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DPP4 dipeptidyl peptidase 4 [ Homo sapiens (human) ]

Gene ID: 1803, updated on 27-Nov-2024

Summary

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Official Symbol
DPP4provided by HGNC
Official Full Name
dipeptidyl peptidase 4provided by HGNC
Primary source
HGNC:HGNC:3009
See related
Ensembl:ENSG00000197635 MIM:102720; AllianceGenome:HGNC:3009
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CD26; ADABP; ADCP2; DPPIV; TP103
Summary
The DPP4 gene encodes dipeptidyl peptidase 4, which is identical to adenosine deaminase complexing protein-2, and to the T-cell activation antigen CD26. It is an intrinsic type II transmembrane glycoprotein and a serine exopeptidase that cleaves X-proline dipeptides from the N-terminus of polypeptides. Dipeptidyl peptidase 4 is highly involved in glucose and insulin metabolism, as well as in immune regulation. This protein was shown to be a functional receptor for Middle East respiratory syndrome coronavirus (MERS-CoV), and protein modeling suggests that it may play a similar role with SARS-CoV-2, the virus responsible for COVID-19. [provided by RefSeq, Apr 2020]
Annotation information
Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in SARS-CoV-2 infection.
Expression
Biased expression in small intestine (RPKM 70.7), placenta (RPKM 57.1) and 13 other tissues See more
Orthologs
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Genomic context

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See DPP4 in Genome Data Viewer
Location:
2q24.2
Exon count:
28
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (161992245..162074215, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (162448837..162530851, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (162848755..162930725, complement)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene solute carrier family 4 member 10 Neighboring gene uncharacterized LOC105373722 Neighboring gene ribulose-5-phosphate-3-epimerase pseudogene 5 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:162854969-162855469 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_54939 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16715 Neighboring gene Sharpr-MPRA regulatory region 3711 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16716 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12061 Neighboring gene DPP4 promoter region Neighboring gene DPP4 -4.2 kb glucocorticoid response element Neighboring gene translocase of inner mitochondrial membrane 8A pseudogene 1 Neighboring gene DPP4 divergent transcript Neighboring gene EIF3E pseudogene 2

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Adipose dipeptidyl peptidase-4 and obesity: correlation with insulin resistance and depot-specific release from adipose tissue in vivo and in vitro. Sell H, et al. Diabetes Care, 2013 Dec. PMID 24130353, Free PMC Article
  2. Polymorphisms in dipeptidyl peptidase IV gene are associated with the risk of myocardial infarction in patients with atherosclerosis. Aghili N, et al. Neuropeptides, 2012 Dec. PMID 23122333
  3. Dipeptidylpeptidase 4 negatively regulates colony-stimulating factor activity and stress hematopoiesis. Broxmeyer HE, et al. Nat Med, 2012 Dec. PMID 23160239, Free PMC Article
  4. Dipeptidyl peptidase 4 inhibition may facilitate healing of chronic foot ulcers in patients with type 2 diabetes. Marfella R, et al. Exp Diabetes Res, 2012. PMID 23197976, Free PMC Article
  5. Serum levels of advanced glycation end products (AGEs) are independently correlated with circulating levels of dipeptidyl peptidase-4 (DPP-4) in humans. Tahara N, et al. Clin Biochem, 2013 Mar. PMID 23219738

See all (614) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Exploring the conformational dynamics and key amino acids in the CD26-caveolin-1 interaction and potential therapeutic interventions.
    Title: Exploring the conformational dynamics and key amino acids in the CD26-caveolin-1 interaction and potential therapeutic interventions.
  2. Neuro-molecular perspectives on long COVID-19 impacted cerebrovascular diseases - a role for dipeptidyl peptidase IV.
    Title: Neuro-molecular perspectives on long COVID-19 impacted cerebrovascular diseases - a role for dipeptidyl peptidase IV.
  3. Dipeptidyl peptidase 4 interacts with porcine coronavirus PHEV spikes and mediates host range expansion.
    Title: Dipeptidyl peptidase 4 interacts with porcine coronavirus PHEV spikes and mediates host range expansion.
  4. Interleukin 13-Induced Inflammation Increases DPP4 Abundance but Does Not Enhance Middle East Respiratory Syndrome Coronavirus Replication in Airway Epithelia.
    Title: Interleukin 13-Induced Inflammation Increases DPP4 Abundance but Does Not Enhance Middle East Respiratory Syndrome Coronavirus Replication in Airway Epithelia.
  5. Increased Thyroid DPP4 Expression Is Associated With Inflammatory Process in Patients With Hashimoto Thyroiditis.
    Title: Increased Thyroid DPP4 Expression Is Associated With Inflammatory Process in Patients With Hashimoto Thyroiditis.
  6. Role of the Senescence-Associated Factor Dipeptidyl Peptidase 4 in the Pathogenesis of SARS-CoV-2 Infection.
    Title: Role of the Senescence-Associated Factor Dipeptidyl Peptidase 4 in the Pathogenesis of SARS-CoV-2 Infection.
  7. Contribution of amino acids in the active site of dipeptidyl peptidase 4 to the catalytic action of the enzyme.
    Title: Contribution of amino acids in the active site of dipeptidyl peptidase 4 to the catalytic action of the enzyme.
  8. A Systems Biology Approach Unveils a Critical Role of DPP4 in Upper Gastrointestinal Cancer Patient Outcomes.
    Title: A Systems Biology Approach Unveils a Critical Role of DPP4 in Upper Gastrointestinal Cancer Patient Outcomes.
  9. Association of DPP-4 Concentrations with the Occurrence of Gestational Diabetes Mellitus and Excessive Gestational Weight Gain.
    Title: Association of DPP-4 Concentrations with the Occurrence of Gestational Diabetes Mellitus and Excessive Gestational Weight Gain.
  10. m6A reader IGF2BP2 promotes lymphatic metastasis by stabilizing DPP4 in papillary thyroid carcinoma.
    Title: m6A reader IGF2BP2 promotes lymphatic metastasis by stabilizing DPP4 in papillary thyroid carcinoma.
Submit: New GeneRIF Correction See all GeneRIFs (486)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Biological insights from 108 schizophrenia-associated genetic loci.
EBI GWAS Catalog
Common genetic variants associated with cognitive performance identified using the proxy-phenotype method.
EBI GWAS Catalog
Common variants at 12q14 and 12q24 are associated with hippocampal volume.
EBI GWAS Catalog
Novel risk loci for rheumatoid arthritis in Han Chinese and congruence with risk variants in Europeans.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction Pubs
Knockdown of dipeptidyl-peptidase 4 (DPP4) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells PubMed

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env SDF-1alpha and HIV-1 gp120 induce the appearance of pseudopodia in which CD26 and CXCR4 co-localize PubMed
env Infection of cells with Macrophage-tropic HIV-1 confers preferential survival to cells with low CD26 levels; the third hypervariable region (V3) of the HIV-1 gp120 envelope protein plays an important role in this selection process PubMed
env Although CD26 has been described as a cofactor for HIV-1 gp120 mediated entry into cells, no evidence of a CD26-gp120 interaction was observed in vitro by using glutathione S-transferase-tagged HIV-1 gp120 PubMed
env Apoptosis is observed in CD4+ cells expressing the HIV-1 gp120/gp41 complex and with enhanced levels of CD26, but is not detected in cell lines expressing an uncleavable precursor of HIV-1 gp160 PubMed
env CD26 (dipeptidyl peptidase IV) cleaves the highly conserved V3 loop of HIV-1 gp120 and functions as a cofactor for entry of HIV-1 in CD4+ human cells; coexpression of human CD4 and CD26 in murine NIH 3T3 cells renders them permissive to HIV-1 PubMed
env HIV-1 gp120 inhibits adenosine deaminase (ADA) binding to CD26 (dipeptidyl-peptidase 4) in both CD4+ and CD4- cells; this effect requires the interaction of gp120 with CD4 or CXCR4 PubMed
env Treatment of CD4+ T cells with HIV-1 gp120 significantly increases CD4 association with CD3, CD45RA, CD45RB, CD59, CD38, CD26 and HLA class I, and decreases that with CD45RC PubMed
Envelope transmembrane glycoprotein gp41 env Apoptosis is observed in CD4+ cells expressing the HIV-1 gp120/gp41 complex and with enhanced levels of CD26, but is not detected in cell lines expressing an uncleavable precursor of HIV-1 gp160 PubMed
Tat tat Microarray analysis indicates HIV-1 Tat-induced upregulation of dipeptidylpeptidase 4 (DPP4; CD26; adenosine deaminase complexing protein 2) in primary human brain microvascular endothelial cells PubMed
tat HIV-1 Tat induces tyrosine phosphorylation of DPPIV in Tat/DPPIV-coexpressing cells PubMed
tat HIV1-Tat co-localizes and coimmunoprecipitates with human Dipeptidyl peptidase IV (DPPIV) protein PubMed
tat The N-terminal nine amino acids of HIV-1 Tat mediate the binding of Tat to CD26 PubMed
tat HIV-1 Tat inhibits the enzymatic activity of CD26, thereby suppressing DNA synthesis and IL-1 beta production, stimulating secretion of IL-1 receptor antagonist and TNF-alpha, and causing, at least in part, the immunosuppressive effects of Tat PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables aminopeptidase activity IEA
Inferred from Electronic Annotation
more info
  
enables chemorepellent activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables chemorepellent activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables dipeptidyl-peptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables dipeptidyl-peptidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protease binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein homodimerization activity IPI
Inferred from Physical Interaction
more info
 PubMed 
enables serine-type endopeptidase activity EXP
Inferred from Experiment
more info
 PubMed 
enables serine-type peptidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables signaling receptor binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables virus receptor activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in T cell activation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in T cell costimulation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in behavioral fear response IEA
Inferred from Electronic Annotation
more info
  
involved_in cell adhesion IEA
Inferred from Electronic Annotation
more info
  
involved_in endothelial cell migration IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in glucagon processing TAS
Traceable Author Statement
more info
  
involved_in locomotory exploration behavior IEA
Inferred from Electronic Annotation
more info
  
involved_in membrane fusion NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in negative chemotaxis IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of extracellular matrix disassembly IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of neutrophil chemotaxis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in peptide hormone processing TAS
Traceable Author Statement
more info
  
involved_in positive regulation of cell population proliferation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in proteolysis IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in proteolysis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in psychomotor behavior IEA
Inferred from Electronic Annotation
more info
  
involved_in receptor-mediated endocytosis of virus by host cell NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in receptor-mediated virion attachment to host cell NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in regulation of cell-cell adhesion mediated by integrin IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in response to hypoxia IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in symbiont entry into host cell NAS
Non-traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
located_in apical plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cell surface IDA
Inferred from Direct Assay
more info
 PubMed 
located_in endocytic vesicle IDA
Inferred from Direct Assay
more info
 PubMed 
located_in extracellular exosome HDA PubMed 
located_in extracellular region TAS
Traceable Author Statement
more info
  
located_in focal adhesion HDA PubMed 
located_in intercellular canaliculus IEA
Inferred from Electronic Annotation
more info
  
located_in lamellipodium IDA
Inferred from Direct Assay
more info
 PubMed 
located_in lamellipodium membrane IEA
Inferred from Electronic Annotation
more info
  
located_in lysosomal membrane HDA PubMed 
located_in membrane HDA PubMed 
located_in membrane raft IEA
Inferred from Electronic Annotation
more info
  
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
dipeptidyl peptidase 4
Names
ADCP-2
DPP IV
Gly-Pro naphthylamidase
Post-proline dipeptidyl aminopeptidase IV
T-cell activation antigen CD26
Xaa-Pro-dipeptidylaminopeptidase
adenosine deaminase complexing protein 2
dipeptidyl peptidase IV
dipeptidylpeptidase 4
dipeptidylpeptidase IV (CD26, adenosine deaminase complexing protein 2)
NP_001366533.1
NP_001366534.1
NP_001366535.1
NP_001926.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001379604.1 → NP_001366533.1  dipeptidyl peptidase 4 isoform 2

    Status: REVIEWED

    Source sequence(s)
    AC008063
    Consensus CDS
    CCDS92882.1
    UniProtKB/TrEMBL
    A0A7I2V2R5, A0A7I2V2X8
    Related
    ENSP00000503161.1, ENST00000676810.1
    Conserved Domains (3) summary
    pfam00326
    Location:558 → 762
    Peptidase_S9; Prolyl oligopeptidase family
    pfam00930
    Location:107 → 477
    DPPIV_N; Dipeptidyl peptidase IV (DPP IV) N-terminal region
    pfam18811
    Location:38 → 57
    DPPIV_rep; Dipeptidyl peptidase IV (DPP IV) low complexity region

  2. NM_001379605.1 → NP_001366534.1  dipeptidyl peptidase 4 isoform 3

    Status: REVIEWED

    Source sequence(s)
    AC008063
    UniProtKB/TrEMBL
    A0A7I2V2R5
    Conserved Domains (3) summary
    pfam00326
    Location:557 → 761
    Peptidase_S9; Prolyl oligopeptidase family
    pfam00930
    Location:106 → 476
    DPPIV_N; Dipeptidyl peptidase IV (DPP IV) N-terminal region
    pfam18811
    Location:37 → 56
    DPPIV_rep; Dipeptidyl peptidase IV (DPP IV) low complexity region

  3. NM_001379606.1 → NP_001366535.1  dipeptidyl peptidase 4 isoform 4

    Status: REVIEWED

    Source sequence(s)
    AC008063
    UniProtKB/TrEMBL
    A0A7I2V2R5
    Conserved Domains (3) summary
    pfam00930
    Location:108 → 460
    DPPIV_N; Dipeptidyl peptidase IV (DPP IV) N-terminal region
    pfam00326
    Location:541 → 745
    Peptidase_S9; Prolyl oligopeptidase family
    pfam18811
    Location:38 → 58
    DPPIV_rep; Dipeptidyl peptidase IV (DPP IV) low complexity region

  4. NM_001935.4 → NP_001926.2  dipeptidyl peptidase 4 isoform 1

    See identical proteins and their annotated locations for NP_001926.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1).
    Source sequence(s)
    BC065265
    Consensus CDS
    CCDS2216.1
    UniProtKB/Swiss-Prot
    P27487, Q53TN1
    UniProtKB/TrEMBL
    A0A7I2V2R5
    Related
    ENSP00000353731.3, ENST00000360534.8
    Conserved Domains (3) summary
    COG1506
    Location:398 → 764
    DAP2; Dipeptidyl aminopeptidase/acylaminoacyl peptidase [Amino acid transport and metabolism]
    pfam00326
    Location:559 → 763
    Peptidase_S9; Prolyl oligopeptidase family
    pfam00930
    Location:108 → 478
    DPPIV_N; Dipeptidyl peptidase IV (DPP IV) N-terminal region

RNA

  1. NR_166822.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC008063
    Related
    ENST00000678566.1

  2. NR_166823.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC008063
    Related
    ENST00000676479.1

  3. NR_166824.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC008063
    Related
    ENST00000678668.1

  4. NR_166825.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC008063
    Related
    ENST00000679104.1

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

    Range
    161992245..162074215 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    162448837..162530851 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P27487.2 GenPept UniProtKB/Swiss-Prot:P27487

Gene LinkOut

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