Prolyl endopeptidase (PREP)
The protein contains 710 amino acids for an estimated molecular weight of 80700 Da.
Cleaves peptide bonds on the C-terminal side of prolyl residues within peptides that are up to approximately 30 amino acids long. (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.
- 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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| Variant | Description |
|---|---|
| dbSNP:rs12192054 | |
| dbSNP:rs1051484 |
The reference OMIM entry for this protein is 600400
Prolyl endopeptidase; prep
Prolyl oligopeptidase
CLONING
Prolyl endopeptidase (EC 3.4.21.26) is a large cytosolic enzyme that belongs to a distinct class of serine peptidases. The enzyme is involved in the maturation and degradation of peptide hormones and neuropeptides. PREP cleaves peptide bonds at the C-terminal side of proline residues. Its activity is confined to action on oligopeptides of less than 10 kD and it has an absolute requirement for the trans-configuration of the peptide bond preceding proline. Vanhoof et al. (1994) sequenced the human cDNA encoding prolyl endopeptidase. A complete cDNA was 2,562 nucleotides long and contained an open reading frame coding for a protein of 710 amino acids. Comparison of the sequences from human lymphocyte PREP and that of pig brain showed 97% identity. Also known as prolyl oligopeptidase, this enzyme shows sequence similarity with dipeptidyl peptidase IV (102720) and acylaminoacyl peptidase (102645) (Goossens et al., 1996).BIOCHEMICAL FEATURES
- Crystal Structure Fulop et al. (1998) reported the 1.4-angstrom resolution crystal structure of the porcine PREP enzyme. The enzyme contains a peptidase domain with an alpha/beta hydrolase fold, and its catalytic triad (ser554, his680, asp641) is covered by the central tunnel of an unusual beta propeller. This domain makes PREP an oligopeptidase by excluding large structured peptides from the active site. In this way, the propeller protects larger peptides and proteins from proteolysis in the cytosol.GENE FUNCTION
Using fluorimetric analysis of PREP and pyroglutamyl peptidase I (PGPEP1; 610694) enzyme activity in seminal fractions from fertile men and subfertile patients, Valdivia et al. (2004) showed increased specific activities of both enzymes in necrozoospermic semen (defined as having more that 50% dead spermatozoa) in comparison to normozoospermic semen. PGEP1 activity was highest in the particulate sperm fraction, whereas PREP activity was highest in the soluble sperm fraction. Valdivia et al. (2004) hypothesized that PGPEP1 and PREP may play a role in mediating sperm death by regulating the levels of thyrotropin-releasing hormone (TRH; 613879) analogs and in mediating sperm death associated with necrozoospermia.MAPPING
By fluorescence in situ hybridization, Goossens et al. (1996) mapped the PREP gene to 6q22. ... 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
Nov. 23, 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 600400 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed