Cloned (Comment) | Organism |
---|---|
gene Thop1, genotyping, enzyme expression analysis | Mus musculus |
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 | Comment | Organism | Structure |
---|---|---|---|
Pro-Ile | - |
Mus musculus |
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 | Comment | Organism | Structure |
---|---|---|---|
Zn2+ | a zinc-dependent endopeptidase | Mus musculus |
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 | UniProt | Comment | Textmining |
---|---|---|---|
Mus musculus | Q8C1A5 | - |
- |
Mus musculus C57BL/6 | Q8C1A5 | - |
- |
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 | 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 | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
gonadotrophin-releasing hormone + H2O | - |
Mus musculus | ? | - |
? | |
gonadotrophin-releasing hormone + H2O | - |
Mus musculus C57BL/6 | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
THOP1 | - |
Mus musculus |
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 |