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P22411

- DPP4_PIG

UniProt

P22411 - DPP4_PIG

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Protein

Dipeptidyl peptidase 4

Gene
DPP4, CD26
Organism
Sus scrofa (Pig)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.1 Publication

Catalytic activityi

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 regulationi

Inhibited by GPC3 and diprotin A By similarity.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei630 – 6301Charge relay system By similarity
Active sitei708 – 7081Charge relay system By similarity
Active sitei740 – 7401Charge relay system By similarity

GO - Molecular functioni

  1. aminopeptidase activity Source: UniProtKB-KW
  2. dipeptidyl-peptidase activity Source: UniProtKB
  3. protease binding Source: UniProtKB
  4. protein homodimerization activity Source: UniProtKB
  5. receptor binding Source: UniProtKB
  6. serine-type endopeptidase activity Source: InterPro

GO - Biological processi

  1. cell adhesion Source: UniProtKB-KW
  2. endothelial cell migration Source: UniProtKB
  3. negative regulation of extracellular matrix disassembly Source: UniProtKB
  4. positive regulation of cell proliferation Source: UniProtKB
  5. regulation of cell-cell adhesion mediated by integrin Source: Ensembl
  6. response to hypoxia Source: Ensembl
  7. T cell activation Source: Ensembl
  8. T cell costimulation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Aminopeptidase, Hydrolase, Protease, Serine protease

Keywords - Biological processi

Cell adhesion

Enzyme and pathway databases

BRENDAi3.4.14.5. 6170.
ReactomeiREACT_209721. Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
REACT_225961. Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP).

Protein family/group databases

MEROPSiS09.003.

Names & Taxonomyi

Protein namesi
Recommended 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:
Alternative name(s):
Dipeptidyl peptidase IV membrane form
Alternative name(s):
Dipeptidyl peptidase IV soluble form
Gene namesi
Name:DPP4
Synonyms:CD26
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
ProteomesiUP000008227: Chromosome 15

Subcellular locationi

Chain 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.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 66Cytoplasmic Reviewed prediction
Transmembranei7 – 2721Helical; Signal-anchor for type II membrane protein; Reviewed predictionAdd
BLAST
Topological domaini28 – 766739Extracellular Reviewed predictionAdd
BLAST

GO - Cellular componenti

  1. apical plasma membrane Source: UniProtKB-SubCell
  2. cell surface Source: UniProtKB
  3. endocytic vesicle Source: UniProtKB
  4. extracellular vesicular exosome Source: Ensembl
  5. integral component of membrane Source: UniProtKB-KW
  6. intercellular canaliculus Source: Ensembl
  7. invadopodium membrane Source: UniProtKB
  8. lamellipodium Source: UniProtKB
  9. lamellipodium membrane Source: UniProtKB-SubCell
  10. lysosomal membrane Source: Ensembl
  11. membrane raft Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 766766Dipeptidyl peptidase 4 membrane formPRO_0000027217Add
BLAST
Chaini38 – 766729Dipeptidyl peptidase 4 soluble formPRO_0000027218Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi85 – 851N-linked (GlcNAc...)1 Publication
Glycosylationi92 – 921N-linked (GlcNAc...)1 Publication
Glycosylationi229 – 2291N-linked (GlcNAc...)1 Publication
Glycosylationi279 – 2791N-linked (GlcNAc...)1 Publication
Glycosylationi321 – 3211N-linked (GlcNAc...)1 Publication
Disulfide bondi385 ↔ 394
Disulfide bondi444 ↔ 447
Disulfide bondi454 ↔ 472
Disulfide bondi649 ↔ 762
Glycosylationi685 – 6851N-linked (GlcNAc...)1 Publication

Post-translational modificationi

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.1 Publication
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.

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP22411.

Interactioni

Subunit structurei

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.1 Publication

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000016843.

Structurei

Secondary structure

1
766
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi45 – 506
Beta strandi60 – 623
Beta strandi64 – 729
Beta strandi75 – 806
Turni81 – 833
Beta strandi87 – 904
Helixi92 – 965
Beta strandi98 – 1003
Beta strandi104 – 1074
Beta strandi111 – 12212
Beta strandi124 – 1263
Beta strandi128 – 1369
Turni137 – 1404
Beta strandi152 – 1576
Beta strandi159 – 1624
Beta strandi164 – 1685
Beta strandi171 – 1777
Turni191 – 1933
Beta strandi194 – 1985
Helixi201 – 2066
Beta strandi209 – 2124
Beta strandi214 – 2163
Beta strandi220 – 22910
Beta strandi235 – 2406
Beta strandi250 – 2556
Beta strandi265 – 2728
Helixi273 – 2753
Beta strandi283 – 2875
Helixi291 – 2944
Beta strandi298 – 30710
Beta strandi310 – 3178
Beta strandi320 – 33011
Turni332 – 3343
Helixi341 – 3433
Beta strandi344 – 3485
Beta strandi350 – 3523
Beta strandi354 – 3585
Beta strandi368 – 3769
Beta strandi378 – 3803
Beta strandi382 – 3887
Beta strandi394 – 3974
Beta strandi400 – 4023
Beta strandi404 – 4107
Beta strandi412 – 4209
Helixi422 – 4243
Beta strandi429 – 4357
Beta strandi438 – 4469
Turni447 – 4493
Turni451 – 4533
Beta strandi456 – 4616
Beta strandi465 – 4728
Beta strandi474 – 4774
Beta strandi479 – 4846
Turni485 – 4884
Beta strandi489 – 4957
Helixi498 – 5047
Beta strandi506 – 5083
Beta strandi511 – 5199
Beta strandi522 – 5309
Beta strandi536 – 5383
Beta strandi540 – 5467
Helixi563 – 5697
Beta strandi574 – 5785
Beta strandi584 – 5863
Helixi588 – 5914
Helixi592 – 5943
Turni598 – 6003
Helixi601 – 61414
Beta strandi619 – 62911
Helixi631 – 64010
Turni641 – 6433
Beta strandi648 – 6547
Helixi659 – 6613
Helixi664 – 6718
Turni676 – 6794
Helixi680 – 6845
Helixi689 – 6979
Beta strandi698 – 7058
Beta strandi709 – 7113
Helixi713 – 72513
Beta strandi731 – 7355
Helixi745 – 76218

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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[»]
ProteinModelPortaliP22411.
SMRiP22411. Positions 39-766.

Miscellaneous databases

EvolutionaryTraceiP22411.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG1506.
GeneTreeiENSGT00740000115496.
HOGENOMiHOG000231875.
HOVERGENiHBG005527.
KOiK01278.
OMAiETKFWYQ.
OrthoDBiEOG761BT2.
TreeFamiTF313309.

Family and domain databases

Gene3Di2.140.10.30. 1 hit.
3.40.50.1820. 1 hit.
InterProiIPR029058. AB_hydrolase.
IPR002471. Pept_S9_AS.
IPR001375. Peptidase_S9.
IPR002469. Peptidase_S9B.
[Graphical view]
PfamiPF00930. DPPIV_N. 1 hit.
PF00326. Peptidase_S9. 1 hit.
[Graphical view]
SUPFAMiSSF53474. SSF53474. 1 hit.
PROSITEiPS00708. PRO_ENDOPEP_SER. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P22411-1 [UniParc]FASTAAdd to Basket

« Hide

MKTPWKVLLG LLGIAALVTV ITVPVVLLNK GTDDAAADSR RTYTLTDYLK    50
STFRVKFYTL QWISDHEYLY KQENNILLFN AEYGNSSIFL ENSTFDELGY 100
STNDYSVSPD RQFILFEYNY VKQWRHSYTA SYDIYDLNKR QLITEERIPN 150
NTQWITWSPV GHKLAYVWNN DIYVKNEPNL SSQRITWTGK ENVIYNGVTD 200
WVYEEEVFSA YSALWWSPNG TFLAYAQFND TEVPLIEYSF YSDESLQYPK 250
TVRIPYPKAG AENPTVKFFV VDTRTLSPNA SVTSYQIVPP ASVLIGDHYL 300
CGVTWVTEER ISLQWIRRAQ NYSIIDICDY DESTGRWISS VARQHIEIST 350
TGWVGRFRPA EPHFTSDGNS FYKIISNEEG YKHICHFQTD KSNCTFITKG 400
AWEVIGIEAL TSDYLYYISN EHKGMPGGRN LYRIQLNDYT KVTCLSCELN 450
PERCQYYSAS FSNKAKYYQL RCFGPGLPLY TLHSSSSDKE LRVLEDNSAL 500
DKMLQDVQMP SKKLDVINLH GTKFWYQMIL PPHFDKSKKY PLLIEVYAGP 550
CSQKVDTVFR LSWATYLAST ENIIVASFDG RGSGYQGDKI MHAINRRLGT 600
FEVEDQIEAT RQFSKMGFVD DKRIAIWGWS YGGYVTSMVL GAGSGVFKCG 650
IAVAPVSKWE YYDSVYTERY MGLPTPEDNL DYYRNSTVMS RAENFKQVEY 700
LLIHGTADDN VHFQQSAQLS KALVDAGVDF QTMWYTDEDH GIASNMAHQH 750
IYTHMSHFLK QCFSLP 766
Length:766
Mass (Da):88,242
Last modified:September 13, 2004 - v3
Checksum:i8800D520BAEA856D
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti32 – 321Missing1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY198323 mRNA. Translation: AAO43404.1.
X73276 mRNA. Translation: CAA51717.1.
PIRiI47134.
S14746.
RefSeqiNP_999422.1. NM_214257.1.
UniGeneiSsc.16236.

Genome annotation databases

EnsembliENSSSCT00000017306; ENSSSCP00000016843; ENSSSCG00000015894.
ENSSSCT00000035225; ENSSSCP00000028692; ENSSSCG00000015894.
GeneIDi397492.
KEGGissc:397492.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY198323 mRNA. Translation: AAO43404.1 .
X73276 mRNA. Translation: CAA51717.1 .
PIRi I47134.
S14746.
RefSeqi NP_999422.1. NM_214257.1.
UniGenei Ssc.16236.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1ORV X-ray 1.80 A/B/C/D 39-766 [» ]
1ORW X-ray 2.84 A/B/C/D 39-766 [» ]
2AJ8 X-ray 2.11 A/B/C/D 39-766 [» ]
2AJB X-ray 2.75 A/B/C/D 39-766 [» ]
2AJC X-ray 1.95 A/B/C/D 39-766 [» ]
2AJD X-ray 2.56 A/B/C/D 39-766 [» ]
2BUA X-ray 2.56 A/B/C/D 39-766 [» ]
2BUC X-ray 2.50 A/B/C/D 39-766 [» ]
ProteinModelPortali P22411.
SMRi P22411. Positions 39-766.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9823.ENSSSCP00000016843.

Chemistry

BindingDBi P22411.
ChEMBLi CHEMBL3813.

Protein family/group databases

MEROPSi S09.003.

Proteomic databases

PaxDbi P22411.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSSSCT00000017306 ; ENSSSCP00000016843 ; ENSSSCG00000015894 .
ENSSSCT00000035225 ; ENSSSCP00000028692 ; ENSSSCG00000015894 .
GeneIDi 397492.
KEGGi ssc:397492.

Organism-specific databases

CTDi 1803.

Phylogenomic databases

eggNOGi COG1506.
GeneTreei ENSGT00740000115496.
HOGENOMi HOG000231875.
HOVERGENi HBG005527.
KOi K01278.
OMAi ETKFWYQ.
OrthoDBi EOG761BT2.
TreeFami TF313309.

Enzyme and pathway databases

BRENDAi 3.4.14.5. 6170.
Reactomei REACT_209721. Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
REACT_225961. Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP).

Miscellaneous databases

EvolutionaryTracei P22411.

Family and domain databases

Gene3Di 2.140.10.30. 1 hit.
3.40.50.1820. 1 hit.
InterProi IPR029058. AB_hydrolase.
IPR002471. Pept_S9_AS.
IPR001375. Peptidase_S9.
IPR002469. Peptidase_S9B.
[Graphical view ]
Pfami PF00930. DPPIV_N. 1 hit.
PF00326. Peptidase_S9. 1 hit.
[Graphical view ]
SUPFAMi SSF53474. SSF53474. 1 hit.
PROSITEi PS00708. PRO_ENDOPEP_SER. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiDPP4_PIG
AccessioniPrimary (citable) accession number: P22411
Secondary accession number(s): Q866G2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: September 13, 2004
Last modified: September 3, 2014
This is version 120 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi