Tripeptidyl-peptidase 2 (TPP2)
The protein contains 1249 amino acids for an estimated molecular weight of 138350 Da.
Component of the proteolytic cascade acting downstream of the 26S proteasome in the ubiquitin-proteasome pathway. May be able to complement the 26S proteasome function to some extent under conditions in which the latter is inhibited. Stimulates adipogenesis (By similarity). (updated: April 1, 2015)
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.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- 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.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
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 190470
Tripeptidyl peptidase ii; tpp2
CLONING
Balow et al. (1983) discovered a mammalian peptidase that, at neutral pH, removes tripeptides from the N terminus of longer peptides. Later designated tripeptidyl peptidase II, it is a high molecular mass serine exopeptidase, consisting of subunits with molecular mass 135,000. The amino acid sequence surrounding the serine residue at the active site is similar to the peptidases of the subtilisin class, whereas other mammalian serine peptidases are of the trypsin class. The enzyme has been purified from human erythrocytes. Tomkinson and Jonsson (1991) and Tomkinson (1991) isolated cDNA clones for the enzyme. The deduced amino acid sequence, 1,196 residues, shows 56% similarity between its N-terminal part and the bacterial enzyme subtilisin.GENE FUNCTION
Geier et al. (1999) reported that mouse TppII copurified with 26S proteasomes (see 603146) as a large particle. Electron microscopy displayed a rod-shaped, dynamic supramolecular structure. TppII exhibited enhanced activity in proteasome inhibitor-adapted cells and degraded polypeptides by exo- as well as predominantly trypsin-like endoproteolytic cleavage. The authors suggested that TppII may participate in extralysosomal polypeptide degradation and may in part account for nonproteasomal epitope generation as postulated for certain major histocompatibility complex class I alleles. In addition, TppII may be able to substitute for some metabolic functions of the proteasome. Seifert et al. (2003) determined that TPP2 was essential for the generation of a human immunodeficiency virus-1 (HIV-1)-Nef protein epitope in dendritic cells and did not require 20S or 26S proteasomes, which were incapable of generating the epitope in vitro. In vivo, TPP2-specific small interfering (si)RNA abrogated epitope presentation. The authors concluded that TPP2 can work in combination with or independently of the proteasome. Huai et al. (2008) generated mice lacking Tpp2, which were viable and appeared normal, but after 1 year had an aged appearance and elevated mortality. Likewise, thymic involution and thymocyte subpopulations were slightly altered in the older mutant mice. Splenic and peripheral CD8+ T cells were decreased in younger and older mice, respectively. The older mice had pronounced lymphopenia due to apoptosis of stimulated T cells. Premature cellular senescence also occurred in fibroblasts coinciding with upregulation of p53 (191170) and dysregulation of Nfkb1 (164011). Huai et al. (2008) concluded that TPP2 is important for maintaining normal cellular and systemic physiology.MAPPING
Martinsson et al. (1993) assigned the TPP2 gene to 13q32-q33 using 2 different methods: first, a full-length TTP2 cDNA was used as a probe on Southern blots of DNA from a panel of human/rodent somatic cell hybrids; and second, fluorescence in situ hybridization with the same probe defined the localization to the region stated. Bermingham et al. (1996) mapped Tpp2 to mouse chromosome 1, approximately 7 cM distal to Col3a1 (120180). ... More on the omim web site
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 190470 was added.