This gene encodes a protein that is a member of the S9B family in clan SC of the serine proteases. The protein has been shown to have post-proline dipeptidyl aminopeptidase activity, cleaving Xaa-Pro dipeptides from the N-termini of proteins. Although the activity of this protein is similar to that of dipeptidyl peptidase 4 (DPP4), it does not appear to be membrane bound.
In general, dipeptidyl peptidases appear to be involved in the regulation of the activity of their substrates and have been linked to a variety of diseases including type 2 diabetes, obesity and cancer. Several transcript variants of this gene have been described but not fully characterized.[5] More specifically, DPP9 interacts with the NLRP1 protein and affects the level of activation of the NLRP1 inflammasome. This function involves binding to a complex of full-length NLRP1 and a proinflammatory fragment of NLRP1 after activation by autocleavage.[6][7] A similar mechanism allows DPP9 to regulate the CARD8 inflammasome.[8]
This gene has also been linked to severe COVID-19.
Mutations in NLRP1 that block DPP9 interaction lead to a rare Mendelian condition called Autoinflammation with Arthritis and Dyskeratosis[9][10] A homozygous recessive syndrome dubbed Hatipoğlu syndrome is attributed to mutations in DPP9 with a phenotype of failure to thrive, skin manifestations, pancytopenia, and susceptibility to infections.[11] Genetic analysis of knockout alleles of DPP9 in mice and zebrafish showed a severe phenotype that could be rescued by mutation of NLPR1 in the same report.
Olsen C, Wagtmann N (October 2002). "Identification and characterization of human DPP9, a novel homologue of dipeptidyl peptidase IV". Gene. 299 (1–2): 185–193. doi:10.1016/S0378-1119(02)01059-4. PMID12459266.
Ajami K, Abbott CA, Obradovic M, Gysbers V, Kähne T, McCaughan GW, Gorrell MD (January 2003). "Structural requirements for catalysis, expression, and dimerization in the CD26/DPIV gene family". Biochemistry. 42 (3): 694–701. doi:10.1021/bi026846s. PMID12534281.
Ajami K, Abbott CA, McCaughan GW, Gorrell MD (July 2004). "Dipeptidyl peptidase 9 has two forms, a broad tissue distribution, cytoplasmic localization and DPIV-like peptidase activity". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1679 (1): 18–28. doi:10.1016/j.bbaexp.2004.03.010. PMID15245913.
Ogasawara W, Tanaka C, Suzuki M, Kobayashi G, Ogawa Y, Okada H, Morikawa Y (June 2005). "Isoforms of dipeptidyl aminopeptidase IV from Pseudomonas sp. WO24: role of the signal sequence and overexpression in Escherichia coli". Protein Expression and Purification. 41 (2): 241–251. doi:10.1016/j.pep.2004.10.027. PMID15866709.
Yu DM, Wang XM, Ajami K, McCaughan GW, Gorrell MD (2006). "DP8 and DP9 have extra-enzymatic roles in cell adhesion, migration and apoptosis". Dipeptidyl Aminopeptidases. Advances in Experimental Medicine and Biology. Vol. 575. pp. 63–72. doi:10.1007/0-387-32824-6_7. ISBN978-0-387-29058-4. PMID16700509.
