Xaa-Pro dipeptidase (PEPD)
The protein contains 493 amino acids for an estimated molecular weight of 54548 Da.
Splits dipeptides with a prolyl or hydroxyprolyl residue in the C-terminal position. Plays an important role in collagen metabolism because the high level of iminoacids in collagen. (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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| Variant | Description |
|---|---|
| PD | |
| PD | |
| PD | |
| dbSNP:rs2230062 | |
| dbSNP:rs17570 | |
| PD |
The reference OMIM entry for this protein is 170100
Prolidase deficiency
A number sign (#) is used with this entry because prolidase deficiency is caused by mutation in the gene encoding peptidase D (PEPD; 613230).
DESCRIPTION
Prolidase deficiency is a rare autosomal recessive multisystem disorder associated with massive imidodipeptiduria and lack of or reduced prolidase activity in erythrocytes, leukocytes, or cultured fibroblasts. The disorder is clinically heterogeneous and severity varies widely. Features include chronic, slowly healing ulcerations, mainly on the legs and feet. The ulcers are often preceded by other dermatologic manifestations that may occur anywhere and include erythematous papular eruptions, telangiectasias with pruritus and photosensitivity, impetigo-like eruptions, pruritic eczematous lesions, and necrotic papules. Mild to severe mental retardation is often a feature, and recurrent respiratory tract infections, sometimes fatal, are common. Facial dysmorphism may include low hairline and hirsutism, saddle nose, ocular hypertelorism, micrognathia, a high-arched palate, mandibular protrusion, and exophthalmos. Clinical manifestations are usually detectable after birth or in early childhood, but late-onset cases have been reported (summary by Lupi et al., 2008).CLINICAL FEATURES
Powell et al. (1974) described a patient who excreted massive amounts of glycyl-L-proline and other di- and tri-peptides containing proline. Prolidase, the enzyme known to cleave the bond between the other amino acid and proline (which is carboxyl-terminal), was found to be absent or markedly decreased in the patient's red and white cells. The mother and maternal grandfather had intermediate levels. The father was not available for study. The parents were not known to be related. The proband was a 7-year-old white male with dry, cracked erythematous palms and soles and with obesity from an early age. Mild mental retardation and 'mild diffuse demineralization' of long bones were described. Powell et al. (1975) studied 2 children with prolidase deficiency. Clinical features included chronic dermatitis, frequent infections, splenomegaly, and massive imidodipeptiduria. Powell et al. (1977) reported that chronic ear and sinus infections, chronic skin lesions, and splenomegaly were features. Sheffield et al. (1977) described an 11-year-old boy who was born of consanguineous parents and presented distinctive clinical features of recurrent skin ulceration, lymphedema, hepatosplenomegaly, and mild mental retardation. Massive amounts of dipeptides, most of which had proline or hydroxyproline as the carboxyl residue, were excreted in the urine. Glycylproline predominated. Prolidase deficiency was demonstrable in red cells, fibroblasts, and continuous lymphocyte cultures. Myara et al. (1984) stated that about 20 cases of prolidase deficiency had been reported. Dermatologic features, particularly severe leg ulcers, and mental retardation of variable severity were the main manifestations (Der Kaloustian et al., 1982). Recurrent infections might be due to a disturbance of complement component C1q, which contains a large amount of iminoacids. Most patients have an unusual facial appearance as well as splenomegaly. After gelatin ingestion, excretion of iminoacids in the urine is increased, indicating that iminoacid absorption in the intestine is not modified even though prolidase is deficient in the intestine. Freij et al. (1984) described affected brothers. Leoni et al. (1987) described prolidase deficienc ... 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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 170100 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed