Leucyl-cystinyl aminopeptidase (LNPEP)
The protein contains 1025 amino acids for an estimated molecular weight of 117349 Da.
Release of an N-terminal amino acid, cleaves before cysteine, leucine as well as other amino acids. Degrades peptide hormones such as oxytocin, vasopressin and angiotensin III, and plays a role in maintaining homeostasis during pregnancy. May be involved in the inactivation of neuronal peptides in the brain. Cleaves Met-enkephalin and dynorphin. Binds angiotensin IV and may be the angiotensin IV receptor in the brain. (updated: March 4, 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.
- 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.
- 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.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| dbSNP:rs3797799 | |
| dbSNP:rs12520455 | |
| dbSNP:rs2303138 | |
| dbSNP:rs17087233 | |
| dbSNP:rs11746232 |
Biological Process
Antigen processing and presentation of exogenous peptide antigen via MHC class I
Antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent
Antigen processing and presentation of peptide antigen via MHC class I
Cell-cell signaling
Female pregnancy
Membrane organization
Negative regulation of cold-induced thermogenesis
Peptide catabolic process
Protein catabolic process
Protein polyubiquitination
Proteolysis
Regulation of blood pressure
Signal transduction
SMAD protein signal transduction
The reference OMIM entry for this protein is 151300
Leucyl-cystinyl aminopeptidase; lnpep
Leucine aminopeptidase of placenta
Oxytocinase
Insulin-responsive aminopeptidase, mouse, homolog of; irap
CLONING
Beckman et al. (1966) found 3 placental leucine aminopeptidase (LAP) types. (LAP enzymes in the serum of pregnant women probably are not derived from placenta.) Beckman et al. (1969) stated a preference for the designation amino acid naphthylamidase. The serum level of placental LAP increases during pregnancy and degrades several peptide hormones such as oxytocin (167050) and vasopressin (192340). Rogi et al. (1996) cloned a human placenta cDNA encoding leucyl-cystinyl aminopeptidase, which they symbolized PLAP. The deduced 944-amino acid polypeptide contains the HEXXH consensus sequence of zinc metallopeptidases as well as an N-terminal hydrophobic region that resembles a transmembrane domain. Northern blot analysis detected expression of 3.6-kb and 10.5-kb transcripts in placenta, heart, and skeletal muscle, and a 10.5-kb transcript in brain. Using immunohistochemistry, Nagasaka et al. (1997) localized LNPEP to syncytiotrophoblasts in placenta as well as in fetal and adult vascular endothelial cells, the epithelial lining of several organs, neurons, and sweat gland cells; adult seminal vesicles and prostate; and fetal adipocytes and skeletal muscle.GENE FUNCTION
In muscle and fat cells, insulin (INS; 176730) stimulation activates a signaling cascade that causes intracellular vesicles containing glucose transporter-4 (GLUT4, or SLC2A4; 138190) to translocate to and fuse with the plasma membrane. Using mass spectrometry, Larance et al. (2005) identified Irap as a major membrane protein associated with Glut4 vesicles in cultured mouse adipocytes. The Rab GTPase-activating protein As160 (TBC1D4; 612465), another major constituent of Glut4 vesicles, interacted directly with the cytoplasmic tail of Irap in vitro and in vivo. Since As160 dissociated from Glut4 vesicles upon insulin stimulation, Larance et al. (2005) concluded that interaction between AS160 and IRAP mediates association of AS160 with GLUT4 vesicles. Major histocompatibility complex (MHC) class I molecules present peptides, produced through cytosolic proteasomal degradation of cellular proteins, to cytotoxic T lymphocytes. In dendritic cells, the peptides can also be derived from internalized antigens through a process known as crosspresentation. Saveanu et al. (2009) identified a role for peptide trimming by IRAP in crosspresentation. In human dendritic cells, IRAP was localized to a Rab14+ endosomal storage compartment in which it interacted with MHC class I molecules. IRAP deficiency compromised crosspresentation in vitro and in vivo but did not affect endogenous presentation. Saveanu et al. (2009) proposed the existence of 2 pathways for proteasome-dependent crosspresentation in which final peptide trimming involves IRAP in endosomes and involves the related aminopeptidases in the endoplasmic reticulum.GENE STRUCTURE
Horio et al. (1999) isolated and sequenced genomic clones containing the upstream region of LNPEP and identified 4 GC-rich sequences, a TATA box, and 3 half palindromic estrogen-responsive element (ERE)-like motifs.MAPPING
By FISH, Horio et al. (1999) mapped the LNPEP gene to chromosome 5q14.2-q15.ANIMAL MODEL
Mouse Irap, a zinc-dependent membrane aminopeptidase, is the homolog of human LNPEP. Keller et al. (2002) characterized Irap-null mice with regard to glucose homeostasis and regulation of the insulin-responsive glucose transporter Glut4 (138190). Irap-null mice maintained normal glucose h ... 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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 151300 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed