific activity is highest in brain, endocrine tissues, bone marrow and immune system Mus musculus
-
neuron
-
Mus musculus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
gonadotrophin-releasing hormone + H2O
-
Mus musculus ?
-
?
gonadotrophin-releasing hormone + H2O
-
Mus musculus C57BL/6 ?
-
?

Synonyms

Synonyms Comment Organism
THOP1
-
Mus musculus

General Information

General Information Comment Organism
evolution THOP1 belongs to M3 family of zinc-dependent endopeptidases Mus musculus
malfunction enzyme knockout mice, phenotype, detailed overview Mus musculus
additional information THOP1's maximal enzymatic activity is maintained by partial S-glutathionylation, a mechanism that apparently triggers protein oligomerization to dimeric and trimeric catalytically inactive complexes. Semiquantitative peptidome analyses, overview Mus musculus
physiological function THOP1 is involved in brain disorders such as depression, attention and memory retention deficits, in addition to immune-stimulated neurodegeneration and infection induced inflammation. The predominant intracellular localization of THOP1 suggests that extracellular neuropeptide and hormone degradation may not be its main biological role. THOP1 participates in antigen presentation by major histocompatibility class I (MHC I) molecules acting downstream of the proteasome. THOP1 is a rate-limiting peptidase for bradykinin inactivation in peripheral tissues Mus musculus