Dipeptidyl peptidase-4

DPP4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1J2E, 1N1M, 1NU6, 1NU8, 1PFQ, 1R9M, 1R9N, 1RWQ, 1TK3, 1TKR, 1U8E, 1W1I, 1WCY, 1X70, 2AJL, 2BGN, 2BGR, 2BUB, 2FJP, 2G5P, 2G5T, 2G63, 2HHA, 2I03, 2I78, 2IIT, 2IIV, 2JID, 2OAG, 2OGZ, 2OLE, 2ONC, 2OPH, 2OQI, 2OQV, 2P8S, 2QJR, 2QKY, 2QOE, 2QT9, 2QTB, 2RGU, 2RIP, 3BJM, 3C43, 3C45, 3CCB, 3CCC, 3D4L, 3EIO, 3F8S, 3G0B, 3G0C, 3G0D, 3G0G, 3H0C, 3HAB, 3HAC, 3KWF, 3KWJ, 3NOX, 3O95, 3O9V, 3OC0, 3OPM, 3Q0T, 3Q8W, 3QBJ, 3SWW, 3SX4, 3VJK, 3VJL, 3VJM, 3W2T, 4A5S, 4DSA, 4DSZ, 4DTC, 4G1F, 4JH0, 4KR0, 4L72, 4LKO, 4J3J, 4N8D, 4N8E, 4PNZ, 4PV7, 4QZV, 3WQH, 5KBY, 5ISM, 5I7U
Identifiers
Aliases	DPP4, ADABP, ADCP2, CD26, DPPIV, TP103, dipeptidyl peptidase 4
External IDs	OMIM: 102720; MGI: 94919; HomoloGene: 3279; GeneCards: DPP4; OMA:DPP4 - orthologs
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2q24.2 Start 161,992,245 bp[1] End 162,074,215 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2 C1.3|2 35.85 cM Start 62,160,417 bp[2] End 62,242,575 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Achilles tendon jejunal mucosa parotid gland tendon of biceps brachii duodenum kidney tubule placenta stromal cell of endometrium parietal pleura seminal vesicula Top expressed in jejunum vestibular membrane of cochlear duct seminal vesicula saccule ileum lacrimal gland parotid gland left lobe of liver renal corpuscle migratory enteric neural crest cell More reference expression data BioGPS More reference expression data
Gene ontology Molecular function dipeptidyl-peptidase activity signaling receptor binding identical protein binding peptidase activity hydrolase activity virus receptor activity protein homodimerization activity serine-type peptidase activity protease binding aminopeptidase activity protein binding serine-type endopeptidase activity Cellular component lamellipodium membrane extracellular exosome lysosomal membrane endocytic vesicle integral component of membrane cell projection cell junction lamellipodium apical plasma membrane membrane focal adhesion cell surface intercellular canaliculus membrane raft extracellular region plasma membrane Biological process response to hypoxia T cell costimulation psychomotor behavior behavioral fear response negative regulation of extracellular matrix disassembly regulation of cell-cell adhesion mediated by integrin locomotory exploration behavior endothelial cell migration positive regulation of cell population proliferation T cell activation cell adhesion viral entry into host cell regulation of insulin secretion proteolysis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1803 13482 Ensembl ENSG00000197635 ENSMUSG00000035000 UniProt P27487 P28843 RefSeq (mRNA) NM_001935 NM_001159543 NM_010074 RefSeq (protein) NP_001926 NP_001366533 NP_001366534 NP_001366535 NP_001153015 NP_034204 Location (UCSC) Chr 2: 161.99 – 162.07 Mb Chr 2: 62.16 – 62.24 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Dipeptidyl peptidase-4 (DPP4 or DPPIV), 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.^[5] DPP4 is related to FAP, DPP8, and DPP9. The enzyme was discovered in 1966 by Hopsu-Havu and Glenner,^[6] and as a result of various studies on chemism, was called dipeptidyl peptidase IV [DP IV].

The protein encoded by the DPP4 gene is an enzyme expressed on the surface of most cell types and is associated with immune regulation, signal transduction, and apoptosis. It is a type II transmembrane glycoprotein, but a soluble form, which lacks the intracellular and transmembrane part, is present in blood plasma and various body fluids. DPP-4 is a serine exopeptidase that cleaves X-proline or X-alanine dipeptides from the N-terminus of polypeptides. Peptide bonds involving the cyclic amino acid proline cannot be cleaved by the majority of proteases and an N-terminal X-proline "shields" various biopeptides.^[7] Extracellular proline-specific proteases therefore play an important role in the regulation of these biopeptides.

DPP-4 is known to cleave a broad range of substrates including growth factors, chemokines, neuropeptides, and vasoactive peptides.^[8][9] The cleaved substrates lose their biological activity in the majority of cases, but in the case of the chemokine RANTES and neuropeptide Y, DPP-4 mediated cleavage leads to a shift in the receptor subtype binding.^[8]

DPP4 plays a major role in glucose metabolism. It is responsible for the degradation of incretins such as GLP-1.^[10] Furthermore, it appears to work as a suppressor in the development of some tumors.^{[11][12][13][14]}

DPP-4 also binds the enzyme adenosine deaminase specifically and with high affinity. The significance of this interaction has yet to be established.

Animal studies suggest its pathogenetic role in development of fibrosis of various organs, such as liver and kidney.^[15][16]

CD26/DPPIV plays an important role in tumor biology, and is useful as a marker for various cancers, with its levels either on the cell surface or in the serum increased in some neoplasms and decreased in others.^[17]

A class of oral hypoglycemics called dipeptidyl peptidase-4 inhibitors works by inhibiting the action of this enzyme, thereby prolonging incretin effect in vivo.^[18]

Middle East respiratory syndrome coronavirus has been found to bind to DPP4. It is found on the surface of cells in the airways (such as the lungs) and kidneys. Scientists may be able to use this to their advantage by blocking the virus's entry into the cell.^[19]

DPP4,^[20] or its Mycobacterial homologue MtDPP,^[21] might play a role in the pathogenesis of tuberculosis via cleavage of the chemokine C-X-C motif chemokine ligand 10 (CXCL10).

• Development of dipeptidyl peptidase-4 inhibitors
• Berberine

• The MEROPS online database for peptidases and their inhibitors: S09.003
• Dipeptidyl-Peptidase+IV at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Banting and Best Diabetes Centre at UT dpp4