Aminopeptidase N (ANPEP)
The protein contains 967 amino acids for an estimated molecular weight of 109540 Da.
Broad specificity aminopeptidase which plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. Also involved in the processing of various peptides including peptide hormones, such as angiotensin III and IV, neuropeptides, and chemokines. May also be involved the cleavage of peptides bound to major histocompatibility complex class II molecules of antigen presenting cells. May have a role in angiogenesis and promote cholesterol crystallization. May have a role in amino acid transport by acting as binding partner of amino acid transporter SLC6A19 and regulating its activity (By similarity).', '(Microbial infection) Acts as a receptor for human coronavirus 229E/HCoV-229E. In case of human coronavirus 229E (HCoV-229E) infection, serves as receptor for HCoV-229E spike glycoprotein.', '(Microbial infection) Mediates as well Human cytomegalovirus (HCMV) infection. (updated: July 31, 2019)
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.
- 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.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.
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No binding partner found
Biological Process
Angiogenesis
Angiotensin maturation
Cell differentiation
Cell-cell signaling
Cellular protein metabolic process
Neutrophil degranulation
Peptide catabolic process
Proteolysis
Regulation of blood pressure
Signal transduction
Cellular Component
Cytoplasm
Cytosol
Endoplasmic reticulum-Golgi intermediate compartment
External side of plasma membrane
Extracellular exosome
Extracellular space
Integral component of membrane
Integral component of plasma membrane
Lysosomal membrane
Nucleus
Plasma membrane
Secretory granule membrane
The reference OMIM entry for this protein is 151530
Alanyl aminopeptidase; anpep
Aminopeptidase n; pepn
Cd13 antigen; cd13
Leukocyte surface antigen gp150; gp150
DESCRIPTION
Alanyl aminopeptidase, or aminopeptidase N (EC 3.4.11.2), is located in the small intestinal and renal microvillar membrane, as well as in other plasma membranes. In small intestine, it plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases (Kruse et al., 1988). Aminopeptidase N is also a potent angiogenic regulator (Petrovic et al., 2007).CLONING
A surface antigen glycoprotein of about 150 kD, GP150, is recognized by monoclonal antibodies MY7 and MCS2. Look et al. (1986) isolated the complete GP150 gene, or ANPEP, from a human placenta genomic library. Look et al. (1989) determined the complete primary structure of GP150, or CD13. The predicted 967-amino acid integral membrane protein has a 24-amino acid hydrophobic segment near its N terminus. Sequence analysis indicated that the hydrophobic segment is not cleaved, but rather serves as both a signal for membrane insertion and as a stable membrane-spanning segment. The remainder of the molecule consists of a large extracellular C-terminal domain that contains a pentapeptide consensus sequence characteristic of members of the zinc-binding metalloproteinase superfamily. Sequence comparisons with enzymes of this class showed that CD13 is identical to aminopeptidase N, an enzyme thought to be involved in metabolism of regulatory peptides by diverse cell types, including small intestinal and renal tubular epithelial cells, macrophages, granulocytes, and synaptic membranes from the central nervous system.GENE FUNCTION
Delmas et al. (1992) showed that aminopeptidase N acts as a receptor for the transmissible gastroenteritis virus (TGEV), a major pathogen causing fatal diarrhea in newborn pigs. Yeager et al. (1992) showed that human aminopeptidase N is a receptor for one strain of human coronavirus that is an important cause of upper respiratory tract infections. Wisner et al. (2006) showed that opiorphin, an analgesic pentapeptide originating from PROL1 (608936), was a physiologic inhibitor of neutral ecto-endopeptidase (MME; 120520) and ecto-aminopeptidase N. Using fluorescence microscopy and a matrigel invasion assay, Petrovic et al. (2007) showed that CD13 was required for endothelial cell invasion in response to bradykinin. Inhibition of CD13 abrogated internalization of bradykinin receptor B2 (BDKRB2; 113503) and reduced endothelial cell motility. Membrane disruption experiments indicated that CD13 was necessary for membrane integrity and membrane protein organization.MAPPING
By study of somatic cell hybrid DNA and by in situ hybridization, Look et al. (1986) assigned the GP150 gene to chromosome 15q25-q26. This chromosomal location coincides with that of the oncogene FES (190030), which is also expressed in myeloid cells. Like FES, GP150 is distal to the breakpoint in t(15;17)(q22;q21.1) of acute promyelocytic leukemia. By analysis of mouse-human somatic cell hybrids, Watt and Willard (1990) assigned the ANPEP gene, which they called PEPN, to chromosome 15q11-qter. With a genomic DNA probe, they detected a frequent DraIII polymorphism useful as a marker for human chromosome 15. By probing DNA from rodent-human cell hybrids with cDNA, Kruse et al. (1988) demonstrated that the ANPEP gene is located on chromosome 15q13-qter. Kruse et al. (1988) stated that ANPEP is identical to peptidase E in the A-B-C-D-E-S system of nomenclature; however, PEPE has been mapped to c ... More on the omim web site
Aug. 19, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
April 12, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 5, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
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 151530 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed