Xaa-Pro aminopeptidase 1 (XPNPEP1)
The protein contains 623 amino acids for an estimated molecular weight of 69918 Da.
Contributes to the degradation of bradykinin. Catalyzes the removal of a penultimate prolyl residue from the N-termini of peptides, such as Arg-Pro-Pro. (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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The reference OMIM entry for this protein is 602443
X-prolyl aminopeptidase 1; xpnpep1
X-prolyl aminopeptidase-like; xpnpepl
Aminopeptidase p-like
Aminopeptidase p, soluble; samp
Aminopeptidase p, cytosolic
App1
DESCRIPTION
X-prolyl aminopeptidase (EC 3.4.11.9) is a proline-specific metalloaminopeptidase that specifically catalyzes the removal of any unsubstituted N-terminal amino acid that is adjacent to a penultimate proline residue. Because of its specificity toward proline, it has been suggested that X-prolyl aminopeptidase is important in the maturation and degradation of peptide hormones, neuropeptides, and tachykinins, as well as in the digestion of otherwise resistant dietary protein fragments, thereby complementing the pancreatic peptidases. Deficiency of X-prolyl aminopeptidase results in excretion of large amounts of imino-oligopeptides in urine (Blau et al., 1988).CLONING
X-prolyl aminopeptidase has been isolated from different tissues and species. Vergas Romero et al. (1995) reported the complete amino acid sequence of the pig kidney enzyme. The nucleotide sequences of the X-prolyl aminopeptidase-encoding genes (pepP) from several microorganisms have been reported. By RT-PCR of phytohemagglutinin-stimulated lymphocyte mRNA, Vanhoof et al. (1997) isolated a novel human cDNA, named XPNPEPL, that encodes a 623-amino acid protein exhibiting 44% sequence identity and 62% sequence similarity to pig kidney X-prolyl aminopeptidase and high sequence homology to proteins in S. pombe and S. cerevisiae. Northern blot analysis indicated ubiquitous expression of XPNPEPL as a 2.7-kb transcript, with the highest expression in pancreas, followed by heart and muscle. Sprinkle et al. (2000) cloned XPNPEPL, which they termed soluble aminopeptidase P (SAMP), or XPNPEP1. They noted the presence of 4 blocks of sequences homologous to E. coli methionine aminopeptidase, which is part of the 'pita-bread fold' family. Like the bacteria enzyme, XPNPEPL contains a putative proton shuttle (residue 395) and 5 divalent metal ligands (residues 415, 426, 485, 523, and 537). Sprinkle et al. (2000) proposed that the enzyme inactivates bradykinin and is part of an intracellular kallikrein-kinin system, possibly in secretory vesicles. Cottrell et al. (2000) cloned and characterized XPNPEPL, which they designated cytosolic APP. They identified an arg residue at position 332 instead of the pro residue reported by Vanhoof et al. (1997) and determined that the cytosolic protein is 43% identical to membrane aminopeptidase P (XPNPEP2; 300145). The cytosolic enzyme lacks the hydrophobic signal sequences for an N-terminal signal peptide and a C-terminal GPI anchor found in the membrane-bound enzyme. Immunoblot analysis showed expression of a 71-kD homodimer protein capable of hydrolyzing bradykinin in a divalent cation-dependent manner, similar to XPNPEP2. The principal metal in the purified recombinant protein was manganese, at an approximately 1:1 molar ratio. Using RT-PCR, Ersahin et al. (2005) detected APP1 expression in all human tissues examined with high expression in pancreas, liver, kidney, and testis. There was fairly uniform expression in T cells, B cells, and monocytes. APP1 functions as a soluble cytosolic homodimer of about 70 kD and exhibits broad substrate specificity.GENE FUNCTION
Oh et al. (2004) described a hypothesis-driven, systems biology approach to identifying a small subset of proteins induced at the tissue-blood interface that are inherently accessible to antibodies injected intravenously. They used subcellular fractionation, subtractive proteomics, and bioinformatics to identify endothelial cell surface proteins exh ... 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 602443 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed