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DPP9

Function

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:29382749, PubMed:30291141, PubMed:33731929, PubMed:36112693). Acts as a key inhibitor of caspase-1-dependent monocyte and macrophage pyroptosis in resting cells by preventing activation of NLRP1 and CARD8 (PubMed:27820798, PubMed:29967349, PubMed:30291141, PubMed:31525884, PubMed:32796818, PubMed:36112693, PubMed:36357533). Sequesters the cleaved C-terminal part of NLRP1 and CARD8, which respectively constitute the active part of the NLRP1 and CARD8 inflammasomes, in a ternary complex, thereby preventing their oligomerization and activation (PubMed:33731929, PubMed:33731932, PubMed:34019797). The dipeptidyl peptidase activity is required to suppress NLRP1 and CARD8; however, neither NLRP1 nor CARD8 are bona fide substrates of DPP9, suggesting the existence of substrate(s) required for NLRP1 and CARD8 inhibition (PubMed:33731929).

Involvement in disease

Hatipoglu immunodeficiency syndrome

HATIS

An autosomal recessive immunologic disorder manifesting in infancy or early childhood, and characterized by failure to thrive, short stature, skin pigmentation abnormalities, pancytopenia, and susceptibility to recurrent infections.

None

The disease is caused by variants affecting the gene represented in this entry.

Sequence Similarities

Belongs to the peptidase S9B family. DPPIV subfamily.

Tissue Specificity

Ubiquitously expressed, with highest levels in liver, heart and muscle, and lowest levels in brain.

Cellular localization

Alternative names

DPRP2, DPP9, Dipeptidyl peptidase 9, DP9, Dipeptidyl peptidase IV-related protein 2, Dipeptidyl peptidase IX, Dipeptidyl peptidase-like protein 9, DPRP-2, DPP IX, DPLP9

swissprot:Q86TI2 omim:608258 entrezGene:91039