ID   XPP3_HUMAN              Reviewed;         507 AA.
AC   Q9NQH7; B2R9G1; B7Z790; B7Z7B2; Q6I9V9; Q8NDA6; Q9BV27; Q9BVH0;
DT   31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   27-MAR-2024, entry version 188.
DE   RecName: Full=Xaa-Pro aminopeptidase 3 {ECO:0000312|HGNC:HGNC:28052};
DE            Short=X-Pro aminopeptidase 3;
DE            EC=3.4.11.9 {ECO:0000269|PubMed:25609706, ECO:0000269|PubMed:28476889};
DE   AltName: Full=Aminopeptidase P3;
DE            Short=APP3;
DE   Flags: Precursor;
GN   Name=XPNPEP3;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA   Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT   "Cloning of human full open reading frames in Gateway(TM) system entry
RT   vector (pDONR201).";
RL   Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX   PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA   Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA   Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA   Beare D.M., Dunham I.;
RT   "A genome annotation-driven approach to cloning the human ORFeome.";
RL   Genome Biol. 5:R84.1-R84.11(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 4 AND 5).
RC   TISSUE=Esophageal carcinoma, and Testis;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Testis;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=10591208; DOI=10.1038/990031;
RA   Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA   Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA   Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA   Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA   Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA   Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA   Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA   Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA   Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA   Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA   Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA   Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA   Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA   Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA   Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA   Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA   Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA   Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA   Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA   Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA   Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA   Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA   Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA   Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA   Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA   Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA   Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA   Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA   Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA   Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA   Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA   Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA   Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA   McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA   Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA   Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA   Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA   Wright H.;
RT   "The DNA sequence of human chromosome 22.";
RL   Nature 402:489-495(1999).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC   TISSUE=Lung;
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   [8]
RP   IDENTIFICATION OF ISOFORMS 1 AND 2, AND TISSUE SPECIFICITY.
RX   PubMed=15708373; DOI=10.1016/j.abb.2004.12.023;
RA   Ersahin C., Szpaderska A.M., Orawski A.T., Simmons W.H.;
RT   "Aminopeptidase P isozyme expression in human tissues and peripheral blood
RT   mononuclear cell fractions.";
RL   Arch. Biochem. Biophys. 435:303-310(2005).
RN   [9]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [10]
RP   FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH TNFRSF1B AND TRAF2,
RP   SUBCELLULAR LOCATION (ISOFORMS 1 AND 2), CLEAVAGE OF TRANSIT PEPTIDE,
RP   MUTAGENESIS OF ARG-18; 29-ARG-ARG-30; 39-ARG-ARG-40; ARG-44; HIS-314;
RP   ASP-342 AND GLU-475, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=25609706; DOI=10.1242/jcs.149385;
RA   Inoue M., Kamada H., Abe Y., Higashisaka K., Nagano K., Mukai Y.,
RA   Yoshioka Y., Tsutsumi Y., Tsunoda S.;
RT   "Aminopeptidase P3, a new member of the TNF-TNFR2 signaling complex,
RT   induces phosphorylation of JNK1 and JNK2.";
RL   J. Cell Sci. 128:656-669(2015).
RN   [11]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=25944712; DOI=10.1002/pmic.201400617;
RA   Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA   Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT   "N-terminome analysis of the human mitochondrial proteome.";
RL   Proteomics 15:2519-2524(2015).
RN   [12]
RP   X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 54-507 IN COMPLEX WITH INHIBITOR
RP   APSTATIN AND MANGANESE IONS, FUNCTION, CATALYTIC ACTIVITY,
RP   BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RX   PubMed=28476889; DOI=10.1074/jbc.m117.783357;
RA   Singh R., Jamdar S.N., Goyal V.D., Kumar A., Ghosh B., Makde R.D.;
RT   "Structure of the human aminopeptidase XPNPEP3 and comparison of its in
RT   vitro activity with Icp55 orthologs: Insights into diverse cellular
RT   processes.";
RL   J. Biol. Chem. 292:10035-10047(2017).
RN   [13]
RP   VARIANT NPHPL1 CYS-453, AND SUBCELLULAR LOCATION.
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   [14]
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 (PubMed:25609706,
CC       PubMed:28476889). Also shows low activity towards peptides with Ala or
CC       Ser at the P1 position (PubMed:28476889). {ECO:0000269|PubMed:25609706,
CC       ECO:0000269|PubMed:28476889}.
CC   -!- FUNCTION: [Isoform 1]: Promotes TNFRSF1B-mediated phosphorylation of
CC       MAPK8/JNK1 and MAPK9/JNK2, suggesting a function as an adapter protein
CC       for TNFRSF1B; the effect is independent of XPNPEP3 peptidase activity.
CC       May inhibit apoptotic cell death induced via TNF-TNFRSF1B signaling.
CC       {ECO:0000269|PubMed:25609706}.
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:25609706,
CC         ECO:0000269|PubMed:28476889};
CC   -!- COFACTOR:
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000269|PubMed:28476889};
CC       Note=Binds 2 manganese ions per subunit. {ECO:0000269|PubMed:28476889};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=1.62 mM for Met-Pro-Ala {ECO:0000269|PubMed:28476889};
CC         KM=2.45 mM for Leu-Pro-Ala {ECO:0000269|PubMed:28476889};
CC         KM=3.06 mM for Phe-Pro-Ala {ECO:0000269|PubMed:28476889};
CC         KM=0.55 mM for Tyr-Pro-Ala {ECO:0000269|PubMed:28476889};
CC         KM=4.91 mM for Tyr-Ser-Ser {ECO:0000269|PubMed:28476889};
CC         KM=4.2 mM for Tyr-Ala-Ala {ECO:0000269|PubMed:28476889};
CC         KM=3.74 mM for Tyr-Ser-Ser-Ala-Ala-Ala-Ala
CC         {ECO:0000269|PubMed:28476889};
CC   -!- SUBUNIT: Homodimer (PubMed:28476889). Isoform 1 interacts with
CC       TNFRSF1B/TNFR2 (activated) and TRAF2 (PubMed:25609706).
CC       {ECO:0000269|PubMed:25609706, ECO:0000269|PubMed:28476889}.
CC   -!- SUBCELLULAR LOCATION: [Isoform 1]: Mitochondrion
CC       {ECO:0000269|PubMed:20179356, ECO:0000269|PubMed:25609706}. Cytoplasm
CC       {ECO:0000269|PubMed:25609706}. Note=Mainly mitochondrial. Translocates
CC       to the cytoplasm following TNFRSF1B activation.
CC       {ECO:0000269|PubMed:25609706}.
CC   -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC       {ECO:0000269|PubMed:25609706}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=5;
CC       Name=1; Synonyms=m {ECO:0000303|PubMed:28476889};
CC         IsoId=Q9NQH7-1; Sequence=Displayed;
CC       Name=2; Synonyms=c {ECO:0000303|PubMed:28476889};
CC         IsoId=Q9NQH7-2; Sequence=VSP_021296;
CC       Name=3;
CC         IsoId=Q9NQH7-3; Sequence=VSP_021297, VSP_021298;
CC       Name=4;
CC         IsoId=Q9NQH7-4; Sequence=VSP_040142;
CC       Name=5;
CC         IsoId=Q9NQH7-5; Sequence=VSP_040143, VSP_040144;
CC   -!- TISSUE SPECIFICITY: Isoform 1 and isoform 2 are widely expressed, with
CC       isoform 1 being more abundant. {ECO:0000269|PubMed:15708373}.
CC   -!- DISEASE: Nephronophthisis-like nephropathy 1 (NPHPL1) [MIM:613159]: An
CC       autosomal recessive disorder with features of nephronophthisis, a
CC       cystic kidney disease leading to end-stage renal failure.
CC       Nephronophthisis is histologically characterized by modifications of
CC       the tubules with thickening of the basement membrane, interstitial
CC       fibrosis and, in the advanced stages, medullary cysts. Typical clinical
CC       manifestation are chronic renal failure, anemia, polyuria, polydipsia,
CC       isosthenuria, and growth retardation. Associations with extrarenal
CC       symptoms are frequent. In NPHPL1 patients, extrarenal symptoms include
CC       hypertension, essential tremor, sensorineural hearing loss and gout.
CC       Severely affected individuals can manifest a mitochondrial disorder
CC       with isolated complex I deficiency activity in muscle, seizures,
CC       intellectual disability and hypertrophic dilated cardiomyopathy.
CC       {ECO:0000269|PubMed:20179356}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the peptidase M24B family. {ECO:0000305}.
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DR   EMBL; CR457396; CAG33677.1; -; mRNA.
DR   EMBL; AL365514; CAB97210.1; -; mRNA.
DR   EMBL; CR456442; CAG30328.1; -; mRNA.
DR   EMBL; AK301635; BAH13526.1; -; mRNA.
DR   EMBL; AK301758; BAH13548.1; -; mRNA.
DR   EMBL; AK313770; BAG36508.1; -; mRNA.
DR   EMBL; AL834310; CAD38980.1; -; mRNA.
DR   EMBL; AL035450; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; Z98048; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471095; EAW60399.1; -; Genomic_DNA.
DR   EMBL; BC001208; AAH01208.1; -; mRNA.
DR   EMBL; BC001681; AAH01681.1; -; mRNA.
DR   EMBL; BC004989; AAH04989.1; -; mRNA.
DR   CCDS; CCDS14007.1; -. [Q9NQH7-1]
DR   RefSeq; NP_071381.1; NM_022098.3. [Q9NQH7-1]
DR   PDB; 5X49; X-ray; 1.65 A; A/B=54-507.
DR   PDBsum; 5X49; -.
DR   AlphaFoldDB; Q9NQH7; -.
DR   SMR; Q9NQH7; -.
DR   BioGRID; 121997; 81.
DR   CORUM; Q9NQH7; -.
DR   IntAct; Q9NQH7; 51.
DR   MINT; Q9NQH7; -.
DR   STRING; 9606.ENSP00000349658; -.
DR   ChEMBL; CHEMBL3831223; -.
DR   MEROPS; M24.026; -.
DR   iPTMnet; Q9NQH7; -.
DR   PhosphoSitePlus; Q9NQH7; -.
DR   SwissPalm; Q9NQH7; -.
DR   BioMuta; XPNPEP3; -.
DR   DMDM; 74761652; -.
DR   EPD; Q9NQH7; -.
DR   jPOST; Q9NQH7; -.
DR   MassIVE; Q9NQH7; -.
DR   MaxQB; Q9NQH7; -.
DR   PaxDb; 9606-ENSP00000349658; -.
DR   PeptideAtlas; Q9NQH7; -.
DR   ProteomicsDB; 82154; -. [Q9NQH7-1]
DR   ProteomicsDB; 82155; -. [Q9NQH7-2]
DR   ProteomicsDB; 82156; -. [Q9NQH7-3]
DR   ProteomicsDB; 82157; -. [Q9NQH7-4]
DR   ProteomicsDB; 82158; -. [Q9NQH7-5]
DR   Pumba; Q9NQH7; -.
DR   Antibodypedia; 259; 179 antibodies from 27 providers.
DR   DNASU; 63929; -.
DR   Ensembl; ENST00000357137.9; ENSP00000349658.4; ENSG00000196236.13. [Q9NQH7-1]
DR   GeneID; 63929; -.
DR   KEGG; hsa:63929; -.
DR   MANE-Select; ENST00000357137.9; ENSP00000349658.4; NM_022098.4; NP_071381.1.
DR   UCSC; uc003azh.4; human. [Q9NQH7-1]
DR   AGR; HGNC:28052; -.
DR   CTD; 63929; -.
DR   DisGeNET; 63929; -.
DR   GeneCards; XPNPEP3; -.
DR   GeneReviews; XPNPEP3; -.
DR   HGNC; HGNC:28052; XPNPEP3.
DR   HPA; ENSG00000196236; Low tissue specificity.
DR   MalaCards; XPNPEP3; -.
DR   MIM; 613159; phenotype.
DR   MIM; 613553; gene.
DR   neXtProt; NX_Q9NQH7; -.
DR   OpenTargets; ENSG00000196236; -.
DR   Orphanet; 93589; Late-onset nephronophthisis.
DR   PharmGKB; PA147357130; -.
DR   VEuPathDB; HostDB:ENSG00000196236; -.
DR   eggNOG; KOG2414; Eukaryota.
DR   GeneTree; ENSGT00940000153657; -.
DR   HOGENOM; CLU_017266_1_1_1; -.
DR   InParanoid; Q9NQH7; -.
DR   OMA; DSYFWYL; -.
DR   OrthoDB; 1377484at2759; -.
DR   PhylomeDB; Q9NQH7; -.
DR   TreeFam; TF314484; -.
DR   BRENDA; 3.4.11.9; 2681.
DR   PathwayCommons; Q9NQH7; -.
DR   SABIO-RK; Q9NQH7; -.
DR   SignaLink; Q9NQH7; -.
DR   BioGRID-ORCS; 63929; 25 hits in 1154 CRISPR screens.
DR   ChiTaRS; XPNPEP3; human.
DR   GeneWiki; XPNPEP3; -.
DR   GenomeRNAi; 63929; -.
DR   Pharos; Q9NQH7; Tbio.
DR   PRO; PR:Q9NQH7; -.
DR   Proteomes; UP000005640; Chromosome 22.
DR   RNAct; Q9NQH7; Protein.
DR   Bgee; ENSG00000196236; Expressed in buccal mucosa cell and 183 other cell types or tissues.
DR   ExpressionAtlas; Q9NQH7; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR   GO; GO:0004177; F:aminopeptidase activity; IMP:MGI.
DR   GO; GO:0030145; F:manganese ion binding; IDA:UniProtKB.
DR   GO; GO:0070006; F:metalloaminopeptidase activity; IDA:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR   GO; GO:0003094; P:glomerular filtration; IMP:MGI.
DR   GO; GO:0016485; P:protein processing; IMP:MGI.
DR   GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
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.
DR   Genevisible; Q9NQH7; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Aminopeptidase; Cytoplasm;
KW   Disease variant; Hydrolase; Manganese; Metal-binding; Metalloprotease;
KW   Mitochondrion; Nephronophthisis; Protease; Reference proteome;
KW   Transit peptide.
FT   TRANSIT         1..31
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:25609706"
FT   CHAIN           32..507
FT                   /note="Xaa-Pro aminopeptidase 3"
FT                   /id="PRO_0000255654"
FT   REGION          54..79
FT                   /note="Interaction with TNFRSF1B"
FT                   /evidence="ECO:0000269|PubMed:25609706"
FT   BINDING         300
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000269|PubMed:28476889,
FT                   ECO:0007744|PDB:5X49"
FT   BINDING         331
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:28476889,
FT                   ECO:0007744|PDB:5X49"
FT   BINDING         331
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000269|PubMed:28476889,
FT                   ECO:0007744|PDB:5X49"
FT   BINDING         342
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:28476889,
FT                   ECO:0007744|PDB:5X49"
FT   BINDING         342
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:28476889,
FT                   ECO:0007744|PDB:5X49"
FT   BINDING         342
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000269|PubMed:28476889,
FT                   ECO:0000305|PubMed:25609706, ECO:0007744|PDB:5X49"
FT   BINDING         424
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:28476889,
FT                   ECO:0007744|PDB:5X49"
FT   BINDING         424
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000269|PubMed:28476889,
FT                   ECO:0007744|PDB:5X49"
FT   BINDING         431
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000269|PubMed:28476889,
FT                   ECO:0007744|PDB:5X49"
FT   BINDING         451
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:28476889,
FT                   ECO:0007744|PDB:5X49"
FT   BINDING         451
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000269|PubMed:28476889,
FT                   ECO:0007744|PDB:5X49"
FT   BINDING         475
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:28476889,
FT                   ECO:0007744|PDB:5X49"
FT   BINDING         475
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:28476889,
FT                   ECO:0007744|PDB:5X49"
FT   BINDING         475
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000269|PubMed:28476889,
FT                   ECO:0000305|PubMed:25609706, ECO:0007744|PDB:5X49"
FT   VAR_SEQ         1..79
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:17974005"
FT                   /id="VSP_021296"
FT   VAR_SEQ         1..23
FT                   /note="Missing (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_040142"
FT   VAR_SEQ         265..288
FT                   /note="AFIETMFTSKAPVEEAFLYAKFEF -> KSVLLARHGGSRLYSHHFGRPRLS
FT                   (in isoform 5)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_040143"
FT   VAR_SEQ         265..278
FT                   /note="AFIETMFTSKAPVE -> RQGFSVLSRLVSNS (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_021297"
FT   VAR_SEQ         279..507
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_021298"
FT   VAR_SEQ         289..507
FT                   /note="Missing (in isoform 5)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_040144"
FT   VARIANT         450
FT                   /note="I -> L (in dbSNP:rs17002243)"
FT                   /id="VAR_051573"
FT   VARIANT         453
FT                   /note="G -> C (in NPHPL1; dbSNP:rs267607179)"
FT                   /evidence="ECO:0000269|PubMed:20179356"
FT                   /id="VAR_063820"
FT   MUTAGEN         18
FT                   /note="R->A: Prevents cleavage of N-terminal transit
FT                   peptide; when associated with A-29-30-A; A-39-40-A and
FT                   A-44."
FT                   /evidence="ECO:0000269|PubMed:25609706"
FT   MUTAGEN         29..30
FT                   /note="RR->AA: Prevents cleavage of N-terminal transit
FT                   peptide; when associated with A-18; A-39-40-A and A-44."
FT                   /evidence="ECO:0000269|PubMed:25609706"
FT   MUTAGEN         39..40
FT                   /note="RR->AA: Prevents cleavage of N-terminal transit
FT                   peptide; when associated with A-18; A-29-30-A and A-44."
FT                   /evidence="ECO:0000269|PubMed:25609706"
FT   MUTAGEN         44
FT                   /note="R->A: Prevents cleavage of N-terminal transit
FT                   peptide; when associated with A-18; A-29-30-A and
FT                   A-39-40-A."
FT                   /evidence="ECO:0000269|PubMed:25609706"
FT   MUTAGEN         314
FT                   /note="H->A: Impairs catalytic activity."
FT                   /evidence="ECO:0000269|PubMed:25609706"
FT   MUTAGEN         342
FT                   /note="D->A: Impairs catalytic activity."
FT                   /evidence="ECO:0000269|PubMed:25609706"
FT   MUTAGEN         475
FT                   /note="E->A: Impairs catalytic activity."
FT                   /evidence="ECO:0000269|PubMed:25609706"
FT   CONFLICT        340
FT                   /note="V -> A (in Ref. 1; CAG33677)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        486
FT                   /note="L -> F (in Ref. 7; AAH01681)"
FT                   /evidence="ECO:0000305"
FT   STRAND          62..64
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   HELIX           69..85
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   STRAND          94..100
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   STRAND          106..108
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   HELIX           119..125
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   STRAND          133..138
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   STRAND          147..153
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   HELIX           158..164
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   HELIX           170..177
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   STRAND          180..184
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   HELIX           185..191
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   HELIX           192..196
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   STRAND          200..203
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   HELIX           212..218
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   HELIX           220..227
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   STRAND          229..231
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   HELIX           237..244
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   HELIX           249..271
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   STRAND          275..278
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   HELIX           279..292
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   STRAND          297..300
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   STRAND          303..306
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   HELIX           307..311
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   STRAND          320..322
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   STRAND          327..332
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   STRAND          334..336
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   STRAND          343..348
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   HELIX           355..373
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   HELIX           381..398
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   HELIX           405..411
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   HELIX           412..417
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   STRAND          427..431
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   STRAND          447..450
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   STRAND          453..456
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   HELIX           465..467
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   STRAND          470..473
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   STRAND          475..479
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   STRAND          482..484
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   TURN            488..491
FT                   /evidence="ECO:0007829|PDB:5X49"
FT   HELIX           496..502
FT                   /evidence="ECO:0007829|PDB:5X49"
SQ   SEQUENCE   507 AA;  57034 MW;  82D886736ABD0B5B CRC64;
     MPWLLSAPKL VPAVANVRGL SGCMLCSQRR YSLQPVPERR IPNRYLGQPS PFTHPHLLRP
     GEVTPGLSQV EYALRRHKLM SLIQKEAQGQ SGTDQTVVVL SNPTYYMSND IPYTFHQDNN
     FLYLCGFQEP DSILVLQSLP GKQLPSHKAI LFVPRRDPSR ELWDGPRSGT DGAIALTGVD
     EAYTLEEFQH LLPKMKAETN MVWYDWMRPS HAQLHSDYMQ PLTEAKAKSK NKVRGVQQLI
     QRLRLIKSPA EIERMQIAGK LTSQAFIETM FTSKAPVEEA FLYAKFEFEC RARGADILAY
     PPVVAGGNRS NTLHYVKNNQ LIKDGEMVLL DGGCESSCYV SDITRTWPVN GRFTAPQAEL
     YEAVLEIQRD CLALCFPGTS LENIYSMMLT LIGQKLKDLG IMKNIKENNA FKAARKYCPH
     HVGHYLGMDV HDTPDMPRSL PLQPGMVITI EPGIYIPEDD KDAPEKFRGL GVRIEDDVVV
     TQDSPLILSA DCPKEMNDIE QICSQAS
//