XPP2_MOUSE
ID XPP2_MOUSE Reviewed; 674 AA.
AC B1AVD1; Q3TA51; Q3TPA9; Q8BVD6; Q91Y31; Q91ZH9;
DT 18-JAN-2017, integrated into UniProtKB/Swiss-Prot.
DT 08-APR-2008, sequence version 1.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Xaa-Pro aminopeptidase 2 {ECO:0000305};
DE EC=3.4.11.9 {ECO:0000250|UniProtKB:Q95333};
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|MGI:MGI:2180001};
DE Flags: Precursor;
GN Name=Xpnpep2 {ECO:0000312|MGI:MGI:2180001};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090 {ECO:0000312|Proteomes:UP000000589};
RN [1] {ECO:0000312|EMBL:AAK52065.1}
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=BALB/cJ {ECO:0000312|EMBL:AAK52065.1};
RC TISSUE=Lung {ECO:0000312|EMBL:AAK52065.1};
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|EMBL:AAL26562.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Prueitt R.L., Zinn A.R.;
RT "Mouse membrane bound aminopeptidase P.";
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000312|EMBL:BAC37415.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAE37828.1}, and
RC NOD {ECO:0000312|EMBL:BAE42819.1};
RC TISSUE=Colon {ECO:0000312|EMBL:BAC37415.1},
RC Heart {ECO:0000312|EMBL:BAE37828.1}, and
RC Spleen {ECO:0000312|EMBL:BAE42819.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4] {ECO:0000312|Proteomes:UP000000589}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J {ECO:0000312|Proteomes:UP000000589};
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5] {ECO:0000312|EMBL:EDL29066.1}
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 [6] {ECO:0000312|EMBL:AAI40978.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain {ECO:0000312|EMBL:AAI40978.1};
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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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:0000250|UniProtKB:Q95333}.
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:0000250|UniProtKB:Q95333};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q95333};
CC -!- SUBUNIT: Homotrimer. {ECO:0000250|UniProtKB:Q95333}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q95333};
CC Lipid-anchor, GPI-anchor {ECO:0000250|UniProtKB:Q95333}.
CC -!- TISSUE SPECIFICITY: Strongly expressed in small intestine, heart and
CC lung. Also detected in testis, skeletal muscle, spleen, liver, kidney,
CC brain, uterus, eye, lymph node, thymus, stomach, prostate and bone
CC marrow. {ECO:0000269|PubMed:12941294}.
CC -!- DEVELOPMENTAL STAGE: Expressed in embryos from 7 days onwards, with
CC highest expression at 15 days. {ECO:0000269|PubMed:12941294}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q99MA2}.
CC -!- SIMILARITY: Belongs to the peptidase M24B family.
CC {ECO:0000255|RuleBase:RU000590, ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC37415.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAE37828.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAE42819.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF367247; AAK52065.1; -; mRNA.
DR EMBL; AF428102; AAL26562.1; -; mRNA.
DR EMBL; AK078835; BAC37415.1; ALT_FRAME; mRNA.
DR EMBL; AK164538; BAE37828.1; ALT_FRAME; mRNA.
DR EMBL; AK172086; BAE42819.1; ALT_FRAME; mRNA.
DR EMBL; AL672274; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466570; EDL29066.1; -; Genomic_DNA.
DR EMBL; BC140977; AAI40978.1; -; mRNA.
DR CCDS; CCDS30106.1; -.
DR RefSeq; NP_001276658.1; NM_001289729.1.
DR RefSeq; NP_573476.2; NM_133213.2.
DR RefSeq; XP_006541495.1; XM_006541432.1.
DR AlphaFoldDB; B1AVD1; -.
DR SMR; B1AVD1; -.
DR STRING; 10090.ENSMUSP00000076951; -.
DR MEROPS; M24.005; -.
DR GlyGen; B1AVD1; 4 sites.
DR iPTMnet; B1AVD1; -.
DR PhosphoSitePlus; B1AVD1; -.
DR jPOST; B1AVD1; -.
DR MaxQB; B1AVD1; -.
DR PaxDb; B1AVD1; -.
DR PeptideAtlas; B1AVD1; -.
DR PRIDE; B1AVD1; -.
DR ProteomicsDB; 300188; -.
DR Antibodypedia; 16116; 181 antibodies from 28 providers.
DR DNASU; 170745; -.
DR Ensembl; ENSMUST00000077775; ENSMUSP00000076951; ENSMUSG00000037005.
DR GeneID; 170745; -.
DR KEGG; mmu:170745; -.
DR UCSC; uc009tbv.1; mouse.
DR CTD; 7512; -.
DR MGI; MGI:2180001; Xpnpep2.
DR VEuPathDB; HostDB:ENSMUSG00000037005; -.
DR eggNOG; KOG2413; Eukaryota.
DR GeneTree; ENSGT00940000157196; -.
DR OMA; WQDGLNY; -.
DR OrthoDB; 417805at2759; -.
DR PhylomeDB; B1AVD1; -.
DR TreeFam; TF314183; -.
DR Reactome; R-MMU-163125; Post-translational modification: synthesis of GPI-anchored proteins.
DR BioGRID-ORCS; 170745; 4 hits in 72 CRISPR screens.
DR PRO; PR:B1AVD1; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; B1AVD1; protein.
DR Bgee; ENSMUSG00000037005; Expressed in small intestine Peyer's patch and 60 other tissues.
DR ExpressionAtlas; B1AVD1; baseline and differential.
DR Genevisible; Q91ZH9; MM.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0070062; C:extracellular exosome; ISO:MGI.
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; Glycoprotein; GPI-anchor; Hydrolase;
KW Lipoprotein; Membrane; Metal-binding; Protease; Reference proteome; Signal;
KW Zinc.
FT SIGNAL 1..22
FT /evidence="ECO:0000250|UniProtKB:Q99MA2"
FT CHAIN 23..650
FT /note="Xaa-Pro aminopeptidase 2"
FT /evidence="ECO:0000305"
FT /id="PRO_5008409937"
FT PROPEP 651..674
FT /note="Removed in mature form"
FT /evidence="ECO:0000305"
FT /id="PRO_0000438729"
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 270
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"
FT CONFLICT 13
FT /note="V -> I (in Ref. 1; AAI40978, 3; BAE42819 and 6;
FT AAK52065)"
FT /evidence="ECO:0000305"
FT CONFLICT 64
FT /note="W -> C (in Ref. 2; AAL26562)"
FT /evidence="ECO:0000305"
FT CONFLICT 323
FT /note="L -> I (in Ref. 3; BAE42819)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 674 AA; 76434 MW; BCC0C9BE53E4D996 CRC64;
MAQAYWQCYP WLVLLCACAW SYPEPKYLGR EDVRNCSTSP ERLPVTAVNT TMRLAALRQQ
METWNLSAYI IPDTDAHMSE YIGKPDKRRE WISGFTGSAG TAVVTMGKAA VWTDSRYWTQ
AERQMDCNWE LHKEVSISSI VAWILAEVPD GQNVGFDPFL FSVDSWKNYD QGFQDSSRHL
LSVTTNLVDV AWGSERPPVP SQPIYALPKE FTGSTWQEKV SAVRSYMEHH AKTPTGVLLS
ALDETAWLFN LRSSDIPYNP FFYSYALLTN SSIRLFVNKS RFSLETLQYL NTNCTLPMCV
QLEDYSQVRD SVKAYASGDV KILIGVSYTT YGVYEVIPKE KLVTDTYSPV MLIKAVKNSK
EQALLKSSHV RDAVAVIQYL VWLEKNVPKG TVDEFSGAEY IDELRRNENF SSGPSFETIS
ASGLNAALAH YSPTKELHRK LSSDEMYLVD SGGQYWDGTT DITRTVHWGT PTAFQKEAYT
RVLMGNIDLS RLVFPAATSG RVIEAFARRA LWEVGLNYGH GTGHGIGNFL CVHEWPVGFQ
YNNIAMAKGM FTSIEPGYYH DGEFGIRLED VALVVEAKTK YPGDYLTFEL VSFVPYDRNL
IDVRLLSPEQ LQYLNRYYQT IRENVGPELQ RRQLLEEFAW LEQHTEPLSA RAPHIISWTS
LWVASALAIL SWSS
