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P22411

- DPP4_PIG

UniProt

P22411 - DPP4_PIG

Protein

Dipeptidyl peptidase 4

Gene

DPP4

Organism
Sus scrofa (Pig)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 121 (01 Oct 2014)
      Sequence version 3 (13 Sep 2004)
      Previous versions | rss
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    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.By similarity1 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.PROSITE-ProRule annotation

    Enzyme regulationi

    Inhibited by GPC3 and diprotin A.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei630 – 6301Charge relay systemPROSITE-ProRule annotation
    Active sitei708 – 7081Charge relay systemPROSITE-ProRule annotation
    Active sitei740 – 7401Charge relay systemPROSITE-ProRule annotation

    GO - Molecular functioni

    1. dipeptidyl-peptidase activity Source: UniProtKB
    2. protease binding Source: UniProtKB
    3. protein homodimerization activity Source: UniProtKB
    4. receptor binding Source: UniProtKB
    5. 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

    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 By similarity; Single-pass type II membrane protein By similarity. Cell projectioninvadopodium membrane By similarity; Single-pass type II membrane protein By similarity. Cell projectionlamellipodium membrane By similarity; 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.By similarity

    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

    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
    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.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.By similarity

    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.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP22411.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 66CytoplasmicSequence Analysis
    Topological domaini28 – 766739ExtracellularSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei7 – 2721Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the peptidase S9B family. DPPIV subfamily.Curated

    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

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti32 – 321Missing(PubMed:7903569)Curated

    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: October 1, 2014
    This is version 121 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