DPP4

Protein identityUniProt · HPA

UniProt accession

P27487

Gene

DPP4

Ensembl

ENSG00000197635

Chromosome

2

Canonical length

766 aa

Protein class

CD markers, Enzymes, FDA approved drug targets, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins, Transporters

Secretome location

Secreted to blood

Quaternary structure

Homodimer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

766 residues, UniProt reviewed canonical sequence.

>P27487|DPP4
     1  MKTPWKVLLG LLGAAALVTI ITVPVVLLNK GTDDATADSR KTYTLTDYLK NTYRLKLYSL
    61  RWISDHEYLY KQENNILVFN AEYGNSSVFL ENSTFDEFGH SINDYSISPD GQFILLEYNY
   121  VKQWRHSYTA SYDIYDLNKR QLITEERIPN NTQWVTWSPV GHKLAYVWNN DIYVKIEPNL
   181  PSYRITWTGK EDIIYNGITD WVYEEEVFSA YSALWWSPNG TFLAYAQFND TEVPLIEYSF
   241  YSDESLQYPK TVRVPYPKAG AVNPTVKFFV VNTDSLSSVT NATSIQITAP ASMLIGDHYL
   301  CDVTWATQER ISLQWLRRIQ NYSVMDICDY DESSGRWNCL VARQHIEMST TGWVGRFRPS
   361  EPHFTLDGNS FYKIISNEEG YRHICYFQID KKDCTFITKG TWEVIGIEAL TSDYLYYISN
   421  EYKGMPGGRN LYKIQLSDYT KVTCLSCELN PERCQYYSVS FSKEAKYYQL RCSGPGLPLY
   481  TLHSSVNDKG LRVLEDNSAL DKMLQNVQMP SKKLDFIILN ETKFWYQMIL PPHFDKSKKY
   541  PLLLDVYAGP CSQKADTVFR LNWATYLAST ENIIVASFDG RGSGYQGDKI MHAINRRLGT
   601  FEVEDQIEAA RQFSKMGFVD NKRIAIWGWS YGGYVTSMVL GSGSGVFKCG IAVAPVSRWE
   661  YYDSVYTERY MGLPTPEDNL DHYRNSTVMS RAENFKQVEY LLIHGTADDN VHFQQSAQIS
   721  KALVDVGVDF QAMWYTDEDH GIASSTAHQH IYTHMSHFIK QCFSLP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DPP4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.23

Highest tissue expression

147 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DPP4.

Disease | ImmuneIEDB

Conditions an epitope on DPP4 was assayed in.

• multiple sclerosis B cell
• amyotrophic lateral sclerosis B cell
• neuromyelitis optica B cell

ReferencesPubMed · IEDB

Publications for DPP4 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.62

gnomAD pLI

0

gnomAD missense Z

0.79

DepMap mean gene effect

0.03

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• behavioral fear response
• cell adhesion
• endothelial cell migration
• locomotory exploration behavior
• membrane fusion
• negative regulation of extracellular matrix disassembly
• negative regulation of neutrophil chemotaxis
• peptide hormone processing
• positive regulation of cell population proliferation
• proteolysis
• psychomotor behavior
• receptor-mediated endocytosis of virus by host cell
• receptor-mediated virion attachment to host cell
• regulation of cell-cell adhesion mediated by integrin
• response to hypoxia
• symbiont entry into host cell
• T cell activation
• T cell costimulation
• glucagon processing

Molecular functions

• aminopeptidase activity
• chemorepellent activity
• dipeptidyl-peptidase activity
• identical protein binding
• protease binding
• protein homodimerization activity
• serine-type endopeptidase activity
• serine-type peptidase activity
• signaling receptor binding
• virus receptor activity

Cellular components

• apical plasma membrane
• cell surface
• endocytic vesicle
• extracellular exosome
• extracellular region
• focal adhesion
• intercellular canaliculus
• lamellipodium
• lamellipodium membrane
• lysosomal membrane
• membrane
• membrane raft
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Peptidase S9, prolyl oligopeptidase, catalytic domain
• Dipeptidylpeptidase IV, N-terminal domain
• Peptidase S9, serine active site
• Alpha/Beta hydrolase fold
• Serine protease S9B/DPPIV
• Prolyl oligopeptidase family
• Dipeptidyl peptidase IV (DPP IV) N-terminal region

KeywordsUniProt

• Aminopeptidase
• Cell adhesion
• Cell junction
• Cell membrane
• Cell projection
• Disulfide bond
• Glycoprotein
• Host-virus interaction
• Hydrolase
• Membrane
• Protease
• Receptor
• Secreted
• Serine protease
• Signal-anchor
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of DPP4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CAV1
• GPC3
• IGF2R
• PTPRC
• ADA