DPP9

Dipeptidyl peptidase 9 is an enzyme that in humans is encoded by the DPP9 gene.^[5]

DPP9
Identifiers
Aliases	DPP9, DP9, DPLP9, DPRP-2, DPRP2, dipeptidyl peptidase 9, DPP IX
External IDs	OMIM: 608258; MGI: 2443967; HomoloGene: 16385; GeneCards: DPP9; OMA:DPP9 - orthologs
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19p13.3 Start 4,675,224 bp[1] End 4,724,673 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17|17 D Start 56,493,807 bp[2] End 56,525,905 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gastrocnemius muscle muscle of thigh right lobe of liver granulocyte pancreatic ductal cell appendix upper lobe of left lung mucosa of transverse colon epithelium of colon apex of heart Top expressed in interventricular septum islet of Langerhans muscle of thigh internal carotid artery Rostral migratory stream lacrimal gland knee joint external carotid artery primary visual cortex skeletal muscle tissue More reference expression data BioGPS n/a
Gene ontology Molecular function peptidase activity serine-type peptidase activity aminopeptidase activity hydrolase activity identical protein binding Cellular component nucleus cytoplasm cytosol Biological process proteolysis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 91039 224897 Ensembl ENSG00000142002 ENSMUSG00000001229 UniProt Q86TI2 Q8BVG4 RefSeq (mRNA) NM_139159 NM_001365987 NM_172624 NM_001360284 RefSeq (protein) NP_631898 NP_001352916 NP_766212 NP_001347213 Location (UCSC) Chr 19: 4.68 – 4.72 Mb Chr 17: 56.49 – 56.53 Mb PubMed search [3] [4]
Wikidata
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Function

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]

Animal studies

Genetic analysis of knockout alleles of DPP9 in mice and zebrafish showed a severe phenotype that could be rescued by mutation of NLPR1.^[9]

Clinical significance

Mutations in NLRP1 that block DPP9 interaction lead to a rare Mendelian condition called Autoinflammation with Arthritis and Dyskeratosis^[10][11] 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.^[9]

This gene has also been linked to severe COVID-19.^[12]