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Protein

Xaa-Pro aminopeptidase 2

Gene

XPNPEP2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Enzyme 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

    GO - Biological processi

    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

    HGNCiHGNC:12823. XPNPEP2.

    Subcellular locationi

    • Cell membrane By similarity; Lipid-anchorGPI-anchor By similarity

    GO - Cellular componenti

    • anchored component of membrane Source: UniProtKB-KW
    • extracellular exosome Source: UniProtKB
    • extracellular region Source: Reactome
    • membrane Source: ProtInc
    • plasma membrane Source: Reactome

    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...)Sequence analysis1
    Glycosylationi49N-linked (GlcNAc...)Sequence analysis1
    Glycosylationi65N-linked (GlcNAc...)Sequence analysis1
    Glycosylationi278N-linked (GlcNAc...)Sequence analysis1
    Glycosylationi291N-linked (GlcNAc...)Sequence 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.

    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.
    CleanExiHS_XPNPEP2.
    ExpressionAtlasiO43895. baseline and differential.
    GenevisibleiO43895. HS.

    Organism-specific databases

    HPAiCAB025136.
    CAB025269.
    HPA000339.

    Interactioni

    Subunit structurei

    Homotrimer.By similarity

    Protein-protein interaction databases

    MINTiMINT-5002270.
    STRINGi9606.ENSP00000360147.

    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.
    OMAiSPEHLQY.
    OrthoDBiEOG091G0A2Q.
    PhylomeDBiO43895.
    TreeFamiTF314183.

    Family and domain databases

    CDDicd01085. APP. 1 hit.
    Gene3Di3.40.350.10. 1 hit.
    3.90.230.10. 1 hit.
    InterProiView protein in InterPro
    IPR029149. Creatin/AminoP/Spt16_NTD.
    IPR028980. Creatinase/Aminopeptidase_P_N.
    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.

    Sequencei

    Sequence statusi: Complete.

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

    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

    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. Translation: CAA19220.1.
    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

    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. Translation: CAA19220.1.
    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

    MINTiMINT-5002270.
    STRINGi9606.ENSP00000360147.

    Chemistry databases

    ChEMBLiCHEMBL4610.
    GuidetoPHARMACOLOGYi1579.

    Protein family/group databases

    MEROPSiM24.005.

    PTM databases

    iPTMnetiO43895.
    PhosphoSitePlusiO43895.

    Polymorphism and mutation databases

    BioMutaiXPNPEP2.

    Proteomic databases

    EPDiO43895.
    PaxDbiO43895.
    PeptideAtlasiO43895.
    PRIDEiO43895.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

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

    Organism-specific databases

    CTDi7512.
    DisGeNETi7512.
    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.
    OMAiSPEHLQY.
    OrthoDBiEOG091G0A2Q.
    PhylomeDBiO43895.
    TreeFamiTF314183.

    Enzyme and pathway databases

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

    Miscellaneous databases

    GeneWikiiXPNPEP2.
    GenomeRNAii7512.
    PROiO43895.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000122121.
    CleanExiHS_XPNPEP2.
    ExpressionAtlasiO43895. baseline and differential.
    GenevisibleiO43895. HS.

    Family and domain databases

    CDDicd01085. APP. 1 hit.
    Gene3Di3.40.350.10. 1 hit.
    3.90.230.10. 1 hit.
    InterProiView protein in InterPro
    IPR029149. Creatin/AminoP/Spt16_NTD.
    IPR028980. Creatinase/Aminopeptidase_P_N.
    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: March 15, 2017
    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

    Complete proteome, Reference proteome

    Documents

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

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.