Thimet oligopeptidase (THOP1)
The protein contains 689 amino acids for an estimated molecular weight of 78840 Da.
Involved in the metabolism of neuropeptides under 20 amino acid residues long. Involved in cytoplasmic peptide degradation. Able to degrade the amyloid-beta precursor protein and generate amyloidogenic fragments. (updated: Oct. 25, 2017)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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The reference OMIM entry for this protein is 601117
Thimet oligopeptidase 1; thop1
Top
CLONING
Proteases involved in the amyloidogenic processing of amyloid precursor protein (APP; 104760) represent likely candidates for the site of mutation in a form of familial Alzheimer disease (AD2; 104310). Formation of toxic amyloid in the brain parenchyma and cerebral vasculature in Alzheimer disease requires the proteolytic release of the 39- to 43-amino acid amyloid beta peptide from its precursor, APP. Papastoitsis et al. (1994) purified and characterized a metalloprotease from human Alzheimer disease brain that was able to cleave a synthetic peptide encompassing the amino-terminus of amyloid beta peptide and generate amyloidogenic fragments from recombinant human APP. Sequence comparison revealed that this enzyme, THOP1, has high homology to the previously described rat metalloendopeptidase 24.15 (EC 3.4.24.15). The beta-secretase-like activity of the human enzyme in vitro in combination with its localization in neurons and its co-localization with APP in transport vesicles purified from rabbit optic nerve rendered this enzyme an interesting candidate for amyloidogenic processing of APP. By immunocytochemical and Western blot analysis of mouse pituitary corticotrophic cells, Garrido et al. (1999) observed a punctate distribution and variable intense nuclear staining for endogenous Thop1. Thop1 colocalized with syntaxin-6 (STX6; 603944) in the juxtanuclear region and was found in small vesicular organelles throughout the cell body, colocalizing with ACTH in some organelles.GENE FUNCTION
Most antigenic peptides presented on major histocompatibility complex (MHC) class I molecules are generated by proteasomes during protein processing. To determine if cytosolic peptidases destroy these peptides, York et al. (2003) overexpressed TOP in cells. They found that TOP overexpression reduced presentation of antigenic peptides by class I MHC molecules, but not by class II molecules, which present peptides generated in the endoplasmic reticulum and in endosomes, where TOP is not expressed. Prevention of TOP expression by small interfering RNA enhanced class I antigenic peptide presentation. York et al. (2003) concluded that TOP is involved in degrading peptides released from the proteasome and limits the extent of antigen presentation. Norman et al. (2003) showed that neurolysin (NLN; 611530) and THOP1 have endopeptidase activity and demonstrated their presence in ovine aortic and human umbilical vein endothelial cells. Both membrane and soluble THOP1 catalyzed cleavage of bradykinin at the phe5-ser6 bond, although there were other kininases active at this peptide bond.MAPPING
Using a cDNA encoding the rat Thop1 enzyme, Meckelein et al. (1996) assigned the human THOP1 gene to chromosome 19 by hybridization to DNA from human/rodent somatic cell hybrids. By fluorescence in situ hybridization, they localized the gene to 19q13.3. However, after localizing the THOP1 gene to the high-resolution cosmid contig map of human chromosome 19, Torres et al. (1998) found that the FISH mapping to 19q13.3 by Meckelein et al. (1996) was incorrect. Results of the hybridization and FISH mapping of positive clones indicated localization of THOP1 to 19p13.3, thus excluding THOP1 as a candidate gene for AD2. ... More on the omim web site
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601117 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed