Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Xaa-Pro aminopeptidase 2

Gene

XPNPEP2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

A metalloprotease that may play a role in the inflammatory process and other reactions produced in response to injury or infection. May also play a role in the metabolism of the vasodilator bradykinin.

Catalytic activityi

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

Cofactori

Mn2+By similarityNote: Binds 2 manganese ions per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi450Manganese 2By similarity1
Metal bindingi461Manganese 1By similarity1
Metal bindingi461Manganese 2By similarity1
Metal bindingi555Manganese 1By similarity1
Metal bindingi569Manganese 1By similarity1
Metal bindingi569Manganese 2By similarity1

GO - Molecular functioni

  • aminopeptidase activity Source: ProtInc
  • metal ion binding Source: UniProtKB-KW
  • metalloaminopeptidase activity Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Aminopeptidase, Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Manganese, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:HS04545-MONOMER.

Protein family/group databases

MEROPSiM24.005.

Names & Taxonomyi

Protein namesi
Recommended name:
Xaa-Pro aminopeptidase 2 (EC:3.4.11.9)
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

GO - Cellular componenti

  • anchored component of membrane Source: UniProtKB-KW
  • extracellular exosome Source: UniProtKB
  • membrane Source: ProtInc
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

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 formBy similarityAdd 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

Heavily glycosylated.

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.

Gene expression databases

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

Organism-specific databases

HPAiCAB025136.
CAB025269.
HPA000339.

Interactioni

Subunit structurei

Homotrimer.

Protein-protein interaction databases

MINTiMINT-5002270.
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.
OMAiSPEHLQY.
OrthoDBiEOG091G0A2Q.
PhylomeDBiO43895.
TreeFamiTF314183.

Family and domain databases

CDDicd01085. APP. 1 hit.
Gene3Di3.40.350.10. 1 hit.
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]

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 → I.1 PublicationCorresponds to variant rs138365897dbSNPEnsembl.1
Natural variantiVAR_071311223V → I.1 PublicationCorresponds to variant rs61733030dbSNPEnsembl.1
Natural variantiVAR_071312232K → N.1 PublicationCorresponds to variant rs41311662dbSNPEnsembl.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

BindingDBiO43895.
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

BioCyciZFISH:HS04545-MONOMER.

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.
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 nameiXPP2_HUMAN
AccessioniPrimary (citable) accession number: O43895
Secondary accession number(s): A0AV16, O75994
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 15, 2002
Last sequence update: November 15, 2002
Last modified: November 30, 2016
This is version 140 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

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.