Dipeptidyl peptidase-4
Encyclopedia
Dipeptidyl peptidase-4 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
.
expressed on the surface of most cell types and is associated with immune regulation, signal transduction
and apoptosis
. It is an intrinsic membrane glycoprotein
and a serine exopeptidase that cleaves X-proline dipeptides from the N-terminus of polypeptides.
It is a rather indiscriminate enzyme for which a diverse range of substrates
are known. The substrates of CD26/DPPIV are proline(or alanine)-containing peptides and include growth factor
s, chemokine
s, neuropeptide
s, and vasoactive peptides.
DPP4 is related to attractin
, FAP
, DPP8
and DPP9
.
DPP4 plays a major role in glucose
metabolism. It is responsible for the degradation of incretin
s such as GLP-1
.
Furthermore, it appears to work as a suppressor in the development of cancer
and tumours.
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.
DPP-4 also binds the enzyme adenosine deaminase
specifically and with high affinity. The significance of this interaction has yet to be established.
work by inhibiting the action of this enzyme, thereby prolonging incretin effect in vivo.
Cluster of differentiation
The cluster of differentiation is a protocol used for the identification and investigation of cell surface molecules present on white blood cells, providing targets for immunophenotyping of cells...
26) is a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that, in humans, is encoded by the DPP4 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
The protein encoded by the DPP4 gene is an antigenic enzymeEnzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
expressed on the surface of most cell types and is associated with immune regulation, signal transduction
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
and apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
. It is an intrinsic membrane glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
and a serine exopeptidase that cleaves X-proline dipeptides from the N-terminus of polypeptides.
It is a rather indiscriminate enzyme for which a diverse range of substrates
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...
are known. The substrates of CD26/DPPIV are proline(or alanine)-containing peptides and include growth factor
Growth factor
A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation and cellular differentiation. Usually it is a protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes....
s, chemokine
Chemokine
Chemokines are a family of small cytokines, or proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines...
s, neuropeptide
Neuropeptide
Neuropeptides are small protein-like molecules used by neurons to communicate with each other. They are neuronal signaling molecules, influence the activity of the brain in specific ways and are thus involved in particular brain functions, like analgesia, reward, food intake, learning and...
s, and vasoactive peptides.
DPP4 is related to attractin
ATRN
Attractin is a protein that in humans is encoded by the ATRN gene.Attractin is a Group XI C-type lectin.-Further reading:...
, FAP
FAP (gene)
Fibroblast activation protein, alpha also known as seprase or 170 kDa melanoma membrane-bound gelatinase is a protein that in humans is encoded by the FAP gene.- Function :...
, DPP8
DPP8
Dipeptidyl peptidase 8 is an enzyme that in humans is encoded by the DPP8 gene.-References:NotesFurther reading...
and DPP9
DPP9
Dipeptidyl peptidase 9 is an enzyme that in humans is encoded by the DPP9 gene.-Further reading:...
.
DPP4 plays a major role in glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
metabolism. It is responsible for the degradation of incretin
Incretin
Incretins are a group of gastrointestinal hormones that cause an increase in the amount of insulin released from the beta cells of the islets of Langerhans after eating, even before blood glucose levels become elevated. They also slow the rate of absorption of nutrients into the blood stream by...
s such as GLP-1
Glucagon-like peptide-1
Glucagon-like peptide-1 is derived from the transcription product of the proglucagon gene. The major source of GLP-1 in the body is the intestinal L cell that secretes GLP-1 as a gut hormone. The biologically active forms of GLP-1 are: GLP-1- and GLP-1-NH2...
.
Furthermore, it appears to work as a suppressor in the development of cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
and tumours.
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.
DPP-4 also binds the enzyme adenosine deaminase
Adenosine deaminase
Adenosine deaminase is an enzyme involved in purine metabolism. It is needed for the breakdown of adenosine from food and for the turnover of nucleic acids in tissues.-Reactions:...
specifically and with high affinity. The significance of this interaction has yet to be established.
Clinical significance
A new class of oral hypoglycemics called dipeptidyl peptidase-4 inhibitorsDipeptidyl peptidase-4 inhibitors
Inhibitors of dipeptidyl peptidase 4, also DPP-4 inhibitors or gliptins, are a class of oral hypoglycemics that block DPP-4. They can be used to treat diabetes mellitus type 2....
work by inhibiting the action of this enzyme, thereby prolonging incretin effect in vivo.
External links
- The MEROPSMeropsMerops may refer to:* Merops , a genus of bee-eaters.* MEROPS, an on-line database for peptidases.It may also refer to several figures from Greek mythology:* King of Ethiopia, husband of Clymene, who lay with Helios and bore Phaethon...
online database for peptidases and their inhibitors: S09.003