DPP4 dipeptidyl peptidase 4 [Homo sapiens (human)] - Gene

Summary

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: mouse all
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Genomic context

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_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:456160 (e-PCR)
- UniSTS:157476

SHGC-118 (e-PCR)
- UniSTS:9518

DPP4 (e-PCR)
- UniSTS:505438

RH47162 (e-PCR)
- UniSTS:15204

RH17451 (e-PCR)
- UniSTS:672

DPP4_22 (e-PCR)
- UniSTS:277168

SHGC-12694 (e-PCR)
- UniSTS:80816

GDB:207675 (e-PCR)
- UniSTS:156121

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 more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in focal adhesion	HDA more info	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 more info	PubMed
located_in membrane	HDA more info	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

EC 3.4.14.5

NP_001366534.1

EC 3.4.14.5

NP_001366535.1

EC 3.4.14.5

NP_001926.2

EC 3.4.14.5

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)

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
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
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
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

NR_166822.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC008063

Related

ENST00000678566.1
NR_166823.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC008063

Related

ENST00000676479.1
NR_166824.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC008063

Related

ENST00000678668.1
NR_166825.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC008063

Related

ENST00000679104.1