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Q9NQW7 (XPP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:XPNPEP1
Synonyms:XPNPEPL, XPNPEPL1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length623 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 activity

Release of any N-terminal amino acid, including proline, that is linked to proline, even from a dipeptide or tripeptide. Ref.3 Ref.15

Cofactor

Binds 2 manganese ions per subunit. Ref.3 Ref.15

Enzyme regulation

Inhibited by apstatin and the metal ion chelators EDTA and 1,10-phenanthroline. Partially inhibited by dithiothreitol. Not inhibited by enalaprilat or amastatin. Ref.3

Subunit structure

Homodimer. Ref.3 Ref.15

Subcellular location

Cytoplasm By similarity UniProtKB O54975.

Tissue specificity

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

Sequence similarities

Belongs to the peptidase M24B family.

Biophysicochemical properties

Kinetic parameters:

KM=100.6 µM for bradykinin Ref.3 Ref.15

KM=308 µM for the tripeptide Arg-Pro-Pro

pH dependence:

Optimum pH is 8.2. Ref.3

Sequence caution

The sequence CAD38640.1 differs from that shown. Reason: Erroneous initiation.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 Ref.1 (identifier: Q9NQW7-1)

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.
Isoform 2 Ref.4 (identifier: Q9NQW7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     398-421: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q9NQW7-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MAASRKPPRVRVNHQDFQLRNLRIIEPNEVTHSGDTGVETDGRM
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.11
Chain2 – 623622Xaa-Pro aminopeptidase 1
PRO_0000185083

Sites

Metal binding4151Manganese 1
Metal binding4261Manganese 1
Metal binding4261Manganese 2
Metal binding4891Manganese 2
Metal binding5231Manganese 2
Metal binding5371Manganese 1
Metal binding5371Manganese 2

Amino acid modifications

Modified residue3041N6-acetyllysine Ref.12

Natural variations

Alternative sequence11M → MAASRKPPRVRVNHQDFQLR NLRIIEPNEVTHSGDTGVET DGRM in isoform 3.
VSP_045250
Alternative sequence398 – 42124Missing in isoform 2. Ref.4
VSP_051752

Experimental info

Mutagenesis411E → A: Reduces activity by 10%. Ref.15
Mutagenesis4771W → E: Interferes with dimerization and reduces activity by 94%. Ref.15
Sequence conflict901W → C in AAH13417. Ref.10
Sequence conflict1311K → R in BAF82125. Ref.4
Sequence conflict3321R → P Ref.1
Sequence conflict3321R → P Ref.2
Sequence conflict4961N → D Ref.7
Sequence conflict4981H → R Ref.7
Sequence conflict5721I → T in BAF82125. Ref.4

Secondary structure

................................................................................................................... 623
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: DF4F5AF41E2F3876

FASTA62369,918
        10         20         30         40         50         60 
MPPKVTSELL RQLRQAMRNS EYVTEPIQAY IIPSGDAHQS EYIAPCDCRR AFVSGFDGSA 

        70         80         90        100        110        120 
GTAIITEEHA AMWTDGRYFL QAAKQMDSNW TLMKMGLKDT PTQEDWLVSV LPEGSRVGVD 

       130        140        150        160        170        180 
PLIIPTDYWK KMAKVLRSAG HHLIPVKENL VDKIWTDRPE RPCKPLLTLG LDYTGISWKD 

       190        200        210        220        230        240 
KVADLRLKMA ERNVMWFVVT ALDEIAWLFN LRGSDVEHNP VFFSYAIIGL ETIMLFIDGD 

       250        260        270        280        290        300 
RIDAPSVKEH LLLDLGLEAE YRIQVHPYKS ILSELKALCA DLSPREKVWV SDKASYAVSE 

       310        320        330        340        350        360 
TIPKDHRCCM PYTPICIAKA VKNSAESEGM RRAHIKDAVA LCELFNWLEK EVPKGGVTEI 

       370        380        390        400        410        420 
SAADKAEEFR RQQADFVDLS FPTISSTGPN GAIIHYAPVP ETNRTLSLDE VYLIDSGAQY 

       430        440        450        460        470        480 
KDGTTDVTRT MHFGTPTAYE KECFTYVLKG HIAVSAAVFP TGTKGHLLDS FARSALWDSG 

       490        500        510        520        530        540 
LDYLHGTGHG VGSFLNVHEG PCGISYKTFS DEPLEAGMIV TDEPGYYEDG AFGIRIENVV 

       550        560        570        580        590        600 
LVVPVKTKYN FNNRGSLTFE PLTLVPIQTK MIDVDSLTDK ECDWLNNYHL TCRDVIGKEL 

       610        620 
QKQGRQEALE WLIRETQPIS KQH 

« Hide

Isoform 2 [UniParc].

Checksum: 6F6A7D909E1CC84D
Show »

FASTA59967,227
Isoform 3 [UniParc].

Checksum: 59D0596A49C93B17
Show »

FASTA66674,798

References

« Hide 'large scale' references
[1]"Isolation and sequence analysis of a human cDNA clone (XPNPEPL) homologous to X-prolyl aminopeptidase (aminopeptidase P)."
Vanhoof G., Goossens F., Juliano M.A., Juliano L., Hendriks D., Schatteman K., Lin A.H., Scharpe S.
Cytogenet. Cell Genet. 78:275-280(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Lymphocyte.
[2]"Cloning, chromosomal sublocalization of the human soluble aminopeptidase P gene (XPNPEP1) to 10q25.3 and conservation of the putative proton shuttle and metal ligand binding sites with XPNPEP2."
Sprinkle T.J., Caldwell C., Ryan J.W.
Arch. Biochem. Biophys. 378:51-56(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]"Cloning, expression, and characterization of human cytosolic aminopeptidase P: a single manganese(II)-dependent enzyme."
Cottrell G.S., Hooper N.M., Turner A.J.
Biochemistry 39:15121-15128(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CATALYTIC ACTIVITY, COFACTOR, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT.
Tissue: Pancreatic adenocarcinoma.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[5]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[7]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Adipose tissue.
[8]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Colon, Ovary and Placenta.
[11]"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides."
Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J.
Nat. Biotechnol. 21:566-569(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-11.
Tissue: Platelet.
[12]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-304, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"Structure of human cytosolic X-prolyl aminopeptidase: a double Mn(II)-dependent dimeric enzyme with a novel three-domain subunit."
Li X., Lou Z., Li X., Zhou W., Ma M., Cao Y., Geng Y., Bartlam M., Zhang X.C., Rao Z.
J. Biol. Chem. 283:22858-22866(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH MANGANESE IONS, COFACTOR, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF GLU-41 AND TRP-477, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001161076.1. NM_001167604.1.
NP_065116.3. NM_020383.3.
UniGeneHs.390623.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3CTZX-ray1.60A1-623[»]
ProteinModelPortalQ9NQW7.
SMRQ9NQW7. Positions 3-619.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113346. 39 interactions.
IntActQ9NQW7. 7 interactions.
MINTMINT-3039782.
STRING9606.ENSP00000358694.

Chemistry

BindingDBQ9NQW7.
ChEMBLCHEMBL3782.

Protein family/group databases

MEROPSM24.009.

PTM databases

PhosphoSiteQ9NQW7.

Polymorphism databases

DMDM68566146.

Proteomic databases

PaxDbQ9NQW7.
PRIDEQ9NQW7.

Protocols and materials databases

DNASU7511.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000369680; ENSP00000358694; ENSG00000108039. [Q9NQW7-1]
ENST00000502935; ENSP00000421566; ENSG00000108039. [Q9NQW7-3]
GeneID7511.
KEGGhsa:7511.
UCSCuc001kyp.2. human.
uc001kyq.2. human. [Q9NQW7-1]

Organism-specific databases

CTD7511.
GeneCardsGC10M111614.
HGNCHGNC:12822. XPNPEP1.
HPACAB025196.
HPA030419.
HPA030420.
HPA030422.
MIM602443. gene.
neXtProtNX_Q9NQW7.
PharmGKBPA37415.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0006.
HOGENOMHOG000255713.
HOVERGENHBG002934.
InParanoidQ9NQW7.
KOK01262.
OMAYRPGKWG.
PhylomeDBQ9NQW7.
TreeFamTF314183.

Enzyme and pathway databases

BRENDA3.4.11.9. 2681.

Gene expression databases

ArrayExpressQ9NQW7.
BgeeQ9NQW7.
CleanExHS_XPNPEP1.
GenevestigatorQ9NQW7.

Family and domain databases

Gene3D3.90.230.10. 1 hit.
InterProIPR000587. Creatinase_N.
IPR000994. Pept_M24_structural-domain.
IPR001131. Peptidase_M24B_aminopep-P_CS.
[Graphical view]
PfamPF01321. Creatinase_N. 1 hit.
PF00557. Peptidase_M24. 1 hit.
[Graphical view]
SUPFAMSSF55920. SSF55920. 1 hit.
PROSITEPS00491. PROLINE_PEPTIDASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSXPNPEP1. human.
EvolutionaryTraceQ9NQW7.
GeneWikiXPNPEP1.
GenomeRNAi7511.
NextBio29395.
PROQ9NQW7.
SOURCESearch...

Entry information

Entry nameXPP1_HUMAN
AccessionPrimary (citable) accession number: Q9NQW7
Secondary accession number(s): A8K071 expand/collapse secondary AC list , G5E9Y2, O15250, Q53EX6, Q8N3Q0, Q96D23
Entry history
Integrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 117 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM