Dipeptidyl peptidase 9 (DPP9)
The protein contains 863 amino acids for an estimated molecular weight of 98263 Da.
Dipeptidyl peptidase that cleaves off N-terminal dipeptides from proteins having a Pro or Ala residue at position 2 (PubMed:12662155, PubMed:16475979, PubMed:19667070, PubMed:30291141, PubMed:29382749). Acts as an inhibitor of caspase-1-dependent monocyte and macrophage pyroptosis: inhibits pyroptosis by preventing activation of NLRP1 and CARD8 via an unknown mechanism (PubMed:27820798, PubMed:30291141, PubMed:29967349, PubMed:31525884, PubMed:32796818). (updated: June 2, 2021)
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.
- 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.
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Biological Process
The reference OMIM entry for this protein is 608258
Dipeptidyl peptidase ix; dpp9
Dipeptidyl peptidase iv-related protein 2; dprp2
CLONING
By searching an EST database for sequences similar to the catalytic domain of DPP4 (102720), followed by PCR and 5-prime RACE of skeletal muscle and chronic myelogenous leukemia (K-562) cell line cDNA libraries, Olsen and Wagtmann (2002) cloned DPP9. The deduced 863-amino acid protein has a calculated molecular mass of about 98 kD. An alternatively spliced transcript cloned from the K-562 cell line cDNA library lacks exon 2 in the 5-prime untranslated region and encodes the same deduced protein. Use of an alternate start codon would result in a DPP9 protein with 29 more amino acids. DPP9 contains an active-site serine protease motif (GWSYG) and 2 N-glycosylation sites. The order and spacing of the serine, aspartic acid, and histidine residues that form the catalytic triad in DPP9 are conserved with DPP4. DPP9 lacks an N-terminal signal sequence and transmembrane domain. It shares 58% amino acid identity with DPP8 (606879) and 92% identity with mouse Dpp9. Northern blot analysis detected ubiquitous expression of a 4.4-kb transcript. Highest expression was in skeletal muscle, heart, and liver, and lowest expression was in brain. Western blot analysis detected expression of DPP9 in all cell lines examined, including a T-lymphoblastoid cell line that does not express DPP4. In vitro translation resulted in a soluble protein with an apparent molecular mass of 98 kD by SDS-PAGE. By PCR, Qi et al. (2003) cloned DPP9 from a colon cDNA library. DPP9 shares 19% amino acid identity with DPP4, with the greatest similarity in the C-terminal sequences. It shares 20% amino acid identity with DPP10 (608209). Northern blot analysis revealed ubiquitous expression of a 4.5-kb transcript, with highest expression in liver and muscle. Transcripts of 5.0 and 1.4 kb were also found in liver. Western blot analysis detected recombinant DPP9 expressed as a cytosolic protein of 100 kD.GENE FUNCTION
By biochemical analysis using several synthetic peptides, Qi et al. (2003) determined that DPP9 and DPP8 showed prolyl oligopeptidase activity similar to that displayed by DPP4. Maximum activity was measured between pH 7.5 and 8.5. Activity was inhibited by broad serine protease inhibitors, but not by aprotinin, which is specific for trypsin-like serine proteases.GENE STRUCTURE
Olsen and Wagtmann (2002) determined that the DPP9 gene contains 22 exons and spans 48.7 kb. The promoter region has features typical for promoters of housekeeping genes, namely a high GC content, multiple sites for initiation of transcription, and lack of a TATAA box.MAPPING
By genomic sequence analysis, Olsen and Wagtmann (2002) mapped the DPP9 gene to chromosome 19p13.3. They mapped the mouse Dpp9 gene to a region of mouse chromosome 17 that shows homology of synteny with human chromosome 19p13.3. ... More on the omim web site
July 1, 2021: 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 608258 was added.