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Protein

Dipeptidyl peptidase 8

Gene

DPP8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Dipeptidyl peptidase that cleaves off N-terminal dipeptides from proteins having a Pro or Ala residue at position 2. May play a role in T-cell activation and immune function.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.3 Publications

Enzyme regulationi

Inhibited by zinc. Inhibited by the serine proteinase inhibitor 4-(2-aminoethyl)benzenesulphonyl fluoride (AEBSF), and by di-isopropylfuorophosphate. Specifically inhibited by isoindoline derivatives.3 Publications

Kineticsi

  1. KM=208 µM for Ala-Pro-AMC3 Publications
  2. KM=130 µM for Ala-Pro-AFC3 Publications
  3. KM=120 µM for H-Ala-Pro-pNa3 Publications
  4. KM=1420 µM for H-Ala-Ala-pNa3 Publications
  5. KM=310 µM for H-Arg-Pro-pNa3 Publications
  6. KM=2050 µM for H-Asp-Pro-pNa3 Publications
  7. KM=480 µM for H-Gly-Pro-pNa3 Publications

    pH dependencei

    Optimum pH is 7.4-8.5. Little activity below pH 6.5.3 Publications

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei755Charge relay systemCurated1
    Active sitei833Charge relay systemCurated1
    Active sitei865Charge relay systemCurated1

    GO - Molecular functioni

    • dipeptidyl-peptidase activity Source: UniProtKB
    • serine-type peptidase activity Source: UniProtKB-KW

    GO - Biological processi

    • immune response Source: UniProtKB
    • proteolysis Source: UniProtKB

    Keywordsi

    Molecular functionAminopeptidase, Hydrolase, Protease, Serine protease

    Enzyme and pathway databases

    SABIO-RKiQ6V1X1

    Protein family/group databases

    ESTHERihuman-DPP8 DPP4N_Peptidase_S9
    MEROPSiS09.018

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Dipeptidyl peptidase 8 (EC:3.4.14.5)
    Short name:
    DP8
    Alternative name(s):
    Dipeptidyl peptidase IV-related protein 1
    Short name:
    DPRP-1
    Dipeptidyl peptidase VIII
    Short name:
    DPP VIII
    Prolyl dipeptidase DPP8
    Gene namesi
    Name:DPP8
    Synonyms:DPRP1
    ORF Names:MSTP097, MSTP135, MSTP141
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 15

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000074603.18
    HGNCiHGNC:16490 DPP8
    MIMi606819 gene
    neXtProtiNX_Q6V1X1

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi275E → K: 13-fold reduction in affinity for Ala-Pro-AFC; no effect on subcellular location. 1 Publication1
    Mutagenesisi755S → A: Abolishes activity; no effect on subcellular location. 1 Publication1
    Mutagenesisi833D → A: Abolishes activity; no effect on subcellular location. 1 Publication1
    Mutagenesisi865H → A: Abolishes activity; no effect on subcellular location. 1 Publication1

    Organism-specific databases

    DisGeNETi54878
    OpenTargetsiENSG00000074603
    PharmGKBiPA27470

    Chemistry databases

    ChEMBLiCHEMBL4657
    GuidetoPHARMACOLOGYi2356

    Polymorphism and mutation databases

    BioMutaiDPP8
    DMDMi67460301

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001224131 – 898Dipeptidyl peptidase 8Add BLAST898

    Proteomic databases

    EPDiQ6V1X1
    MaxQBiQ6V1X1
    PaxDbiQ6V1X1
    PeptideAtlasiQ6V1X1
    PRIDEiQ6V1X1
    ProteomicsDBi67709
    67710 [Q6V1X1-2]
    67711 [Q6V1X1-3]
    67712 [Q6V1X1-4]
    67713 [Q6V1X1-5]
    67714 [Q6V1X1-6]

    PTM databases

    iPTMnetiQ6V1X1
    PhosphoSitePlusiQ6V1X1

    Expressioni

    Tissue specificityi

    Ubiquitously expressed, with highest levels in testis, placenta, prostate, muscle and brain.2 Publications

    Inductioni

    In activated T-cells.1 Publication

    Gene expression databases

    BgeeiENSG00000074603
    ExpressionAtlasiQ6V1X1 baseline and differential
    GenevisibleiQ6V1X1 HS

    Organism-specific databases

    HPAiHPA008706

    Interactioni

    Protein-protein interaction databases

    BioGridi120226, 30 interactors
    IntActiQ6V1X1, 4 interactors
    MINTiQ6V1X1
    STRINGi9606.ENSP00000339208

    Chemistry databases

    BindingDBiQ6V1X1

    Structurei

    Secondary structure

    1898
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi58 – 69Combined sources12
    Turni73 – 75Combined sources3
    Beta strandi81 – 87Combined sources7
    Beta strandi93 – 103Combined sources11
    Beta strandi111 – 121Combined sources11
    Beta strandi124 – 126Combined sources3
    Beta strandi133 – 136Combined sources4
    Helixi150 – 158Combined sources9
    Helixi161 – 164Combined sources4
    Beta strandi169 – 172Combined sources4
    Turni173 – 175Combined sources3
    Beta strandi177 – 182Combined sources6
    Beta strandi185 – 190Combined sources6
    Beta strandi215 – 220Combined sources6
    Beta strandi227 – 232Combined sources6
    Beta strandi235 – 240Combined sources6
    Turni241 – 243Combined sources3
    Beta strandi246 – 248Combined sources3
    Beta strandi255 – 257Combined sources3
    Helixi259 – 261Combined sources3
    Beta strandi264 – 268Combined sources5
    Helixi271 – 276Combined sources6
    Beta strandi281 – 285Combined sources5
    Beta strandi293 – 295Combined sources3
    Beta strandi297 – 307Combined sources11
    Beta strandi313 – 317Combined sources5
    Helixi321 – 323Combined sources3
    Beta strandi326 – 330Combined sources5
    Beta strandi340 – 350Combined sources11
    Beta strandi356 – 366Combined sources11
    Helixi368 – 371Combined sources4
    Turni372 – 374Combined sources3
    Beta strandi375 – 383Combined sources9
    Beta strandi390 – 396Combined sources7
    Beta strandi401 – 407Combined sources7
    Helixi409 – 411Combined sources3
    Beta strandi412 – 414Combined sources3
    Helixi419 – 428Combined sources10
    Beta strandi436 – 442Combined sources7
    Beta strandi453 – 455Combined sources3
    Beta strandi463 – 471Combined sources9
    Turni472 – 474Combined sources3
    Beta strandi478 – 485Combined sources8
    Turni493 – 496Combined sources4
    Turni501 – 504Combined sources4
    Beta strandi508 – 514Combined sources7
    Beta strandi517 – 519Combined sources3
    Beta strandi530 – 532Combined sources3
    Turni533 – 536Combined sources4
    Beta strandi537 – 542Combined sources6
    Beta strandi551 – 559Combined sources9
    Beta strandi569 – 577Combined sources9
    Beta strandi581 – 589Combined sources9
    Beta strandi591 – 593Combined sources3
    Beta strandi596 – 603Combined sources8
    Beta strandi609 – 611Combined sources3
    Beta strandi613 – 621Combined sources9
    Beta strandi634 – 639Combined sources6
    Beta strandi643 – 651Combined sources9
    Beta strandi660 – 667Combined sources8
    Beta strandi678 – 680Combined sources3
    Turni683 – 686Combined sources4
    Helixi687 – 694Combined sources8
    Beta strandi698 – 702Combined sources5
    Beta strandi708 – 710Combined sources3
    Helixi712 – 715Combined sources4
    Helixi716 – 718Combined sources3
    Turni722 – 724Combined sources3
    Helixi726 – 740Combined sources15
    Beta strandi744 – 754Combined sources11
    Helixi756 – 767Combined sources12
    Turni769 – 771Combined sources3
    Beta strandi772 – 779Combined sources8
    Helixi784 – 786Combined sources3
    Helixi789 – 796Combined sources8
    Helixi799 – 801Combined sources3
    Helixi803 – 808Combined sources6
    Helixi811 – 817Combined sources7
    Beta strandi820 – 830Combined sources11
    Turni834 – 838Combined sources5
    Helixi839 – 850Combined sources12
    Beta strandi856 – 860Combined sources5
    Beta strandi864 – 866Combined sources3
    Helixi870 – 887Combined sources18
    Helixi891 – 895Combined sources5

    3D structure databases

    ProteinModelPortaliQ6V1X1
    SMRiQ6V1X1
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the peptidase S9B family. DPPIV subfamily.Curated

    Phylogenomic databases

    eggNOGiKOG2281 Eukaryota
    COG1506 LUCA
    GeneTreeiENSGT00760000119233
    HOVERGENiHBG061620
    InParanoidiQ6V1X1
    KOiK08655
    OMAiCPEAETT
    OrthoDBiEOG091G05F9
    PhylomeDBiQ6V1X1
    TreeFamiTF313309

    Family and domain databases

    Gene3Di2.140.10.30, 1 hit
    3.40.50.1820, 1 hit
    InterProiView protein in InterPro
    IPR029058 AB_hydrolase
    IPR001375 Peptidase_S9
    IPR002469 Peptidase_S9B_N
    IPR038554 Peptidase_S9B_N_sf
    PfamiView protein in Pfam
    PF00930 DPPIV_N, 1 hit
    PF00326 Peptidase_S9, 1 hit
    SUPFAMiSSF53474 SSF53474, 1 hit

    Sequences (6)i

    Sequence statusi: Complete.

    This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q6V1X1-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MWKRSEQMKI KSGKCNMAAA METEQLGVEI FETADCEENI ESQDRPKLEP
    60 70 80 90 100
    FYVERYSWSQ LKKLLADTRK YHGYMMAKAP HDFMFVKRND PDGPHSDRIY
    110 120 130 140 150
    YLAMSGENRE NTLFYSEIPK TINRAAVLML SWKPLLDLFQ ATLDYGMYSR
    160 170 180 190 200
    EEELLRERKR IGTVGIASYD YHQGSGTFLF QAGSGIYHVK DGGPQGFTQQ
    210 220 230 240 250
    PLRPNLVETS CPNIRMDPKL CPADPDWIAF IHSNDIWISN IVTREERRLT
    260 270 280 290 300
    YVHNELANME EDARSAGVAT FVLQEEFDRY SGYWWCPKAE TTPSGGKILR
    310 320 330 340 350
    ILYEENDESE VEIIHVTSPM LETRRADSFR YPKTGTANPK VTFKMSEIMI
    360 370 380 390 400
    DAEGRIIDVI DKELIQPFEI LFEGVEYIAR AGWTPEGKYA WSILLDRSQT
    410 420 430 440 450
    RLQIVLISPE LFIPVEDDVM ERQRLIESVP DSVTPLIIYE ETTDIWINIH
    460 470 480 490 500
    DIFHVFPQSH EEEIEFIFAS ECKTGFRHLY KITSILKESK YKRSSGGLPA
    510 520 530 540 550
    PSDFKCPIKE EIAITSGEWE VLGRHGSNIQ VDEVRRLVYF EGTKDSPLEH
    560 570 580 590 600
    HLYVVSYVNP GEVTRLTDRG YSHSCCISQH CDFFISKYSN QKNPHCVSLY
    610 620 630 640 650
    KLSSPEDDPT CKTKEFWATI LDSAGPLPDY TPPEIFSFES TTGFTLYGML
    660 670 680 690 700
    YKPHDLQPGK KYPTVLFIYG GPQVQLVNNR FKGVKYFRLN TLASLGYVVV
    710 720 730 740 750
    VIDNRGSCHR GLKFEGAFKY KMGQIEIDDQ VEGLQYLASR YDFIDLDRVG
    760 770 780 790 800
    IHGWSYGGYL SLMALMQRSD IFRVAIAGAP VTLWIFYDTG YTERYMGHPD
    810 820 830 840 850
    QNEQGYYLGS VAMQAEKFPS EPNRLLLLHG FLDENVHFAH TSILLSFLVR
    860 870 880 890
    AGKPYDLQIY PQERHSIRVP ESGEHYELHL LHYLQENLGS RIAALKVI
    Length:898
    Mass (Da):103,358
    Last modified:July 5, 2004 - v1
    Checksum:i60B0D036F026DE2A
    GO
    Isoform 2 (identifier: Q6V1X1-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         723-773: Missing.

    Show »
    Length:847
    Mass (Da):97,464
    Checksum:iAB07EF0087231B56
    GO
    Isoform 3 (identifier: Q6V1X1-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-16: Missing.

    Show »
    Length:882
    Mass (Da):101,422
    Checksum:iAD801C302DB4652B
    GO
    Isoform 4 (identifier: Q6V1X1-4) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-16: Missing.
         674-773: Missing.

    Show »
    Length:782
    Mass (Da):89,908
    Checksum:i784922477DB8F5B5
    GO
    Isoform 5 (identifier: Q6V1X1-5) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         674-722: Missing.

    Show »
    Length:849
    Mass (Da):97,739
    Checksum:i4B6C88F29CA55475
    GO
    Isoform 6 (identifier: Q6V1X1-6) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         358-530: Missing.

    Show »
    Length:725
    Mass (Da):83,398
    Checksum:i0476E0AEBD94131B
    GO

    Sequence cautioni

    The sequence AAQ13623 differs from that shown. Reason: Frameshift at several positions.Curated
    The sequence AAQ13650 differs from that shown. Reason: Frameshift at several positions.Curated
    The sequence AAQ13657 differs from that shown. Reason: Erroneous initiation.Curated
    The sequence BAA91059 differs from that shown. Reason: Frameshift at position 486.Curated
    The sequence BAB55395 differs from that shown. Reason: Erroneous initiation.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti233S → G in BC040203 (PubMed:15489334).Curated1
    Sequence conflicti570G → S in BAB55395 (PubMed:14702039).Curated1
    Sequence conflicti673Q → K in AAQ13650 (Ref. 6) Curated1
    Sequence conflicti686Y → F in AAQ13650 (Ref. 6) Curated1
    Sequence conflicti693 – 694AS → PF in AAQ13650 (Ref. 6) Curated2
    Sequence conflicti701V → G in AAQ13650 (Ref. 6) Curated1
    Sequence conflicti709H → P in AAQ13650 (Ref. 6) Curated1
    Sequence conflicti720Y → F in AAQ13650 (Ref. 6) Curated1
    Sequence conflicti799 – 803PDQNE → LTRMN in AAQ13623 (Ref. 6) Curated5
    Sequence conflicti820S → F in AAQ13623 (Ref. 6) Curated1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0138601 – 16Missing in isoform 3 and isoform 4. 3 PublicationsAdd BLAST16
    Alternative sequenceiVSP_013861358 – 530Missing in isoform 6. 1 PublicationAdd BLAST173
    Alternative sequenceiVSP_013862674 – 773Missing in isoform 4. 2 PublicationsAdd BLAST100
    Alternative sequenceiVSP_013863674 – 722Missing in isoform 5. 1 PublicationAdd BLAST49
    Alternative sequenceiVSP_013864723 – 773Missing in isoform 2. 2 PublicationsAdd BLAST51

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF221634 mRNA Translation: AAG29766.1
    AF221635 mRNA Translation: AAG29767.1
    AF221636 mRNA Translation: AAG29768.1
    AF221637 mRNA Translation: AAG29769.1
    AY172659 mRNA Translation: AAO17261.1
    AY354202 mRNA Translation: AAQ63887.1
    AK000290 mRNA Translation: BAA91059.1 Frameshift.
    AK027826 mRNA Translation: BAB55395.1 Different initiation.
    BC030688 mRNA Translation: AAH30688.3
    BC040203 mRNA No translation available.
    AF176779 mRNA Translation: AAQ13657.1 Different initiation.
    AF175225 mRNA Translation: AAQ13650.1 Frameshift.
    AF173382 mRNA Translation: AAQ13623.1 Frameshift.
    CCDSiCCDS10207.1 [Q6V1X1-1]
    CCDS10208.1 [Q6V1X1-2]
    CCDS10209.1 [Q6V1X1-4]
    CCDS10210.1 [Q6V1X1-3]
    RefSeqiNP_001307804.1, NM_001320875.1 [Q6V1X1-1]
    NP_001307805.1, NM_001320876.1 [Q6V1X1-3]
    NP_060213.2, NM_017743.5 [Q6V1X1-4]
    NP_569118.1, NM_130434.4 [Q6V1X1-3]
    NP_932064.1, NM_197960.3 [Q6V1X1-1]
    NP_932065.1, NM_197961.3 [Q6V1X1-2]
    XP_016877862.1, XM_017022373.1 [Q6V1X1-1]
    XP_016877863.1, XM_017022374.1 [Q6V1X1-2]
    UniGeneiHs.458609
    Hs.591106

    Genome annotation databases

    EnsembliENST00000300141; ENSP00000300141; ENSG00000074603 [Q6V1X1-3]
    ENST00000321147; ENSP00000318111; ENSG00000074603 [Q6V1X1-2]
    ENST00000341861; ENSP00000339208; ENSG00000074603 [Q6V1X1-1]
    ENST00000358939; ENSP00000351817; ENSG00000074603 [Q6V1X1-4]
    ENST00000559233; ENSP00000453954; ENSG00000074603 [Q6V1X1-1]
    GeneIDi54878
    KEGGihsa:54878
    UCSCiuc002aov.4 human [Q6V1X1-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Similar proteinsi

    Entry informationi

    Entry nameiDPP8_HUMAN
    AccessioniPrimary (citable) accession number: Q6V1X1
    Secondary accession number(s): Q7Z4C8
    , Q7Z4D3, Q7Z4E1, Q8IWG7, Q8NEM5, Q96JX1, Q9HBM2, Q9HBM3, Q9HBM4, Q9HBM5, Q9NXF4
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 7, 2005
    Last sequence update: July 5, 2004
    Last modified: June 20, 2018
    This is version 128 of the entry and version 1 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 15
      Human chromosome 15: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. Peptidase families
      Classification of peptidase families and list of entries
    5. SIMILARITY comments
      Index of protein domains and families

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