ID 5NTC_HUMAN Reviewed; 561 AA.
AC P49902; B7Z382; D3DR91; Q5JUV5;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 27-MAR-2024, entry version 205.
DE RecName: Full=Cytosolic purine 5'-nucleotidase {ECO:0000305|PubMed:1659319};
DE EC=3.1.3.5 {ECO:0000269|PubMed:10092873, ECO:0000269|PubMed:12907246, ECO:0000269|PubMed:1659319, ECO:0000269|PubMed:9371705};
DE EC=3.1.3.99 {ECO:0000269|PubMed:10092873, ECO:0000269|PubMed:12907246, ECO:0000269|PubMed:1659319, ECO:0000269|PubMed:9371705};
DE AltName: Full=Cytosolic 5'-nucleotidase II {ECO:0000303|PubMed:17405878};
DE Short=cN-II {ECO:0000303|PubMed:17405878};
DE AltName: Full=Cytosolic IMP/GMP-specific 5'-nucleotidase {ECO:0000303|PubMed:9371705};
DE AltName: Full=Cytosolic nucleoside phosphotransferase 5'N {ECO:0000305|PubMed:1659319};
DE EC=2.7.1.77 {ECO:0000269|PubMed:1659319, ECO:0000269|PubMed:9371705};
DE AltName: Full=High Km 5'-nucleotidase {ECO:0000303|PubMed:21396942};
GN Name=NT5C2 {ECO:0000312|HGNC:HGNC:8022}; Synonyms=NT5B, NT5CP, PNT5;
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 [MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=7999131; DOI=10.1006/bbrc.1994.2752;
RA Oka J., Matsumoto A., Hosokawa Y., Inoue S.;
RT "Molecular cloning of human cytosolic purine 5'-nucleotidase.";
RL Biochem. Biophys. Res. Commun. 205:917-922(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Hippocampus;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ALA-3.
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph;
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 [6]
RP IDENTIFICATION, FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY REGULATION.
RX PubMed=1659319; DOI=10.1016/0003-9861(91)90125-3;
RA Tozzi M.G., Camici M., Pesi R., Allegrini S., Sgarrella F., Ipata P.L.;
RT "Nucleoside phosphotransferase activity of human colon carcinoma cytosolic
RT 5'-nucleotidase.";
RL Arch. Biochem. Biophys. 291:212-217(1991).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RC TISSUE=Thymus;
RX PubMed=9371705; DOI=10.1042/bj3280483;
RA Allegrini S., Pesi R., Tozzi M.G., Fiol C.J., Johnson R.B., Eriksson S.;
RT "Bovine cytosolic IMP/GMP-specific 5'-nucleotidase: cloning and expression
RT of active enzyme in Escherichia coli.";
RL Biochem. J. 328:483-487(1997).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, SUBUNIT, AND REGION.
RX PubMed=10092873; DOI=10.1046/j.1432-1327.1999.00099.x;
RA Spychala J., Chen V., Oka J., Mitchell B.S.;
RT "ATP and phosphate reciprocally affect subunit association of human
RT recombinant High Km 5'-nucleotidase. Role for the C-terminal polyglutamic
RT acid tract in subunit association and catalytic activity.";
RL Eur. J. Biochem. 259:851-858(1999).
RN [9]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=12907246; DOI=10.1016/s0006-2952(03)00290-9;
RA Mazzon C., Rampazzo C., Scaini M.C., Gallinaro L., Karlsson A., Meier C.,
RA Balzarini J., Reichard P., Bianchi V.;
RT "Cytosolic and mitochondrial deoxyribonucleotidases: activity with
RT substrate analogs, inhibitors and implications for therapy.";
RL Biochem. Pharmacol. 66:471-479(2003).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-502, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-418 AND SER-511, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP INVOLVEMENT IN SPG45.
RX PubMed=24482476; DOI=10.1126/science.1247363;
RA Novarino G., Fenstermaker A.G., Zaki M.S., Hofree M., Silhavy J.L.,
RA Heiberg A.D., Abdellateef M., Rosti B., Scott E., Mansour L., Masri A.,
RA Kayserili H., Al-Aama J.Y., Abdel-Salam G.M., Karminejad A., Kara M.,
RA Kara B., Bozorgmehri B., Ben-Omran T., Mojahedi F., Mahmoud I.G.,
RA Bouslam N., Bouhouche A., Benomar A., Hanein S., Raymond L., Forlani S.,
RA Mascaro M., Selim L., Shehata N., Al-Allawi N., Bindu P.S., Azam M.,
RA Gunel M., Caglayan A., Bilguvar K., Tolun A., Issa M.Y., Schroth J.,
RA Spencer E.G., Rosti R.O., Akizu N., Vaux K.K., Johansen A., Koh A.A.,
RA Megahed H., Durr A., Brice A., Stevanin G., Gabriel S.B., Ideker T.,
RA Gleeson J.G.;
RT "Exome sequencing links corticospinal motor neuron disease to common
RT neurodegenerative disorders.";
RL Science 343:506-511(2014).
RN [14] {ECO:0007744|PDB:2J2C, ECO:0007744|PDB:2JC9, ECO:0007744|PDB:2JCM}
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 1-536 IN COMPLEX WITH ADENOSINE
RP AND MAGNESIUM IONS, COFACTOR, AND SUBUNIT.
RX PubMed=17405878; DOI=10.1074/jbc.m700917200;
RA Wallden K., Stenmark P., Nyman T., Flodin S., Graeslund S., Loppnau P.,
RA Bianchi V., Nordlund P.;
RT "Crystal structure of human cytosolic 5'-nucleotidase II: insights into
RT allosteric regulation and substrate recognition.";
RL J. Biol. Chem. 282:17828-17836(2007).
RN [15] {ECO:0007744|PDB:2XCV, ECO:0007744|PDB:2XCW, ECO:0007744|PDB:2XCX, ECO:0007744|PDB:2XJB, ECO:0007744|PDB:2XJC, ECO:0007744|PDB:2XJD, ECO:0007744|PDB:2XJE, ECO:0007744|PDB:2XJF}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 1-536 OF MUTANT ASN-52 IN COMPLEX
RP WITH MAGNESIUM; IMP; GMP; DGMP; UMP AND ALLOSTERIC EFFECTORS, REACTION
RP MECHANISM, COFACTOR, ACTIVITY REGULATION, SUBSTRATE SPECIFICITY, SUBUNIT,
RP ACTIVE SITE, AND MUTAGENESIS OF ASP-52.
RX PubMed=21396942; DOI=10.1016/j.jmb.2011.02.059;
RA Wallden K., Nordlund P.;
RT "Structural basis for the allosteric regulation and substrate recognition
RT of human cytosolic 5'-nucleotidase II.";
RL J. Mol. Biol. 408:684-696(2011).
RN [16]
RP VARIANT SPG45 PRO-460.
RX PubMed=28884889; DOI=10.1002/ajmg.a.38414;
RA Straussberg R., Onoufriadis A., Konen O., Zouabi Y., Cohen L., Lee J.Y.W.,
RA Hsu C.K., Simpson M.A., McGrath J.A.;
RT "Novel homozygous missense mutation in NT5C2 underlying hereditary spastic
RT paraplegia SPG45.";
RL Am. J. Med. Genet. A 173:3109-3113(2017).
CC -!- FUNCTION: Broad specificity cytosolic 5'-nucleotidase that catalyzes
CC the dephosphorylation of 6-hydroxypurine nucleoside 5'-monophosphates
CC (PubMed:1659319, PubMed:9371705, PubMed:10092873, PubMed:12907246). In
CC addition, possesses a phosphotransferase activity by which it can
CC transfer a phosphate from a donor nucleoside monophosphate to an
CC acceptor nucleoside, preferably inosine, deoxyinosine and guanosine
CC (PubMed:1659319, PubMed:9371705). Has the highest activities for IMP
CC and GMP followed by dIMP, dGMP and XMP (PubMed:1659319, PubMed:9371705,
CC PubMed:10092873, PubMed:12907246). Could also catalyze the transfer of
CC phosphates from pyrimidine monophosphates but with lower efficiency
CC (PubMed:1659319, PubMed:9371705). Through these activities regulates
CC the purine nucleoside/nucleotide pools within the cell (PubMed:1659319,
CC PubMed:9371705, PubMed:10092873, PubMed:12907246).
CC {ECO:0000269|PubMed:10092873, ECO:0000269|PubMed:12907246,
CC ECO:0000269|PubMed:1659319, ECO:0000269|PubMed:9371705}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-phosphate + H2O = a ribonucleoside +
CC phosphate; Xref=Rhea:RHEA:12484, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:18254, ChEBI:CHEBI:43474, ChEBI:CHEBI:58043; EC=3.1.3.5;
CC Evidence={ECO:0000269|PubMed:10092873, ECO:0000269|PubMed:12907246,
CC ECO:0000269|PubMed:1659319, ECO:0000269|PubMed:17405878,
CC ECO:0000269|PubMed:9371705};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12485;
CC Evidence={ECO:0000305|PubMed:1659319};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxyribonucleoside + a ribonucleoside 5'-phosphate = a
CC 2'-deoxyribonucleoside 5'-phosphate + a ribonucleoside;
CC Xref=Rhea:RHEA:19961, ChEBI:CHEBI:18254, ChEBI:CHEBI:18274,
CC ChEBI:CHEBI:58043, ChEBI:CHEBI:65317; EC=2.7.1.77;
CC Evidence={ECO:0000269|PubMed:1659319, ECO:0000269|PubMed:9371705};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + IMP = inosine + phosphate; Xref=Rhea:RHEA:27718,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17596, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:58053; EC=3.1.3.99;
CC Evidence={ECO:0000269|PubMed:10092873, ECO:0000269|PubMed:12907246,
CC ECO:0000269|PubMed:1659319, ECO:0000269|PubMed:9371705};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27719;
CC Evidence={ECO:0000305|PubMed:1659319};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GMP + H2O = guanosine + phosphate; Xref=Rhea:RHEA:27714,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:16750, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:58115; Evidence={ECO:0000250|UniProtKB:D3ZMY7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27715;
CC Evidence={ECO:0000250|UniProtKB:D3ZMY7};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dIMP + H2O = 2'-deoxyinosine + phosphate;
CC Xref=Rhea:RHEA:29383, ChEBI:CHEBI:15377, ChEBI:CHEBI:28997,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:61194;
CC Evidence={ECO:0000250|UniProtKB:D3ZMY7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:29384;
CC Evidence={ECO:0000250|UniProtKB:D3ZMY7};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dGMP + H2O = 2'-deoxyguanosine + phosphate;
CC Xref=Rhea:RHEA:29379, ChEBI:CHEBI:15377, ChEBI:CHEBI:17172,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57673;
CC Evidence={ECO:0000269|PubMed:12907246, ECO:0000269|PubMed:1659319};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:29380;
CC Evidence={ECO:0000305|PubMed:1659319};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + XMP = phosphate + xanthosine; Xref=Rhea:RHEA:28530,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:18107, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57464; Evidence={ECO:0000250|UniProtKB:D3ZMY7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:28531;
CC Evidence={ECO:0000250|UniProtKB:D3ZMY7};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GMP + inosine = guanosine + IMP; Xref=Rhea:RHEA:69584,
CC ChEBI:CHEBI:16750, ChEBI:CHEBI:17596, ChEBI:CHEBI:58053,
CC ChEBI:CHEBI:58115; Evidence={ECO:0000269|PubMed:1659319,
CC ECO:0000269|PubMed:9371705};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dGMP + inosine = 2'-deoxyguanosine + IMP;
CC Xref=Rhea:RHEA:69580, ChEBI:CHEBI:17172, ChEBI:CHEBI:17596,
CC ChEBI:CHEBI:57673, ChEBI:CHEBI:58053;
CC Evidence={ECO:0000269|PubMed:1659319, ECO:0000269|PubMed:9371705};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dIMP + inosine = 2'-deoxyinosine + IMP; Xref=Rhea:RHEA:69572,
CC ChEBI:CHEBI:17596, ChEBI:CHEBI:28997, ChEBI:CHEBI:58053,
CC ChEBI:CHEBI:61194; Evidence={ECO:0000269|PubMed:1659319,
CC ECO:0000269|PubMed:9371705};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=inosine + UMP = IMP + uridine; Xref=Rhea:RHEA:69588,
CC ChEBI:CHEBI:16704, ChEBI:CHEBI:17596, ChEBI:CHEBI:57865,
CC ChEBI:CHEBI:58053; Evidence={ECO:0000269|PubMed:1659319,
CC ECO:0000269|PubMed:9371705};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=CMP + inosine = cytidine + IMP; Xref=Rhea:RHEA:69592,
CC ChEBI:CHEBI:17562, ChEBI:CHEBI:17596, ChEBI:CHEBI:58053,
CC ChEBI:CHEBI:60377; Evidence={ECO:0000269|PubMed:1659319,
CC ECO:0000269|PubMed:9371705};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=AMP + inosine = adenosine + IMP; Xref=Rhea:RHEA:69596,
CC ChEBI:CHEBI:16335, ChEBI:CHEBI:17596, ChEBI:CHEBI:58053,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:1659319,
CC ECO:0000269|PubMed:9371705};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:17405878, ECO:0000269|PubMed:21396942,
CC ECO:0007744|PDB:2J2C, ECO:0007744|PDB:2JC9, ECO:0007744|PDB:2JCM,
CC ECO:0007744|PDB:2XCV, ECO:0007744|PDB:2XCW, ECO:0007744|PDB:2XJB,
CC ECO:0007744|PDB:2XJC, ECO:0007744|PDB:2XJD, ECO:0007744|PDB:2XJE};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000269|PubMed:17405878,
CC ECO:0000269|PubMed:21396942, ECO:0007744|PDB:2J2C,
CC ECO:0007744|PDB:2JC9, ECO:0007744|PDB:2JCM, ECO:0007744|PDB:2XCV,
CC ECO:0007744|PDB:2XCW, ECO:0007744|PDB:2XJB, ECO:0007744|PDB:2XJC,
CC ECO:0007744|PDB:2XJD, ECO:0007744|PDB:2XJE};
CC -!- ACTIVITY REGULATION: Allosterically activated by various compounds
CC including ATP, 2,3-BPG/2,3-Bisphosphoglyceric acid and Ap4A/P1,P4-
CC bis(5'-adenosyl) tetraphosphate (PubMed:1659319, PubMed:10092873,
CC PubMed:21396942). Binding of an allosteric activator is a prerequisiste
CC to magnesium and substrate binding (PubMed:21396942). Inhibited by
CC inorganic phosphate (PubMed:10092873). {ECO:0000269|PubMed:10092873,
CC ECO:0000269|PubMed:1659319, ECO:0000269|PubMed:21396942}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=20 uM for IMP (in presence of the allosteric activator ATP)
CC {ECO:0000269|PubMed:1659319};
CC KM=83 uM for IMP (in absence of allosteric activator)
CC {ECO:0000269|PubMed:1659319};
CC Vmax=36.7 nmol/min/mg enzyme for the hydrolysis of IMP
CC {ECO:0000269|PubMed:1659319};
CC Vmax=0.54 umol/min/mg enzyme for the hydrolysis of IMP (in absence of
CC allosteric activator) {ECO:0000269|PubMed:10092873};
CC Vmax=16.5 umol/min/mg enzyme for the hydrolysis of IMP (in the
CC presence of 3 mM ATP) {ECO:0000269|PubMed:10092873};
CC Vmax=25 nmol/min/mg enzyme for the hydrolysis dGMP (in presence of
CC the allosteric activator ATP) {ECO:0000269|PubMed:1659319};
CC Vmax=18.6 nmol/min/mg enzyme for the transfer of phosphate from dIMP
CC to inosine (in presence of the allosteric activator ATP)
CC {ECO:0000269|PubMed:1659319};
CC Vmax=15.2 nmol/min/mg enzyme for the transfer of phosphate from GMP
CC to inosine (in presence of the allosteric activator ATP)
CC {ECO:0000269|PubMed:1659319};
CC Vmax=14.6 nmol/min/mg enzyme for the transfer of phosphate from IMP
CC to inosine (in presence of the allosteric activator ATP)
CC {ECO:0000269|PubMed:1659319};
CC Vmax=14.1 nmol/min/mg enzyme for the transfer of phosphate from dGMP
CC to inosine (in presence of the allosteric activator ATP)
CC {ECO:0000269|PubMed:1659319};
CC Vmax=4.9 nmol/min/mg enzyme for the transfer of phosphate from UMP to
CC inosine (in presence of the allosteric activator ATP)
CC {ECO:0000269|PubMed:1659319};
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:10092873,
CC ECO:0000269|PubMed:17405878, ECO:0000269|PubMed:21396942}.
CC -!- INTERACTION:
CC P49902; P48047: ATP5PO; NbExp=3; IntAct=EBI-742084, EBI-355815;
CC P49902; P51116: FXR2; NbExp=3; IntAct=EBI-742084, EBI-740459;
CC P49902; Q8IVS8: GLYCTK; NbExp=3; IntAct=EBI-742084, EBI-748515;
CC P49902; Q7L9L4: MOB1B; NbExp=3; IntAct=EBI-742084, EBI-2558745;
CC P49902; Q86TA1: MOB3B; NbExp=3; IntAct=EBI-742084, EBI-751703;
CC P49902; Q70IA8: MOB3C; NbExp=3; IntAct=EBI-742084, EBI-9679267;
CC P49902; Q9Y5B8: NME7; NbExp=4; IntAct=EBI-742084, EBI-744782;
CC P49902; Q6ZVK8: NUDT18; NbExp=3; IntAct=EBI-742084, EBI-740486;
CC P49902; O00560: SDCBP; NbExp=3; IntAct=EBI-742084, EBI-727004;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:9371705}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P49902-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P49902-2; Sequence=VSP_054235;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:9371705}.
CC -!- DISEASE: Spastic paraplegia 45, autosomal recessive (SPG45)
CC [MIM:613162]: A form of spastic paraplegia, a neurodegenerative
CC disorder characterized by a slow, gradual, progressive weakness and
CC spasticity of the lower limbs. Rate of progression and the severity of
CC symptoms are quite variable. Initial symptoms may include difficulty
CC with balance, weakness and stiffness in the legs, muscle spasms, and
CC dragging the toes when walking. In some forms of the disorder, bladder
CC symptoms (such as incontinence) may appear, or the weakness and
CC stiffness may spread to other parts of the body. Some SPG45 patients
CC manifest intellectual disability, contractures and learning disability.
CC {ECO:0000269|PubMed:24482476, ECO:0000269|PubMed:28884889}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the 5'(3')-deoxyribonucleotidase family.
CC {ECO:0000305}.
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DR EMBL; D38524; BAA07529.1; -; mRNA.
DR EMBL; AK295593; BAH12118.1; -; mRNA.
DR EMBL; AL139817; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL360001; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW49656.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49657.1; -; Genomic_DNA.
DR EMBL; BC001595; AAH01595.1; -; mRNA.
DR CCDS; CCDS7544.1; -. [P49902-1]
DR CCDS; CCDS91339.1; -. [P49902-2]
DR PIR; JC2436; JC2436.
DR RefSeq; NP_001127845.1; NM_001134373.2. [P49902-1]
DR RefSeq; NP_036361.1; NM_012229.4. [P49902-1]
DR RefSeq; XP_005269693.1; XM_005269636.4.
DR RefSeq; XP_005269696.1; XM_005269639.4.
DR PDB; 2J2C; X-ray; 2.20 A; A=1-536.
DR PDB; 2JC9; X-ray; 1.50 A; A=1-536.
DR PDB; 2JCM; X-ray; 2.15 A; A=1-536.
DR PDB; 2XCV; X-ray; 2.30 A; A=1-536.
DR PDB; 2XCW; X-ray; 1.90 A; A=1-536.
DR PDB; 2XCX; X-ray; 2.30 A; A=1-536.
DR PDB; 2XJB; X-ray; 2.30 A; A=1-536.
DR PDB; 2XJC; X-ray; 2.00 A; A=1-536.
DR PDB; 2XJD; X-ray; 2.00 A; A=1-536.
DR PDB; 2XJE; X-ray; 2.30 A; A=1-536.
DR PDB; 2XJF; X-ray; 2.10 A; A=1-536.
DR PDB; 4H4B; X-ray; 2.90 A; A=1-536.
DR PDB; 5CQZ; X-ray; 2.90 A; A/B=1-536.
DR PDB; 5CR7; X-ray; 2.90 A; A/B=1-536.
DR PDB; 5K7Y; X-ray; 1.79 A; A=1-536.
DR PDB; 5L4Z; X-ray; 1.84 A; A=1-536.
DR PDB; 5L50; X-ray; 1.64 A; A=1-536.
DR PDB; 5OPK; X-ray; 1.74 A; A=3-488.
DR PDB; 5OPL; X-ray; 1.80 A; A=1-536.
DR PDB; 5OPM; X-ray; 1.68 A; A=3-488.
DR PDB; 5OPN; X-ray; 1.77 A; A=3-488.
DR PDB; 5OPO; X-ray; 2.00 A; A=3-488.
DR PDB; 5OPP; X-ray; 1.70 A; A=3-488.
DR PDB; 6DD3; X-ray; 1.98 A; A=1-536.
DR PDB; 6DDB; X-ray; 2.80 A; A/B=1-536.
DR PDB; 6DDC; X-ray; 2.91 A; A/B=1-536.
DR PDB; 6DDH; X-ray; 2.35 A; A=1-536.
DR PDB; 6DDK; X-ray; 2.50 A; A/B=1-561.
DR PDB; 6DDL; X-ray; 2.26 A; A/B=1-523.
DR PDB; 6DDO; X-ray; 2.48 A; A/B=1-561.
DR PDB; 6DDQ; X-ray; 2.31 A; A/B=1-561.
DR PDB; 6DDX; X-ray; 2.90 A; A=1-536.
DR PDB; 6DDY; X-ray; 1.80 A; A=1-536.
DR PDB; 6DDZ; X-ray; 1.97 A; A=1-536.
DR PDB; 6DE0; X-ray; 2.05 A; A=1-523.
DR PDB; 6DE1; X-ray; 2.15 A; A=1-561.
DR PDB; 6DE2; X-ray; 2.10 A; A=1-561.
DR PDB; 6DE3; X-ray; 3.06 A; A=1-561.
DR PDB; 6FIR; X-ray; 2.50 A; A=1-536.
DR PDB; 6FIS; X-ray; 2.30 A; A=1-536.
DR PDB; 6FIU; X-ray; 2.50 A; A=1-536.
DR PDB; 6FIW; X-ray; 2.20 A; A=1-536.
DR PDB; 6FXH; X-ray; 2.30 A; A=1-561.
DR PDBsum; 2J2C; -.
DR PDBsum; 2JC9; -.
DR PDBsum; 2JCM; -.
DR PDBsum; 2XCV; -.
DR PDBsum; 2XCW; -.
DR PDBsum; 2XCX; -.
DR PDBsum; 2XJB; -.
DR PDBsum; 2XJC; -.
DR PDBsum; 2XJD; -.
DR PDBsum; 2XJE; -.
DR PDBsum; 2XJF; -.
DR PDBsum; 4H4B; -.
DR PDBsum; 5CQZ; -.
DR PDBsum; 5CR7; -.
DR PDBsum; 5K7Y; -.
DR PDBsum; 5L4Z; -.
DR PDBsum; 5L50; -.
DR PDBsum; 5OPK; -.
DR PDBsum; 5OPL; -.
DR PDBsum; 5OPM; -.
DR PDBsum; 5OPN; -.
DR PDBsum; 5OPO; -.
DR PDBsum; 5OPP; -.
DR PDBsum; 6DD3; -.
DR PDBsum; 6DDB; -.
DR PDBsum; 6DDC; -.
DR PDBsum; 6DDH; -.
DR PDBsum; 6DDK; -.
DR PDBsum; 6DDL; -.
DR PDBsum; 6DDO; -.
DR PDBsum; 6DDQ; -.
DR PDBsum; 6DDX; -.
DR PDBsum; 6DDY; -.
DR PDBsum; 6DDZ; -.
DR PDBsum; 6DE0; -.
DR PDBsum; 6DE1; -.
DR PDBsum; 6DE2; -.
DR PDBsum; 6DE3; -.
DR PDBsum; 6FIR; -.
DR PDBsum; 6FIS; -.
DR PDBsum; 6FIU; -.
DR PDBsum; 6FIW; -.
DR PDBsum; 6FXH; -.
DR AlphaFoldDB; P49902; -.
DR SMR; P49902; -.
DR BioGRID; 116627; 137.
DR IntAct; P49902; 24.
DR MINT; P49902; -.
DR STRING; 9606.ENSP00000339479; -.
DR BindingDB; P49902; -.
DR ChEMBL; CHEMBL3708197; -.
DR DrugBank; DB00171; ATP.
DR DrugBank; DB00811; Ribavirin.
DR DrugBank; DB06408; Taribavirin.
DR DrugCentral; P49902; -.
DR DEPOD; NT5C2; -.
DR GlyGen; P49902; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P49902; -.
DR MetOSite; P49902; -.
DR PhosphoSitePlus; P49902; -.
DR BioMuta; NT5C2; -.
DR DMDM; 1703012; -.
DR EPD; P49902; -.
DR jPOST; P49902; -.
DR MassIVE; P49902; -.
DR MaxQB; P49902; -.
DR PaxDb; 9606-ENSP00000339479; -.
DR PeptideAtlas; P49902; -.
DR ProteomicsDB; 56174; -. [P49902-1]
DR ProteomicsDB; 6498; -.
DR Pumba; P49902; -.
DR TopDownProteomics; P49902-1; -. [P49902-1]
DR Antibodypedia; 18107; 262 antibodies from 32 providers.
DR DNASU; 22978; -.
DR Ensembl; ENST00000343289.9; ENSP00000339479.5; ENSG00000076685.19. [P49902-1]
DR Ensembl; ENST00000404739.8; ENSP00000383960.3; ENSG00000076685.19. [P49902-1]
DR Ensembl; ENST00000674696.1; ENSP00000502679.1; ENSG00000076685.19. [P49902-1]
DR Ensembl; ENST00000675326.1; ENSP00000502205.1; ENSG00000076685.19. [P49902-1]
DR Ensembl; ENST00000675985.1; ENSP00000502215.1; ENSG00000076685.19. [P49902-2]
DR Ensembl; ENST00000676428.1; ENSP00000501689.1; ENSG00000076685.19. [P49902-1]
DR Ensembl; ENST00000676449.1; ENSP00000502801.1; ENSG00000076685.19. [P49902-1]
DR GeneID; 22978; -.
DR KEGG; hsa:22978; -.
DR MANE-Select; ENST00000404739.8; ENSP00000383960.3; NM_001351169.2; NP_001338098.1.
DR UCSC; uc001kwq.4; human. [P49902-1]
DR AGR; HGNC:8022; -.
DR CTD; 22978; -.
DR DisGeNET; 22978; -.
DR GeneCards; NT5C2; -.
DR HGNC; HGNC:8022; NT5C2.
DR HPA; ENSG00000076685; Low tissue specificity.
DR MalaCards; NT5C2; -.
DR MIM; 600417; gene.
DR MIM; 613162; phenotype.
DR neXtProt; NX_P49902; -.
DR OpenTargets; ENSG00000076685; -.
DR Orphanet; 320396; Autosomal recessive spastic paraplegia type 45.
DR PharmGKB; PA31801; -.
DR VEuPathDB; HostDB:ENSG00000076685; -.
DR eggNOG; KOG2469; Eukaryota.
DR GeneTree; ENSGT00940000162369; -.
DR HOGENOM; CLU_017845_3_0_1; -.
DR InParanoid; P49902; -.
DR OrthoDB; 3626840at2759; -.
DR PhylomeDB; P49902; -.
DR TreeFam; TF315266; -.
DR BioCyc; MetaCyc:HS01216-MONOMER; -.
DR BRENDA; 3.1.3.5; 2681.
DR PathwayCommons; P49902; -.
DR Reactome; R-HSA-2161541; Abacavir metabolism.
DR Reactome; R-HSA-74259; Purine catabolism.
DR Reactome; R-HSA-9755088; Ribavirin ADME.
DR SABIO-RK; P49902; -.
DR SignaLink; P49902; -.
DR BioGRID-ORCS; 22978; 15 hits in 1177 CRISPR screens.
DR ChiTaRS; NT5C2; human.
DR EvolutionaryTrace; P49902; -.
DR GenomeRNAi; 22978; -.
DR Pharos; P49902; Tbio.
DR PRO; PR:P49902; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P49902; Protein.
DR Bgee; ENSG00000076685; Expressed in parotid gland and 207 other cell types or tissues.
DR ExpressionAtlas; P49902; baseline and differential.
DR Genevisible; P49902; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProt.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0008253; F:5'-nucleotidase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0050484; F:GMP 5'-nucleotidase activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0050483; F:IMP 5'-nucleotidase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050146; F:nucleoside phosphotransferase activity; IDA:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProt.
DR GO; GO:0106411; F:XMP 5'-nucleosidase activity; IEA:UniProtKB-EC.
DR GO; GO:0046085; P:adenosine metabolic process; IBA:GO_Central.
DR GO; GO:0000255; P:allantoin metabolic process; IDA:MGI.
DR GO; GO:0046054; P:dGMP metabolic process; IDA:UniProtKB.
DR GO; GO:0046037; P:GMP metabolic process; IDA:UniProtKB.
DR GO; GO:0006204; P:IMP catabolic process; IDA:MGI.
DR GO; GO:0046040; P:IMP metabolic process; IDA:UniProtKB.
DR GO; GO:0050689; P:negative regulation of defense response to virus by host; IDA:UniProt.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProt.
DR CDD; cd07522; HAD_cN-II; 1.
DR Gene3D; 3.40.50.1000; HAD superfamily/HAD-like; 2.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR008380; HAD-SF_hydro_IG_5-nucl.
DR InterPro; IPR023214; HAD_sf.
DR InterPro; IPR016695; Pur_nucleotidase.
DR NCBIfam; TIGR02244; HAD-IG-Ncltidse; 1.
DR PANTHER; PTHR12103; 5'-NUCLEOTIDASE DOMAIN-CONTAINING; 1.
DR PANTHER; PTHR12103:SF17; CYTOSOLIC PURINE 5'-NUCLEOTIDASE; 1.
DR Pfam; PF05761; 5_nucleotid; 1.
DR PIRSF; PIRSF017434; Purine_5'-nucleotidase; 1.
DR SUPFAM; SSF56784; HAD-like; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Allosteric enzyme; Alternative splicing; ATP-binding;
KW Cytoplasm; Disease variant; Hereditary spastic paraplegia; Hydrolase;
KW Magnesium; Metal-binding; Neurodegeneration; Nucleotide metabolism;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..561
FT /note="Cytosolic purine 5'-nucleotidase"
FT /id="PRO_0000064389"
FT REGION 538..561
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 548..561
FT /note="Required for tetramer assembly"
FT /evidence="ECO:0000269|PubMed:10092873"
FT ACT_SITE 52
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:21396942"
FT ACT_SITE 54
FT /note="Proton donor"
FT /evidence="ECO:0000305|PubMed:21396942"
FT BINDING 52
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XJC"
FT BINDING 52
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XCV, ECO:0007744|PDB:2XCW"
FT BINDING 52
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:17405878,
FT ECO:0000269|PubMed:21396942, ECO:0007744|PDB:2J2C,
FT ECO:0007744|PDB:2JC9, ECO:0007744|PDB:2JCM,
FT ECO:0007744|PDB:2XCV, ECO:0007744|PDB:2XCW,
FT ECO:0007744|PDB:2XJB, ECO:0007744|PDB:2XJC,
FT ECO:0007744|PDB:2XJD, ECO:0007744|PDB:2XJE"
FT BINDING 54
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XJC"
FT BINDING 54
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XCV, ECO:0007744|PDB:2XCW"
FT BINDING 54
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:17405878,
FT ECO:0000269|PubMed:21396942, ECO:0007744|PDB:2J2C,
FT ECO:0007744|PDB:2JC9, ECO:0007744|PDB:2JCM,
FT ECO:0007744|PDB:2XCV, ECO:0007744|PDB:2XCW,
FT ECO:0007744|PDB:2XJB, ECO:0007744|PDB:2XJC,
FT ECO:0007744|PDB:2XJD, ECO:0007744|PDB:2XJE"
FT BINDING 144
FT /ligand="(2R)-2,3-bisphosphoglycerate"
FT /ligand_id="ChEBI:CHEBI:58248"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XCV, ECO:0007744|PDB:2XJF"
FT BINDING 144
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XCW, ECO:0007744|PDB:2XJD,
FT ECO:0007744|PDB:2XJE"
FT BINDING 144
FT /ligand="dATP"
FT /ligand_id="ChEBI:CHEBI:61404"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XJB"
FT BINDING 154
FT /ligand="adenosine"
FT /ligand_id="ChEBI:CHEBI:16335"
FT /ligand_label="1"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:17405878,
FT ECO:0007744|PDB:2JC9"
FT BINDING 154
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XCW, ECO:0007744|PDB:2XJD,
FT ECO:0007744|PDB:2XJE"
FT BINDING 154
FT /ligand="dATP"
FT /ligand_id="ChEBI:CHEBI:61404"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XJB"
FT BINDING 154
FT /ligand="P(1),P(4)-bis(5'-adenosyl) tetraphosphate"
FT /ligand_id="ChEBI:CHEBI:58141"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XJC"
FT BINDING 202
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XJC"
FT BINDING 202
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XCV, ECO:0007744|PDB:2XCW"
FT BINDING 206
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XJC"
FT BINDING 206
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XCV, ECO:0007744|PDB:2XCW"
FT BINDING 215
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XJC"
FT BINDING 215
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XCV, ECO:0007744|PDB:2XCW"
FT BINDING 249
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XJC"
FT BINDING 249
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XCV, ECO:0007744|PDB:2XCW"
FT BINDING 250
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XJC"
FT BINDING 250
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XCV, ECO:0007744|PDB:2XCW"
FT BINDING 251
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XCV, ECO:0007744|PDB:2XCW"
FT BINDING 292
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XJC"
FT BINDING 292
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XCV, ECO:0007744|PDB:2XCW"
FT BINDING 351
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:17405878,
FT ECO:0000269|PubMed:21396942, ECO:0007744|PDB:2J2C,
FT ECO:0007744|PDB:2JC9, ECO:0007744|PDB:2JCM"
FT BINDING 362
FT /ligand="(2R)-2,3-bisphosphoglycerate"
FT /ligand_id="ChEBI:CHEBI:58248"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XCV, ECO:0007744|PDB:2XJF"
FT BINDING 362
FT /ligand="P(1),P(4)-bis(5'-adenosyl) tetraphosphate"
FT /ligand_id="ChEBI:CHEBI:58141"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XJC"
FT BINDING 436
FT /ligand="adenosine"
FT /ligand_id="ChEBI:CHEBI:16335"
FT /ligand_label="2"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:17405878,
FT ECO:0007744|PDB:2JC9"
FT BINDING 453
FT /ligand="adenosine"
FT /ligand_id="ChEBI:CHEBI:16335"
FT /ligand_label="1"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:17405878,
FT ECO:0007744|PDB:2JC9"
FT BINDING 453
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XCW, ECO:0007744|PDB:2XJD,
FT ECO:0007744|PDB:2XJE"
FT BINDING 453
FT /ligand="dATP"
FT /ligand_id="ChEBI:CHEBI:61404"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XJB"
FT BINDING 453
FT /ligand="P(1),P(4)-bis(5'-adenosyl) tetraphosphate"
FT /ligand_id="ChEBI:CHEBI:58141"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XJC"
FT BINDING 456
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XCW, ECO:0007744|PDB:2XJD,
FT ECO:0007744|PDB:2XJE"
FT BINDING 456
FT /ligand="dATP"
FT /ligand_id="ChEBI:CHEBI:61404"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XJB"
FT BINDING 457
FT /ligand="(2R)-2,3-bisphosphoglycerate"
FT /ligand_id="ChEBI:CHEBI:58248"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XCV, ECO:0007744|PDB:2XJF"
FT BINDING 457
FT /ligand="P(1),P(4)-bis(5'-adenosyl) tetraphosphate"
FT /ligand_id="ChEBI:CHEBI:58141"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:21396942,
FT ECO:0007744|PDB:2XJC"
FT MOD_RES 418
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 502
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 511
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 527
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3V1L4"
FT VAR_SEQ 1..34
FT /note="MSTSWSDRLQNAADMPANMDKHALKKYRREAYHR -> MSKEG (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054235"
FT VARIANT 3
FT /note="T -> A (in dbSNP:rs10883841)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_024244"
FT VARIANT 136
FT /note="Q -> R (in dbSNP:rs12262171)"
FT /id="VAR_030242"
FT VARIANT 460
FT /note="L -> P (in SPG45; uncertain significance)"
FT /evidence="ECO:0000269|PubMed:28884889"
FT /id="VAR_079707"
FT MUTAGEN 52
FT /note="D->N: Loss of 5' nucleotidase activity."
FT /evidence="ECO:0000269|PubMed:21396942"
FT HELIX 5..13
FT /evidence="ECO:0007829|PDB:2JC9"
FT HELIX 21..28
FT /evidence="ECO:0007829|PDB:2JC9"
FT HELIX 31..33
FT /evidence="ECO:0007829|PDB:2JC9"
FT STRAND 36..39
FT /evidence="ECO:0007829|PDB:2JC9"
FT HELIX 43..45
FT /evidence="ECO:0007829|PDB:2JC9"
FT STRAND 48..51
FT /evidence="ECO:0007829|PDB:2JC9"
FT TURN 55..57
FT /evidence="ECO:0007829|PDB:2JC9"
FT STRAND 58..60
FT /evidence="ECO:0007829|PDB:6DE1"
FT HELIX 64..79
FT /evidence="ECO:0007829|PDB:2JC9"
FT HELIX 84..88
FT /evidence="ECO:0007829|PDB:2JC9"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:2JC9"
FT TURN 104..107
FT /evidence="ECO:0007829|PDB:2JC9"
FT STRAND 108..112
FT /evidence="ECO:0007829|PDB:2JC9"
FT STRAND 117..123
FT /evidence="ECO:0007829|PDB:2JC9"
FT STRAND 126..128
FT /evidence="ECO:0007829|PDB:5OPL"
FT HELIX 130..136
FT /evidence="ECO:0007829|PDB:2JC9"
FT HELIX 138..140
FT /evidence="ECO:0007829|PDB:6DDL"
FT TURN 147..149
FT /evidence="ECO:0007829|PDB:2JC9"
FT STRAND 150..152
FT /evidence="ECO:0007829|PDB:2JC9"
FT HELIX 156..158
FT /evidence="ECO:0007829|PDB:2JC9"
FT HELIX 159..174
FT /evidence="ECO:0007829|PDB:2JC9"
FT STRAND 178..181
FT /evidence="ECO:0007829|PDB:2JC9"
FT STRAND 184..187
FT /evidence="ECO:0007829|PDB:2JC9"
FT STRAND 190..193
FT /evidence="ECO:0007829|PDB:2JC9"
FT HELIX 194..210
FT /evidence="ECO:0007829|PDB:2JC9"
FT HELIX 214..220
FT /evidence="ECO:0007829|PDB:2JC9"
FT HELIX 222..225
FT /evidence="ECO:0007829|PDB:2JC9"
FT HELIX 231..242
FT /evidence="ECO:0007829|PDB:2JC9"
FT STRAND 243..248
FT /evidence="ECO:0007829|PDB:2JC9"
FT HELIX 253..263
FT /evidence="ECO:0007829|PDB:2JC9"
FT STRAND 266..271
FT /evidence="ECO:0007829|PDB:2JC9"
FT HELIX 279..282
FT /evidence="ECO:0007829|PDB:2JC9"
FT STRAND 284..289
FT /evidence="ECO:0007829|PDB:2JC9"
FT HELIX 294..296
FT /evidence="ECO:0007829|PDB:2JC9"
FT STRAND 302..306
FT /evidence="ECO:0007829|PDB:2JC9"
FT TURN 307..310
FT /evidence="ECO:0007829|PDB:2JC9"
FT STRAND 312..315
FT /evidence="ECO:0007829|PDB:6DDQ"
FT HELIX 320..323
FT /evidence="ECO:0007829|PDB:6DDQ"
FT STRAND 327..329
FT /evidence="ECO:0007829|PDB:2JC9"
FT HELIX 332..339
FT /evidence="ECO:0007829|PDB:2JC9"
FT HELIX 343..345
FT /evidence="ECO:0007829|PDB:2JC9"
FT STRAND 346..351
FT /evidence="ECO:0007829|PDB:2JC9"
FT HELIX 353..357
FT /evidence="ECO:0007829|PDB:2JC9"
FT HELIX 358..364
FT /evidence="ECO:0007829|PDB:2JC9"
FT STRAND 367..371
FT /evidence="ECO:0007829|PDB:2JC9"
FT HELIX 375..384
FT /evidence="ECO:0007829|PDB:2JC9"
FT HELIX 386..398
FT /evidence="ECO:0007829|PDB:2JC9"
FT TURN 403..405
FT /evidence="ECO:0007829|PDB:6DDL"
FT TURN 417..420
FT /evidence="ECO:0007829|PDB:5OPO"
FT HELIX 421..432
FT /evidence="ECO:0007829|PDB:2JC9"
FT STRAND 440..443
FT /evidence="ECO:0007829|PDB:2JC9"
FT STRAND 446..448
FT /evidence="ECO:0007829|PDB:5OPN"
FT HELIX 449..457
FT /evidence="ECO:0007829|PDB:2JC9"
FT STRAND 459..463
FT /evidence="ECO:0007829|PDB:2JC9"
FT HELIX 465..470
FT /evidence="ECO:0007829|PDB:2JC9"
FT HELIX 485..487
FT /evidence="ECO:0007829|PDB:2JC9"
FT HELIX 503..506
FT /evidence="ECO:0007829|PDB:6DDL"
FT TURN 548..550
FT /evidence="ECO:0007829|PDB:6DDQ"
SQ SEQUENCE 561 AA; 64970 MW; 4C27D762575E0EA2 CRC64;
MSTSWSDRLQ NAADMPANMD KHALKKYRRE AYHRVFVNRS LAMEKIKCFG FDMDYTLAVY
KSPEYESLGF ELTVERLVSI GYPQELLSFA YDSTFPTRGL VFDTLYGNLL KVDAYGNLLV
CAHGFNFIRG PETREQYPNK FIQRDDTERF YILNTLFNLP ETYLLACLVD FFTNCPRYTS
CETGFKDGDL FMSYRSMFQD VRDAVDWVHY KGSLKEKTVE NLEKYVVKDG KLPLLLSRMK
EVGKVFLATN SDYKYTDKIM TYLFDFPHGP KPGSSHRPWQ SYFDLILVDA RKPLFFGEGT
VLRQVDTKTG KLKIGTYTGP LQHGIVYSGG SSDTICDLLG AKGKDILYIG DHIFGDILKS
KKRQGWRTFL VIPELAQELH VWTDKSSLFE ELQSLDIFLA ELYKHLDSSS NERPDISSIQ
RRIKKVTHDM DMCYGMMGSL FRSGSRQTLF ASQVMRYADL YAASFINLLY YPFSYLFRAA
HVLMPHESTV EHTHVDINEM ESPLATRNRT SVDFKDTDYK RHQLTRSISE IKPPNLFPLA
PQEITHCHDE DDDEEEEEEE E
//
