XPP3_HUMAN
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 03-AUG-2022, entry version 179.
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=4.20 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; 67.
DR CORUM; Q9NQH7; -.
DR IntAct; Q9NQH7; 48.
DR MINT; Q9NQH7; -.
DR STRING; 9606.ENSP00000349658; -.
DR ChEMBL; CHEMBL3831223; -.
DR MEROPS; M24.026; -.
DR iPTMnet; Q9NQH7; -.
DR PhosphoSitePlus; Q9NQH7; -.
DR BioMuta; XPNPEP3; -.
DR DMDM; 74761652; -.
DR EPD; Q9NQH7; -.
DR jPOST; Q9NQH7; -.
DR MassIVE; Q9NQH7; -.
DR MaxQB; Q9NQH7; -.
DR PaxDb; Q9NQH7; -.
DR PeptideAtlas; Q9NQH7; -.
DR PRIDE; 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 Antibodypedia; 259; 153 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 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; GWADTEL; -.
DR OrthoDB; 352329at2759; -.
DR PhylomeDB; Q9NQH7; -.
DR TreeFam; TF314484; -.
DR BRENDA; 3.4.11.9; 2681.
DR PathwayCommons; Q9NQH7; -.
DR SignaLink; Q9NQH7; -.
DR BioGRID-ORCS; 63929; 24 hits in 1077 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 181 other tissues.
DR ExpressionAtlas; Q9NQH7; baseline and differential.
DR Genevisible; Q9NQH7; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
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:0008233; F:peptidase activity; IBA:GO_Central.
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 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 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 A-
FT 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 A-39-40-
FT 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
