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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

DPP4 Gene

protein-coding   GIFtS: 75
GCID: GC02M162812

Dipeptidyl-Peptidase 4

(Previous names: dipeptidylpeptidase IV (CD26, adenosine deaminase complexing...)
(Previous symbols: CD26, ADCP2)
Microbiology & Infectious Diseases Congress
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
About This Section

Aliases
Dipeptidyl-Peptidase 41 2     TP1032 3
ADCP21 2 3 5     DPP IV2 3
CD261 2 3 5     T-Cell Activation Antigen CD262 3
Adenosine Deaminase Complexing Protein 21 2 3     EC 3.4.14.53 8
Dipeptidylpeptidase IV (CD26, Adenosine Deaminase Complexing Protein 2)1 2     DPPIV2
Dipeptidyl Peptidase IV2 3     Dipeptidyl Peptidase 42
ADABP2 3     Dipeptidylpeptidase 42
ADCP-22 3     CD26 Antigen3

External Ids:    HGNC: 30091   Entrez Gene: 18032   Ensembl: ENSG000001976357   OMIM: 1027205   UniProtKB: P274873   

Export aliases for DPP4 gene to outside databases

Previous GC identifers: GC02M160902 GC02M161376 GC02M163051 GC02M162674 GC02M162557 GC02M154730


(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for DPP4 Gene:
The protein encoded by this gene 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. (provided by RefSeq, Jul 2008)

GeneCards Summary for DPP4 Gene: 
DPP4 (dipeptidyl-peptidase 4) is a protein-coding gene. Diseases associated with DPP4 include mental depression, and hepatosplenic t-cell lymphoma, and among its related super-pathways are Incretin Synthesis, Secretion, and Inactivation and Insulin Processing. GO annotations related to this gene include protein homodimerization activity and serine-type endopeptidase activity. An important paralog of this gene is DPP8.

UniProtKB/Swiss-Prot: DPP4_HUMAN, P27487
Function: 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. When overexpressed, enhanced cell proliferation, a
process inhibited by GPC3. Acts also as a serine exopeptidase with a dipeptidyl peptidase activity that regulates
various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic
growth factors, neuropeptides and peptide hormones. Removes N-terminal dipeptides sequentially from polypeptides
having unsubstituted N-termini provided that the penultimate residue is proline

summary for DPP4 Gene:
Dipeptidyl Peptidase IV (DPP-IV) (also known as CD26) is a ubiquitous, membrane-bound enzyme that has roles
in nutrition, metabolism, the immune and endocrine systems, bone marrow mobilization, cancer growth and cell
adhesion. DDP-IV catalyzes the hydrolysis of N-terminal dipeptides from polypeptides with proline or alanine
in the penultimate position. This enzyme has many natural substrates including GLP-1, GIP, PACAP 38, NPY and
GRP. DPP-IV exists as a homodimer and each monomer consists of two domains; an alpha/beta hydrolase domain
and an eight-blade beta-propeller domain. DDP-IV binds to, but does not cleave, adenosine deaminase, kidney
Na+/H+ ion exchanger and fibronectin, which localizes these molecules to the cell surface. A soluble form of
DDP-IV does also exist, although it is only known to function in relation to T-cell proliferation. The human
gene encoding DPP-IV is localized to chromosome 2q24.2.

Gene Wiki entry for DPP4 (Dipeptidyl peptidase-4) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000002.11  NT_005403.17  NC_018913.2  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the DPP4 gene promoter:
         AML1a   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidDPP4 promoter sequence
   Search SABiosciences Chromatin IP Primers for DPP4

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat DPP4


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 2q24.3   Ensembl cytogenetic band:  2q24.2   HGNC cytogenetic band: 2q24.2

DPP4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
DPP4 gene location

GeneLoc information about chromosome 2         GeneLoc Exon Structure

GeneLoc location for GC02M162812:  view genomic region     (about GC identifiers)

Start:
162,848,751 bp from pter      End:
162,931,052 bp from pter
Size:
82,302 bases      Orientation:
minus strand

(According to UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MAXQB RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
About This Section

UniProtKB/Swiss-Prot: DPP4_HUMAN, P27487 (See protein sequence)
Recommended Name: Dipeptidyl peptidase 4  
Size: 766 amino acids; 88279 Da
Subunit: Monomer. Homodimer or heterodimer with Seprase (FAP). Requires homodimerization for optimal dipeptidyl
peptidase activity and T-cell costimulation. Found in a membrane raft complex, at least composed of BCL10,
CARD11, DPP4 and IKBKB. Associates with collagen. Interacts with PTPRC; the interaction is enhanced in a
interleukin-12-dependent manner in activated lymphocytes. Interacts (extracellular domain) with ADA; does not
inhibit its dipeptidyl peptidase activity. Interacts with CAV1 (via the N-terminus); the interaction is direct.
Interacts (via cytoplasmic tail) with CARD11 (via PDZ domain); its homodimerization is necessary for interaction
with CARD11. Interacts with IGF2R; the interaction is direct. Interacts with GPC3. Interacts with human
coronavirus-EMC spike protein and acts as a receptor for this virus
Subcellular location: Dipeptidyl peptidase 4 soluble form: Secreted. Note=Detected in the serum and the seminal
fluid
Subcellular location: Cell membrane; Single-pass type II membrane protein. Apical cell membrane; Single-pass type
II membrane protein. Cell projection, invadopodium membrane; Single-pass type II membrane protein. Cell
projection, lamellipodium membrane; Single-pass type II membrane protein. Cell junction. Membrane raft.
Note=Translocated to the apical membrane through the concerted action of N- and O-Glycans and its association
with lipid microdomains containing cholesterol and sphingolipids. Redistributed to membrane rafts in T-cell in a
interleukin-12-dependent activation. Its interaction with CAV1 is necessary for its translocation to membrane
rafts. Colocalized with PTPRC in membrane rafts. Colocalized with FAP in invadopodia and lamellipodia of
migratory activated endothelial cells in collagenous matrix. Colocalized with FAP on endothelial cells of
capillary-like microvessels but not large vessels within invasive breast ductal carcinoma. Colocalized with ADA
at the cell junction in lymphocyte-epithelial cell adhesion. Colocalized with IGF2R in internalized cytoplasmic
vesicles adjacent to the cell surface
Miscellaneous: Level of plasma concentrations of the soluble form (SDPP) can be managed as a colon carcinoma
diagnostic and prognostic marker
6/79 PDB 3D structures from and Proteopedia for DPP4 (see all 79):
1J2E (3D)        1N1M (3D)        1NU6 (3D)        1NU8 (3D)        1PFQ (3D)        1R9M (3D)    
Secondary accessions: Q53TN1

Explore the universe of human proteins at neXtProt for DPP4: NX_P27487

Explore proteomics data for DPP4 at MOPED 

Post-translational modifications:

  • UniProtKB: The soluble form (Dipeptidyl peptidase 4 soluble form also named SDPP) derives from the membrane form (Dipeptidyl
    peptidase 4 membrane form also named MDPP) by proteolytic processing
  • UniProtKB: N- and O-Glycosylated
  • UniProtKB: Phosphorylated. Mannose 6-phosphate residues in the carbohydrate moiety are necessary for interaction with IGF2R
    in activated T-cells. Mannose 6-phosphorylation is induced during T-cell activation
  • View modification sites using PhosphoSitePlus
  • View neXtProt modification sites for NX_P27487

  • 4/12 DME Specific Peptides for DPP4 (P27487) (see all 12)
     GDHYLCDV  FDKSKKYP  RNLYKIQL  VYAGPCSQK 

    DPP4 Protein expression data from MOPED1, PaxDb2 and MAXQB3 :    About this image 

    DPP4 Protein Expression
    REFSEQ proteins: NP_001926.2  
    ENSEMBL proteins: 
     ENSP00000353731   ENSP00000402259   ENSP00000401359   ENSP00000410264  
    Reactome Protein details: P27487
    Human Recombinant Protein Products for DPP4: 
    Browse Purified and Recombinant Proteins at EMD Millipore
    R&D Systems Recombinant & Natural Proteins for DPP4 (DPPIV/CD26)
    Enzo Life Sciences proteins for DPP4
    OriGene Purified Protein for DPP4
    OriGene Protein Over-expression Lysate for DPP4
    OriGene MassSpec for DPP4 
    OriGene Custom Protein Services for DPP4
    GenScript Custom Purified and Recombinant Proteins Services for DPP4
    Novus Biologicals DPP4 Proteins
    Novus Biologicals DPP4 Lysates
    Sino Biological Recombinant Protein for DPP4
    Sino Biological Cell Lysate for DPP4 
    ProSpec Recombinant Protein for DPP4
    Cloud-Clone Corp. Proteins for DPP4 

    Gene Ontology (GO): 5/13 cellular component terms (GO ID links to tree view) (see all 13):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005765lysosomal membrane IDA17897319
    GO:0005886plasma membrane IDA16670267
    GO:0009986cell surface IDA10900005
    GO:0016020membrane ----
    GO:0016021integral to membrane IEA--

    DPP4 for ontologies           About GeneDecksing



    DPP4 Antibody Products: 
    Browse EMD Millipore's Extensive Line of Mono- and Polyclonal Antibodies
    R&D Systems Antibodies for DPP4 (DPPIV/CD26)
    OriGene Antibodies for DPP4
    OriGene Custom Antibody Services for DPP4
    GenScript Custom Superior Antibodies Services for DPP4
    Novus Biologicals DPP4 Antibodies
    Abcam antibodies for DPP4
    Cloud-Clone Corp. Antibodies for DPP4 
    ThermoFisher Antibody for DPP4
    LSBio Antibodies in human, mouse, rat for DPP4 

    Assay Products for DPP4: 
    EMD Millipore Kits and Assays for the Analysis of DPP4
    OriGene Custom Assay Services for DPP4
    R&D Systems ELISAs for DPP4 (DPPIV/CD26)         (see all)
    GenScript DPP4-Activity-based Protease Assay for Compound Screening
    Enzo Life Sciences assays for DPP4
    Cloud-Clone Corp. ELISAs for DPP4 
    Cloud-Clone Corp. CLIAs for DPP4


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    HGNC Gene Families: 
    CD: CD molecules

    IUPHAR Guide to PHARMACOLOGY protein family classification: Dipeptidyl peptidase IV 
    Endopeptidases

    3 InterPro protein domains:
     IPR001375 Peptidase_S9
     IPR002471 Pept_S9_AS
     IPR002469 Peptidase_S9B

    Graphical View of Domain Structure for InterPro Entry P27487

    ProtoNet protein and cluster: P27487

    2 Blocks protein domains:
    IPB002469 Dipeptidylpeptidase IV (CD26)
    IPB002471 Prolyl endopeptidase


    UniProtKB/Swiss-Prot: DPP4_HUMAN, P27487
    Domain: The extracellular cysteine-rich region is necessary for association with collagen, dimer formation and
    optimal dipeptidyl peptidase activity
    Similarity: Belongs to the peptidase S9B family. DPPIV subfamily


    DPP4 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
    About This Section

    Molecular Function:

         UniProtKB/Swiss-Prot Summary: DPP4_HUMAN, P27487
    Function: 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. When overexpressed, enhanced cell proliferation, a
    process inhibited by GPC3. Acts also as a serine exopeptidase with a dipeptidyl peptidase activity that regulates
    various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic
    growth factors, neuropeptides and peptide hormones. Removes N-terminal dipeptides sequentially from polypeptides
    having unsubstituted N-termini provided that the penultimate residue is proline
    Catalytic activity: Release of an N-terminal dipeptide, Xaa-Yaa- -Zaa-, from a polypeptide, preferentially when
    Yaa is Pro, provided Zaa is neither Pro nor hydroxyproline
    Enzyme regulation: Inhibited by GPC3 and diprotin A
    Induction: Up-regulated by IL12/interleukin-12 on activated T-cells. IL12-activated cells expressed enhanced
    levels of DPP4 but not mRNAs. Down-regulated by TNF. Up-regulated in migratory endothelial cells and in the
    invasive endothelial cells in tumors

         Genatlas biochemistry entry for DPP4:
    peptidase,dipeptidyl IV (intestinal),regulated by hepatocyte nuclear factor 1 alpha

         Enzyme Number (IUBMB): EC 3.4.14.51 2

         Gene Ontology (GO): 5/9 molecular function terms (GO ID links to tree view) (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0002020protease binding IPI16651416
    GO:0004177aminopeptidase activity IEA--
    GO:0004252serine-type endopeptidase activity IEA--
    GO:0005102receptor binding IPI10900005
    GO:0005515protein binding IPI14684150
         
    DPP4 for ontologies           About GeneDecksing


    Phenotypes:
         3 MGI mutant phenotypes (inferred from 2 alleles(MGI details for Dpp4):
     endocrine/exocrine gland  growth/size  homeostasis/metabolism 

    DPP4 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-out Dpp4tm1Nwa for DPP4

       inGenious Targeting Laboratory - Custom generated mouse model solutions for DPP4 
       inGenious Targeting Laboratory - Custom generated inducible mouse model solutions for DPP4

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for DPP4 
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for DPP4 

    miRNA
    Products:
        
    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat DPP4
    8/12 QIAGEN miScript miRNA Assays for microRNAs that regulate DPP4 (see all 12):
    hsa-miR-124* hsa-miR-4324 hsa-miR-4291 hsa-miR-448 hsa-miR-3660 hsa-miR-29a hsa-miR-29c hsa-miR-3672
    SwitchGear 3'UTR luciferase reporter plasmidDPP4 3' UTR sequence
    Inhib. RNA
    Products:
        
    Browse for Gene Knock-down Tools from EMD Millipore
    OriGene RNAi products in human, mouse, rat for DPP4
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat DPP4

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for DPP4
    Sirion Biotech Customized adenovirus for overexpression of DPP4

    Clone
    Products:
         
    Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
    OriGene clones in human, mouse for DPP4 (see all 7)
    OriGene ORF clones in mouse, rat for DPP4
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: DPP4 (NM_001935)
    Sino Biological Human cDNA Clone for DPP4
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for DPP4
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat DPP4
    Sirion Biotech Customized lentivirus for stable overexpression of DPP4 
                         Customized lentivirus expression plasmids for stable overexpression of DPP4 

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for DPP4
    Search LifeMap BioReagents cell lines for DPP4
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for DPP4


    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene).
    About This Section

    SuperPaths for DPP4 About                                                                                                See pathways by source

    SuperPathContained pathways About
    1Synthesis, Secretion, and Inactivation of Glucagon-like Peptide-1 (GLP-1)
    Synthesis, Secretion, and Inactivation of Glucagon-like Peptide-1 (GLP-1)0.89
    Incretin Synthesis, Secretion, and Inactivation0.89
    Synthesis, Secretion, and Inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP)0.89
    2Insulin Processing
    Peptide hormone metabolism0.39
    3Asparagine N-linked glycosylation
    Metabolism of proteins0.35
    4Selected targets of HNF1
    Selected targets of HNF1
    5Protein digestion and absorption
    Protein digestion and absorption

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 EMD Millipore Pathway for DPP4
        Selected targets of HNF1



    5        Reactome Pathways for DPP4
        Synthesis, Secretion, and Inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP)
    Incretin Synthesis, Secretion, and Inactivation
    Metabolism of proteins
    Peptide hormone metabolism
    Synthesis, Secretion, and Inactivation of Glucagon-like Peptide-1 (GLP-1)


    1         Kegg Pathway  (Kegg details for DPP4):
        Protein digestion and absorption


    DPP4 for pathways           About GeneDecksing

    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for DPP4

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    5/53 Interacting proteins for DPP4 (P274872, 3 ENSP000003537314) via UniProtKB, MINT, STRING, and/or I2D (see all 53)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    CCL11P516712, 3, ENSP000003022344MINT-8090954 I2D: score=2 STRING: ENSP00000302234
    CXCL11O146252, 3, ENSP000003068844MINT-8091131 I2D: score=2 STRING: ENSP00000306884
    CXCL12P480612, 3, ENSP000003635484MINT-8091118 I2D: score=2 STRING: ENSP00000363548
    CXCL9Q073252, 3, ENSP000003549014MINT-8091083 I2D: score=2 STRING: ENSP00000354901
    GHRHP012862, 3, ENSP000002375274MINT-8090823 I2D: score=1 STRING: ENSP00000237527
    About this table

    Gene Ontology (GO): 5/9 biological process terms (GO ID links to tree view) (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001666response to hypoxia IDA16670267
    GO:0006508proteolysis IEA--
    GO:0007155cell adhesion IEA--
    GO:0008284positive regulation of cell proliferation IDA17549790
    GO:0010716negative regulation of extracellular matrix disassembly IDA16651416

    DPP4 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    DPP4 for compounds           About GeneDecksing

    EMD Millipore small molecules for DPP4:
    Small Molecule - inhibitor
    Enzo Life Sciences drugs & compounds for DPP4

    Compounds for DPP4 available from Tocris Bioscience    About this table
    CompoundAction CAS #
    K 579Dipeptidyl peptidase IV (DPP-IV) inhibitor[440100-64-1]
    PK 44 phosphatePotent and selective dipeptidyl peptidase IV (DPP-IV) inhibitor[1017682-65-3]
    NVP DPP 728 dihydrochloride Potent, orally active dipeptidyl peptidase IV (DPP-IV) inhibitor [247016-69-9]
    DPPI 1c hydrochlorideDipeptidyl peptidase IV (DPP-IV) inhibitor[866396-34-1]

    1 HMDB Compound for DPP4    About this table
    CompoundSynonyms CAS #PubMed Ids
    Hydroxyproline(2S,4R)-4-hydroxy-2-pyrrolidinecarboxylic acid (see all 21)51-35-4--

    10/52 DrugBank Compounds for DPP4 (see all 52)    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    SitagliptinMK-0431 (see all 3)486460-32-6targetinhibitor16868220 19065993 17593236 18182122 16338283 17315049 17352516 11752352 17407649 16855072 16490580 16682937
    (2s)-Pyrrolidin-2-Ylmethylamine-- --target--17139284 17016423 10592235
    2-Amino-3-Methyl-1-Pyrrolidin-1-Yl-Butan-1-One-- --target--17139284 17016423 10592235
    5-(Aminomethyl)-6-(2,4-Dichlorophenyl)-2-(3,5-Dimethoxyphenyl)Pyrimidin-4-Amine-- --target--17139284 17016423 10592235
    Alpha-D-Mannose-- 3458-28-4target--17139284 17016423 10592235
    VildagliptinEQUA (see all 8)274901-16-5targetinhibitor19149538 8100523 15562200
    Diisopropylphosphono Group-- --target--17139284 17016423
    (1S)-2-[(2S,5R)-2-(AMINOMETHYL)-5-ETHYNYLPYRROLIDIN-1-YL]-1-CYCLOPENTYL-2-OXOETHANAMINE-- --target--10592235
    (1S)-2-[(2S,5R)-2-(AMINOMETHYL)-5-PROP-1-YN-1-YLPYRROLIDIN-1-YL]-1-CYCLOPENTYL-2-OXOETHANAMINE-- --target--10592235
    (1S,2R,5S)-5-[3-(TRIFLUOROMETHYL)-5,6-DIHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRAZIN-7(8H)-YL]-2-(2,4,5-TRIFLUOROPHENYL)CYCLOHEXANAMINE-- --target--10592235

    10/81 Novoseek inferred chemical compound relationships for DPP4 gene (see all 81)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    vildagliptin 96.9 109 15907807 (4), 17456545 (4), 17559747 (2), 17486328 (2) (see all 69)
    sitagliptin 96.5 123 16338283 (4), 18174966 (3), 16855072 (3), 17315049 (3) (see all 78)
    incretin 95.9 198 12517256 (3), 16939389 (3), 18979908 (3), 19780719 (3) (see all 99)
    saxagliptin 92.2 25 19051153 (4), 20460554 (2), 19444391 (2), 16364232 (2) (see all 17)
    exenatide 91.1 44 19421968 (2), 18363534 (1), 16724926 (1), 17566392 (1) (see all 30)
    liraglutide 89.7 22 17566392 (1), 19170358 (1), 19330494 (1), 20298625 (1) (see all 16)
    metformin 84.3 43 15842525 (5), 17559747 (2), 17300594 (2), 16043735 (1) (see all 28)
    pro-boropro 79.6 4 7918465 (1), 7892748 (1), 8103356 (1)
    (2r)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8h)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine 73.3 4 15634008 (2), 16338283 (1)
    pramlintide 71.3 5 16215105 (1), 17983555 (1), 16627399 (1), 18035865 (1) (see all 5)

    Search CenterWatch for drugs/clinical trials and news about DPP4

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Sirion Biotech, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section

    REFSEQ mRNAs for DPP4 gene: 
    NM_001935.3  

    Unigene Cluster for DPP4:

    Dipeptidyl-peptidase 4
    Hs.368912  [show with all ESTs]
    Unigene Representative Sequence: NM_001935
    10 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000360534(uc002ubz.3 uc010fpb.3) ENST00000434918 ENST00000491591
    ENST00000490286 ENST00000494507 ENST00000468903 ENST00000416189 ENST00000497461(uc002uca.1 uc002ucb.1)
    ENST00000461836 ENST00000413651
    Congresses - knowledge worth sharing:  
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

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    Additional mRNA sequence: 

    AB451339.1 AB451488.1 AK314798.1 AY429531.1 AY429532.1 AY429533.1 BC013329.2 BC065265.1 
    M74777.1 M80536.1 X60708.1 

    10 DOTS entries:

    DT.91801581  DT.95158537  DT.100790607  DT.91744488  DT.121006132  DT.121006110  DT.75167565  DT.100689591 
    DT.121006125  DT.91744489 

    24/277 AceView cDNA sequences (see all 277):

    BM831056 BQ427580 AI091652 BQ021261 BX381370 BQ019734 BP334755 AA613759 
    BX110831 AU105699 AU105696 AA031955 NM_001935 AI273039 AI768728 CR618494 
    AL708589 AI420984 AA931228 BC065265 BC013329 AW299669 BE885391 BM768944 

    GeneLoc Exon Structure

    5/12 Alternative Splicing Database (ASD) splice patterns (SP) for DPP4 (see all 12)    About this scheme

    ExUns: 1 ^ 2a · 2b · 2c ^ 3 ^ 4a · 4b ^ 5 ^ 6 ^ 7a · 7b ^ 8 ^ 9 ^ 10a · 10b ^ 11a · 11b ^ 12a · 12b ^ 13 ^ 14a · 14b ^ 15 ^ 16 ^ 17 ^ 18 ^
    SP1:                                            -           -     -                                                     -                       -               
    SP2:                                                        -     -                                                     -                                       
    SP3:        -                                   -           -     -                                                                                             
    SP4:                                            -           -     -                                                                                             
    SP5:                                                                                                                                                            

    ExUns: 19 ^ 20 ^ 21 ^ 22 ^ 23a · 23b ^ 24 ^ 25 ^ 26 ^ 27 ^ 28 ^ 29 ^ 30 ^ 31
    SP1:              -                                                                     
    SP2:                                                                                    
    SP3:                                                                                    
    SP4:                                                                                    
    SP5:                                                                                    


    ECgene alternative splicing isoforms for DPP4

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    DPP4 expression in normal human tissues (normalized intensities)      DPP4 embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: GCTGGGAACC
    DPP4 Expression
    About this image


    DPP4 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database 
     5/11 selected tissues (see all 11) fully expand
     
     Kidney (Urinary System)    fully expand to see all 4 entries
             Proximal Tubule Cells Proximal Tubule
             S-shaped Body
     
     Chorion (Extraembryonic Tissues)
             Chorionic Mesenchymal Stromal Cells Chorionic Villus
     
     Lower Urinary Tract (Urinary System)
             visceral organ   
     
     Eye (Sensory Organs)
             Human corneal endothelial cells
     
     Oral Cavity (Gastrointestinal Tract)
             Salivary gland   

    See DPP4 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for DPP4

    SOURCE GeneReport for Unigene cluster: Hs.368912

    UniProtKB/Swiss-Prot: DPP4_HUMAN, P27487
    Tissue specificity: Expressed specifically in lymphatic vessels but not in blood vessels in the skin, small
    intestine, esophagus, ovary, breast and prostate glands. Not detected in lymphatic vessels in the lung, kidney,
    uterus, liver and stomach (at protein level). Expressed in the poorly differentiated crypt cells of the small
    intestine as well as in the mature villous cells. Expressed at very low levels in the colon

        SABiosciences Expression via Pathway-Focused PCR Arrays including DPP4: 
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              Diabetes in human mouse rat
              Cell Motility in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

    This gene was present in the common ancestor of animals and fungi.

    Orthologs for DPP4 gene from 8/18 species (see all 18)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Dpp41 , 5 dipeptidylpeptidase 41, 5 86.65(n)1
    85.24(a)1
      2 (35.85 cM)5
    134821  NM_010074.31  NP_034204.11 
     623300735 
    chicken
    (Gallus gallus)
    Aves DPP41 dipeptidyl-peptidase 4 68.03(n)
    65.08(a)
      424187  NM_001031255.1  NP_001026426.1 
    lizard
    (Anolis carolinensis)
    Reptilia DPP46
    Uncharacterized protein
    63(a)
    1 ↔ 1
    GL343359.1(634053-711896)
    African clawed frog
    (Xenopus laevis)
    Amphibia LOC3978882 dipeptidyl-peptidase IV 75.6(n)    Y08932.1 
    zebrafish
    (Danio rerio)
    Actinopterygii dpp41 dipeptidyl-peptidase 4 61.09(n)
    57.96(a)
      100301982  NM_001161337.1  NP_001154809.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta CG113193
    CG110341
    dipeptidyl-peptidase IV3
    CG110341
    33(a)
    (best of 3)3
    45.77(n)1
    36.75(a)1
      338101  NM_135117.21  NP_608961.21 
    worm
    (Caenorhabditis elegans)
    Secernentea C27C12.73 dipeptidyl aminopeptidase like 30(a)
    (best of 3)
      X(14867078-14873371)   --
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes DAP2(YHR028C)4 Dipeptidyl aminopeptidase, synthesized as a glycosylated more   --   8(167434-164978) 856423  NP_011893.1 


    ENSEMBL Gene Tree for DPP4 (if available)
    TreeFam Gene Tree for DPP4 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for DPP4 gene
    DPP82  FAP2  DPP102  DPP62  DPP92  
    3 SIMAP similar genes for DPP4 using alignment to 4 protein entries:     DPP4_HUMAN (see all proteins):
    FAP    DPP10    DPP6

    DPP4 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/1884 SNPs in DPP4 are shown (see all 1884)    About this table     
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 2 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1926020261,2
    --162848261(+) CCTGAC/TCTCGT 1 -- ds50010--------
    rs1835133371,2
    --162848492(+) TATGAA/TATAAG 1 -- ds50010--------
    rs1878152211,2
    --162848550(+) TGATAA/GGAGAA 1 -- ds50010--------
    rs1925023321,2
    --162848688(+) CAAGAG/TCCTTT 1 -- ds50010--------
    rs1848410071,2
    --162848689(+) AAGAGA/CCTTTC 1 -- ds50010--------
    rs1455260571,2
    --162848713(+) CCATAC/TGCCAG 1 -- ds50010--------
    rs1896030711,2
    --162848751(+) AGTCAC/TTACTT 1 -- ds50010--------
    rs1814393311,2
    C--162848808(+) TAGTAC/TGTAGA 1 -- ut310--------
    rs1846139161,2
    --162848965(+) ATACAA/GATATT 1 -- ut310--------
    rs115379901,2
    C,F,H--162849048(-) AAAAAA/CAATAC 1 -- ut31 ese32Minor allele frequency- C:0.01NS NA 178

    HapMap Linkage Disequilibrium report for DPP4 (162848751 - 162931052 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 2 variations for DPP4:    About this table     
    Variant IDTypeSubtypePubMed ID
    nsv3008CNV Insertion18451855
    nsv834439CNV Gain17160897


    Human Gene Mutation Database (HGMD): DPP4
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section
    OMIM gene information: 102720    OMIM disorders: --

    20/125 diseases for DPP4 (see all 125):    About MalaCards
    mental depression    hepatosplenic t-cell lymphoma    simpson-golabi-behmel syndrome    alk-negative anaplastic large cell lymphoma
    arc syndrome    short bowel syndrome    follicular adenoma    eating disorder
    angioedema    glucose intolerance    follicular thyroid carcinoma    cutaneous leishmaniasis
    fabry disease    liver disease    cardiovascular disease risk factor )    mycosis fungoides
    bulimia nervosa    severe combined immunodeficiency    celiac disease    cystadenocarcinoma

    4 diseases from the University of Copenhagen DISEASES database for DPP4:
    Diabetes mellitus     Hypoglycemia     Hyperglycemia     Nasopharyngitis

    DPP4 for disorders           About GeneDecksing

    10/95 Novoseek inferred disease relationships for DPP4 gene (see all 95)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    hypoglycemia 80.1 18 18641927 (1), 19444259 (1), 19820277 (1), 19170358 (1) (see all 17)
    niddm 75.3 69 18019673 (3), 18425967 (2), 16503716 (2), 17190843 (2) (see all 55)
    hyperglycemia 57.2 11 15864535 (3), 16939389 (1), 17160910 (1), 18035865 (1) (see all 8)
    sezary syndrome 49.5 2 11392886 (1), 16197392 (1)
    insulin resistance 47.5 4 19333209 (1), 12524666 (1), 15934925 (1)
    nasopharyngitis 42.7 1 17622601 (1)
    goiter adenomatous 38.3 1 7591305 (1)
    hyperinsulinemia 36.6 6 18319497 (1), 18812476 (1), 15770466 (1), 19128990 (1)
    impaired glucose tolerance 35.1 6 12808880 (2), 9792533 (1), 15330741 (1), 12524666 (1)
    colon adenocarcinoma 31.7 4 1968064 (1), 7903248 (1), 11772392 (1)

    Genetic Association Database (GAD): DPP4
    Human Genome Epidemiology (HuGE) Navigator: DPP4 (8 documents)

    Export disorders for DPP4 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
    About This Section

    PubMed articles for DPP4 gene, integrated from 9 sources (see all 1124):
    (articles sorted by number of sources associating them with DPP4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Direct association of adenosine deaminase with a T cell activation antigen, CD26. (PubMed id 8101391)1, 2, 3, 9 Kameoka J.... Morimoto C. (1993)
    2. Internalization of CD26 by mannose 6-phosphate/insulin-like growth factor II receptor contributes to T cell activation. (PubMed id 10900005)1, 2, 9 Ikushima H....Morimoto C. (2000)
    3. N-linked glycosylation of dipeptidyl peptidase IV (CD26): effects on enzyme activity, homodimer formation, and adenosine deaminase binding. (PubMed id 14691230)1, 2, 9 Aertgeerts K.... Swanson R.V. (2004)
    4. Caveolin-1 triggers T-cell activation via CD26 in association with CARMA1. (PubMed id 17287217)1, 2, 9 Ohnuma K....Morimoto C. (2007)
    5. A marker for neoplastic progression of human melanocytes is a cell surface ectopeptidase. (PubMed id 8096237)1, 2, 9 Morrison M.E....Houghton A.N. (1993)
    6. Dipeptidyl peptidase IV (CD 26) gene expression in enterocyte-like colon cancer cell lines HT-29 and Caco-2. Cloning of the complete human coding sequence and changes of dipeptidyl peptidase IV mRNA levels during cell differentiation. (PubMed id 1347043)1, 2, 9 Darmoul D....Barbat A. (1992)
    7. Regulation of epithelial and lymphocyte cell adhesion by adenosine deaminase-CD26 interaction. (PubMed id 11772392)1, 2, 9 Gines S....Franco R. (2002)
    8. 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. (PubMed id 16651416)1, 2, 9 Ghersi G....Chen W.T. (2006)
    9. Intestinal dipeptidyl peptidase IV is efficiently sorted to the apical membrane through the concerted action of N- and O-glycans as well as association with lipid microdomains. (PubMed id 11773049)1, 2, 9 Alfalah M.... Naim H.Y. (2002)
    10. Expression of sucrase-isomaltase and dipeptidylpeptidase IV in human small intestine and colon. (PubMed id 1677636)1, 2, 9 Gorvel J.P....Maroux S. (1991)

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section
    Entrez Gene: 1803 HGNC: 3009 AceView: DPP4 Ensembl:ENSG00000197635 euGenes: HUgn1803
    ECgene: DPP4 Kegg: 1803 H-InvDB: DPP4

    (According to HUGE)
    About This Section
      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    PharmGKB entry for DPP4 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for DPP4 Genetics and Cytogenetics in Oncology and Haematology
    Wikipedia http://en.wikipedia.org/wiki/Dipeptidyl_peptidase-4

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    Patent Information for DPP4 gene:
    Search GeneIP for patents involving DPP4

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0 and Sirion Biotech, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Sirion Biotech, Cell lines from GenScript, and LifeMap BioReagents, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or Enzo Life Sciences, In Situ Hybridization Assays from
    Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory, genOway)
    About This Section

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     Codon Optimization
     Protein Production and Purification
     Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for DPP4
     SwitchGear 3'UTR luciferase reporter plasmids for DPP4
     SwitchGear Promoter luciferase reporter plasmids for DPP4
     ThermoFisher Antibody for DPP4
     Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat DPP4
     inGenious Targeting Laboratory - Custom generated mouse model solutions for DPP4
     inGenious Targeting Laboratory - Custom generated inducible mouse model solutions for DPP4
    Customized:
     lentivirus for stable overexpression of DPP4
     lentivirus expression plasmids for stable overexpression of DPP4
     adenovirus for overexpression of DPP4
     LSBio Antibodies in human, mouse, rat for DPP4
    Customized transgenic rodents for:
     Humanization
     Biomarker expression
     Off-target effect monitoring
     Translational medicine
     Tissue-specific gene expresssion
     Time-controlled gene expresssion
           
    GeneCards Homepage - Last full update: 23 Oct 2013 - Incrementals: 4 Nov 2013 , 7 Nov 2013 , 23 Jan 2014

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    (GIFtS: 73)
    transforming growth factor, beta 1
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