ID XPP3_MOUSE Reviewed; 506 AA.
AC B7ZMP1; Q8BHT9;
DT 30-NOV-2010, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 1.
DT 27-MAR-2024, entry version 101.
DE RecName: Full=Xaa-Pro aminopeptidase 3 {ECO:0000312|MGI:MGI:2445217};
DE Short=X-Pro aminopeptidase 3;
DE EC=3.4.11.9;
DE AltName: Full=Aminopeptidase P3;
DE Short=APP3;
DE Flags: Precursor;
GN Name=Xpnpep3;
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=NOD; TISSUE=Thymus;
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 [2]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Kidney, Liver, and Testis;
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).
RN [5]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=20179356; DOI=10.1172/jci40076;
RA O'Toole J.F., Liu Y., Davis E.E., Westlake C.J., Attanasio M., Otto E.A.,
RA Seelow D., Nurnberg G., Becker C., Nuutinen M., Karppa M., Ignatius J.,
RA Uusimaa J., Pakanen S., Jaakkola E., van den Heuvel L.P., Fehrenbach H.,
RA Wiggins R., Goyal M., Zhou W., Wolf M.T., Wise E., Helou J., Allen S.J.,
RA Murga-Zamalloa C.A., Ashraf S., Chaki M., Heeringa S., Chernin G.,
RA Hoskins B.E., Chaib H., Gleeson J., Kusakabe T., Suzuki T., Isaac R.E.,
RA Quarmby L.M., Tennant B., Fujioka H., Tuominen H., Hassinen I., Lohi H.,
RA van Houten J.L., Rotig A., Sayer J.A., Rolinski B., Freisinger P.,
RA Madhavan S.M., Herzer M., Madignier F., Prokisch H., Nurnberg P.,
RA Jackson P.K., Khanna H., Katsanis N., Hildebrandt F.;
RT "Individuals with mutations in XPNPEP3, which encodes a mitochondrial
RT protein, develop a nephronophthisis-like nephropathy.";
RL J. Clin. Invest. 120:791-802(2010).
RN [6]
RP ERRATUM OF PUBMED:20179356.
RA O'Toole J.F., Liu Y., Davis E.E., Westlake C.J., Attanasio M., Otto E.A.,
RA Seelow D., Nurnberg G., Becker C., Nuutinen M., Karppa M., Ignatius J.,
RA Uusimaa J., Pakanen S., Jaakkola E., van den Heuvel L.P., Fehrenbach H.,
RA Wiggins R., Goyal M., Zhou W., Wolf M.T., Wise E., Helou J., Allen S.J.,
RA Murga-Zamalloa C.A., Ashraf S., Chaki M., Heeringa S., Chernin G.,
RA Hoskins B.E., Chaib H., Gleeson J., Kusakabe T., Suzuki T., Isaac R.E.,
RA Quarmby L.M., Tennant B., Fujioka H., Tuominen H., Hassinen I., Lohi H.,
RA van Houten J.L., Rotig A., Sayer J.A., Rolinski B., Freisinger P.,
RA Madhavan S.M., Herzer M., Madignier F., Prokisch H., Nurnberg P.,
RA Jackson P.K., Khanna H., Katsanis N., Hildebrandt F.;
RL J. Clin. Invest. 120:1362-1362(2010).
CC -!- FUNCTION: Catalyzes the removal of a penultimate prolyl residue from
CC the N-termini of peptides, such as Leu-Pro-Ala. Also shows low activity
CC towards peptides with Ala or Ser at the P1 position. Promotes TNFRSF1B-
CC mediated phosphorylation of MAPK8/JNK1 and MAPK9/JNK2, suggesting a
CC function as an adapter protein for TNFRSF1B; the effect is independent
CC of XPNPEP3 peptidase activity. May inhibit apoptotic cell death induced
CC via TNF-TNFRSF1B signaling. {ECO:0000250|UniProtKB:Q9NQH7}.
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:Q9NQH7};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q9NQH7};
CC Note=Binds 2 manganese ions per subunit.
CC {ECO:0000250|UniProtKB:Q9NQH7};
CC -!- SUBUNIT: Homodimer. Interacts with TNFRSF1B/TNFR2 (activated) and
CC TRAF2. {ECO:0000250|UniProtKB:Q9NQH7}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q9NQH7}.
CC Cytoplasm {ECO:0000250|UniProtKB:Q9NQH7}. Note=Mainly mitochondrial.
CC Translocates to the cytoplasm following TNFRSF1B activation.
CC {ECO:0000250|UniProtKB:Q9NQH7}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=B7ZMP1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=B7ZMP1-2; Sequence=VSP_040145, VSP_040146;
CC -!- TISSUE SPECIFICITY: Expressed in brain, kidney, heart, liver, skeletal
CC muscle and testis. {ECO:0000269|PubMed:20179356}.
CC -!- SIMILARITY: Belongs to the peptidase M24B family. {ECO:0000305}.
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DR EMBL; AK088324; BAC40282.1; -; mRNA.
DR EMBL; CH466550; EDL04573.1; -; Genomic_DNA.
DR EMBL; CH466550; EDL04574.1; -; Genomic_DNA.
DR EMBL; BC137569; AAI37570.1; -; mRNA.
DR EMBL; BC144717; AAI44718.1; -; mRNA.
DR CCDS; CCDS27668.1; -. [B7ZMP1-2]
DR CCDS; CCDS84182.1; -. [B7ZMP1-1]
DR RefSeq; NP_001334004.1; NM_001347075.1. [B7ZMP1-1]
DR RefSeq; NP_796284.1; NM_177310.2. [B7ZMP1-2]
DR AlphaFoldDB; B7ZMP1; -.
DR SMR; B7ZMP1; -.
DR BioGRID; 236455; 3.
DR STRING; 10090.ENSMUSP00000132822; -.
DR MEROPS; M24.026; -.
DR iPTMnet; B7ZMP1; -.
DR PhosphoSitePlus; B7ZMP1; -.
DR SwissPalm; B7ZMP1; -.
DR EPD; B7ZMP1; -.
DR jPOST; B7ZMP1; -.
DR MaxQB; B7ZMP1; -.
DR PaxDb; 10090-ENSMUSP00000038331; -.
DR PeptideAtlas; B7ZMP1; -.
DR ProteomicsDB; 299798; -. [B7ZMP1-1]
DR ProteomicsDB; 299799; -. [B7ZMP1-2]
DR Pumba; B7ZMP1; -.
DR Antibodypedia; 259; 179 antibodies from 27 providers.
DR DNASU; 321003; -.
DR Ensembl; ENSMUST00000041609.11; ENSMUSP00000038331.5; ENSMUSG00000022401.13. [B7ZMP1-2]
DR Ensembl; ENSMUST00000163754.9; ENSMUSP00000132822.2; ENSMUSG00000022401.13. [B7ZMP1-1]
DR GeneID; 321003; -.
DR KEGG; mmu:321003; -.
DR UCSC; uc007wwo.1; mouse. [B7ZMP1-2]
DR UCSC; uc011zwj.1; mouse. [B7ZMP1-1]
DR AGR; MGI:2445217; -.
DR CTD; 63929; -.
DR MGI; MGI:2445217; Xpnpep3.
DR VEuPathDB; HostDB:ENSMUSG00000022401; -.
DR eggNOG; KOG2414; Eukaryota.
DR GeneTree; ENSGT00940000153657; -.
DR HOGENOM; CLU_017266_1_1_1; -.
DR InParanoid; B7ZMP1; -.
DR OMA; DSYFWYL; -.
DR OrthoDB; 1377484at2759; -.
DR PhylomeDB; B7ZMP1; -.
DR TreeFam; TF314484; -.
DR BioGRID-ORCS; 321003; 0 hits in 60 CRISPR screens.
DR ChiTaRS; Xpnpep3; mouse.
DR PRO; PR:B7ZMP1; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; B7ZMP1; Protein.
DR Bgee; ENSMUSG00000022401; Expressed in manus and 216 other cell types or tissues.
DR ExpressionAtlas; B7ZMP1; baseline and differential.
DR Genevisible; B7ZMP1; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0004177; F:aminopeptidase activity; ISO:MGI.
DR GO; GO:0030145; F:manganese ion binding; ISO:MGI.
DR GO; GO:0070006; F:metalloaminopeptidase activity; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0003094; P:glomerular filtration; ISO:MGI.
DR GO; GO:0016485; P:protein processing; ISO:MGI.
DR GO; GO:0006508; P:proteolysis; ISO:MGI.
DR CDD; cd01087; Prolidase; 1.
DR Gene3D; 3.90.230.10; Creatinase/methionine aminopeptidase superfamily; 1.
DR Gene3D; 3.40.350.10; Creatinase/prolidase N-terminal domain; 1.
DR InterPro; IPR007865; Aminopep_P_N.
DR InterPro; IPR029149; Creatin/AminoP/Spt16_NTD.
DR InterPro; IPR036005; Creatinase/aminopeptidase-like.
DR InterPro; IPR000994; Pept_M24.
DR PANTHER; PTHR43226; XAA-PRO AMINOPEPTIDASE 3; 1.
DR PANTHER; PTHR43226:SF4; XAA-PRO AMINOPEPTIDASE 3; 1.
DR Pfam; PF05195; AMP_N; 1.
DR Pfam; PF00557; Peptidase_M24; 1.
DR SMART; SM01011; AMP_N; 1.
DR SUPFAM; SSF55920; Creatinase/aminopeptidase; 1.
DR SUPFAM; SSF53092; Creatinase/prolidase N-terminal domain; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Hydrolase; Manganese; Metal-binding;
KW Mitochondrion; Reference proteome; Transit peptide.
FT TRANSIT 1..31
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 32..506
FT /note="Xaa-Pro aminopeptidase 3"
FT /id="PRO_0000401208"
FT REGION 54..79
FT /note="Interaction with TNFRSF1B"
FT /evidence="ECO:0000250|UniProtKB:Q9NQH7"
FT BINDING 300
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NQH7"
FT BINDING 331
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9NQH7"
FT BINDING 331
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NQH7"
FT BINDING 342
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9NQH7"
FT BINDING 342
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9NQH7"
FT BINDING 342
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NQH7"
FT BINDING 423
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9NQH7"
FT BINDING 423
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NQH7"
FT BINDING 430
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NQH7"
FT BINDING 450
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9NQH7"
FT BINDING 450
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NQH7"
FT BINDING 474
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9NQH7"
FT BINDING 474
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9NQH7"
FT BINDING 474
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NQH7"
FT VAR_SEQ 353..386
FT /note="FTAPQAELYEAVLEIQRACLTLCSPGTSLENIYS -> LLENTALIMLAITS
FT GWMSMTLQTCLGHSLCSLEW (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_040145"
FT VAR_SEQ 387..506
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_040146"
SQ SEQUENCE 506 AA; 56677 MW; E1F36BDA1F92C023 CRC64;
MPSLLSTPKL APVLARLRGL SGCMSCLQRR YSLQPAPVKK IPNRYLGQPS PVTHPHLLRP
GEVTPGLSQV EYALRRHKLM ALVHKEAQGH SGTDHTVVVL SNPTYYMSND IPYTFHQDNN
FLYLCGFQEP DSILVLQSFS GKQLPSHKAM LFVPRRDPGR ELWDGPRSGT DGAIALTGVD
EAYPLEEFQH LLPKLRAETN MVWYDWMKPS HAQLHSDYMQ PLTEAKARSK NKVRSVQQLI
QRLRLVKSPS EIKRMQIAGK LTSEAFIETM FASKAPIDEA FLYAKFEFEC RARGADILAY
PPVVAGGNRS NTLHYVKNNQ LIKDGEMVLL DGGCESSCYV SDITRTWPVN GRFTAPQAEL
YEAVLEIQRA CLTLCSPGTS LENIYSMMLT LIGQKLKDLG ITKTSKESAF KAARKYCPHH
VGHYLGMDVH DTPDMPRSLP LQPGMVITVE PGIYIPEDDR DAPEKFRGLG VRIEDDVVVT
QDSPLILSAD CPKEMNDIEQ ICSRTS
//
