Cytosolic non-specific dipeptidase (CNDP2)
The protein contains 475 amino acids for an estimated molecular weight of 52878 Da.
Hydrolyzes a variety of dipeptides including L-carnosine but has a strong preference for Cys-Gly (PubMed:19346245). Acts as a functional tumor suppressor in gastric cancer via activation of the mitogen-activated protein kinase (MAPK) pathway. An elevated level of CNDP2 activates the p38 and JNK MAPK pathways to induce cell apoptosis, and a lower level of CNDP2 activates the ERK MAPK pathway to promote cell proliferation (PubMed:24395568). Isoform 2 may play a role as tumor suppressor in hepatocellular carcinoma (HCC) cells (PubMed:17121880). Catalyzes the production of N-lactoyl-amino acids from lactate and amino acids by reverse proteolysis (PubMed:25964343). (updated: Sept. 27, 2017)
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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| Variant | Description |
|---|---|
| dbSNP:rs2278161 |
The reference OMIM entry for this protein is 169800
Peptidase a; pepa
Carnosinase 2; cn2
Cndp2
Nonspecific dipeptidase, cytosolic
Carnosinase, tissue
DESCRIPTION
CNDP2, also known as tissue carnosinase and peptidase A (EC 3.4.13.18), is a nonspecific dipeptidase rather than a selective carnosinase (Teufel et al., 2003).CLONING
Lewis et al. (1968) identified genetically variable peptidases determined by alleles at 2 separate and not closely linked structural loci, PEPA and PEPB (169900). The peptidases were present in red cells. Teufel et al. (2003) assembled overlapping ESTs derived from human brain cDNA libraries to obtain full-length CN2. The deduced 473-amino acid protein has a calculated molecular mass of 52.9 kD. CN2 contains essential histidine and carboxyl residues in the metal-binding site, as well as 3 N-glycosylation sites. CN2 shares 49% amino acid identity with CN1 (CNDP1; 609064), but it lacks the N-terminal signal sequence found in CN1. mRNA dot blot analysis detected CN2 expression in all adult and fetal tissues examined. Western blot analysis detected widespread protein expression. Highest levels were in kidney and liver, with lower levels in brain, spleen, ovary, testis, lung, and pancreas. No protein expression was found in heart. Size-exclusion chromatography indicated that purified recombinant CN2 created a homodimer of 90 kD. The monomer migrated at 54 kD, as indicated by SDS-PAGE.GENE FUNCTION
Lewis et al. (1968) showed that PEPA and PEPB were capable of hydrolyzing di- and tripeptides. Teufel et al. (2003) found carnosinase activity in the cytoplasmic fraction of CN2-transfected Chinese hamster ovary cells. Strong carnosine degradation was found at the nonphysiologic pH of 9.5. Carnosine degradation was increased 5-fold in the presence of 0.1 mM Mn(2+). CN2 did not hydrolyze carnosine at pH 7.5. In the presence of Mn(2+), CN2 degraded pro-ala and ser-gln at pH 7.5. However, the velocity of pro-ala degradation was higher at pH 9.5. CN2 also degraded leu-his, ser-his, and tyr-his, but it did not hydrolyze homocarnosine.MAPPING
Lewis and Harris (1969) stated that peptidases A, B, C (170000), and D (613230) are products of separate gene loci and that E (170200) probably is also. Cook et al. (1972) found no sign of close linkage of peptidases A, B, C and D. There were 'hints' of linkage between PEPB and Gm (see 147100), between PEPC and Rh (111700), and between PEPD, Lutheran (111200), and secretor (182100). The second is noteworthy because of the assignment of both PEPC and Rh to chromosome 1. By analysis of mouse-human somatic cell hybrids, Creagan et al. (1973) concluded that the structural locus for peptidase A is on chromosome 18. Arthur et al. (1975) presented evidence to narrow the localization to chromosome 18q23. In the cell line with the ring(18) from a patient with ring(18) mosaicism, Rocchi et al. (1984) found that the level of PEPA was 55% of that in the 46,XX line from the same patient. Namba et al. (1988) showed dosage effect in 2 patients with trisomy 18.MOLECULAR GENETICS
Data on gene frequencies of allelic variants were tabulated by Roychoudhury and Nei (1988). ... More on the omim web site
Feb. 10, 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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 169800 was added.