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Protein

Xaa-Pro aminopeptidase 1

Gene

XPNPEP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
    Metal bindingi415Manganese 11
    Metal bindingi426Manganese 11
    Metal bindingi426Manganese 21
    Metal bindingi489Manganese 21
    Metal bindingi523Manganese 21
    Metal bindingi537Manganese 11
    Metal bindingi537Manganese 21

    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
    Complete GO annotation...

    Keywords - Molecular functioni

    Aminopeptidase, Hydrolase, Metalloprotease, Protease

    Keywords - Ligandi

    Manganese, Metal-binding

    Enzyme and pathway databases

    BioCyciZFISH:HS03058-MONOMER.
    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

    HGNCiHGNC:12822. XPNPEP1.

    Subcellular locationi

    GO - Cellular componenti

    • cytoplasm Source: UniProtKB
    • extracellular exosome Source: UniProtKB
    Complete GO annotation...

    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.

    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. 71 interactors.
    IntActiQ9NQW7. 8 interactors.
    MINTiMINT-3039782.
    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.
    OMAiPGKWGIR.
    OrthoDBiEOG091G0A2Q.
    PhylomeDBiQ9NQW7.
    TreeFamiTF314183.

    Family and domain databases

    CDDicd01085. APP. 1 hit.
    Gene3Di3.40.350.10. 2 hits.
    3.90.230.10. 1 hit.
    InterProiIPR029149. 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.
    [Graphical view]
    PfamiPF01321. Creatinase_N. 1 hit.
    PF00557. Peptidase_M24. 1 hit.
    PF16188. Peptidase_M24_C. 1 hit.
    [Graphical view]
    SUPFAMiSSF53092. SSF53092. 1 hit.
    SSF55920. SSF55920. 1 hit.
    PROSITEiPS00491. PROLINE_PEPTIDASE. 1 hit.
    [Graphical view]

    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

    Cross-referencesi

    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.

    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...

    Protein-protein interaction databases

    BioGridi113346. 71 interactors.
    IntActiQ9NQW7. 8 interactors.
    MINTiMINT-3039782.
    STRINGi9606.ENSP00000421566.

    Chemistry databases

    BindingDBiQ9NQW7.
    ChEMBLiCHEMBL3782.
    GuidetoPHARMACOLOGYi1578.

    Protein family/group databases

    MEROPSiM24.009.

    PTM databases

    iPTMnetiQ9NQW7.
    PhosphoSitePlusiQ9NQW7.

    Polymorphism and mutation databases

    BioMutaiXPNPEP1.
    DMDMi68566146.

    Proteomic databases

    EPDiQ9NQW7.
    MaxQBiQ9NQW7.
    PaxDbiQ9NQW7.
    PeptideAtlasiQ9NQW7.
    PRIDEiQ9NQW7.

    Protocols and materials databases

    DNASUi7511.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

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

    Organism-specific databases

    CTDi7511.
    DisGeNETi7511.
    GeneCardsiXPNPEP1.
    HGNCiHGNC:12822. XPNPEP1.
    HPAiCAB025196.
    HPA030419.
    HPA030420.
    HPA030422.
    MIMi602443. gene.
    neXtProtiNX_Q9NQW7.
    OpenTargetsiENSG00000108039.
    PharmGKBiPA37415.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG2413. Eukaryota.
    COG0006. LUCA.
    GeneTreeiENSGT00390000013970.
    HOGENOMiHOG000255713.
    HOVERGENiHBG002934.
    InParanoidiQ9NQW7.
    KOiK01262.
    OMAiPGKWGIR.
    OrthoDBiEOG091G0A2Q.
    PhylomeDBiQ9NQW7.
    TreeFamiTF314183.

    Enzyme and pathway databases

    BioCyciZFISH:HS03058-MONOMER.
    BRENDAi3.1.8.1. 2681.
    3.4.11.9. 2681.

    Miscellaneous databases

    ChiTaRSiXPNPEP1. human.
    EvolutionaryTraceiQ9NQW7.
    GeneWikiiXPNPEP1.
    GenomeRNAii7511.
    PROiQ9NQW7.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000108039.
    CleanExiHS_XPNPEP1.
    ExpressionAtlasiQ9NQW7. baseline and differential.
    GenevisibleiQ9NQW7. HS.

    Family and domain databases

    CDDicd01085. APP. 1 hit.
    Gene3Di3.40.350.10. 2 hits.
    3.90.230.10. 1 hit.
    InterProiIPR029149. 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.
    [Graphical view]
    PfamiPF01321. Creatinase_N. 1 hit.
    PF00557. Peptidase_M24. 1 hit.
    PF16188. Peptidase_M24_C. 1 hit.
    [Graphical view]
    SUPFAMiSSF53092. SSF53092. 1 hit.
    SSF55920. SSF55920. 1 hit.
    PROSITEiPS00491. PROLINE_PEPTIDASE. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiXPP1_HUMAN
    AccessioniPrimary (citable) accession number: Q9NQW7
    Secondary accession number(s): A8K071
    , G5E9Y2, G8JLB2, O15250, Q53EX6, Q8N3Q0, Q96D23
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 5, 2005
    Last sequence update: January 23, 2007
    Last modified: November 30, 2016
    This is version 142 of the entry and version 3 of the sequence. [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

    Documents

    1. Human chromosome 10
      Human chromosome 10: 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

    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.