DPP4
HGNC:3009 2q23-qter MIM.102720 Enterz:1803
The protein encoded by the gene DPP4 is identical to adenosine deaminase complexing protein-2, and to the T-cell activation antigen CD26.
It is an intrinsic membrane glycoprotein and a serine exopeptidase that cleaves X-proline dipeptides from the N-terminus of polypeptides.
Fibroblast activation protein (FAP)/seprase and dipeptidylpeptidase-IV (DPP-IV)/CD26 are serine integral membrane proteases. They are involved in tissue remodelling, cancer invasion and metastases, mechanisms that are controversial.
Central role for the serine protease activity of FAP and DPP-4/CD26 in protecting articular cartilage against invasion by synovial fibroblasts in rheumatoid arthritis
Serum CD26 is related to non-inflammatory benign gastrointestinal tract pathologies (excluding rectal bleeding, changes in bowel habits, haemorrhoids, diverticula) and to inflammatory benign gastrointestinal tract pathologies.
DPPIV may be involved in the increased sensitivity to paclitaxel of epithelial ovarian carcinoma (EOC) cells regardless of the involvement of DPPIV activity.
Impaired recruitment of HHT-1 mononuclear cells to the ischaemic heart is due to an altered CXCR4/CD26 balance.
DPP8 and DPP9 prevail over canonical DPP-IV/CD26 and FAPalpha in all examined meningioma patients
Increased plasma DPP-4 activity in obesity is not associated with a generalized augmented incretin hormone metabolism.
FAP and DPP-IV are consistently expressed in bone and soft tissue tumour cells that are histogenetically related to activated fibroblasts and/or myofibroblasts, irrespective of their malignancy.
Decreased circulating number of iNKT cells and CD26 on iNKT cells can be important for the immunopathogenesis by exacerbating Th1-related inflammation in systemic lupus erythematosus
Report persistent expression of CD26/DPPIV after treatment with infliximab in psoriasis despite clinical improvement. (Letter)
D6 cooperates with CD26 in the negative regulation of CCL14 by the selective degradation of its biologically active isoform.
CD26 was absent in follicular and mantle cell lymphomas, high in multiple myelomas, hairy cell leukaemias, and variable in chronic lymphocytic leukaemias, in CD5(neg) B-cell chronic lymphoproliferative diseases and in diffuse large cell lymphomas.
CD26 expression on T cell lines increases SDF-1-alpha-mediated invasion.
CD26 is an endogenous inhibitor of T cell motility through inhibition of TSP-1 expression and chemokines stimulate cell polarity and migration through abrogation of the CD26-dependent inhibition.
CD26 has a role in progression of B-chronic lymphocytic leukemia.
Selective inhibition of DPP-IV does not impair T dependent immune responses to antigenic challenge.
Genetic analysis does not support the notion that DPP4 polymorphisms could modulate the cardiovascular disease risk profile among obese patients.
The ratio of ApoCI’:ApoCI in plasma is determined by the activity of dipeptidyl peptidase IV, DPP-IV (also known as the leucocyte antigen CD26), which was found to be elevated up to 3-fold in mucopolysacharidoses patients.
Dipeptidyl peptidase IV serum level in diabetic patients serum level in diabetic patients
Results indicate that the plasma levels of sCD26 and sCD30 are significantly higher in patients with non-healing form of CL than patients with healing form of CL or healthy control.
Effects on basal collagen metabolism following DPP4 inhibition in vivo are demonstrated and the amyloid peptide is identified as a novel DPP4 substrate.
Differences of DPPIV level in esophageal carcinomas compared with normal epithelium showed that esophageal malignancies were associated with an increased amount of cell surface-bound DPPIV.
Serum levels of soluble CD26 in patients with scleroderma; the DPPIV activity may be associated with fibrosis of the skin, lung, and other organs as a result of metabolic aberrations of collagen
Degradation of CXCL12 by CD26/DPPIV may be involved in the metastatic cascades of Prostate cancer.
Alogliptin potently inhibited human DPP-4 in vitro (mean IC(50), 6.9 nM) and exhibited > 10,000-fold selectivity for DPP-4.
DPPIV-expression and enzyme activity, Ki-67 antigen and K16 are significantly upregulated in the centre and inner margin of the psoriatic lesion compared to clinically uninvolved skin and the healthy volunteers skin.
Increased plasma PAI-1 levels in CD36 deficiency may be due to abnormal fatty acids metabolism.
These results identify dipeptidyl peptidase IV as a novel lymphatic marker and mediator of lymphatic endothelial cell functions.
Report modulation of substance P signaling by dipeptidyl peptidase-IV enzymatic activity in human glioma cell lines.
findings demonstrate regulatory effects of DPPIV for the recruitment of eosinophils; furthermore, they illustrate that inhibitors of DPPIV have the potential to interfere with chemokine-mediated effects in vivo including but not limited to allergy
DPPIV in exosome-like vesicles was metabolically active in cleaving substance P and glucose-dependent insulinotropic polypeptide to release N-terminal dipeptides
DPP-IV may play a role in converting endogenous beta-melanocortin MSH(5-22) to more potent peptides that regulate energy homeostasis in the hypothalamus.
Upregulated in synovial fluid monocytes in patients juvenile rheumatoid arthritis.
Since hepatic glycogen synthesis, a GLP-1 action, was impaired, the altered expressions of GLP-1 and DPPIV may be involved in the development of HCV-associated glucose intolerance.
DPP-IV enzyme activity appears to be depressed in response to poor glycaemic control in type 2 diabetes.
DPPIV and SDF-1alpha/CXCR4 play crucial roles in regulating the migratory potential of HPMCs, which may be involved in the re-epithelialization of denuded basement membrane at the site of peritoneal injury.
Serum DPPIV activity and staining intensity of CD26 in liver are correlated with histopathologic grade of NASH (Non-alcoholic steatohepatitis)and hepatosteatosis. DPPIV can be proposed as a candidate with several potential functions in NASH pathogenesis.
role for CD26 in in vivo engraftment of hematopoietic stem cells from human umbilical cord blood into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice
Plasma sCD26 was significantly elevated in asthmatic patients regardless of inhaled corticosteroid treatment (all P < 0.05). Cell surface CD26 expression was up-regulated especially on CD4+ and iNKT lymphocytes (all P < 0.05) but not on other cell types.
Increased Dipeptidyl-Peptidase IV activity is associated with astrocytic tumours.
The CD26 structure indicates how substrate specificity is achieved and reveals a new and unexpected opening to the active site.
Levels in blood are suppresse after administration of vildagliptin to type 2 diabetics.
Both the glycosylated and unglycosylated forms of GPC3 interact with CD26 peptidase, resulting in inhibition of the enzyme.
HIV-1 Tat-derived nonapeptides Tat-(1-9) and Trp2-Tat-(1-9) bind to the active site of dipeptidyl-peptidase IV
analysis of human dipeptidyl peptidase IV in its apo and diprotin B-complexed forms.
The adhesion mechanism by endometrial CD26 may be involved in human blastocyst implantation.
dipeptidyl peptidase-IV activity in synovial fluid and plasma of patients with rheumatoid and psoriatic arthritis.
DPPIV functions as a tumor suppressor, and its downregulation may contribute to the loss of growth control in NSCLC cells
CD26 interferes with transduction pathway(s) needed for the maturation of T cells and plays an important role in T lymphocyte homeostasis in peripheral blood.
Expression of the seprase-DPPIV complex is restricted to migratory cells involved in wound closure
Crystal structures of DPPIV in the free form and in complex with the first 10 residues of the physiological substrate, neuropeptide Y (residues 1-10; tNPY)
CD26/DPPIV is likely to directly modulate various SDF-1alpha induced functions
CD26/DPPIV involvement in tumor biology and its potential role in cancer development and behavior
functional role of DP IV and APN in the sebaceous gland apparatus and for their inhibitors, used alone or in combination, as completely new substances possibly affecting acne pathogenesis in a therapeutic manner.
upregulation of dipeptidyl peptidase IV is apparently accompanied by decreased proliferation or survival of glioma cells
Clustered charged amino acids of human adenosine deaminase comprise a functional epitope for binding the adenosine deaminase complexing protein CD26/dipeptidyl peptidase IV.
galectin-3 and CD26/DPPIV as preoperative diagnostic markers for thyroid nodules
Adenosine down-regulates the surface expression of DPP4 on HT29 cells.
A mutant stromal cell derived factor-1 that does not interact with heparan sulsfate is readily cleaved by Dipepidtyl peptidase IV.
CD26-caveolin-1 interaction plays a role in the up-regulation of CD86 on TT-loaded monocytes and subsequent engagement with CD28 on T cells, leading to antigen-specific T cell activation.
Crystal structure of CD26/dipeptidyl-peptidase IV in complex with adenosine deaminase
CD26 has an essential role in human T-cell activation, as well as its ability to regulate the biological effects of selected chemokines through its DPPIV activity.
The DAP IV from Pseudomonas sp. WO24 is expressed as 82 and 84-kDa isoforms, having two Met, Met-1 and Met-12, in its N-terminal sequence.
Intestinal dipeptidyl peptidase IV is efficiently sorted to the apical membrane through the concerted action of N- and O-glycans
Decrease of serum dipeptidylpeptidase activity in severe sepsis patients: relationship to procalcitonin.
Glycosylation of DPPIV is not a prerequisite for catalysis, dimerization, or adenosine deaminase binding.
Adult T-cell leukemia cells down-regulate CD26 antigens by means of epigenetic machinery; faintly detected transcripts of the gene were aberrantly methylated at the CpG islands within the promoter region in parallel with the advancement of ATL
strong physical linkage of CD26 with CD45RA outside lipid rafts may be responsible for the attenuation of T-cell activation signaling through CD26
PLG has the potential to simultaneously regulate calcium signaling pathways and regulate pHi via an association with NHE3 linked to DPP IV, necessary for tumor cell proliferation and invasiveness
both wild HNF-1alpha and wild HNF-1beta have a stimulatory effect on DPP-IV gene expression, but that mutant hepatocyte nuclear factors (HNF)-1alpha and mutant HNF-1beta attenuate the stimulatory effect
Serum levels are decreased in patients with Crohn and inflammatory bowel disease who are clinically depressed.
This enzyme is a marker of mood in anorexia nervosa and bulimia nervosa patients.
This enzyme is active in prostatic secretions and prostate cancer.
This enzyme suppresses ovarian carcinoma in peritoneal dissemination in vitro and in vivo.
Adhesion to mesothelial is increased by overexpression of dipeptidyl peptidase IV.
This enzyme is expressed in endometrial adenocarcinoma and is negatively correlated with tumor grade.
This enzyme is expressed in cutaneous infiltrates from patients with cutaneous T-cell lymphoma.
CD26 plays a role in the digestion of an immunodominant epitope in celiac disease.
An increase in this enzyme is associated with graft rejection. Inhibition of this enzyme prevents kieney graft rejection.
This protein acts synergistically with APN to regulate T cell function.
Protein-protein interactions dependent on this enzyme are investigated using surface plasmon resonance.
The kinetics of this enzyme are examined, after cloning in Pichia pastoris.
The active site of this enzyme is examined and compared with Porphyromonas gingivalis.
Crystals of dipeptidylpeptidase IV belongs to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 118.04, b = 125.92, c = 136.84 A, and diffracts beyond 2.6 A resolution
Chronic hyperglycaemia induces a significant increase in DPP-IV activity in type 1 and type 2 diabetes
the catalytic mechanism of dipeptidyl peptidase IV requires tyrosine 547
the C-terminal loop as essential for dimer formation and optimal catalysis
decreased circulating CD26 levels in arthritis may influence CD26-mediated regulation of the chemotactic SDF-1/CXCR4 axis
comparison of the structure of X-PDAP from Lactococcus lactis (PepX) with its human counterpart DPP-IV
CD26 and cell surface adenosine deaminase are selectively expressed on ALK-positive, but not on ALK-negative, anaplastic large cell lymphoma and Hodgkin’s lymphoma
Ligation of CD26 by caveolin-1 recruits a complex, including CD26 and CARMA1, which functions in lymphocyte activation.
Expressed in normal endometrial glandular cells, but expression in endometrial adenocarcinoma is down-regulated with increasing grade. Regulatory role in neoplastic transformation and progression of endometrial adenocarcinomas.
catalytic properties and inhibition of this proline-specific enzyme
analysis of substrate binding sites of human dipeptidyl peptidase-IV
adenosine downregulation of DPPIV from the surface of colon cancer cells occurs independently of the classic receptors, and is mediated by a novel cell-surface mechanism that induces an increase in protein tyrosine phosphatase activity.
The dipeptidyl peptidase IV gene family contains the four peptidases dipeptidyl peptidase IV, fibroblast activation protein, dipeptidyl peptidase 8 and dipeptidyl peptidase 9.
DPIV mediated transcellular proteolysis
Soluble CD26 induces T cell proliferation in Antigen presenting cells
elevated serum levels in chronic hepatitis C and other viral infections suggest that this activity originates not only from the liver, but also from other sources such as peripheral blood cells involved in the control of viral infections.
The process of CXCL12/SDF-1 alpha cleavage by CD26/DPPIV on a subpopulation of cord blood CD34+ cells represents a novel regulatory mechanism in hemopoietic stem and progenitor cells for the migration, homing, and mobilization of these cells.
This enzyme is a marker in thyroid tumors.
Involvement in extravillous trophoblast invasion and differentiation
DPPIV activity is depressed in individuals with hypertension during acute ACEI-associated angioedema.
Chromogranin B (586-602) peptide can serve as a substrate for the lymphocyte surface glycoprotein CD26, also known as dipeptidyl peptidase IV (DPP IV), generating a new peptide ER-15 (CgB(588-602))
Report the structure of human dipeptidyl peptidase IV especially focusing on a unique eight-bladed beta-propeller domain; discuss the way for the access of the substrate to this domain.
Adenosine deaminase binding is diminished by mutation of ADA residues known to interact with CD26.
Plasma DPP-IV hyperactivity in the obese did not seem to be affected by the overweight degree. Selective DPP-IV inhibitors could represent an ideal approach to obesity management.
The presence of dipeptidyl peptidase IV can be used to support diagnosis of deep penetrating nevi in doubtful cases. Loss of dipeptidyl peptidase IV may also be causally linked to the transition of invasive to metastatic phenotypes.
Significantly higher serum DPP IV and aminopeptidase N activities (P<0.001) were found in tonsillar hypertrophy patients compared with those with recurrent tonsillitis
Pathology
DPP4 is a marker in thyroid tumors.
Examination of expression and enzymatic activity in recipients of kidney allografts.
Increased adhesion of ovarian carcinoma cells to mesothelial cells by overexpression of dipeptidyl peptidase IV.
Fibroblast activation protein (FAP)/seprase and DPP-IV are consistently expressed in bone and soft tissue tumour cells that are histogenetically related to activated fibroblasts and/or myofibroblasts, irrespective of their malignancy. DPP-IV is also expressed in monocyte-macrophage lineage cells.
References
Histogenesis-specific expression of fibroblast activation protein and dipeptidylpeptidase-IV in human bone and soft tissue tumours. Dohi O, Ohtani H, Hatori M, Sato E, Hosaka M, Nagura H, Itoi E, Kokubun S. Histopathology. 2009 Oct;55(4):432-40.PMID: #19817894#