XPP3_RAT
ID XPP3_RAT Reviewed; 506 AA.
AC B5DEQ3;
DT 30-NOV-2010, integrated into UniProtKB/Swiss-Prot.
DT 14-OCT-2008, sequence version 1.
DT 03-AUG-2022, entry version 70.
DE RecName: Full=Xaa-Pro aminopeptidase 3 {ECO:0000312|RGD:1589063};
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 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;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pituitary;
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 [2]
RP 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 [3]
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 -!- TISSUE SPECIFICITY: Expressed in the kidney, specifically in
CC intercalated cells, but not in principal cells, of the distal
CC convoluted tubule and cortical collecting duct (at protein level).
CC {ECO:0000269|PubMed:20179356}.
CC -!- SIMILARITY: Belongs to the peptidase M24B family. {ECO:0000305}.
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DR EMBL; BC168759; AAI68759.1; -; mRNA.
DR RefSeq; NP_001124054.2; NM_001130582.2.
DR AlphaFoldDB; B5DEQ3; -.
DR SMR; B5DEQ3; -.
DR IntAct; B5DEQ3; 2.
DR STRING; 10116.ENSRNOP00000061709; -.
DR MEROPS; M24.026; -.
DR iPTMnet; B5DEQ3; -.
DR PhosphoSitePlus; B5DEQ3; -.
DR PaxDb; B5DEQ3; -.
DR PeptideAtlas; B5DEQ3; -.
DR GeneID; 685823; -.
DR KEGG; rno:685823; -.
DR UCSC; RGD:1589063; rat.
DR CTD; 63929; -.
DR RGD; 1589063; Xpnpep3.
DR eggNOG; KOG2414; Eukaryota.
DR InParanoid; B5DEQ3; -.
DR OrthoDB; 352329at2759; -.
DR PhylomeDB; B5DEQ3; -.
DR PRO; PR:B5DEQ3; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR GO; GO:0004177; F:aminopeptidase activity; ISO:RGD.
DR GO; GO:0030145; F:manganese ion binding; ISO:RGD.
DR GO; GO:0070006; F:metalloaminopeptidase activity; ISO:RGD.
DR GO; GO:0008233; F:peptidase activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0003094; P:glomerular filtration; ISO:RGD.
DR GO; GO:0016485; P:protein processing; ISO:RGD.
DR GO; GO:0006508; P:proteolysis; ISO:RGD.
DR Gene3D; 3.40.350.10; -; 1.
DR Gene3D; 3.90.230.10; -; 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 Pfam; PF05195; AMP_N; 1.
DR Pfam; PF00557; Peptidase_M24; 1.
DR SMART; SM01011; AMP_N; 1.
DR SUPFAM; SSF53092; SSF53092; 1.
DR SUPFAM; SSF55920; SSF55920; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Hydrolase; Manganese; Metal-binding; Mitochondrion;
KW 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_0000401209"
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"
SQ SEQUENCE 506 AA; 56455 MW; 6B793744D67B09F1 CRC64;
MLSLLSTPRL VPVIARLRGL SGCMSCLQRR YSLQPVPVKE IPNRYLGQPS PVTHPHLLRP
GEVTPGLSQV EYALRRHKLM ALVHKEAQGH SGTDHTVVVL SNPIHYMSND IPYTFHQDNS
FLYLCGFQEP DSILVLQSCS GKQLPSHKAM LFVPRRDPGR ELWDGPRSGT DGAIALTGVD
DAYPLEEFQH LLPKLRAETN MVWYDWMKPS HAQLHSDYMQ PLTEAKATSK NKVRSVQHLI
QHLRLIKSPA EIKRMQIAGK LTSEAFIETM FASKAPVDEA FLYAKFEFEC RARGADILAY
PPVVAGGNRS NTLHYVKNNQ LIKDGEMVLL DGGCESSCYV SDITRTWPVN GRFTAPQAEL
YEAVLEIQKA CLTLCSPGTS LENIYSMMLT LMGQKLKDLG IIKTSKESAF KAARKYCPHH
VGHYLGMDVH DTPDMPRSLP LQPGMVITVE PGIYIPEGDT DAPEKFRGLG VRIEDDVVVT
QDSPLILSAD CPKEVNDIEQ ICSRTS
