DPP4N_Peptidase_S9

Relationship

Family: DPP4N_Peptidase_S9

Block: X

Parent Family: Peptidase_S9

Comment

Dipeptidyl petidase IV related proteins (EC 3.4.14.5) (DPP IV) important for the activation or inactivation of extracellular endocrine paracrine and autocrine peptides. DPPIV is synonymous with CD26 (important in HIV infection). Some members lack active serine and are probably not enzymes. The prototype structure has a 8-bladed beta-propeller N-terminal domain which guide substrates to the active site and a transmembrane segment. DPP4 is a cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to 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 association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation. The novel emerging coronavirus Middle East respiratory syndrome coronavirus (MERS-CoV) binds cells through DPP4. Mutations in the DPP6 gene are linked to autosomal dominant mental retardation.(Liao et al 2013). The dipeptidyl-aminopeptidase-like protein 6 is an integral voltage sensor-interacting beta-subunit of neuronal K(V)4.2 channels. Structures of the complex are available (Kise et al.). DPP8 and DPP9 are cytosolic peptidases. Have dpp activity similar to dpp4. The first identified endogenous DPP9 substrate is the tumor epitope RU13442 (VPYGSFKHV). Inhibition or silencing of DPP9, but not DPP8, led to increased presentation of this antigen on MHC class I alleles to cytotoxic T-cells, linking DPP9 to the MHC class I antigen presentation pathway. Small ubiquitin-like protein modifier SUMO1 acts as an allosteric activator of DPP9. By binding to an armlike motif in DPP9; DPP9 functions as an endogenous inhibitor of NLRP1 inflammasome. DPP9 interacts with a unique autoproteolytic domain found in NLRP1 and CARD8. Dipeptidyl peptidase 4 (DPP4) is expressed by specific bacterial taxa of the microbiota. Microbial DPP4 is able to decrease the active glucagon like peptide-1 (GLP-1) and disrupt glucose metabolism in mice with a leaky gut. Sitagliptin, has little effect on microbial DPP4. daurisoline-d4 (Dau-d4) is a selective microbial DPP4 inhibitor that improves glucose tolerance in diabetic mice.

Database

Sequences

Peptide in Fasta
Nucleotide in Fasta
Alignment with Multalin Text only
Seed alignment with MAFFT No colour
Alignment with MAFFT No colour
Dendrogram The dnd file

Structures (182)

Genes Proteins in DPP4N_Peptidase_S9 family (829)

Fragments of genes in DPP4N_Peptidase_S9 family (13)

Structures in DPP4N_Peptidase_S9 family (182)

Substrates in DPP4N_Peptidase_S9 family (14)

Inhibitors in DPP4N_Peptidase_S9 family (159)

References (30)

Title : Microbial-host-isozyme analyses reveal microbial DPP4 as a potential antidiabetic target - Wang_2023_Science_381_eadd5787
Author(s) : Wang K , Zhang Z , Hang J , Liu J , Guo F , Ding Y , Li M , Nie Q , Lin J , Zhuo Y , Sun L , Luo X , Zhong Q , Ye C , Yun C , Zhang Y , Wang J , Bao R , Pang Y , Wang G , Gonzalez FJ , Lei X , Qiao J , Jiang C
Ref : Science , 381 :eadd5787 , 2023
PubMedID: 37535747
Gene_locus related to this paper: bactn-BT4193

Title : New insights into the role of dipeptidyl peptidase 8 and dipeptidyl peptidase 9 and their inhibitors - Cui_2022_Front.Pharmacol_13_1002871
Author(s) : Cui C , Tian X , Wei L , Wang Y , Wang K , Fu R
Ref : Front Pharmacol , 13 :1002871 , 2022
PubMedID: 36172198
Gene_locus related to this paper: human-DPP8 , human-DPP9

Title : Structural basis of gating modulation of Kv4 channel complexes - Kise_2021_Nature__
Author(s) : Kise Y , Kasuya G , Okamoto HH , Yamanouchi D , Kobayashi K , Kusakizako T , Nishizawa T , Nakajo K , Nureki O
Ref : Nature , : , 2021
PubMedID: 34552243
Gene_locus related to this paper: human-DPP6

Title : A novel structure associated with aging is augmented in the DPP6-KO mouse brain - Lin_2020_Acta.Neuropathol.Commun_8_197
Author(s) : Lin L , Petralia RS , Lake R , Wang YX , Hoffman DA
Ref : Acta Neuropathologica Commun , 8 :197 , 2020
PubMedID: 33225987
Gene_locus related to this paper: human-DPP6 , mouse-DPP6

Title : A comparative study of the binding properties, dipeptidyl peptidase-4 (DPP-4) inhibitory activity and glucose-lowering efficacy of the DPP-4 inhibitors alogliptin, linagliptin, saxagliptin, sitagliptin and vildagliptin in mice - Berger_2018_Endocrinol.Diabetes.Metab_1_e00002
Author(s) : Berger JP , SinhaRoy R , Pocai A , Kelly TM , Scapin G , Gao YD , Pryor KAD , Wu JK , Eiermann GJ , Xu SS , Zhang X , Tatosian DA , Weber AE , Thornberry NA , Carr RD
Ref : Endocrinol Diabetes Metab , 1 :e00002 , 2018
PubMedID: 30815539
Gene_locus related to this paper: human-DPP4

Title : Crystal structure of Porphyromonas gingivalis dipeptidyl peptidase 4 and structure-activity relationships based on inhibitor profiling - Rea_2017_Eur.J.Med.Chem_139_482
Author(s) : Rea D , Van Elzen R , De Winter H , Van Goethem S , Landuyt B , Luyten W , Schoofs L , Van der Veken P , Augustyns K , De Meester I , Fulop V , Lambeir AM
Ref : Eur Journal of Medicinal Chemistry , 139 :482 , 2017
PubMedID: 28826083
Gene_locus related to this paper: porgi-DPP

Title : Mapping the Specific Amino Acid Residues That Make Hamster DPP4 Functional as a Receptor for Middle East Respiratory Syndrome Coronavirus - van Doremalen_2016_J.Virol_90_5499
Author(s) : van Doremalen N , Miazgowicz KL , Munster VJ
Ref : J Virol , 90 :5499 , 2016
PubMedID: 27030263
Gene_locus related to this paper: human-DPP4

Title : The Dipeptidyl Peptidase Family, Prolyl Oligopeptidase, and Prolyl Carboxypeptidase in the Immune System and Inflammatory Disease, Including Atherosclerosis - Waumans_2015_Front.Immunol_6_387
Author(s) : Waumans Y , Baerts L , Kehoe K , Lambeir AM , De Meester I
Ref : Front Immunol , 6 :387 , 2015
PubMedID: 26300881

Title : Identification of residues on human receptor DPP4 critical for MERS-CoV binding and entry - Song_2014_Virology_471-473C_49
Author(s) : Song W , Wang Y , Wang N , Wang D , Guo J , Fu L , Shi X
Ref : Virology , 471-473C :49 , 2014
PubMedID: 25461530
Gene_locus related to this paper: human-DPP4

Title : Distribution, classification, domain architectures and evolution of prolyl oligopeptidases in prokaryotic lineages - Kaushik_2014_BMC.Genomics_15_985
Author(s) : Kaushik S , Sowdhamini R
Ref : BMC Genomics , 15 :985 , 2014
PubMedID: 25407321

Title : Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26 - Lu_2013_Nature_500_227
Author(s) : Lu G , Hu Y , Wang Q , Qi J , Gao F , Li Y , Zhang Y , Zhang W , Yuan Y , Bao J , Zhang B , Shi Y , Yan J , Gao GF
Ref : Nature , 500 :227 , 2013
PubMedID: 23831647
Gene_locus related to this paper: human-DPP4

Title : Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4 - Wang_2013_Cell.Res_23_986
Author(s) : Wang N , Shi X , Jiang L , Zhang S , Wang D , Tong P , Guo D , Fu L , Cui Y , Liu X , Arledge KC , Chen YH , Zhang L , Wang X
Ref : Cell Res , 23 :986 , 2013
PubMedID: 23835475
Gene_locus related to this paper: human-DPP4

Title : Loss-of-function variation in the DPP6 gene is associated with autosomal dominant microcephaly and mental retardation - Liao_2013_Eur.J.Med.Genet_56_484
Author(s) : Liao C , Fu F , Li R , Yang WQ , Liao HY , Yan JR , Li J , Li SY , Yang X , Li DZ
Ref : Eur Journal of Medical Genetics , 56 :484 , 2013
PubMedID: 23832105
Gene_locus related to this paper: human-DPP6

Title : A Novel SUMO1-specific Interacting Motif in Dipeptidyl Peptidase 9 (DPP9) That Is Important for Enzymatic Regulation - Pilla_2012_J.Biol.Chem_287_44320
Author(s) : Pilla E , Moller U , Sauer G , Mattiroli F , Melchior F , Geiss-Friedlander R
Ref : Journal of Biological Chemistry , 287 :44320 , 2012
PubMedID: 23152501
Gene_locus related to this paper: human-DPP9

Title : The dipeptidyl peptidase IV family in cancer and cell biology - Yu_2010_FEBS.J_277_1126
Author(s) : Yu DM , Yao TW , Chowdhury S , Nadvi NA , Osborne B , Church WB , McCaughan GW , Gorrell MD
Ref : Febs J , 277 :1126 , 2010
PubMedID: 20074209

Title : The dipeptidyl-aminopeptidase-like protein 6 is an integral voltage sensor-interacting beta-subunit of neuronal K(V)4.2 channels - Dougherty_2009_Channels.(Austin)_3_122
Author(s) : Dougherty K , Tu L , Deutsch C , Covarrubias M
Ref : Channels (Austin) , 3 :122 , 2009
PubMedID: 19372736
Gene_locus related to this paper: human-DPP6

Title : The Simpson-Golabi-Behmel syndrome causative glypican-3, binds to and inhibits the dipeptidyl peptidase activity of CD26 - Davoodi_2007_Proteomics_7_2300
Author(s) : Davoodi J , Kelly J , Gendron NH , Mackenzie AE
Ref : Proteomics , 7 :2300 , 2007
PubMedID: 17549790

Title : The protease complex consisting of dipeptidyl peptidase IV and seprase plays a role in the migration and invasion of human endothelial cells in collagenous matrices - Ghersi_2006_Cancer.Res_66_4652
Author(s) : Ghersi G , Zhao Q , Salamone M , Yeh Y , Zucker S , Chen WT
Ref : Cancer Research , 66 :4652 , 2006
PubMedID: 16651416

Title : Expression, purification and preliminary crystallographic analysis of dipeptidyl peptidase IV from Porphyromonas gingivalis - Rea_2004_Acta.Crystallogr.D.Biol.Crystallogr_60_1871
Author(s) : Rea D , Lambeir AM , Kumagai Y , De Meester I , Scharpe S , Fulop V
Ref : Acta Crystallographica D Biol Crystallogr , 60 :1871 , 2004
PubMedID: 15388936
Gene_locus related to this paper: porgi-DPP

Title : The crystal structure of dipeptidyl peptidase IV (CD26) reveals its functional regulation and enzymatic mechanism - Engel_2003_Proc.Natl.Acad.Sci.U.S.A_100_5063
Author(s) : Engel M , Hoffmann T , Wagner L , Wermann M , Heiser U , Kiefersauer R , Huber R , Bode W , Demuth HU , Brandstetter H
Ref : Proc Natl Acad Sci U S A , 100 :5063 , 2003
PubMedID: 12690074
Gene_locus related to this paper: pig-dpp4

Title : The structure and function of human dipeptidyl peptidase IV, possessing a unique eight-bladed beta-propeller fold - Hiramatsu_2003_Biochem.Biophys.Res.Commun_302_849
Author(s) : Hiramatsu H , Kyono K , Higashiyama Y , Fukushima C , Shima H , Sugiyama S , Inaka K , Yamamoto A , Shimizu R
Ref : Biochemical & Biophysical Research Communications , 302 :849 , 2003
PubMedID: 12646248
Gene_locus related to this paper: human-DPP4

Title : Cloning and characterization of dipeptidyl peptidase 10, a new member of an emerging subgroup of serine proteases - Qi_2003_Biochem.J_373_179
Author(s) : Qi SY , Riviere PJ , Trojnar J , Junien JL , Akinsanya KO
Ref : Biochemical Journal , 373 :179 , 2003
PubMedID: 12662155
Gene_locus related to this paper: human-DPP8 , human-DPP9 , human-DPP10 , mouse-dpp9 , mouse-dpp10

Title : Crystal structure of human dipeptidyl peptidase IV\/CD26 in complex with a substrate analog - Rasmussen_2003_Nat.Struct.Biol_10_19
Author(s) : Rasmussen HB , Branner S , Wiberg FC , Wagtmann N
Ref : Nat Struct Biol , 10 :19 , 2003
PubMedID: 12483204
Gene_locus related to this paper: human-DPP4

Title : Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance - Conarello_2003_Proc.Natl.Acad.Sci.U.S.A_100_6825
Author(s) : Conarello SL , Li Z , Ronan J , Roy RS , Zhu L , Jiang G , Liu F , Woods J , Zycband E , Moller DE , Thornberry NA , Zhang BB
Ref : Proc Natl Acad Sci U S A , 100 :6825 , 2003
PubMedID: 12748388
Gene_locus related to this paper: mouse-dpp4

Title : Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26 - Marguet_2000_Proc.Natl.Acad.Sci.U.S.A_97_6874
Author(s) : Marguet D , Baggio L , Kobayashi T , Bernard AM , Pierres M , Nielsen PF , Ribel U , Watanabe T , Drucker DJ , Wagtmann N
Ref : Proc Natl Acad Sci U S A , 97 :6874 , 2000
PubMedID: 10823914

Title : Enzymatic properties of dipeptidyl aminopeptidase IV produced by the periodontal pathogen Porphyromonas gingivalis and its participation in virulence - Kumagai_2000_Infect.Immun_68_716
Author(s) : Kumagai Y , Konishi K , Gomi T , Yagishita H , Yajima A , Yoshikawa M
Ref : Infect Immun , 68 :716 , 2000
PubMedID: 10639438
Gene_locus related to this paper: porgi-DPP

Title : Two highly conserved glutamic acid residues in the predicted beta propeller domain of dipeptidyl peptidase IV are required for its enzyme activity - Abbott_1999_FEBS.Lett_458_278
Author(s) : Abbott CA , McCaughan GW , Gorrell MD
Ref : FEBS Letters , 458 :278 , 1999
PubMedID: 10570924

Title : Dipeptidyl-peptidase IV secreted by Aspergillus fumigatus, a fungus pathogenic to humans - Beauvais_1997_Infect.Immun_65_3042
Author(s) : Beauvais A , Monod M , Wyniger J , Debeaupuis JP , Grouzmann E , Brakch N , Svab J , Hovanessian AG , Latge JP
Ref : Infect Immun , 65 :3042 , 1997
PubMedID: 9234752
Gene_locus related to this paper: aspfu-DPP4

Title : Direct association of adenosine deaminase with a T cell activation antigen, CD26 - Kameoka_1993_Science_261_466
Author(s) : Kameoka J , Tanaka T , Nojima Y , Schlossman SF , Morimoto C
Ref : Science , 261 :466 , 1993
PubMedID: 8101391

Title : Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7-36)amide, peptide histidine methionine and is responsible for their degradation in human serum - Mentlein_1993_Eur.J.Biochem_214_829
Author(s) : Mentlein R , Gallwitz B , Schmidt WE
Ref : European Journal of Biochemistry , 214 :829 , 1993
PubMedID: 8100523