Acylamino-acid-releasing enzyme (APEH)
The protein contains 732 amino acids for an estimated molecular weight of 81225 Da.
This enzyme catalyzes the hydrolysis of the N-terminal peptide bond of an N-acetylated peptide to generate an N-acetylated amino acid and a peptide with a free N-terminus. It preferentially cleaves off Ac-Ala, Ac-Met and Ac-Ser. (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.
- 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.
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.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| dbSNP:rs3816877 |
Biological Process
Amyloid-beta metabolic process
Neutrophil degranulation
Proteolysis
Translational termination
The reference OMIM entry for this protein is 102645
Acylpeptide hydrolase; aph
N-acylaminoacylpeptide hydrolase; apeh
CLONING
Naylor et al. (1989) showed that the DNF15S2 locus is transcribed in normal lung and in small cell lung cancer. They presented the sequence of the gene. They pointed out that the activity of aminoacylase-1, which is encoded by the ACY1 gene located at 3p21 (104620), was lacking in the same small cell lung cancer cell line that lacked DNF15S1. Jones et al. (1991) pointed out an 87% identity between the cDNA sequence that encodes acylpeptide hydrolase from porcine liver (Mitta et al., 1989) and the cDNA transcribed from DNF15S2 (Naylor et al., 1989).GENE FUNCTION
Acylpeptide hydrolase (EC 3.4.19.1) catalyzes the hydrolysis of the terminal acetylated amino acid preferentially from small acetylated peptides. The acetylamino acid formed by acylpeptide hydrolase is further processed to acetate and a free amino acid by an aminoacylase. The substrates for the acylpeptide hydrolase and the acylase behave in a reciprocal manner since acylpeptide hydrolase binds but does not process acetylamino acids and the acylase binds acetylpeptides but does not hydrolyze them; however, the 2 enzymes share the same specificity for the acyl group. All of these findings indicate common functional features in the protein structures of the 2 enzymes, which are encoded by the same region of human chromosome 3, namely, 3p21. Jones et al. (1991) suggested that there may be a relationship between the expression of these 2 enzymes and acetylated peptide growth factors in some carcinomas. A polymorphic locus, D3S94, previously localized to 3pter-p14.2 (Kiousis et al., 1989), contains 2 CpG islands and sequences conserved in the hamster and mouse. Ginzinger et al. (1992) isolated cDNAs homologous to the conserved fragments and found 96% sequence similarity to a cDNA derived from the DNF15S2 locus. Furthermore, the sequence of cDNAs derived from both the rat and pig acylpeptide hydrolase showed a high degree of sequence similarity to cDNAs derived from D3S94 and DNF15S2, suggesting that they are all the same locus.NOMENCLATURE
The locus on 3p21 formerly called DNF15S2 and now symbolized APH is known to have 2 polymorphic sites, both detectable with HindIII (Carritt et al., 1986; Goode et al., 1986). (This locus was labeled DNF15S2 by HGM9 in Paris in 1987, D3F15S2E by HGM10 in New Haven in 1989, and D3F15S2 by HGM10.5 in Oxford in 1990.)MAPPING
Harper and Saunders (1981) mapped a probe called lambda-H3 to chromosome 1 by in situ hybridization. This was subsequently called D1S1. Further studies by Carritt et al. (1986) and Goode et al. (1986) indicated that this single-copy sequence actually originated from chromosome 3 and that several homologous sequences were located on chromosome 1. The locus on chromosome 3 was designated DNF15S2 and the locus on chromosome 1 was designated DNF15S1. The DNF15S2 locus was shown to have a high rate of allele loss in both small cell lung cancer and renal cell carcinoma. Naylor et al. (1989) showed that the DNF15S2 locus is located at 3p21. Ginzinger et al. (1992) mapped the DNF15S2 locus to chromosome 3p21.3 by fluorescence in situ hybridization (FISH). ACY1 and APH map to slightly different regions of 3p, 3p21.1 and 3p21.3, respectively. Using pulsed field gel electrophoresis, Boldog et al. (1989) showed that the DNF15S2 locus is not linked to D3S2; since D3S2 is within the same 2.5-Mb region as ACY1, it is likely that ACY1 and APH are not closely linked physically. The homologous g ... 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 102645 was added.