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Dipeptidyl peptidase 9 is an
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
that in humans is encoded by the ''DPP9''
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
. This gene encodes a protein that is a member of the S9B family in clan SC of the
serine protease Serine proteases (or serine endopeptidases) are enzymes that cleave peptide bonds in proteins. Serine serves as the nucleophilic amino acid at the (enzyme's) active site. They are found ubiquitously in both eukaryotes and prokaryotes. ...
s. The protein has been shown to have post-proline
dipeptidyl aminopeptidase Dipeptidyl peptidase is a type of enzyme classified under EC 3.4.14. Types include: * Cathepsin C, dipeptidyl peptidase-1 * Dipeptidyl-peptidase II * DPP3, dipeptidyl peptidase-3 * DPP4, Dipeptidyl peptidase-4 * DPP6, dipeptidyl peptidase-6 * DPP ...
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 Dipeptidyl peptidase-4 (DPP4), also known as adenosine deaminase complexing protein 2 or CD26 (cluster of differentiation 26) is a protein that, in humans, is encoded by the ''DPP4'' gene. DPP4 is related to FAP, DPP8, and DPP9. The enzyme was d ...
), 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 Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, ...
,
obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...
and
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
. Several transcript variants of this gene have been described but not fully characterized. More specifically, DPP9 interacts with the NLRP1 protein and affects the level of activation of the NLPR1 i nflammasome. This function involves binding to a complex of full length NLRP1 and a proinflammatory fragment of NLRP1 after activation by autocleavage. A similar mechanism allows DPP9 to regulate the
CARD8 Caspase recruitment domain-containing protein 8 is a protein that in humans is encoded by the ''CARD8'' gene. Function Caspase recruitment domain (CARD)-containing proteins, such as CARD8, are involved in pathways leading to activation of casp ...
inflammasome. This gene has also been linked to severe
COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was COVID-19 pandemic in Hubei, identified in Wuhan, China, in December ...
.


Medical Genetics

Mutations in NLRP1 that block DPP9 interaction lead to a rare Mendelian condition called Autoinflammation with Arthritis and Dyskeratosis A homozygous recessive syndrome dubbed Hatipoğlu syndrome is attributed to mutations in DPP9 with phenotype of failure to thrive, skin manifestations, pancytopenia, and susceptibility to infections. 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.


References


Further reading

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