Dpp4 Antibody

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Description

Definition and Biological Context of DPP4 Antibody

DPP4 antibody refers to an antibody targeting dipeptidyl peptidase-4 (DPP4), a multifunctional transmembrane glycoprotein also known as CD26. DPP4 is a serine exopeptidase that cleaves X-proline or X-alanine dipeptides from the N-terminus of polypeptides, regulating hormones like glucagon-like peptide-1 (GLP-1) and chemokines . Antibodies against DPP4 are used to study its enzymatic activity, receptor function, and role in diseases such as diabetes, autoimmune disorders, and viral infections .

DPP4 Protein Characteristics

PropertyDetails
Molecular Weight88 kDa (calculated); 55–60 kDa (observed due to cleavage)
Gene SymbolDPP4 (human gene ID: 1803)
Key DomainsCatalytic site (exopeptidase activity), adenosine deaminase-binding
SubstratesGLP-1, GIP, RANTES, neuropeptide Y, MERS-CoV spike protein

DPP4 exists as a dimeric membrane-bound protein or soluble form in plasma. Its enzymatic activity regulates glucose metabolism by degrading incretins, while its non-enzymatic roles include immune modulation via interactions with adenosine deaminase and cell-surface receptors .

Therapeutic Development

  • Diabetes: Anti-DPP4 antibodies inhibit DPP4 enzymatic activity, elevating GLP-1 levels to improve insulin sensitivity. A peptide vaccine targeting DPP4 epitopes (E1, E3) reduced hyperglycemia in diabetic mice .

  • Autoimmune Diseases: DPP4 antibodies modulate immune cell activity (e.g., CD4+ T cells) and are linked to Graves' disease severity .

  • Antiviral Strategies: DPP4 antibodies block MERS-CoV entry by binding to the viral receptor-binding domain .

Diagnostic and Experimental Tools

  • Western Blot (WB): Detects DPP4 at ~55–60 kDa in human and hamster tissues .

  • Immunohistochemistry (IHC): Localizes DPP4 in bronchial epithelium, kidney proximal tubules, and tumor cells .

  • Flow Cytometry: Identifies CD26 (DPP4) expression on T cells and dendritic cells .

Table 1: Select DPP4 Antibodies and Their Properties

Product (Source)HostReactivityApplicationsKey Findings
10940-1-AP (Proteintech)RabbitHuman, HamsterWB, IHC, ELISABinds recombinant DPP4; inhibits enzymatic activity
HPA071236 (Atlas)RabbitHumanIHC, ICC-IFValidated in lung and kidney tissues
E3-KLH conjugate (Study)N/AMurineVaccine developmentInduces neutralizing antibodies, improves glucose tolerance

Notable Studies

  1. DPP4 Vaccine for Diabetes: Immunization with E3-KLH conjugates in mice increased anti-DPP4 titers, inhibited plasma DPP4 activity by 60%, and improved insulin sensitivity without autoimmune toxicity .

  2. MERS-CoV Inhibition: Polyclonal DPP4 antibodies reduced viral infection in human bronchial cells by 90% by blocking receptor binding .

  3. Autoimmune Modulation: Elevated serum DPP4 activity correlates with Graves' disease severity, suggesting diagnostic potential .

Future Directions

  • Targeted Therapies: Engineered antibodies or soluble DPP4 decoys for MERS-CoV and COVID-19 .

  • Biomarker Development: Serum DPP4 levels as indicators of autoimmune disease progression .

  • Dual-Target Inhibitors: Combining enzymatic inhibition with immune checkpoint modulation .

Product Specs

Buffer
Preservative: 0.03% Proclin 300
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Form
Liquid
Lead Time
Made-to-order (12-14 weeks)
Synonyms
Dpp4; Cd26; Dipeptidyl peptidase 4; Bile canaliculus domain-specific membrane glycoprotein; Dipeptidyl peptidase IV; DPP IV; GP110 glycoprotein; T-cell activation antigen CD26; CD antigen CD26
Target Names
Uniprot No.

Target Background

Function
Dipeptidyl peptidase-4 (DPP-4) is a cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. It acts as a positive regulator of T-cell coactivation by binding to various molecules including ADA, CAV1, IGF2R, and PTPRC. Its interaction with CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion. In conjunction with FAP, DPP-4 is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. DPP-4 may also play a role in promoting lymphatic endothelial cells adhesion, migration, and tube formation. When overexpressed, DPP-4 enhances cell proliferation, a process inhibited by GPC3. Furthermore, DPP-4 acts as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including chemokines, mitogenic growth factors, neuropeptides, and peptide hormones. It removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini, provided that the penultimate residue is proline.
Gene References Into Functions

Role of DPP-4 in Various Biological Processes

  1. Studies have shown that gestational glucocorticoid (GC) exposure during late pregnancy impairs glucose homeostasis, leading to increased endoglin levels, atherogenic dyslipidemia, pancreatic beta cell dysfunction, elevated DPP-4 activity, and altered fetal outcomes. This suggests that GC-induced glucose deregulation and inflammation during late gestation occur through an endoglin-/DPP-4-dependent pathway. PMID: 29677638
  2. Proteome profile array screening revealed that DPP-4 reduces matrix metalloproteinase-9, a key downstream effector of ERK-AKT signaling pathways. PMID: 27525674
  3. Research indicates that long-term exposure to DPP-4 inhibitors is compatible with a balanced metabolism overall. PMID: 28895067
  4. Bis-Pyrano Prenyl Isoflavone has been shown to improve glucose homeostasis by inhibiting DPP-4 in hyperglycemic rats. PMID: 27238050
  5. A study has demonstrated that DPP-4 inhibitors exhibit a neuroprotective effect against hyperthermia-induced seizures by reducing the astrocyte-mediated inflammatory response through an NF-kappaB-dependent pathway. This finding suggests that DPP-4 is involved in the incidence and progression of febrile seizures. PMID: 28372289
  6. DPP-4 inhibition using linagliptin may offer a novel treatment strategy for chronic kidney disease. PMID: 27083282
  7. DPP-4 inhibition has been shown to protect against ventricular arrhythmias by attenuating NGF-induced sympathetic innervation via the cAMP/PKA/CREB-dependent antioxidant pathway in non-diabetic infarcted rats. PMID: 26399925
  8. Gemiigliptin, a DPP-4 inhibitor, exerts a preventative effect on the proliferation and migration of VSMCs via Nrf2. PMID: 26187356
  9. While differences in DPP-4 expression have been observed in steatotic rat liver, these variations are not related to differences in the methylation of its gene promoter. PMID: 26359413
  10. Inhibition of renal DPP-4 activity induced by saxagliptin may contribute to mitigating renal injury in hypertension-related renal injury. PMID: 25936515
  11. DPP-4 inhibition reduces T2DM-induced increase in post-MI acute mortality, potentially by restoring the autophagic response through attenuation of Bcl-2-Beclin-1 interaction. PMID: 26259714
  12. Vildagliptin, a DPP-4 inhibitor, has been shown to attenuate oxidative stress and cardiac fibrosis, improving cardiac function in rats with chronic myocardial infarction. PMID: 25823534
  13. Findings indicate a positive correlation between reduced stress-responsiveness and increased central NPY in DPP4mut rats. PMID: 25635612
  14. DPP-4 inhibitors have been observed to reduce macrophage infiltration via glucagon-like peptide-1-dependent signaling in a nephritis model. This suggests that the control of inflammation by DPP-4 inhibitors is beneficial for the treatment of nondiabetic kidney disease models. PMID: 25656369
  15. Bone marrow-derived cells, but not the kidney, represent a source of sDPP4. Leukocyte or macrophage subpopulations could be potential candidates for further investigation. PMID: 24874705
  16. DPP-4 regulates the expression of hemoglobin genes and may play a role in preserving renal function. PMID: 25122001
  17. Maternal deprivation, a model for postnatal stress experience, significantly influences postnatal lung development in rats. This development is modulated by the DPP-4 system. PMID: 24357522
  18. Long-term deficiency of DPP-4 activity has been shown to improve cardiac performance against pressure overload in rats. PMID: 24416433
  19. A low level of DPP-4 activity contributes to maintaining intestinal homeostasis. PMID: 23832365
  20. Circulating DPP-4 activity is associated with poorer cardiovascular outcomes in heart failure. PMID: 23894014
  21. High-fat and high-cholesterol diets increase DPP-4 expression in intestinal lymph. PMID: 23535306
  22. DPP-4 is a promising in situ marker of biliary functionality, not only in normal but also in fatty rats. PMID: 23361237
  23. Long-term loss of DPP-4 activity enhances the capability against ROS stress, which is more than GLP-1 dependent pathway. PMID: 23359639
  24. DPP-4 deficiency restores ischemia (but not G-CSF)-induced stem cell mobilization and improves vascular recovery in diabetic animals. PMID: 23184393
  25. GLP-1 analogs may serve as a novel therapeutic drug to alleviate obesity-induced liver injury by reducing bile acid synthesis and improving liver bile secretory function. PMID: 22918684
  26. Dipeptidyl peptidase IV regulates the proliferation of preglomerular vascular smooth muscle and mesangial cells. PMID: 22802229
  27. Research provides new evidence on the regulatory roles of DPP-4 in chronic heart failure. PMID: 23035207
  28. Seven days after artery occlusion, dipeptidyl peptidase IV immunoreactivity was found in the perikarya of surviving cortical neurons of the ipsilateral hemisphere. PMID: 22373413
  29. APN and DPPIV activity levels are related to the development of arthritis, with the potential to either protect against or induce susceptibility. PMID: 21982785
  30. A study demonstrates a reduction of anabolic effects on energy homeostasis and a centrally enhanced NPY-expression in DPP4-deficient rats under high caloric food intake. DPP4-deficiency also altered intracorporal fat distribution. PMID: 20887754
  31. Plasma DPP-4 activity changes in accordance with the progression of hyperinsulinemic obesity and pancreatic islet atrophy. PMID: 21139073
  32. Monosodium glutamate and/or food deprivation decreased the activity of dipeptidyl peptidase 4 in the soluble and membrane fraction from the hypothalamus and in the membrane fraction from the hippocampus. PMID: 20153005
  33. Reduced airway inflammation in CD26-deficient F344 rats appears to be mediated by differences in the recruitment and activity of Tregs. PMID: 20560982
  34. APM and DPPIV-DI are respectively related to the downregulation of somatostatin in food-deprived rats, and to the recovery of energy balance in monosodium glutamate obese rats during food deprivation. PMID: 19876009
  35. These findings demonstrate a negative regulatory role of the bronchus-associated lymphatic tissue -specific expression of CD26 in T-cell adhesion during an asthma-like inflammation. PMID: 19501934
  36. The 6A3 epitope was stably exposed in both native and denatured rDPP IV. Data mapped the 6A3 epitope to a surface-exposed Thr331-dependent motif D329KTTLVWN, only 11 amino acids away from L311QWLRRI on the same plane as the fifth beta-propeller blade. PMID: 19804410
  37. Immunoreactive endomorphin 2 was generated extracellularly by a membrane-bound DPP-IV, which was switched to "synthase" mode by the hydrolase inhibitor Ile-Pro-Ile. PMID: 19540879
  38. Clustered charged amino acids of human adenosine deaminase comprise a functional epitope for binding the adenosine deaminase complexing protein CD26/dipeptidyl peptidase IV. PMID: 11901152
  39. DPPIV deficiency results in improved glucose tolerance and ameliorated insulin resistance. PMID: 12031691
  40. Research has provided insights into the kinetics of DPPIV, its dimerization, and gelatinase activity. PMID: 12675219
  41. An increase in DPPIV is associated with graft rejection. Inhibition of DPPIV prevents heart graft rejection. PMID: 12675233
  42. The three-dimensional structure of DPPIV has been determined using cryo-TEM and single particle analysis. PMID: 12705886
  43. Studies have identified DPPIV-binding sites in fibronectin and the effect of binding site peptides on DPPIV/poly-fibronectin adhesion and metastasis. PMID: 12716896
  44. The behavioral repertoire and response to ethanol were characterized in dipeptidyl peptidase IV (DPPIV/CD26)-deficient, mutant Japanese, German, and wild-type-like F344 rat substrains. PMID: 14568317
  45. Research suggests the presence of a yet to be characterized signaling mechanism whereby DPP IV has access to c-Src-containing signaling platforms. PMID: 16478473
  46. Short-term DP IV inhibition does not eliminate the satiety actions of exogenously administered peptide YY at the doses tested. PMID: 16802131
  47. Research findings extend earlier observations and illustrate the role of CD26/DPP IV in alloantigen-mediated immune responses. PMID: 16962474
  48. The X-ray structure confirms that the binding mode of rat DPPIV is similar to the parent xanthines. PMID: 17010607
  49. Inhibition of intragraft DPP IV activity significantly reduced ischemia/reperfusion-associated pulmonary injury, allowing for successful transplantation after 18 hours of ischemia. PMID: 17175274
  50. Rats with a high-fat diet exhibited a significant increase in DPP-IV expression and activity in the intestine and kidneys, but no change in the liver. PMID: 17583752

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Database Links
Protein Families
Peptidase S9B family, DPPIV subfamily
Subcellular Location
[Dipeptidyl peptidase 4 soluble form]: Secreted.; Cell membrane; Single-pass type II membrane protein. Apical cell membrane; Single-pass type II membrane protein. Cell projection, invadopodium membrane; Single-pass type II membrane protein. Cell projection, lamellipodium membrane; Single-pass type II membrane protein. Cell junction. Membrane raft.
Tissue Specificity
Expressed in bile ducts and other epithelial brush borders (small intestine, kidney, colon, pancreatic duct); acinar structures in salivary glands; endothelial structures and T cell areas in thymus, spleen and lymph node.

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