DPP9
DPP9 (dipeptidyl peptidase 9) is a cytosolic and nuclear serine protease that removes N-terminal dipeptides from proteins carrying proline or alanine at position 2. It also acts as a brake on inflammasome activation in resting monocytes and macrophages. Browse Assay Genie's current range of DPP9 research reagents below, or read on for the biology behind the target.
DPP9 is a dipeptidase that cleaves N-terminal dipeptides from proteins with a Pro or Ala residue at position 2. NCBI describes post-proline dipeptidyl aminopeptidase activity, removing Xaa-Pro dipeptides from protein N-termini. In general, dipeptidyl peptidases appear to regulate the activity of their substrates, and the family has been linked to type 2 diabetes, obesity and cancer.
Beyond its catalytic role, DPP9 is a key inhibitor of caspase-1-dependent pyroptosis in resting monocytes and macrophages. It prevents activation of NLRP1 and CARD8 by sequestering the cleaved C-terminal fragment of each, which forms the active part of the respective inflammasome, in a ternary complex. This stops the fragments from oligomerising and activating. DPP9 peptidase activity is needed for this suppression, yet neither NLRP1 nor CARD8 is a bona fide substrate. This suggests that other, still unidentified substrates are required for inhibition.
The DPP9 gene encodes a member of the S9B family in clan SC of the serine proteases, in the DPPIV subfamily, and HGNC places it in the DASH family. Its activity resembles that of dipeptidyl peptidase 4 (DPP4), but it does not appear to be membrane bound. UniProt records the protein in the cytosol and the nucleus. Several transcript variants have been described but not fully characterised. The mouse ortholog is Dpp9. HGNC lists the previous name as dipeptidylpeptidase 9.
DPP9 restrains caspase-1-dependent pyroptosis in resting monocytes and macrophages by preventing NLRP1 and CARD8 activation.
DPP9 cleaves N-terminal dipeptides from proteins with Pro or Ala at position 2, and the substrates needed for NLRP1 and CARD8 inhibition remain to be identified.
DPP9 shares post-proline dipeptidyl peptidase activity with DPP4 but is not membrane bound, making it useful for comparing family members.
Dipeptidyl peptidases regulate substrate activity and have been linked to type 2 diabetes, obesity and cancer.
DPP9 is a dipeptidyl peptidase that removes N-terminal dipeptides from proteins with Pro or Ala at position 2. It also inhibits caspase-1-dependent pyroptosis in resting monocytes and macrophages by holding the cleaved parts of NLRP1 and CARD8 in a ternary complex.
No. DPP9 and DPP4 have similar post-proline dipeptidyl peptidase activity and both belong to the peptidase S9B family, DPPIV subfamily. Unlike DPP4, DPP9 does not appear to be membrane bound, and UniProt places it in the cytosol and nucleus.
Yes, the mouse ortholog is Dpp9. The human gene is in the HGNC DASH family, and HGNC lists the previous name as dipeptidylpeptidase 9. Check the datasheet of any product for its validated reactivity.
Other dipeptidyl peptidases of the DASH and wider DPP groups, relevant to protease and inflammasome research.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q86TI2; product specifications from Assay Genie datasheets.