XPP2_RAT
ID XPP2_RAT Reviewed; 674 AA.
AC Q99MA2;
DT 18-JAN-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Xaa-Pro aminopeptidase 2 {ECO:0000305};
DE EC=3.4.11.9 {ECO:0000269|PubMed:7669781};
DE AltName: Full=Membrane-bound aminopeptidase P {ECO:0000303|PubMed:12941294};
DE Short=Membrane-bound APP {ECO:0000303|PubMed:12941294};
DE Short=mAPP {ECO:0000303|PubMed:12941294};
DE AltName: Full=X-prolyl aminopeptidase 2 {ECO:0000312|RGD:621277};
DE Flags: Precursor;
GN Name=Xpnpep2 {ECO:0000312|RGD:621277};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116 {ECO:0000312|Proteomes:UP000002494};
RN [1] {ECO:0000312|EMBL:AAK30297.1}
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley {ECO:0000312|EMBL:AAK30297.1};
RX PubMed=12941294; DOI=10.1016/s0003-9861(03)00348-5;
RA Ersahin C., Szpaderska A.M., Simmons W.H.;
RT "Rat and mouse membrane aminopeptidase P: structure analysis and tissue
RT distribution.";
RL Arch. Biochem. Biophys. 417:131-140(2003).
RN [2] {ECO:0000312|Proteomes:UP000002494}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway {ECO:0000312|Proteomes:UP000002494};
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [3] {ECO:0000312|EMBL:EDM10905.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000312|EMBL:AAH74017.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung {ECO:0000312|EMBL:AAH74017.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5] {ECO:0000305}
RP PROTEIN SEQUENCE OF 23-47, CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RX PubMed=7669781; DOI=10.1021/bi00035a032;
RA Orawski A.T., Simmons W.H.;
RT "Purification and properties of membrane-bound aminopeptidase P from rat
RT lung.";
RL Biochemistry 34:11227-11236(1995).
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:7669781}.
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:7669781};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q95333};
CC -!- ACTIVITY REGULATION: Inhibited by the chelating agents 1,10-
CC phenanthroline and EDTA. Inhibited by the thiol-containing compounds 2-
CC mercaptoethanol and dithiothreitol. Also inhibited by apstatin,
CC captopril and p-(ch1oromercuri)benzenesulfonic acid. Weakly inhibited
CC by D,L-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid and N-[l-
CC (R,S)-carboxy-(2-phenylethyl)]-Ala-Ala-Phe-p-aminobenzoate. Inhibited
CC by ramiprilat and enalaprilat, in a Mn(2+)-dependent manner. Metal ions
CC have a complex substrate- and concentration-dependent effect on
CC activity. Activity towards Arg-Pro-Pro and Gly-Pro-Hyp is stimulated by
CC Mn(2+) ion concentrations of 10-100 uM and then inhibited at Mn(2+)
CC concentrations of 1-2 mM. Mn(2+) concentrations in excess of 2 mM
CC stimulate activity towards Gly-Pro-Hyp but inhibit activity towards
CC Arg-Pro-Pro. Zn(2+) and Co(2+) ions also inhibit activity towards Arg-
CC Pro-Pro at high concentrations. Activity towards bradykinin is
CC inhibited by Mn(2+) concentrations in excess of 1 mM.
CC {ECO:0000269|PubMed:7669781}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.35 mM for Arg-Pro-Pro (at pH 8.0) {ECO:0000269|PubMed:7669781};
CC KM=0.36 mM for Arg-Pro-Pro (at pH 8.0, in the presence of 4 mM
CC Mn(2+)) {ECO:0000269|PubMed:7669781};
CC KM=0.32 mM for Gly-Pro-Hyp (at pH 8.0) {ECO:0000269|PubMed:7669781};
CC KM=2.0 mM for Gly-Pro-Hyp (at pH 8.0, in the presence of 4 mM Mn(2+))
CC {ECO:0000269|PubMed:7669781};
CC KM=0.021 mM for Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg (bradykinin, at
CC pH 6.8) {ECO:0000269|PubMed:7669781};
CC KM=0.039 mM for Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe (at pH 6.8)
CC {ECO:0000269|PubMed:7669781};
CC KM=0.051 mM for Arg-Pro-Pro-Gly-Phe-Ser-Pro (at pH 6.8)
CC {ECO:0000269|PubMed:7669781};
CC KM=0.032 mM for Arg-Pro-Pro-Gly-Phe-Ser (at pH 6.8)
CC {ECO:0000269|PubMed:7669781};
CC KM=0.048 mM for Arg-Pro-Pro-Gly-Phe (at pH 6.8)
CC {ECO:0000269|PubMed:7669781};
CC KM=0.030 mM for Arg-Pro-Pro-Gly (at pH 6.8)
CC {ECO:0000269|PubMed:7669781};
CC KM=1.0 mM for Arg-Pro-Pro (at pH 6.8) {ECO:0000269|PubMed:7669781};
CC pH dependence:
CC Optimum pH is 7.0 for bradykinin. Active between pH 6.0-11.0.
CC {ECO:0000269|PubMed:7669781};
CC Temperature dependence:
CC Thermostable to 55 degrees Celsius. Complete loss of activity above
CC 70-75 degrees Celsius. {ECO:0000269|PubMed:7669781};
CC -!- SUBUNIT: Homotrimer. {ECO:0000250|UniProtKB:Q95333}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:7669781};
CC Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:7669781}.
CC -!- TISSUE SPECIFICITY: Expressed strongly in lung, liver and heart, and at
CC lower levels in kidney, testis, brain, spleen and skeletal muscle.
CC {ECO:0000269|PubMed:12941294}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:7669781}.
CC -!- SIMILARITY: Belongs to the peptidase M24B family.
CC {ECO:0000255|RuleBase:RU000590, ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF359355; AAK30297.1; -; mRNA.
DR EMBL; AC127934; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC132991; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH473991; EDM10905.1; -; Genomic_DNA.
DR EMBL; BC074017; AAH74017.1; -; mRNA.
DR RefSeq; NP_476496.1; NM_057155.3.
DR RefSeq; XP_008771735.1; XM_008773513.2.
DR AlphaFoldDB; Q99MA2; -.
DR SMR; Q99MA2; -.
DR STRING; 10116.ENSRNOP00000005604; -.
DR BindingDB; Q99MA2; -.
DR ChEMBL; CHEMBL2970; -.
DR MEROPS; M24.005; -.
DR GlyGen; Q99MA2; 3 sites.
DR PaxDb; Q99MA2; -.
DR PRIDE; Q99MA2; -.
DR Ensembl; ENSRNOT00000098779; ENSRNOP00000095320; ENSRNOG00000004009.
DR GeneID; 117522; -.
DR KEGG; rno:117522; -.
DR UCSC; RGD:621277; rat.
DR CTD; 7512; -.
DR RGD; 621277; Xpnpep2.
DR eggNOG; KOG2413; Eukaryota.
DR GeneTree; ENSGT00940000157196; -.
DR HOGENOM; CLU_011781_2_2_1; -.
DR InParanoid; Q99MA2; -.
DR OMA; WQDGLNY; -.
DR OrthoDB; 417805at2759; -.
DR PhylomeDB; Q99MA2; -.
DR TreeFam; TF314183; -.
DR BRENDA; 3.4.11.9; 5301.
DR Reactome; R-RNO-163125; Post-translational modification: synthesis of GPI-anchored proteins.
DR PRO; PR:Q99MA2; -.
DR Proteomes; UP000002494; Chromosome X.
DR Proteomes; UP000234681; Chromosome x.
DR Bgee; ENSRNOG00000004009; Expressed in jejunum and 14 other tissues.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0070062; C:extracellular exosome; ISO:RGD.
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; Protease;
KW Reference proteome; Signal; Zinc.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:7669781"
FT CHAIN 23..650
FT /note="Xaa-Pro aminopeptidase 2"
FT /evidence="ECO:0000305|PubMed:7669781"
FT /id="PRO_5008179703"
FT PROPEP 651..674
FT /note="Removed in mature form"
FT /evidence="ECO:0000305"
FT /id="PRO_0000438730"
FT BINDING 116
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 430
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 450
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 461
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 461
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 524
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 524
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 533
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 555
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 555
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 569
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 569
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT LIPID 650
FT /note="GPI-anchor amidated alanine"
FT /evidence="ECO:0000250|UniProtKB:Q95333"
FT CARBOHYD 65
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 278
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 293
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 674 AA; 76080 MW; 10B127E2A3AF51F2 CRC64;
MAQAYWQCYP WLVLLCACAW SYPGPESLGR EDVRDCSTNP PRLPVTAVNT TMRLAALRQQ
MEKSNLSAYI IPDTDAHMSE YIGKHDERRA WISGFTGSAG TAVVTKKKAA VWTDSRYWTQ
AERQMDCNWE LHKEVSISSI VAWILAEVPD GENVGFDPFL FSVGSWENYD QELQDSNRHL
LSITTNLVDV AWGSERPPVP SQPIYALPKE FTGSTWQEKV SAIRSYMQNH TMAPTGVLLS
ALDETAWLFN LRSSDIPYNP FFYSYTLLTD SSIRLFVNKS RFSLETLQYL NTNCTLPMCV
QLEDYSQIRD GVKAYASGNV KILIGISYTT YGVYDVIPKE KLVTETYSPV MLIKAVKNSK
EQALLKASHV RDAVAVIQYL VWLEKNVPKG TVDEFSGAEH IDQLRRNENF SSGPSFETIS
ASGLNAALAH YSPTKELHRK LSLDEMYLVD SGGQYWDGTT DITRTVHWGT PTAFQKEAYT
RVLMGNIDLS RLVFPAATSG RVVEAFARRA LWEVGLNYGH GTGHGIGNFL CVHEWPVGFQ
YNNMAMAKGM FTSIEPGYYQ DGEFGIRLED VALVVEAKTK YPGTYLTFEL VSFVPYDRNL
IDVSLLSPEQ LQYLNRYYQT IRENIGPELQ RRQLLEEFAW LERHTEPLSA SAPHTTSLAS
MWVASALAIL SWSC
