DPP4 (CD26): A Multifunctional Serine Protease in Immunity, Metabolism, and Cancer
Explore the DPP4 gene, its protein products, associated diseases, tissue expression, mutations, and key molecular pathways.
Gene Information Card
| Symbol | DPP4 |
|---|---|
| Full Name | Dipeptidyl peptidase 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q24.2 |
| NCBI Gene ID | 1803 ncbi.nlm.nih.gov/gene/1803 |
| Ensembl ID | ENSG00000197635 |
| UniProt ID | P27487 |
| OMIM ID | 102720 |
| HGNC ID | 3009 |
| Aliases | ADABP, ADCP2, CD26, DPPIV, TP103 |
Description
The DPP4 gene encodes dipeptidyl peptidase 4 (DPP4), also known as the T-cell activation antigen CD26. This type II transmembrane glycoprotein is a serine exopeptidase that cleaves N-terminal dipeptides from peptides with proline or alanine at the penultimate position. DPP4 is involved in various physiological processes, including glucose metabolism (by inactivating incretins like GLP-1), immune regulation (T-cell activation and costimulation), and cell adhesion. It also exists in a soluble form in plasma. DPP4 has been implicated in several diseases, including type 2 diabetes, autoimmune disorders, and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Type 2 Diabetes | DPP4 degrades incretin hormones (GLP-1, GIP), leading to reduced insulin secretion. DPP4 inhibitors are used to treat this condition. | Clinical use of DPP4 inhibitors; genetic studies linking DPP4 variants to glucose homeostasis. |
| Cancers (e.g., Colon, Lung, Prostate) | DPP4 modulates cancer progression through its role in cell adhesion, migration, and apoptosis. It can act as a tumor suppressor or promoter depending on the context. | Expression studies in tumor tissues; functional assays showing altered cell growth and invasion. |
| Autoimmune Diseases (e.g., Rheumatoid Arthritis) | DPP4 is involved in T-cell activation and proliferation, contributing to the inflammatory process. | Elevated DPP4 activity found in patients; studies on DPP4 inhibitors in autoimmune models. |
| HIV Infection | DPP4/CD26 is involved in T-cell activation and may play a role in HIV pathogenesis, though its exact role is complex. | Studies on CD26 expression in HIV-infected T-cells. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Small Intestine | High | High expression in the brush border membrane. |
| Kidney | High | High expression in the proximal tubules. |
| Liver | Medium | Expressed on bile duct epithelial cells and hepatocytes. |
| Lung | Medium | Expressed on alveolar epithelial cells. |
| Spleen | Medium | Expressed on immune cells. |
| Lymph Node | Medium | Expressed on immune cells. |
| Pancreas | Low | Expressed on pancreatic ductal cells. |
| Brain | Low | Expressed in specific regions. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| T-cells | High | Activated T-cells show high expression. |
| Endothelial cells | Medium | Expressed on the surface of vascular endothelium. |
| Epithelial cells | Medium | Expressed on various epithelial surfaces. |
| Fibroblasts | Low | Expression can be induced by inflammatory signals. |
| HepG2 (Liver cancer) | Medium | Hepatocellular carcinoma cell line. |
| Caco-2 (Colon cancer) | High | Colorectal adenocarcinoma cell line. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs7608798 | SNP | ~30% (G allele) | Associated with altered DPP4 activity and glucose levels. |
| rs4664443 | SNP | ~20% (A allele) | Linked to susceptibility to certain autoimmune diseases. |
| c.1234G>A (p.Val412Ile) | Missense | Rare | Potential effect on enzyme activity; clinical significance uncertain. |
| c.1687C>T (p.Arg563Trp) | Missense | Rare | Reported in a case of atypical DPP4 deficiency. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in DPP4 are rare. They can lead to reduced enzyme activity, potentially affecting incretin metabolism and immune function. Complete deficiency is not commonly observed, suggesting essential roles in development or physiology.
Gain of Function (GOF)
Gain-of-function mutations are not well-documented for DPP4. Increased DPP4 expression or activity is often associated with disease states like cancer and inflammation, but this is typically due to transcriptional or post-translational regulation rather than activating mutations.
Dominant Negative (DN)
No dominant-negative mutations have been described for DPP4. As a homodimer, a mutant subunit could theoretically interfere with the function of the wild-type subunit, but this has not been reported in the literature.
View complete mutation data：
Gene Ontology (GO)
| • serine-type peptidase activity | • dipeptidyl-peptidase activity |
| • protein binding | • identical protein binding |
| • cell adhesion | • proteolysis |
| • T cell costimulation | • signal transduction |
| • plasma membrane | • extracellular exosome |
Pathways
• Incretin metabolism (GLP-1/GIP degradation)
• T-cell receptor signaling pathway
• Cytokine-cytokine receptor interaction
• Cell adhesion molecules (CAMs)
• Proteoglycans in cancer
Protein Summary
The DPP4 protein is a 110 kDa type II transmembrane glycoprotein that functions as a homodimer. It has a short cytoplasmic N-terminal domain, a single transmembrane domain, and a large extracellular C-terminal domain containing the catalytic site. The catalytic triad consists of Ser630, Asp708, and His740. DPP4 is a highly glycosylated protein, and its glycosylation is important for its enzymatic activity and cell surface expression. It is also cleaved from the cell surface to form a soluble, active form found in plasma and other body fluids. The protein is involved in a wide range of functions, including the regulation of glucose metabolism, immune responses, and cell adhesion.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DPP4 Knockout HEK293 Cell Line | EDJ-KQ17679 | Human | 1803 | Details Get a Quote |
| DPP4 Knockout HCT 116 Cell Line | EDJ-KQ19774 | Human | 1803 | Details Get a Quote |
| DPP4 Knockout HeLa Cell Line | EDJ-KQ53108 | Human | 1803 | Details Get a Quote |
| DPP4 Knockout A-549 Cell Line | EDJ-KQ61581 | Human | 1803 | Details Get a Quote |
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