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
Gene location (Human)
Chr.	Chromosome 2 (human)[1]
End	162,074,215 bp[1]
Gene location (Mouse)
Chr.	Chromosome 2 (mouse)[2]
End	62,412,231 bp[2]
RNA expression pattern
	; ; ; ;
	More reference expression data
Gene ontology
Molecular function	• dipeptidyl-peptidase activity; • receptor binding; • identical protein binding; • peptidase activity; • hydrolase activity; • virus receptor activity; • protein homodimerization activity; • serine-type peptidase activity; • protease binding; • aminopeptidase activity; • GO:0001948 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; • invadopodium membrane; • extracellular region; • cell 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 proliferation; • T cell activation; • cell adhesion; • viral entry; • regulation of insulin secretion; • proteolysis;
	Sources:Amigo / QuickGO
Orthologs
	1803
	13482
	ENSG00000197635
	ENSMUSG00000035000
	P27487
	P28843
	NM_001935
	NM_001159543; NM_010074
	NP_001926; NP_001366533; NP_001366534; NP_001366535
	NP_001153015; NP_034204
	Wikidata
View/Edit Human	View/Edit Mouse

Dipeptidyl peptidase-4 (DPP4), 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].

Function

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

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

Clinical significance

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]

gollark: What growth recently? We've got a very bad recession going on.

gollark: It's not exactly worrying since random people on the internet have ~0 actual power.

gollark: As much as I dislike "you don't agree with my political positions thus bees you" being anticentrist instead of anti-sufficiently-politically-different people is odd.

gollark: What's wrong with centrism?

gollark: I should maybe read that, I read Snow Crash ages ago.

References

GRCh38: Ensembl release 89: ENSG00000197635 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000035000 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
Kameoka J, Tanaka T, Nojima Y, Schlossman SF, Morimoto C (July 1993). "Direct association of adenosine deaminase with a T cell activation antigen, CD26". Science. 261 (5120): 466–9. Bibcode:1993Sci...261..466K. doi:10.1126/science.8101391. PMID 8101391.
Hopsu-Havu VK, Glenner GG (1966). "A new dipeptide naphthylamidase hydrolyzing glycyl-prolyl-beta-naphthylamide". Histochemie. Histochemistry. Histochimie. 7 (3): 197–201. doi:10.1007/bf00577838. PMID 5959122.
Vanhoof G, Goossens F, De Meester I, Hendriks D, Scharpé S (June 1995). "Proline motifs in peptides and their biological processing". FASEB Journal. 9 (9): 736–44. doi:10.1096/fasebj.9.9.7601338. PMID 7601338.
Mentlein R (November 1999). "Dipeptidyl-peptidase IV (CD26)--role in the inactivation of regulatory peptides". Regulatory Peptides. 85 (1): 9–24. doi:10.1016/S0167-0115(99)00089-0. PMID 10588446.
Chen X (2006). "Biochemical properties of recombinant prolyl dipeptidases DPP-IV and DPP8". Dipeptidyl Aminopeptidases. Advances in Experimental Medicine and Biology. 575. pp. 27–32. doi:10.1007/0-387-32824-6_3. ISBN 978-0-387-29058-4. PMID 16700505.
Barnett A (November 2006). "DPP-4 inhibitors and their potential role in the management of type 2 diabetes". International Journal of Clinical Practice. 60 (11): 1454–70. doi:10.1111/j.1742-1241.2006.01178.x. PMID 17073841.
Pro B, Dang NH (October 2004). "CD26/dipeptidyl peptidase IV and its role in cancer". Histology and Histopathology. 19 (4): 1345–51. doi:10.14670/HH-19.1345. PMID 15375776.
Masur K, Schwartz F, Entschladen F, Niggemann B, Zaenker KS (December 2006). "DPPIV inhibitors extend GLP-2 mediated tumour promoting effects on intestinal cancer cells". Regulatory Peptides. 137 (3): 147–55. doi:10.1016/j.regpep.2006.07.003. PMID 16908079.
Wesley UV, McGroarty M, Homoyouni A (February 2005). "Dipeptidyl peptidase inhibits malignant phenotype of prostate cancer cells by blocking basic fibroblast growth factor signaling pathway". Cancer Research. 65 (4): 1325–34. doi:10.1158/0008-5472.CAN-04-1852. PMID 15735018.
Busek P, Malík R, Sedo A (March 2004). "Dipeptidyl peptidase IV activity and/or structure homologues (DASH) and their substrates in cancer". The International Journal of Biochemistry & Cell Biology. 36 (3): 408–21. doi:10.1016/S1357-2725(03)00262-0. PMID 14687920.
Kaji K, Yoshiji H, Ikenaka Y, Noguchi R, Aihara Y, Douhara A, Moriya K, Kawaratani H, Shirai Y, Yoshii J, Yanase K, Kitade M, Namisaki T, Fukui H (March 2014). "Dipeptidyl peptidase-4 inhibitor attenuates hepatic fibrosis via suppression of activated hepatic stellate cell in rats". Journal of Gastroenterology. 49 (3): 481–91. doi:10.1007/s00535-013-0783-4. PMID 23475323.
Min HS, Kim JE, Lee MH, Song HK, Kang YS, Lee MJ, Lee JE, Kim HW, Cha JJ, Chung YY, Hyun YY, Han JY, Cha DR (June 2014). "Dipeptidyl peptidase IV inhibitor protects against renal interstitial fibrosis in a mouse model of ureteral obstruction". Laboratory Investigation; A Journal of Technical Methods and Pathology. 94 (6): 598–607. doi:10.1038/labinvest.2014.50. PMID 24687121.
Havre PA, Abe M, Urasaki Y, Ohnuma K, Morimoto C, Dang NH (January 2008). "The role of CD26/dipeptidyl peptidase IV in cancer". Frontiers in Bioscience. 13 (13): 1634–45. doi:10.2741/2787. PMID 17981655.
Rosenstock J, Zinman B (April 2007). "Dipeptidyl peptidase-4 inhibitors and the management of type 2 diabetes mellitus". Current Opinion in Endocrinology, Diabetes and Obesity. 14 (2): 98–107. doi:10.1097/MED.0b013e3280a02f65. PMID 17940427.
Raj VS, Mou H, Smits SL, Dekkers DH, Müller MA, Dijkman R, Muth D, Demmers JA, Zaki A, Fouchier RA, Thiel V, Drosten C, Rottier PJ, Osterhaus AD, Bosch BJ, Haagmans BL (March 2013). "Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC". Nature. ScienceNews. 495 (7440): 251–4. Bibcode:2013Natur.495..251R. doi:10.1038/nature12005. PMID 23486063. Lay summary – ScienceNews.

External links

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

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000197635 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000035000 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid8101391-5] Kameoka J, Tanaka T, Nojima Y, Schlossman SF, Morimoto C (July 1993). "Direct association of adenosine deaminase with a T cell activation antigen, CD26". Science. 261 (5120): 466–9. Bibcode:1993Sci...261..466K. doi:10.1126/science.8101391. PMID 8101391.

[6] Hopsu-Havu VK, Glenner GG (1966). "A new dipeptide naphthylamidase hydrolyzing glycyl-prolyl-beta-naphthylamide". Histochemie. Histochemistry. Histochimie. 7 (3): 197–201. doi:10.1007/bf00577838. PMID 5959122.

[7] Vanhoof G, Goossens F, De Meester I, Hendriks D, Scharpé S (June 1995). "Proline motifs in peptides and their biological processing". FASEB Journal. 9 (9): 736–44. doi:10.1096/fasebj.9.9.7601338. PMID 7601338.

[:0-8] Mentlein R (November 1999). "Dipeptidyl-peptidase IV (CD26)--role in the inactivation of regulatory peptides". Regulatory Peptides. 85 (1): 9–24. doi:10.1016/S0167-0115(99)00089-0. PMID 10588446.

[pmid16700505-9] Chen X (2006). "Biochemical properties of recombinant prolyl dipeptidases DPP-IV and DPP8". Dipeptidyl Aminopeptidases. Advances in Experimental Medicine and Biology. 575. pp. 27–32. doi:10.1007/0-387-32824-6_3. ISBN 978-0-387-29058-4. PMID 16700505.

[pmid17073841-10] Barnett A (November 2006). "DPP-4 inhibitors and their potential role in the management of type 2 diabetes". International Journal of Clinical Practice. 60 (11): 1454–70. doi:10.1111/j.1742-1241.2006.01178.x. PMID 17073841.

[11] Pro B, Dang NH (October 2004). "CD26/dipeptidyl peptidase IV and its role in cancer". Histology and Histopathology. 19 (4): 1345–51. doi:10.14670/HH-19.1345. PMID 15375776.

[12] Masur K, Schwartz F, Entschladen F, Niggemann B, Zaenker KS (December 2006). "DPPIV inhibitors extend GLP-2 mediated tumour promoting effects on intestinal cancer cells". Regulatory Peptides. 137 (3): 147–55. doi:10.1016/j.regpep.2006.07.003. PMID 16908079.

[13] Wesley UV, McGroarty M, Homoyouni A (February 2005). "Dipeptidyl peptidase inhibits malignant phenotype of prostate cancer cells by blocking basic fibroblast growth factor signaling pathway". Cancer Research. 65 (4): 1325–34. doi:10.1158/0008-5472.CAN-04-1852. PMID 15735018.

[14] Busek P, Malík R, Sedo A (March 2004). "Dipeptidyl peptidase IV activity and/or structure homologues (DASH) and their substrates in cancer". The International Journal of Biochemistry & Cell Biology. 36 (3): 408–21. doi:10.1016/S1357-2725(03)00262-0. PMID 14687920.

[pmid23475323-15] Kaji K, Yoshiji H, Ikenaka Y, Noguchi R, Aihara Y, Douhara A, Moriya K, Kawaratani H, Shirai Y, Yoshii J, Yanase K, Kitade M, Namisaki T, Fukui H (March 2014). "Dipeptidyl peptidase-4 inhibitor attenuates hepatic fibrosis via suppression of activated hepatic stellate cell in rats". Journal of Gastroenterology. 49 (3): 481–91. doi:10.1007/s00535-013-0783-4. PMID 23475323.

[pmid24687121-16] Min HS, Kim JE, Lee MH, Song HK, Kang YS, Lee MJ, Lee JE, Kim HW, Cha JJ, Chung YY, Hyun YY, Han JY, Cha DR (June 2014). "Dipeptidyl peptidase IV inhibitor protects against renal interstitial fibrosis in a mouse model of ureteral obstruction". Laboratory Investigation; A Journal of Technical Methods and Pathology. 94 (6): 598–607. doi:10.1038/labinvest.2014.50. PMID 24687121.

[pmid17981655-17] Havre PA, Abe M, Urasaki Y, Ohnuma K, Morimoto C, Dang NH (January 2008). "The role of CD26/dipeptidyl peptidase IV in cancer". Frontiers in Bioscience. 13 (13): 1634–45. doi:10.2741/2787. PMID 17981655.

[pmid17940427-18] Rosenstock J, Zinman B (April 2007). "Dipeptidyl peptidase-4 inhibitors and the management of type 2 diabetes mellitus". Current Opinion in Endocrinology, Diabetes and Obesity. 14 (2): 98–107. doi:10.1097/MED.0b013e3280a02f65. PMID 17940427.

[pmid23486063-19] Raj VS, Mou H, Smits SL, Dekkers DH, Müller MA, Dijkman R, Muth D, Demmers JA, Zaki A, Fouchier RA, Thiel V, Drosten C, Rottier PJ, Osterhaus AD, Bosch BJ, Haagmans BL (March 2013). "Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC". Nature. ScienceNews. 495 (7440): 251–4. Bibcode:2013Natur.495..251R. doi:10.1038/nature12005. PMID 23486063. Lay summary – ScienceNews.

Proteins: clusters of differentiation (see also list of human clusters of differentiation)
1–50	CD1 a-c 1A 1B 1D 1E CD2 CD3 γ δ ε CD4 CD5 CD6 CD7 CD8 a CD9 CD10 CD11 a b c d CD13 CD14 CD15 CD16 A B CD18 CD19 CD20 CD21 CD22 CD23 CD24 CD25 CD26 CD27 CD28 CD29 CD30 CD31 CD32 A B CD33 CD34 CD35 CD36 CD37 CD38 CD39 CD40 CD41 CD42 a b c d CD43 CD44 CD45 CD46 CD47 CD48 CD49 a b c d e f CD50
51–100	CD51 CD52 CD53 CD54 CD55 CD56 CD57 CD58 CD59 CD61 CD62 E L P CD63 CD64 A B C CD66 a b c d e f CD68 CD69 CD70 CD71 CD72 CD73 CD74 CD78 CD79 a b CD80 CD81 CD82 CD83 CD84 CD85 a d e h j k CD86 CD87 CD88 CD89 CD90 CD91 - CD92 CD93 CD94 CD95 CD96 CD97 CD98 CD99 CD100
101–150	CD101 CD102 CD103 CD104 CD105 CD106 CD107 a b CD108 CD109 CD110 CD111 CD112 CD113 CD114 CD115 CD116 CD117 CD118 CD119 CD120 a b CD121 a b CD122 CD123 CD124 CD125 CD126 CD127 CD129 CD130 CD131 CD132 CD133 CD134 CD135 CD136 CD137 CD138 CD140b CD141 CD142 CD143 CD144 CD146 CD147 CD148 CD150
151–200	CD151 CD152 CD153 CD154 CD155 CD156 a b c CD157 CD158 (a d e i k) CD159 a c CD160 CD161 CD162 CD163 CD164 CD166 CD167 a b CD168 CD169 CD170 CD171 CD172 a b g CD174 CD177 CD178 CD179 a b CD180 CD181 CD182 CD183 CD184 CD185 CD186 CD191 CD192 CD193 CD194 CD195 CD196 CD197 CDw198 CDw199 CD200
201–250	CD201 CD202b CD204 CD205 CD206 CD207 CD208 CD209 CDw210 a b CD212 CD213a 1 2 CD217 CD218 (a b) CD220 CD221 CD222 CD223 CD224 CD225 CD226 CD227 CD228 CD229 CD230 CD233 CD234 CD235 a b CD236 CD238 CD239 CD240CE CD240D CD241 CD243 CD244 CD246 CD247 - CD248 CD249
251–300	CD252 CD253 CD254 CD256 CD257 CD258 CD261 CD262 CD263 CD264 CD265 CD266 CD267 CD268 CD269 CD271 CD272 CD273 CD274 CD275 CD276 CD278 CD279 CD280 CD281 CD282 CD283 CD284 CD286 CD288 CD289 CD290 CD292 CDw293 CD294 CD295 CD297 CD298 CD299
301–350	CD300A CD301 CD302 CD303 CD304 CD305 CD306 CD307 CD309 CD312 CD314 CD315 CD316 CD317 CD318 CD320 CD321 CD322 CD324 CD325 CD326 CD328 CD329 CD331 CD332 CD333 CD334 CD335 CD336 CD337 CD338 CD339 CD340 CD344 CD349 CD350

Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)