XPP2_PIG
ID XPP2_PIG Reviewed; 673 AA.
AC Q95333;
DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Xaa-Pro aminopeptidase 2;
DE EC=3.4.11.9 {ECO:0000269|PubMed:1312513, ECO:0000269|PubMed:8870669};
DE AltName: Full=Aminoacylproline aminopeptidase;
DE AltName: Full=Membrane-bound aminopeptidase P;
DE Short=Membrane-bound APP;
DE Short=Membrane-bound AmP;
DE Short=mAmP;
DE AltName: Full=X-Pro aminopeptidase 2;
DE Flags: Precursor;
GN Name=XPNPEP2;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND GPI-ANCHOR.
RC TISSUE=Kidney cortex {ECO:0000303|PubMed:8870669};
RX PubMed=8870669; DOI=10.1042/bj3190197;
RA Hyde R.J., Hooper N.M., Turner A.J.;
RT "Molecular cloning and expression in COS-1 cells of pig kidney
RT aminopeptidase P.";
RL Biochem. J. 319:197-201(1996).
RN [2]
RP PROTEIN SEQUENCE OF 27-649, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT,
RP SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-34; ASN-48; ASN-64; ASN-277;
RP ASN-290 AND ASN-294, AND GPI-ANCHOR AT ALA-649.
RC TISSUE=Kidney cortex {ECO:0000303|PubMed:7744038};
RX PubMed=7744038; DOI=10.1111/j.1432-1033.1995.0262l.x;
RA Vergas Romero C., Neudorfer I., Mann K., Schaefer W.;
RT "Purification and amino acid sequence of aminopeptidase P from pig
RT kidney.";
RL Eur. J. Biochem. 229:262-269(1995).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND ACTIVITY REGULATION.
RX PubMed=1312513; DOI=10.1161/01.hyp.19.3.281;
RA Hooper N.M., Hryszko J., Oppong S.Y., Turner A.J.;
RT "Inhibition by converting enzyme inhibitors of pig kidney aminopeptidase
RT P.";
RL Hypertension 19:281-285(1992).
CC -!- FUNCTION: Membrane-bound metalloprotease which catalyzes the removal of
CC a penultimate prolyl residue from the N-termini of peptides, such as
CC Arg-Pro-Pro. May play a role in the metabolism of the vasodilator
CC bradykinin. {ECO:0000269|PubMed:1312513, ECO:0000269|PubMed:7744038,
CC ECO:0000269|PubMed:8870669}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of any N-terminal amino acid, including proline, that
CC is linked to proline, even from a dipeptide or tripeptide.;
CC EC=3.4.11.9; Evidence={ECO:0000269|PubMed:1312513,
CC ECO:0000269|PubMed:7744038, ECO:0000269|PubMed:8870669};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:1312513};
CC -!- ACTIVITY REGULATION: Inhibited by apstatin and the metal ion chelator
CC EDTA (PubMed:8870669). Potently inhibited by the converting enzyme
CC inhibitors cilazaprilat; enalaprilat; L155,212; ramiprilat and YS 980
CC (PubMed:1312513). Also inhibited to a lesser extent by indolaprilat;
CC quinaprilat; spiraprilat; captopril and zofenoprilat (PubMed:1312513).
CC {ECO:0000269|PubMed:1312513, ECO:0000269|PubMed:8870669}.
CC -!- SUBUNIT: Homotrimer. {ECO:0000269|PubMed:7744038}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:7744038,
CC ECO:0000305|PubMed:8870669}; Lipid-anchor, GPI-anchor
CC {ECO:0000269|PubMed:7744038, ECO:0000269|PubMed:8870669}.
CC -!- TISSUE SPECIFICITY: Kidney. {ECO:0000269|PubMed:8870669}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:7744038}.
CC -!- SIMILARITY: Belongs to the peptidase M24B family. {ECO:0000305}.
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DR EMBL; U55039; AAC48664.1; -; mRNA.
DR PIR; S72440; S72440.
DR RefSeq; NP_001004048.1; NM_001004048.1.
DR RefSeq; XP_005673955.1; XM_005673898.2.
DR RefSeq; XP_013841867.1; XM_013986413.1.
DR AlphaFoldDB; Q95333; -.
DR SMR; Q95333; -.
DR STRING; 9823.ENSSSCP00000013450; -.
DR MEROPS; M24.005; -.
DR iPTMnet; Q95333; -.
DR PaxDb; Q95333; -.
DR PeptideAtlas; Q95333; -.
DR PRIDE; Q95333; -.
DR Ensembl; ENSSSCT00055008082; ENSSSCP00055006400; ENSSSCG00055004094.
DR Ensembl; ENSSSCT00070059641; ENSSSCP00070050803; ENSSSCG00070029594.
DR GeneID; 445538; -.
DR KEGG; ssc:445538; -.
DR CTD; 7512; -.
DR eggNOG; KOG2413; Eukaryota.
DR HOGENOM; CLU_011781_2_2_1; -.
DR InParanoid; Q95333; -.
DR OMA; WQDGLNY; -.
DR OrthoDB; 417805at2759; -.
DR TreeFam; TF314183; -.
DR Reactome; R-SSC-163125; Post-translational modification: synthesis of GPI-anchored proteins.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unassembled WGS sequence.
DR Genevisible; Q95333; SS.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0070062; C:extracellular exosome; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd01085; APP; 1.
DR Gene3D; 3.40.350.10; -; 2.
DR Gene3D; 3.90.230.10; -; 1.
DR InterPro; IPR029149; Creatin/AminoP/Spt16_NTD.
DR InterPro; IPR036005; Creatinase/aminopeptidase-like.
DR InterPro; IPR000587; Creatinase_N.
DR InterPro; IPR000994; Pept_M24.
DR InterPro; IPR033740; Pept_M24B.
DR InterPro; IPR032416; Peptidase_M24_C.
DR InterPro; IPR001131; Peptidase_M24B_aminopep-P_CS.
DR Pfam; PF01321; Creatinase_N; 1.
DR Pfam; PF00557; Peptidase_M24; 1.
DR Pfam; PF16188; Peptidase_M24_C; 1.
DR SUPFAM; SSF53092; SSF53092; 1.
DR SUPFAM; SSF55920; SSF55920; 1.
DR PROSITE; PS00491; PROLINE_PEPTIDASE; 1.
PE 1: Evidence at protein level;
KW Aminopeptidase; Cell membrane; Direct protein sequencing; Glycoprotein;
KW GPI-anchor; Hydrolase; Lipoprotein; Membrane; Metal-binding;
KW Metalloprotease; Protease; Reference proteome; Signal; Zinc.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..649
FT /note="Xaa-Pro aminopeptidase 2"
FT /id="PRO_0000026831"
FT PROPEP 650..673
FT /note="Removed in mature form"
FT /evidence="ECO:0000305"
FT /id="PRO_0000026832"
FT BINDING 115
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 429
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 449
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 449
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 460
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 460
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 523
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 523
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 532
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 554
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 554
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 568
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 568
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT LIPID 649
FT /note="GPI-anchor amidated alanine"
FT /evidence="ECO:0000269|PubMed:7744038"
FT CARBOHYD 34
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:7744038"
FT CARBOHYD 48
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:7744038"
FT CARBOHYD 64
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:7744038"
FT CARBOHYD 277
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:7744038"
FT CARBOHYD 290
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:7744038"
FT CARBOHYD 294
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:7744038"
FT CONFLICT 530
FT /note="C -> G (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 673 AA; 75756 MW; F480F50537CFD1B2 CRC64;
MAQACWGCYP WLVLICACAW GHPKSLNQRE DVRNCSTSPP YLPVTAVNTT AQLTALREQM
LTQNLSAYII PDTDAHMSEY IGECDQRRAW ITGFIGSAGI AVVTERKAAL WTDSRYWTQA
ERQMDCNWEL HKEVSTGHIV TWLLTEIPVG GRVGFDPFLF SIDSWESYDV ALQDADRELV
SITVNLVDLV WGSERPPLPN APIYALQEAF AGSTWQEKVS NIRSQMQKHH ERPTAVLLSA
LDETAWLFNL RSSDIPYNPF FYSYTLLTDS SIRLFANKSR FSSETLQYLN SSCNSSMCVQ
LEDYSQIRDS IQAYTSGDVK IWIGTRYTSY GLYEVIPKEK LVEDDYSPVM ITKAVKNSRE
QALLKASHVR DAVAVIRYLA WLEKNVPTGT VDEFSGAKRV EEFRGEEEFF SGPSFETISA
SGLNAALAHY SPTKELHRKL SSDEMYLLDS GGQYWDGTTD ITRTVHWGTP SAFQKEAYTR
VLIGNIDLSR LVFPAATSGR VVEAFARKAL WDVGLNYGHG TGHGIGNFLC VHEWPVGFQY
GNIPMAEGMF TSIEPGYYQD GEFGIRLEDV ALVVEAKTKY PGTYLTFEVV SLVPYDRKLI
DVSLLSPEQL QYLNRYYQAI REKVGPELQR RGLLEELSWL QRHTEPLSAR AAPTTSLGSL
MTVSALAILG WSV
