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P22411 (DPP4_PIG) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Dipeptidyl peptidase 4

EC=3.4.14.5
Alternative name(s):
Dipeptidyl peptidase IV
Short name=DPP IV
T-cell activation antigen CD26
CD_antigen=CD26

Cleaved into the following 2 chains:

  1. Dipeptidyl peptidase 4 membrane form
    Alternative name(s):
    Dipeptidyl peptidase IV membrane form
  2. Dipeptidyl peptidase 4 soluble form
    Alternative name(s):
    Dipeptidyl peptidase IV soluble form
Gene names
Name:DPP4
Synonyms:CD26
OrganismSus scrofa (Pig) [Reference proteome]
Taxonomic identifier9823 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus

Protein attributes

Sequence length766 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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 By similarity. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline. Ref.1

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 By similarity.

Subunit structure

Monomer. 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 By similarity. Homodimer. Ref.4

Subcellular location

Dipeptidyl peptidase 4 soluble form: Secreted. Note: Detected in the serum and the seminal fluid By similarity.

Cell membrane; Single-pass type II membrane protein. Apical cell membrane; Single-pass type II membrane protein By similarity. Cell projectioninvadopodium membrane; Single-pass type II membrane protein By similarity. Cell projectionlamellipodium membrane; Single-pass type II membrane protein By similarity. Cell junction By similarity. Membrane raft By similarity. 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 By similarity.

Post-translational modification

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.

N- and O-Glycosylated By similarity. Ref.4

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 By similarity.

Sequence similarities

Belongs to the peptidase S9B family. DPPIV subfamily.

Ontologies

Keywords
   Biological processCell adhesion
   Cellular componentCell junction
Cell membrane
Cell projection
Membrane
Secreted
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   Molecular functionAminopeptidase
Hydrolase
Protease
Serine protease
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processT cell activation

Inferred from electronic annotation. Source: Ensembl

T cell costimulation

Inferred from sequence or structural similarity. Source: UniProtKB

cell adhesion

Inferred from electronic annotation. Source: UniProtKB-KW

endothelial cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of extracellular matrix disassembly

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of cell-cell adhesion mediated by integrin

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentapical plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

cell surface

Inferred from sequence or structural similarity. Source: UniProtKB

endocytic vesicle

Inferred from sequence or structural similarity. Source: UniProtKB

extracellular vesicular exosome

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

intercellular canaliculus

Inferred from electronic annotation. Source: Ensembl

invadopodium membrane

Inferred from sequence or structural similarity. Source: UniProtKB

lamellipodium

Inferred from sequence or structural similarity. Source: UniProtKB

lamellipodium membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

lysosomal membrane

Inferred from electronic annotation. Source: Ensembl

membrane raft

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionaminopeptidase activity

Inferred from electronic annotation. Source: UniProtKB-KW

dipeptidyl-peptidase activity

Inferred from sequence or structural similarity. Source: UniProtKB

protease binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein homodimerization activity

Inferred from sequence or structural similarity. Source: UniProtKB

receptor binding

Inferred from sequence or structural similarity. Source: UniProtKB

serine-type endopeptidase activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 766766Dipeptidyl peptidase 4 membrane form
PRO_0000027217
Chain38 – 766729Dipeptidyl peptidase 4 soluble form
PRO_0000027218

Regions

Topological domain1 – 66Cytoplasmic Potential
Transmembrane7 – 2721Helical; Signal-anchor for type II membrane protein; Potential
Topological domain28 – 766739Extracellular Potential

Sites

Active site6301Charge relay system By similarity
Active site7081Charge relay system By similarity
Active site7401Charge relay system By similarity

Amino acid modifications

Glycosylation851N-linked (GlcNAc...) Ref.4
Glycosylation921N-linked (GlcNAc...) Ref.4
Glycosylation2291N-linked (GlcNAc...) Ref.4
Glycosylation2791N-linked (GlcNAc...) Ref.4
Glycosylation3211N-linked (GlcNAc...) Ref.4
Glycosylation6851N-linked (GlcNAc...) Ref.4
Disulfide bond385 ↔ 394
Disulfide bond444 ↔ 447
Disulfide bond454 ↔ 472
Disulfide bond649 ↔ 762

Experimental info

Sequence conflict321Missing Ref.2

Secondary structure

........................................................................................................................................................ 766
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P22411 [UniParc].

Last modified September 13, 2004. Version 3.
Checksum: 8800D520BAEA856D

FASTA76688,242
        10         20         30         40         50         60 
MKTPWKVLLG LLGIAALVTV ITVPVVLLNK GTDDAAADSR RTYTLTDYLK STFRVKFYTL 

        70         80         90        100        110        120 
QWISDHEYLY KQENNILLFN AEYGNSSIFL ENSTFDELGY STNDYSVSPD RQFILFEYNY 

       130        140        150        160        170        180 
VKQWRHSYTA SYDIYDLNKR QLITEERIPN NTQWITWSPV GHKLAYVWNN DIYVKNEPNL 

       190        200        210        220        230        240 
SSQRITWTGK ENVIYNGVTD WVYEEEVFSA YSALWWSPNG TFLAYAQFND TEVPLIEYSF 

       250        260        270        280        290        300 
YSDESLQYPK TVRIPYPKAG AENPTVKFFV VDTRTLSPNA SVTSYQIVPP ASVLIGDHYL 

       310        320        330        340        350        360 
CGVTWVTEER ISLQWIRRAQ NYSIIDICDY DESTGRWISS VARQHIEIST TGWVGRFRPA 

       370        380        390        400        410        420 
EPHFTSDGNS FYKIISNEEG YKHICHFQTD KSNCTFITKG AWEVIGIEAL TSDYLYYISN 

       430        440        450        460        470        480 
EHKGMPGGRN LYRIQLNDYT KVTCLSCELN PERCQYYSAS FSNKAKYYQL RCFGPGLPLY 

       490        500        510        520        530        540 
TLHSSSSDKE LRVLEDNSAL DKMLQDVQMP SKKLDVINLH GTKFWYQMIL PPHFDKSKKY 

       550        560        570        580        590        600 
PLLIEVYAGP CSQKVDTVFR LSWATYLAST ENIIVASFDG RGSGYQGDKI MHAINRRLGT 

       610        620        630        640        650        660 
FEVEDQIEAT RQFSKMGFVD DKRIAIWGWS YGGYVTSMVL GAGSGVFKCG IAVAPVSKWE 

       670        680        690        700        710        720 
YYDSVYTERY MGLPTPEDNL DYYRNSTVMS RAENFKQVEY LLIHGTADDN VHFQQSAQLS 

       730        740        750        760 
KALVDAGVDF QTMWYTDEDH GIASNMAHQH IYTHMSHFLK QCFSLP 

« Hide

References

[1]"Characterisation of human dipeptidyl peptidase IV expressed in Pichia pastoris. A structural and mechanistic comparison between the recombinant human and the purified porcine enzyme."
Baer J., Weber A., Hoffmann T., Stork J., Wermann M., Wagner L., Aust S., Gerhartz B., Demuth H.-U.
Biol. Chem. 384:1553-1563(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
Tissue: Kidney.
[2]"Assignment of the dipeptidylpeptidase IV (DPP4) gene to pig chromosome 15q21."
Thomsen P.D., Qvist H., Marklund L., Andersson L., Sjostrom H., Noren O.
Mamm. Genome 4:604-607(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2-67.
Tissue: Kidney.
[3]"N-terminal amino-acid sequence of pig kidney dipeptidyl peptidase IV solubilized by autolysis."
Seidl R., Mann K., Schaeffer W.
Biol. Chem. Hoppe-Seyler 372:213-214(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 38-71.
Tissue: Kidney.
[4]"The crystal structure of dipeptidyl peptidase IV (CD26) reveals its functional regulation and enzymatic mechanism."
Engel M., Hoffmann T., Wagner L., Wermann M., Heiser U., Kiefersauer R., Huber R., Bode W., Demuth H.-U., Brandstetter H.
Proc. Natl. Acad. Sci. U.S.A. 100:5063-5068(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 39-766, GLYCOSYLATION AT ASN-85; ASN-92; ASN-229; ASN-279; ASN-321 AND ASN-685, HOMODIMERIZATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY198323 mRNA. Translation: AAO43404.1.
X73276 mRNA. Translation: CAA51717.1.
PIRI47134.
S14746.
RefSeqNP_999422.1. NM_214257.1.
UniGeneSsc.16236.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1ORVX-ray1.80A/B/C/D39-766[»]
1ORWX-ray2.84A/B/C/D39-766[»]
2AJ8X-ray2.11A/B/C/D39-766[»]
2AJBX-ray2.75A/B/C/D39-766[»]
2AJCX-ray1.95A/B/C/D39-766[»]
2AJDX-ray2.56A/B/C/D39-766[»]
2BUAX-ray2.56A/B/C/D39-766[»]
2BUCX-ray2.50A/B/C/D39-766[»]
ProteinModelPortalP22411.
SMRP22411. Positions 39-766.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9823.ENSSSCP00000016843.

Chemistry

BindingDBP22411.
ChEMBLCHEMBL3813.

Protein family/group databases

MEROPSS09.003.

Proteomic databases

PaxDbP22411.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSSSCT00000017306; ENSSSCP00000016843; ENSSSCG00000015894.
ENSSSCT00000035225; ENSSSCP00000028692; ENSSSCG00000015894.
GeneID397492.
KEGGssc:397492.

Organism-specific databases

CTD1803.

Phylogenomic databases

eggNOGCOG1506.
GeneTreeENSGT00740000115496.
HOGENOMHOG000231875.
HOVERGENHBG005527.
KOK01278.
OMAETKFWYQ.
OrthoDBEOG761BT2.
TreeFamTF313309.

Enzyme and pathway databases

BRENDA3.4.14.5. 6170.

Family and domain databases

Gene3D2.140.10.30. 1 hit.
3.40.50.1820. 1 hit.
InterProIPR029058. AB_hydrolase.
IPR002471. Pept_S9_AS.
IPR001375. Peptidase_S9.
IPR002469. Peptidase_S9B.
[Graphical view]
PfamPF00930. DPPIV_N. 1 hit.
PF00326. Peptidase_S9. 1 hit.
[Graphical view]
SUPFAMSSF53474. SSF53474. 1 hit.
PROSITEPS00708. PRO_ENDOPEP_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP22411.

Entry information

Entry nameDPP4_PIG
AccessionPrimary (citable) accession number: P22411
Secondary accession number(s): Q866G2
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: September 13, 2004
Last modified: June 11, 2014
This is version 119 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references