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Protein

Xaa-Pro aminopeptidase 2

Gene

XPNPEP2

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

Functioni

Membrane-bound metalloprotease which catalyzes the removal of a penultimate prolyl residue from the N-termini of peptides, such as Arg-Pro-Pro. May play a role in the metabolism of the vasodilator bradykinin.1 Publication

Catalytic activityi

Release of any N-terminal amino acid, including proline, that is linked to proline, even from a dipeptide or tripeptide.1 Publication

Cofactori

Zn2+By similarity

Activity regulationi

Inhibited by apstatin and the chelating agent 1,10-phenanthroline. Also inhibited by high concentrations of Zn2+. Not significantly inhibited by bestatin or phosphoramidon.1 Publication

Kineticsi

  1. KM=0.837 mM for Arg-Pro-Pro1 Publication
  2. KM=75 µM for Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg (bradykinin)1 Publication
  3. KM=56 µM for Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe (bradykinin[1-8])1 Publication
  4. KM=18 µM for synthetic fluorescent substrate Lys(Dnp)-Pro-Pro-Gly-Phe-Ser-Pro-Lys(Abz)NH21 Publication
  5. KM=20 µM for synthetic fluorescent substrate Lys(Dnp)-Pro-Pro-Gly-Lys(Abz)NH21 Publication
  6. KM=19 µM for synthetic fluorescent substrate Lys(Dnp)-Pro-Pro-Lys(Abz)NH21 Publication

    pH dependencei

    Optimum pH is 7.4.1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei116SubstrateBy similarity1
    Binding sitei430Substrate; via tele nitrogenBy similarity1
    Metal bindingi450Zinc 1By similarity1
    Metal bindingi461Zinc 1By similarity1
    Metal bindingi461Zinc 2By similarity1
    Metal bindingi524Zinc 2; via tele nitrogenBy similarity1
    Binding sitei524Substrate; via tele nitrogenBy similarity1
    Binding sitei533Substrate; via tele nitrogenBy similarity1
    Metal bindingi555Zinc 2By similarity1
    Binding sitei555SubstrateBy similarity1
    Metal bindingi569Zinc 1By similarity1
    Metal bindingi569Zinc 2By similarity1

    GO - Molecular functioni

    • aminopeptidase activity Source: ProtInc
    • metal ion binding Source: UniProtKB-KW
    • metalloaminopeptidase activity Source: InterPro

    Keywordsi

    Molecular functionAminopeptidase, Hydrolase, Metalloprotease, Protease
    LigandMetal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiR-HSA-163125 Post-translational modification: synthesis of GPI-anchored proteins

    Protein family/group databases

    MEROPSiM24.005

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Xaa-Pro aminopeptidase 2 (EC:3.4.11.91 Publication)
    Alternative name(s):
    Aminoacylproline aminopeptidase
    Membrane-bound aminopeptidase P
    Short name:
    Membrane-bound APP
    Short name:
    Membrane-bound AmP
    Short name:
    mAmP
    X-Pro aminopeptidase 2
    Gene namesi
    Name:XPNPEP2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome X

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000122121.10
    HGNCiHGNC:12823 XPNPEP2
    MIMi300145 gene
    neXtProtiNX_O43895

    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

    Cell membrane, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Angioedema induced by ACE inhibitors (AEACEI)3 Publications
    Disease susceptibility is associated with variations affecting the gene represented in this entry.
    Disease descriptionA potentially life-threatening side effect of ACE inhibitors that appears in a subset of patients taking these drugs for hypertension and cardiovascular disease treatment. AEACEI is characterized by swelling of the face, lips, tongue, and airway that can lead to suffocation and death if severe.
    See also OMIM:300909

    Organism-specific databases

    DisGeNETi7512
    MalaCardsiXPNPEP2
    MIMi300909 phenotype
    OpenTargetsiENSG00000122121
    Orphaneti100057 Renin-angiotensin-aldosterone system-blocker-induced angioedema
    PharmGKBiPA37416

    Chemistry databases

    ChEMBLiCHEMBL4610
    GuidetoPHARMACOLOGYi1579

    Polymorphism and mutation databases

    BioMutaiXPNPEP2

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Signal peptidei1 – 21Sequence analysisAdd BLAST21
    ChainiPRO_000002682922 – 649Xaa-Pro aminopeptidase 2Add BLAST628
    PropeptideiPRO_0000026830650 – 674Removed in mature formCuratedAdd BLAST25

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Glycosylationi35N-linked (GlcNAc...) asparagineSequence analysis1
    Glycosylationi49N-linked (GlcNAc...) asparagineSequence analysis1
    Glycosylationi65N-linked (GlcNAc...) asparagineSequence analysis1
    Glycosylationi278N-linked (GlcNAc...) asparagineSequence analysis1
    Glycosylationi291N-linked (GlcNAc...) asparagineSequence analysis1
    Lipidationi649GPI-anchor amidated alanineBy similarity1

    Post-translational modificationi

    N-glycosylated.1 Publication

    Keywords - PTMi

    Glycoprotein, GPI-anchor, Lipoprotein

    Proteomic databases

    EPDiO43895
    PaxDbiO43895
    PeptideAtlasiO43895
    PRIDEiO43895
    ProteomicsDBi49219

    PTM databases

    iPTMnetiO43895
    PhosphoSitePlusiO43895

    Expressioni

    Tissue specificityi

    Expressed in kidney, lung, heart, placenta, liver, small intestine and colon. No expression in brain, skeletal muscle, pancreas, spleen, thymus, prostate, testis and ovary.1 Publication

    Gene expression databases

    BgeeiENSG00000122121 Expressed in 98 organ(s), highest expression level in jejunal mucosa
    CleanExiHS_XPNPEP2
    ExpressionAtlasiO43895 baseline and differential
    GenevisibleiO43895 HS

    Organism-specific databases

    HPAiCAB025136
    CAB025269
    HPA000339

    Interactioni

    Subunit structurei

    Homotrimer.By similarity

    Protein-protein interaction databases

    STRINGi9606.ENSP00000360147

    Chemistry databases

    BindingDBiO43895

    Structurei

    3D structure databases

    ProteinModelPortaliO43895
    SMRiO43895
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the peptidase M24B family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiKOG2413 Eukaryota
    COG0006 LUCA
    GeneTreeiENSGT00390000013970
    HOGENOMiHOG000255713
    HOVERGENiHBG002934
    InParanoidiO43895
    KOiK14208
    OMAiPVMVTKA
    OrthoDBiEOG091G0A2Q
    PhylomeDBiO43895
    TreeFamiTF314183

    Family and domain databases

    CDDicd01085 APP, 1 hit
    Gene3Di3.40.350.10, 2 hits
    InterProiView protein in InterPro
    IPR029149 Creatin/AminoP/Spt16_NTD
    IPR036005 Creatinase/aminopeptidase-like
    IPR000587 Creatinase_N
    IPR000994 Pept_M24
    IPR033740 Pept_M24B
    IPR032416 Peptidase_M24_C
    IPR001131 Peptidase_M24B_aminopep-P_CS
    PfamiView protein in Pfam
    PF01321 Creatinase_N, 1 hit
    PF00557 Peptidase_M24, 1 hit
    PF16188 Peptidase_M24_C, 1 hit
    SUPFAMiSSF53092 SSF53092, 1 hit
    SSF55920 SSF55920, 1 hit
    PROSITEiView protein in PROSITE
    PS00491 PROLINE_PEPTIDASE, 1 hit

    Sequence (1+)i

    Sequence statusi: Complete.

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

    This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

    O43895-1 [UniParc]FASTAAdd to basket
    « Hide
            10         20         30         40         50
    MARAHWGCCP WLVLLCACAW GHTKPVDLGG QDVRNCSTNP PYLPVTVVNT
    60 70 80 90 100
    TMSLTALRQQ MQTQNLSAYI IPGTDAHMNE YIGQHDERRA WITGFTGSAG
    110 120 130 140 150
    TAVVTMKKAA VWTDSRYWTQ AERQMDCNWE LHKEVGTTPI VTWLLTEIPA
    160 170 180 190 200
    GGRVGFDPFL LSIDTWESYD LALQGSNRQL VSITTNLVDL VWGSERPPVP
    210 220 230 240 250
    NQPIYALQEA FTGSTWQEKV SGVRSQMQKH QKVPTAVLLS ALEETAWLFN
    260 270 280 290 300
    LRASDIPYNP FFYSYTLLTD SSIRLFANKS RFSSETLSYL NSSCTGPMCV
    310 320 330 340 350
    QIEDYSQVRD SIQAYSLGDV RIWIGTSYTM YGIYEMIPKE KLVTDTYSPV
    360 370 380 390 400
    MMTKAVKNSK EQALLKASHV RDAVAVIRYL VWLEKNVPKG TVDEFSGAEI
    410 420 430 440 450
    VDKFRGEEQF SSGPSFETIS ASGLNAALAH YSPTKELNRK LSSDEMYLLD
    460 470 480 490 500
    SGGQYWDGTT DITRTVHWGT PSAFQKEAYT RVLIGNIDLS RLIFPAATSG
    510 520 530 540 550
    RMVEAFARRA LWDAGLNYGH GTGHGIGNFL CVHEWPVGFQ SNNIAMAKGM
    560 570 580 590 600
    FTSIEPGYYK DGEFGIRLED VALVVEAKTK YPGSYLTFEV VSFVPYDRNL
    610 620 630 640 650
    IDVSLLSPEH LQYLNRYYQT IREKVGPELQ RRQLLEEFEW LQQHTEPLAA
    660 670
    RAPDTASWAS VLVVSTLAIL GWSV
    Length:674
    Mass (Da):75,625
    Last modified:November 15, 2002 - v3
    Checksum:i75949336EDD0F3B4
    GO

    Computationally mapped potential isoform sequencesi

    There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    Q5JZ40Q5JZ40_HUMAN
    Xaa-Pro aminopeptidase 2
    XPNPEP2
    183Annotation score:

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti26V → L in AAB96394 (PubMed:9375790).Curated1
    Sequence conflicti339K → R in AAB96394 (PubMed:9375790).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_071310215T → I1 PublicationCorresponds to variant dbSNP:rs138365897Ensembl.1
    Natural variantiVAR_071311223V → I1 PublicationCorresponds to variant dbSNP:rs61733030Ensembl.1
    Natural variantiVAR_071312232K → N1 PublicationCorresponds to variant dbSNP:rs41311662Ensembl.1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U90724 mRNA Translation: AAB96394.2
    AF195953 Genomic DNA Translation: AAG28480.1
    AL023653 Genomic DNA No translation available.
    BC126174 mRNA Translation: AAI26175.1
    CCDSiCCDS14613.1
    RefSeqiNP_003390.4, NM_003399.5
    UniGeneiHs.170499

    Genome annotation databases

    EnsembliENST00000371106; ENSP00000360147; ENSG00000122121
    GeneIDi7512
    KEGGihsa:7512
    UCSCiuc004eut.2 human

    Keywords - Coding sequence diversityi

    Polymorphism

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U90724 mRNA Translation: AAB96394.2
    AF195953 Genomic DNA Translation: AAG28480.1
    AL023653 Genomic DNA No translation available.
    BC126174 mRNA Translation: AAI26175.1
    CCDSiCCDS14613.1
    RefSeqiNP_003390.4, NM_003399.5
    UniGeneiHs.170499

    3D structure databases

    ProteinModelPortaliO43895
    SMRiO43895
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi9606.ENSP00000360147

    Chemistry databases

    BindingDBiO43895
    ChEMBLiCHEMBL4610
    GuidetoPHARMACOLOGYi1579

    Protein family/group databases

    MEROPSiM24.005

    PTM databases

    iPTMnetiO43895
    PhosphoSitePlusiO43895

    Polymorphism and mutation databases

    BioMutaiXPNPEP2

    Proteomic databases

    EPDiO43895
    PaxDbiO43895
    PeptideAtlasiO43895
    PRIDEiO43895
    ProteomicsDBi49219

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000371106; ENSP00000360147; ENSG00000122121
    GeneIDi7512
    KEGGihsa:7512
    UCSCiuc004eut.2 human

    Organism-specific databases

    CTDi7512
    DisGeNETi7512
    EuPathDBiHostDB:ENSG00000122121.10
    GeneCardsiXPNPEP2
    HGNCiHGNC:12823 XPNPEP2
    HPAiCAB025136
    CAB025269
    HPA000339
    MalaCardsiXPNPEP2
    MIMi300145 gene
    300909 phenotype
    neXtProtiNX_O43895
    OpenTargetsiENSG00000122121
    Orphaneti100057 Renin-angiotensin-aldosterone system-blocker-induced angioedema
    PharmGKBiPA37416
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG2413 Eukaryota
    COG0006 LUCA
    GeneTreeiENSGT00390000013970
    HOGENOMiHOG000255713
    HOVERGENiHBG002934
    InParanoidiO43895
    KOiK14208
    OMAiPVMVTKA
    OrthoDBiEOG091G0A2Q
    PhylomeDBiO43895
    TreeFamiTF314183

    Enzyme and pathway databases

    ReactomeiR-HSA-163125 Post-translational modification: synthesis of GPI-anchored proteins

    Miscellaneous databases

    GeneWikiiXPNPEP2
    GenomeRNAii7512
    PROiPR:O43895
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000122121 Expressed in 98 organ(s), highest expression level in jejunal mucosa
    CleanExiHS_XPNPEP2
    ExpressionAtlasiO43895 baseline and differential
    GenevisibleiO43895 HS

    Family and domain databases

    CDDicd01085 APP, 1 hit
    Gene3Di3.40.350.10, 2 hits
    InterProiView protein in InterPro
    IPR029149 Creatin/AminoP/Spt16_NTD
    IPR036005 Creatinase/aminopeptidase-like
    IPR000587 Creatinase_N
    IPR000994 Pept_M24
    IPR033740 Pept_M24B
    IPR032416 Peptidase_M24_C
    IPR001131 Peptidase_M24B_aminopep-P_CS
    PfamiView protein in Pfam
    PF01321 Creatinase_N, 1 hit
    PF00557 Peptidase_M24, 1 hit
    PF16188 Peptidase_M24_C, 1 hit
    SUPFAMiSSF53092 SSF53092, 1 hit
    SSF55920 SSF55920, 1 hit
    PROSITEiView protein in PROSITE
    PS00491 PROLINE_PEPTIDASE, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiXPP2_HUMAN
    AccessioniPrimary (citable) accession number: O43895
    Secondary accession number(s): A0AV16, O75994
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 15, 2002
    Last sequence update: November 15, 2002
    Last modified: November 7, 2018
    This is version 153 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

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Peptidase families
      Classification of peptidase families and list of entries
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. Human chromosome X
      Human chromosome X: entries, gene names and cross-references to MIM
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