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Protein

Xaa-Pro aminopeptidase 1

Gene

XPNPEP1

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

Functioni

Contributes to the degradation of bradykinin. Catalyzes the removal of a penultimate prolyl residue from the N-termini of peptides, such as Arg-Pro-Pro.

Catalytic activityi

Release of any N-terminal amino acid, including proline, that is linked to proline, even from a dipeptide or tripeptide.2 Publications

Cofactori

Mn2+2 PublicationsNote: Binds 2 manganese ions per subunit.2 Publications

Enzyme regulationi

Inhibited by apstatin and the metal ion chelators EDTA and 1,10-phenanthroline. Partially inhibited by dithiothreitol. Not inhibited by enalaprilat or amastatin.1 Publication

Kineticsi

  1. KM=100.6 µM for bradykinin2 Publications
  2. KM=308 µM for the tripeptide Arg-Pro-Pro2 Publications

    pH dependencei

    Optimum pH is 8.2.2 Publications

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei77SubstrateBy similarity1
    Binding sitei395Substrate; via tele nitrogenBy similarity1
    Metal bindingi415Manganese 1Combined sources1 Publication1
    Metal bindingi426Manganese 1Combined sources1 Publication1
    Metal bindingi426Manganese 2Combined sources1 Publication1
    Metal bindingi489Manganese 2; via tele nitrogenCombined sources1 Publication1
    Binding sitei489Substrate; via tele nitrogenBy similarity1
    Binding sitei498Substrate; via tele nitrogenBy similarity1
    Metal bindingi523Manganese 2Combined sources1 Publication1
    Binding sitei523SubstrateBy similarity1
    Metal bindingi537Manganese 1Combined sources1 Publication1
    Metal bindingi537Manganese 2Combined sources1 Publication1

    GO - Molecular functioni

    • aminopeptidase activity Source: UniProtKB
    • manganese ion binding Source: UniProtKB
    • metalloaminopeptidase activity Source: UniProtKB
    • protein homodimerization activity Source: UniProtKB

    GO - Biological processi

    • bradykinin catabolic process Source: UniProtKB
    • proteolysis Source: UniProtKB

    Keywordsi

    Molecular functionAminopeptidase, Hydrolase, Metalloprotease, Protease
    LigandManganese, Metal-binding

    Enzyme and pathway databases

    BRENDAi3.1.8.1 2681
    3.4.11.9 2681

    Protein family/group databases

    MEROPSiM24.009

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Xaa-Pro aminopeptidase 1 (EC:3.4.11.9)
    Alternative name(s):
    Aminoacylproline aminopeptidase
    Cytosolic aminopeptidase P
    Soluble aminopeptidase P
    Short name:
    sAmp
    X-Pro aminopeptidase 1
    X-prolyl aminopeptidase 1, soluble
    Gene namesi
    Name:XPNPEP1Imported
    Synonyms:XPNPEPLImported, XPNPEPL1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 10

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000108039.17
    HGNCiHGNC:12822 XPNPEP1
    MIMi602443 gene
    neXtProtiNX_Q9NQW7

    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
    Mutagenesisi41E → A: Reduces activity by 10%. 1 Publication1
    Mutagenesisi477W → E: Interferes with dimerization and reduces activity by 94%. 1 Publication1

    Organism-specific databases

    DisGeNETi7511
    OpenTargetsiENSG00000108039
    PharmGKBiPA37415

    Chemistry databases

    ChEMBLiCHEMBL3782
    GuidetoPHARMACOLOGYi1578

    Polymorphism and mutation databases

    BioMutaiXPNPEP1
    DMDMi68566146

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemoved1 Publication
    ChainiPRO_00001850832 – 623Xaa-Pro aminopeptidase 1Add BLAST622

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei304N6-acetyllysineCombined sources1

    Keywords - PTMi

    Acetylation

    Proteomic databases

    EPDiQ9NQW7
    MaxQBiQ9NQW7
    PaxDbiQ9NQW7
    PeptideAtlasiQ9NQW7
    PRIDEiQ9NQW7
    ProteomicsDBi82211
    82212 [Q9NQW7-2]

    PTM databases

    iPTMnetiQ9NQW7
    PhosphoSitePlusiQ9NQW7

    Expressioni

    Tissue specificityi

    Expressed in all tissues tested, including pancreas, heart, muscle, kidney, liver, lung and brain. Highest levels in pancreas.1 Publication

    Gene expression databases

    BgeeiENSG00000108039
    CleanExiHS_XPNPEP1
    ExpressionAtlasiQ9NQW7 baseline and differential
    GenevisibleiQ9NQW7 HS

    Organism-specific databases

    HPAiCAB025196
    HPA030419
    HPA030420
    HPA030422

    Interactioni

    Subunit structurei

    Homodimer.2 Publications

    GO - Molecular functioni

    • protein homodimerization activity Source: UniProtKB

    Protein-protein interaction databases

    BioGridi113346, 78 interactors
    IntActiQ9NQW7, 8 interactors
    MINTiQ9NQW7
    STRINGi9606.ENSP00000421566

    Chemistry databases

    BindingDBiQ9NQW7

    Structurei

    Secondary structure

    1623
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi7 – 16Combined sources10
    Turni20 – 22Combined sources3
    Beta strandi28 – 32Combined sources5
    Helixi45 – 47Combined sources3
    Helixi49 – 54Combined sources6
    Beta strandi62 – 68Combined sources7
    Beta strandi70 – 74Combined sources5
    Helixi76 – 78Combined sources3
    Helixi79 – 85Combined sources7
    Beta strandi90 – 94Combined sources5
    Helixi103 – 110Combined sources8
    Beta strandi116 – 119Combined sources4
    Helixi121 – 123Combined sources3
    Helixi126 – 138Combined sources13
    Beta strandi142 – 145Combined sources4
    Helixi150 – 154Combined sources5
    Helixi171 – 174Combined sources4
    Helixi178 – 190Combined sources13
    Turni191 – 193Combined sources3
    Beta strandi194 – 199Combined sources6
    Helixi202 – 209Combined sources8
    Beta strandi215 – 219Combined sources5
    Beta strandi225 – 231Combined sources7
    Beta strandi233 – 236Combined sources4
    Helixi240 – 243Combined sources4
    Helixi245 – 250Combined sources6
    Turni251 – 254Combined sources4
    Helixi259 – 261Combined sources3
    Beta strandi263 – 266Combined sources4
    Helixi268 – 270Combined sources3
    Helixi271 – 280Combined sources10
    Beta strandi287 – 291Combined sources5
    Helixi296 – 301Combined sources6
    Helixi304 – 306Combined sources3
    Beta strandi307 – 312Combined sources6
    Helixi314 – 320Combined sources7
    Helixi324 – 351Combined sources28
    Helixi352 – 354Combined sources3
    Helixi359 – 371Combined sources13
    Beta strandi376 – 381Combined sources6
    Beta strandi384 – 387Combined sources4
    Helixi388 – 392Combined sources5
    Helixi400 – 402Combined sources3
    Beta strandi412 – 416Combined sources5
    Beta strandi418 – 420Combined sources3
    Beta strandi427 – 431Combined sources5
    Helixi438 – 455Combined sources18
    Helixi465 – 472Combined sources8
    Helixi474 – 478Combined sources5
    Beta strandi487 – 490Combined sources4
    Beta strandi493 – 495Combined sources3
    Beta strandi519 – 522Combined sources4
    Beta strandi525 – 528Combined sources4
    Turni529 – 531Combined sources3
    Beta strandi532 – 535Combined sources4
    Beta strandi537 – 545Combined sources9
    Beta strandi552 – 554Combined sources3
    Beta strandi556 – 561Combined sources6
    Helixi569 – 571Combined sources3
    Helixi574 – 576Combined sources3
    Helixi579 – 602Combined sources24
    Helixi606 – 614Combined sources9

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    3CTZX-ray1.60A1-623[»]
    ProteinModelPortaliQ9NQW7
    SMRiQ9NQW7
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9NQW7

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the peptidase M24B family.Sequence analysis

    Phylogenomic databases

    eggNOGiKOG2413 Eukaryota
    COG0006 LUCA
    GeneTreeiENSGT00390000013970
    HOGENOMiHOG000255713
    HOVERGENiHBG002934
    InParanoidiQ9NQW7
    KOiK01262
    OMAiYWKKMAK
    OrthoDBiEOG091G0A2Q
    PhylomeDBiQ9NQW7
    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

    Sequences (4)i

    Sequence statusi: Complete.

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

    This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 11 Publication (identifier: Q9NQW7-1) [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
    MPPKVTSELL RQLRQAMRNS EYVTEPIQAY IIPSGDAHQS EYIAPCDCRR
    60 70 80 90 100
    AFVSGFDGSA GTAIITEEHA AMWTDGRYFL QAAKQMDSNW TLMKMGLKDT
    110 120 130 140 150
    PTQEDWLVSV LPEGSRVGVD PLIIPTDYWK KMAKVLRSAG HHLIPVKENL
    160 170 180 190 200
    VDKIWTDRPE RPCKPLLTLG LDYTGISWKD KVADLRLKMA ERNVMWFVVT
    210 220 230 240 250
    ALDEIAWLFN LRGSDVEHNP VFFSYAIIGL ETIMLFIDGD RIDAPSVKEH
    260 270 280 290 300
    LLLDLGLEAE YRIQVHPYKS ILSELKALCA DLSPREKVWV SDKASYAVSE
    310 320 330 340 350
    TIPKDHRCCM PYTPICIAKA VKNSAESEGM RRAHIKDAVA LCELFNWLEK
    360 370 380 390 400
    EVPKGGVTEI SAADKAEEFR RQQADFVDLS FPTISSTGPN GAIIHYAPVP
    410 420 430 440 450
    ETNRTLSLDE VYLIDSGAQY KDGTTDVTRT MHFGTPTAYE KECFTYVLKG
    460 470 480 490 500
    HIAVSAAVFP TGTKGHLLDS FARSALWDSG LDYLHGTGHG VGSFLNVHEG
    510 520 530 540 550
    PCGISYKTFS DEPLEAGMIV TDEPGYYEDG AFGIRIENVV LVVPVKTKYN
    560 570 580 590 600
    FNNRGSLTFE PLTLVPIQTK MIDVDSLTDK ECDWLNNYHL TCRDVIGKEL
    610 620
    QKQGRQEALE WLIRETQPIS KQH
    Length:623
    Mass (Da):69,918
    Last modified:January 23, 2007 - v3
    Checksum:iDF4F5AF41E2F3876
    GO
    Isoform 2 (identifier: Q9NQW7-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         398-421: Missing.

    Note: No experimental confirmation available.Curated
    Show »
    Length:599
    Mass (Da):67,227
    Checksum:i6F6A7D909E1CC84D
    GO
    Isoform 3 (identifier: Q9NQW7-3) [UniParc]FASTAAdd to basket

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

    Note: No experimental confirmation available.
    Show »
    Length:666
    Mass (Da):74,798
    Checksum:i59D0596A49C93B17
    GO
    Isoform 4 (identifier: Q9NQW7-4) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-1: M → MAASRKPPRVRVNHQDFQLRNLRIIEPNEVTHSGDTGVETDGRM
         398-421: Missing.

    Show »
    Length:642
    Mass (Da):72,107
    Checksum:i0119CDC61051D1C2
    GO

    Sequence cautioni

    The sequence CAD38640 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti90W → C in AAH13417 (PubMed:15489334).Curated1
    Sequence conflicti131K → R in BAF82125 (PubMed:14702039).Curated1
    Sequence conflicti332R → P in CAA65068 (PubMed:9465902).Curated1
    Sequence conflicti332R → P in AAF97866 (PubMed:10871044).Curated1
    Sequence conflicti496N → D in BAD97233 (PubMed:17974005).Curated1
    Sequence conflicti498H → R in BAD97233 (PubMed:17974005).Curated1
    Sequence conflicti572I → T in BAF82125 (PubMed:14702039).Curated1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0452501M → MAASRKPPRVRVNHQDFQLR NLRIIEPNEVTHSGDTGVET DGRM in isoform 3 and isoform 4. 1 Publication1
    Alternative sequenceiVSP_051752398 – 421Missing in isoform 2 and isoform 4. 1 PublicationAdd BLAST24

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X95762 mRNA Translation: CAA65068.1
    AF195530 mRNA Translation: AAF97866.1
    AF272981 mRNA Translation: AAF75795.1
    AK289436 mRNA Translation: BAF82125.1
    CR456922 mRNA Translation: CAG33203.1
    AK223513 mRNA Translation: BAD97233.1
    AL833411 mRNA Translation: CAD38640.1 Different initiation.
    AL354951 Genomic DNA Translation: CAI14248.1
    CH471066 Genomic DNA Translation: EAW49577.1
    BC005126 mRNA Translation: AAH05126.1
    BC007579 mRNA Translation: AAH07579.1
    BC013417 mRNA Translation: AAH13417.4
    CCDSiCCDS53576.1 [Q9NQW7-4]
    CCDS7560.2 [Q9NQW7-3]
    RefSeqiNP_001161076.1, NM_001167604.1 [Q9NQW7-4]
    NP_001311061.1, NM_001324132.1 [Q9NQW7-1]
    NP_065116.3, NM_020383.3 [Q9NQW7-3]
    UniGeneiHs.390623

    Genome annotation databases

    EnsembliENST00000322238; ENSP00000324011; ENSG00000108039 [Q9NQW7-4]
    ENST00000502935; ENSP00000421566; ENSG00000108039 [Q9NQW7-3]
    GeneIDi7511
    KEGGihsa:7511
    UCSCiuc001kyp.2 human [Q9NQW7-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Similar proteinsi

    Entry informationi

    Entry nameiXPP1_HUMAN
    AccessioniPrimary (citable) accession number: Q9NQW7
    Secondary accession number(s): A8K071
    , G5E9Y2, G8JLB2, O15250, Q53EX6, Q8N3Q0, Q96D23
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 5, 2005
    Last sequence update: January 23, 2007
    Last modified: June 20, 2018
    This is version 152 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, Direct protein sequencing, Reference proteome

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