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Protein

Dipeptidyl peptidase 9

Gene

DPP9

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.

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 the serine proteinase inhibitor 4-(2-aminoethyl)benzenesulphonyl fluoride (AEBSF), and by di-isopropylfuorophosphate.1 Publication

Kineticsi

  1. KM=161 µM for Ala-Pro-AMC2 Publications
  2. KM=180 µM for Ala-Pro-AFC2 Publications

    pH dependencei

    Optimum pH is 7.5-8.5. Little activity below pH 6.5.2 Publications

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei730Charge relay systemBy similarity1
    Active sitei808Charge relay systemBy similarity1
    Active sitei840Charge relay systemBy similarity1

    GO - Molecular functioni

    • aminopeptidase activity Source: UniProtKB-KW
    • identical protein binding Source: IntAct
    • serine-type peptidase activity Source: UniProtKB-KW

    Keywordsi

    Molecular functionAminopeptidase, Hydrolase, Protease, Serine protease

    Enzyme and pathway databases

    SABIO-RKiQ86TI2

    Protein family/group databases

    ESTHERihuman-DPP9 DPP4N_Peptidase_S9
    MEROPSiS09.019

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Dipeptidyl peptidase 9 (EC:3.4.14.5)
    Short name:
    DP9
    Alternative name(s):
    Dipeptidyl peptidase IV-related protein 2
    Short name:
    DPRP-2
    Dipeptidyl peptidase IX
    Short name:
    DPP IX
    Dipeptidyl peptidase-like protein 9
    Short name:
    DPLP9
    Gene namesi
    Name:DPP9
    Synonyms:DPRP2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 19

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000142002.16
    HGNCiHGNC:18648 DPP9
    MIMi608258 gene
    neXtProtiNX_Q86TI2

    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, Nucleus

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi91039
    MalaCardsiDPP9
    OpenTargetsiENSG00000142002
    Orphaneti2032 Idiopathic pulmonary fibrosis
    PharmGKBiPA38620

    Chemistry databases

    ChEMBLiCHEMBL4793
    GuidetoPHARMACOLOGYi2357

    Polymorphism and mutation databases

    DMDMi67460390

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemovedCombined sources
    ChainiPRO_00001224152 – 863Dipeptidyl peptidase 9Add BLAST862

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei2N-acetylalanineCombined sources1

    Keywords - PTMi

    Acetylation

    Proteomic databases

    EPDiQ86TI2
    MaxQBiQ86TI2
    PaxDbiQ86TI2
    PeptideAtlasiQ86TI2
    PRIDEiQ86TI2
    ProteomicsDBi69697
    69698 [Q86TI2-2]
    69700 [Q86TI2-4]

    PTM databases

    iPTMnetiQ86TI2
    PhosphoSitePlusiQ86TI2

    Expressioni

    Tissue specificityi

    Ubiquitously expressed, with highest levels in liver, heart and muscle, and lowest levels in brain.3 Publications

    Gene expression databases

    BgeeiENSG00000142002
    ExpressionAtlasiQ86TI2 baseline and differential
    GenevisibleiQ86TI2 HS

    Organism-specific databases

    HPAiHPA036059

    Interactioni

    Subunit structurei

    Homodimer.1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself2EBI-7475352,EBI-7475352

    GO - Molecular functioni

    • identical protein binding Source: IntAct

    Protein-protein interaction databases

    BioGridi124789, 51 interactors
    IntActiQ86TI2, 5 interactors
    MINTiQ86TI2
    STRINGi9606.ENSP00000262960

    Chemistry databases

    BindingDBiQ86TI2

    Structurei

    Secondary structure

    1863
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi31 – 41Combined sources11
    Beta strandi54 – 60Combined sources7
    Beta strandi70 – 76Combined sources7
    Beta strandi84 – 91Combined sources8
    Beta strandi109 – 111Combined sources3
    Helixi123 – 131Combined sources9
    Beta strandi143 – 145Combined sources3
    Turni146 – 149Combined sources4
    Beta strandi150 – 154Combined sources5
    Beta strandi156 – 163Combined sources8
    Beta strandi178 – 180Combined sources3
    Beta strandi183 – 186Combined sources4
    Beta strandi189 – 193Combined sources5
    Beta strandi200 – 205Combined sources6
    Beta strandi208 – 213Combined sources6
    Turni214 – 216Combined sources3
    Beta strandi219 – 221Combined sources3
    Turni232 – 234Combined sources3
    Beta strandi237 – 240Combined sources4
    Helixi244 – 250Combined sources7
    Beta strandi256 – 258Combined sources3
    Beta strandi271 – 281Combined sources11
    Beta strandi283 – 285Combined sources3
    Beta strandi287 – 291Combined sources5
    Turni295 – 298Combined sources4
    Beta strandi300 – 304Combined sources5
    Beta strandi307 – 310Combined sources4
    Beta strandi314 – 324Combined sources11
    Beta strandi330 – 340Combined sources11
    Helixi342 – 345Combined sources4
    Beta strandi351 – 357Combined sources7
    Beta strandi364 – 369Combined sources6
    Beta strandi375 – 381Combined sources7
    Helixi383 – 385Combined sources3
    Beta strandi386 – 388Combined sources3
    Helixi393 – 402Combined sources10
    Beta strandi410 – 416Combined sources7
    Beta strandi427 – 429Combined sources3
    Beta strandi440 – 446Combined sources7
    Turni447 – 449Combined sources3
    Beta strandi453 – 459Combined sources7
    Beta strandi468 – 470Combined sources3
    Beta strandi478 – 480Combined sources3
    Beta strandi483 – 490Combined sources8
    Beta strandi492 – 494Combined sources3
    Beta strandi505 – 507Combined sources3
    Turni508 – 511Combined sources4
    Beta strandi512 – 517Combined sources6
    Beta strandi526 – 534Combined sources9
    Beta strandi546 – 552Combined sources7
    Beta strandi556 – 564Combined sources9
    Beta strandi566 – 568Combined sources3
    Beta strandi571 – 579Combined sources9
    Helixi584 – 586Combined sources3
    Beta strandi588 – 596Combined sources9
    Beta strandi609 – 614Combined sources6
    Beta strandi620 – 626Combined sources7
    Beta strandi636 – 642Combined sources7
    Beta strandi653 – 655Combined sources3
    Turni658 – 661Combined sources4
    Helixi662 – 670Combined sources9
    Beta strandi673 – 678Combined sources6
    Beta strandi683 – 685Combined sources3
    Helixi687 – 691Combined sources5
    Turni692 – 695Combined sources4
    Turni697 – 699Combined sources3
    Helixi700 – 715Combined sources16
    Beta strandi719 – 729Combined sources11
    Helixi731 – 742Combined sources12
    Turni744 – 746Combined sources3
    Beta strandi748 – 754Combined sources7
    Helixi759 – 761Combined sources3
    Helixi764 – 771Combined sources8
    Helixi774 – 776Combined sources3
    Helixi778 – 783Combined sources6
    Helixi786 – 792Combined sources7
    Beta strandi795 – 805Combined sources11
    Turni809 – 813Combined sources5
    Helixi814 – 826Combined sources13
    Beta strandi831 – 835Combined sources5
    Beta strandi839 – 841Combined sources3
    Helixi845 – 862Combined sources18

    3D structure databases

    ProteinModelPortaliQ86TI2
    SMRiQ86TI2
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the peptidase S9B family. DPPIV subfamily.Curated

    Phylogenomic databases

    eggNOGiKOG2281 Eukaryota
    COG1506 LUCA
    GeneTreeiENSGT00760000119233
    HOGENOMiHOG000006870
    HOVERGENiHBG061620
    InParanoidiQ86TI2
    KOiK08656
    OMAiWASMMEA
    OrthoDBiEOG091G05F9
    PhylomeDBiQ86TI2
    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 (3)i

    Sequence statusi: Complete.

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

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q86TI2-1) [UniParc]FASTAAdd to basket
    Also known as: DPP9-S, Short

    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
    MATTGTPTAD RGDAAATDDP AARFQVQKHS WDGLRSIIHG SRKYSGLIVN
    60 70 80 90 100
    KAPHDFQFVQ KTDESGPHSH RLYYLGMPYG SRENSLLYSE IPKKVRKEAL
    110 120 130 140 150
    LLLSWKQMLD HFQATPHHGV YSREEELLRE RKRLGVFGIT SYDFHSESGL
    160 170 180 190 200
    FLFQASNSLF HCRDGGKNGF MVSPMKPLEI KTQCSGPRMD PKICPADPAF
    210 220 230 240 250
    FSFINNSDLW VANIETGEER RLTFCHQGLS NVLDDPKSAG VATFVIQEEF
    260 270 280 290 300
    DRFTGYWWCP TASWEGSEGL KTLRILYEEV DESEVEVIHV PSPALEERKT
    310 320 330 340 350
    DSYRYPRTGS KNPKIALKLA EFQTDSQGKI VSTQEKELVQ PFSSLFPKVE
    360 370 380 390 400
    YIARAGWTRD GKYAWAMFLD RPQQWLQLVL LPPALFIPST ENEEQRLASA
    410 420 430 440 450
    RAVPRNVQPY VVYEEVTNVW INVHDIFYPF PQSEGEDELC FLRANECKTG
    460 470 480 490 500
    FCHLYKVTAV LKSQGYDWSE PFSPGEDEFK CPIKEEIALT SGEWEVLARH
    510 520 530 540 550
    GSKIWVNEET KLVYFQGTKD TPLEHHLYVV SYEAAGEIVR LTTPGFSHSC
    560 570 580 590 600
    SMSQNFDMFV SHYSSVSTPP CVHVYKLSGP DDDPLHKQPR FWASMMEAAS
    610 620 630 640 650
    CPPDYVPPEI FHFHTRSDVR LYGMIYKPHA LQPGKKHPTV LFVYGGPQVQ
    660 670 680 690 700
    LVNNSFKGIK YLRLNTLASL GYAVVVIDGR GSCQRGLRFE GALKNQMGQV
    710 720 730 740 750
    EIEDQVEGLQ FVAEKYGFID LSRVAIHGWS YGGFLSLMGL IHKPQVFKVA
    760 770 780 790 800
    IAGAPVTVWM AYDTGYTERY MDVPENNQHG YEAGSVALHV EKLPNEPNRL
    810 820 830 840 850
    LILHGFLDEN VHFFHTNFLV SQLIRAGKPY QLQIYPNERH SIRCPESGEH
    860
    YEVTLLHFLQ EYL
    Length:863
    Mass (Da):98,263
    Last modified:June 7, 2005 - v3
    Checksum:i40FE0B78E26CDED5
    GO
    Isoform 2 (identifier: Q86TI2-2) [UniParc]FASTAAdd to basket
    Also known as: DPP9-L, Long

    The sequence of this isoform differs from the canonical sequence as follows:
         1-1: M → MRKVKKLRLDKENTGSWRSFSLNSEGAERM

    Note: Active peptidase. Contains a nuclear localization signal at positions 2-9.1 Publication
    Show »
    Length:892
    Mass (Da):101,669
    Checksum:i2CDB8E40E428AE73
    GO
    Isoform 3 (identifier: Q86TI2-4) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         832-858: Missing.

    Show »
    Length:836
    Mass (Da):95,013
    Checksum:iEF3B224CF112B857
    GO

    Sequence cautioni

    The sequence AAC33801 differs from that shown. Reason: Erroneous gene model prediction.Curated
    The sequence AAC62840 differs from that shown. Reason: Erroneous gene model prediction.Curated
    The sequence AAH37948 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
    The sequence AAL47179 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
    The sequence AAO73880 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
    The sequence BAB70784 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
    The sequence BAC11362 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
    The sequence BAC85150 differs from that shown. Probable cloning artifact.Curated
    The sequence BAD18643 differs from that shown. Aberrant splicing.Curated
    The sequence CAD39039 differs from that shown. Reason: Frameshift at positions 432 and 460.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti204I → N in AAO73880 (PubMed:15245913).Curated1
    Sequence conflicti204I → N in AAQ83119 (PubMed:15245913).Curated1
    Sequence conflicti461L → F in CAD39039 (PubMed:17974005).Curated1
    Sequence conflicti571C → W in BAC85150 (PubMed:14702039).Curated1
    Sequence conflicti709L → P in BAD18643 (PubMed:14702039).Curated1
    Sequence conflicti753G → C in BAB70784 (PubMed:14702039).Curated1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0138651M → MRKVKKLRLDKENTGSWRSF SLNSEGAERM in isoform 2. 4 Publications1
    Alternative sequenceiVSP_013869832 – 858Missing in isoform 3. 1 PublicationAdd BLAST27

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF452102 mRNA Translation: AAL47179.1 Different initiation.
    AY172660 mRNA Translation: AAO17262.1
    AF542510 mRNA Translation: AAO73880.2 Different initiation.
    AY374518 mRNA Translation: AAQ83119.1
    DQ417928 mRNA Translation: ABD83624.1
    AK054656 mRNA Translation: BAB70784.1 Different initiation.
    AK075030 mRNA Translation: BAC11362.1 Different initiation.
    AK122654 mRNA Translation: BAG53644.1
    AK131100 mRNA Translation: BAC85150.1 Sequence problems.
    AK131499 mRNA Translation: BAD18643.1 Sequence problems.
    AC005594 Genomic DNA Translation: AAC33801.1 Sequence problems.
    AC005783 Genomic DNA Translation: AAC62840.1 Sequence problems.
    CH471139 Genomic DNA Translation: EAW69199.1
    CH471139 Genomic DNA Translation: EAW69201.1
    BC000970 mRNA Translation: AAH00970.1
    BC037948 mRNA Translation: AAH37948.1 Different initiation.
    AL834376 mRNA Translation: CAD39039.3 Frameshift.
    CR627380 mRNA Translation: CAH10477.1
    CCDSiCCDS45928.1 [Q86TI2-2]
    RefSeqiNP_631898.3, NM_139159.4 [Q86TI2-2]
    XP_005259730.1, XM_005259673.2 [Q86TI2-2]
    XP_011526710.1, XM_011528408.1 [Q86TI2-2]
    XP_011526712.1, XM_011528410.1 [Q86TI2-1]
    UniGeneiHs.515081

    Genome annotation databases

    EnsembliENST00000262960; ENSP00000262960; ENSG00000142002 [Q86TI2-2]
    ENST00000594671; ENSP00000472224; ENSG00000142002 [Q86TI2-4]
    ENST00000598800; ENSP00000469603; ENSG00000142002 [Q86TI2-1]
    GeneIDi91039
    KEGGihsa:91039
    UCSCiuc002mba.5 human [Q86TI2-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Similar proteinsi

    Entry informationi

    Entry nameiDPP9_HUMAN
    AccessioniPrimary (citable) accession number: Q86TI2
    Secondary accession number(s): O75273
    , O75868, Q1ZZB8, Q6AI37, Q6UAL0, Q6ZMT2, Q6ZNJ5, Q8N2J7, Q8N3F5, Q8WXD8, Q96NT8, Q9BVR3
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 7, 2005
    Last sequence update: June 7, 2005
    Last modified: July 18, 2018
    This is version 143 of the entry and version 3 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 19
      Human chromosome 19: 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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