5NTC_RAT
ID 5NTC_RAT Reviewed; 560 AA.
AC D3ZMY7;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 4.
DT 03-AUG-2022, entry version 81.
DE RecName: Full=Cytosolic purine 5'-nucleotidase {ECO:0000305|PubMed:6260203};
DE EC=3.1.3.5 {ECO:0000269|PubMed:6260203};
DE EC=3.1.3.99 {ECO:0000269|PubMed:6260203};
DE AltName: Full=Cytosolic nucleoside phosphotransferase 5'N {ECO:0000250|UniProtKB:P49902};
DE EC=2.7.1.77 {ECO:0000250|UniProtKB:P49902};
GN Name=Nt5c2 {ECO:0000312|RGD:2323387};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP IDENTIFICATION, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBSTRATE
RP SPECIFICITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=6260203; DOI=10.1016/0005-2744(81)90326-0;
RA Itoh R.;
RT "Purification and some properties of cytosol 5'-nucleotidase from rat
RT liver.";
RL Biochim. Biophys. Acta 657:402-410(1981).
CC -!- FUNCTION: Broad specificity cytosolic 5'-nucleotidase that catalyzes
CC the dephosphorylation of 6-hydroxypurine nucleoside 5'-monophosphates
CC (PubMed:6260203). In addition, possesses a phosphotransferase activity
CC by which it can transfer a phosphate from a donor nucleoside
CC monophosphate to an acceptor nucleoside, preferably inosine,
CC deoxyinosine and guanosine (By similarity). Has the highest activities
CC for IMP and GMP followed by dIMP, dGMP and XMP (PubMed:6260203). Could
CC also catalyze the transfer of phosphates from pyrimidine monophosphates
CC but with lower efficiency (By similarity). Through these activities
CC regulates the purine nucleoside/nucleotide pools within the cell
CC (PubMed:6260203). {ECO:0000250|UniProtKB:P49902,
CC ECO:0000269|PubMed:6260203}.
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:6260203};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12485;
CC Evidence={ECO:0000305|PubMed:6260203};
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:0000250|UniProtKB:P49902};
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:6260203};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27719;
CC Evidence={ECO:0000305|PubMed:6260203};
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:0000269|PubMed:6260203};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27715;
CC Evidence={ECO:0000305|PubMed:6260203};
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:0000269|PubMed:6260203};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:29384;
CC Evidence={ECO:0000305|PubMed:6260203};
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:6260203};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:29380;
CC Evidence={ECO:0000305|PubMed:6260203};
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:0000269|PubMed:6260203};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:28531;
CC Evidence={ECO:0000305|PubMed:6260203};
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:0000250|UniProtKB:P49902};
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:0000250|UniProtKB:P49902};
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:0000250|UniProtKB:P49902};
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:0000250|UniProtKB:P49902};
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:0000250|UniProtKB:P49902};
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:0000250|UniProtKB:P49902};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:6260203};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000250|UniProtKB:P49902};
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:6260203). Binding of an
CC allosteric activator is a prerequisiste to magnesium and substrate
CC binding (By similarity). Inhibited by inorganic phosphate
CC (PubMed:6260203). {ECO:0000250|UniProtKB:P49902,
CC ECO:0000269|PubMed:6260203}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.2 mM for IMP {ECO:0000269|PubMed:6260203};
CC KM=0.7 mM for dIMP {ECO:0000269|PubMed:6260203};
CC KM=0.7 mM for GMP {ECO:0000269|PubMed:6260203};
CC KM=1.1 mM for dGMP {ECO:0000269|PubMed:6260203};
CC pH dependence:
CC Optimum pH is 6.5. {ECO:0000269|PubMed:6260203};
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P49902}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P49902}.
CC -!- SIMILARITY: Belongs to the 5'(3')-deoxyribonucleotidase family.
CC {ECO:0000305}.
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DR EMBL; AC097752; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC105488; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_002728937.1; XM_002728891.5.
DR RefSeq; XP_003753467.1; XM_003753419.4.
DR AlphaFoldDB; D3ZMY7; -.
DR IntAct; D3ZMY7; 1.
DR STRING; 10116.ENSRNOP00000027351; -.
DR jPOST; D3ZMY7; -.
DR PaxDb; D3ZMY7; -.
DR PeptideAtlas; D3ZMY7; -.
DR PRIDE; D3ZMY7; -.
DR GeneID; 100363253; -.
DR KEGG; rno:100363253; -.
DR CTD; 22978; -.
DR RGD; 2323387; Nt5c2.
DR eggNOG; KOG2469; Eukaryota.
DR HOGENOM; CLU_017845_3_0_1; -.
DR InParanoid; D3ZMY7; -.
DR OMA; EESYFAY; -.
DR OrthoDB; 712212at2759; -.
DR TreeFam; TF315266; -.
DR Reactome; R-RNO-2161541; Abacavir metabolism.
DR Reactome; R-RNO-74259; Purine catabolism.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000020179; Expressed in kidney and 19 other tissues.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0008253; F:5'-nucleotidase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0050484; F:GMP 5'-nucleotidase activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISS: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; ISS:UniProtKB.
DR GO; GO:0046085; P:adenosine metabolic process; IDA:RGD.
DR GO; GO:0000255; P:allantoin metabolic process; ISO:RGD.
DR GO; GO:0046055; P:dGMP catabolic process; ISO:RGD.
DR GO; GO:0046054; P:dGMP metabolic process; IDA:UniProtKB.
DR GO; GO:0046038; P:GMP catabolic process; ISO:RGD.
DR GO; GO:0006202; P:GMP catabolic process to guanine; ISO:RGD.
DR GO; GO:0046037; P:GMP metabolic process; IDA:UniProtKB.
DR GO; GO:0006204; P:IMP catabolic process; ISO:RGD.
DR GO; GO:0046040; P:IMP metabolic process; IDA:UniProtKB.
DR GO; GO:0046939; P:nucleotide phosphorylation; ISO:RGD.
DR Gene3D; 3.40.50.1000; -; 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 PANTHER; PTHR12103; PTHR12103; 1.
DR Pfam; PF05761; 5_nucleotid; 1.
DR PIRSF; PIRSF017434; Purine_5'-nucleotidase; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR TIGRFAMs; TIGR02244; HAD-IG-Ncltidse; 1.
PE 1: Evidence at protein level;
KW Allosteric enzyme; ATP-binding; Cytoplasm; Hydrolase; Magnesium;
KW Metal-binding; Nucleotide metabolism; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Transferase.
FT CHAIN 1..560
FT /note="Cytosolic purine 5'-nucleotidase"
FT /id="PRO_0000455115"
FT REGION 541..560
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 548..560
FT /note="Required for tetramer assembly"
FT /evidence="ECO:0000250|UniProtKB:P49902"
FT ACT_SITE 52
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PIRSR:PIRSR017434-1"
FT ACT_SITE 54
FT /note="Proton donor"
FT /evidence="ECO:0000255|PIRSR:PIRSR017434-1"
FT BINDING 52
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000250|UniProtKB:P49902"
FT BINDING 52
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|PIRSR:PIRSR017434-2"
FT BINDING 54
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000250|UniProtKB:P49902"
FT BINDING 54
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|PIRSR:PIRSR017434-2"
FT BINDING 144
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P49902"
FT BINDING 154
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P49902"
FT BINDING 202
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000250|UniProtKB:P49902"
FT BINDING 206
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000250|UniProtKB:P49902"
FT BINDING 215
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000250|UniProtKB:P49902"
FT BINDING 249
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000250|UniProtKB:P49902"
FT BINDING 250
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000250|UniProtKB:P49902"
FT BINDING 251
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000250|UniProtKB:P49902"
FT BINDING 292
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000250|UniProtKB:P49902"
FT BINDING 351
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|PIRSR:PIRSR017434-2"
FT BINDING 453
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P49902"
FT BINDING 456
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P49902"
FT MOD_RES 418
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49902"
FT MOD_RES 502
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49902"
FT MOD_RES 511
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49902"
FT MOD_RES 527
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3V1L4"
SQ SEQUENCE 560 AA; 64866 MW; 8BFA7579DE41B0C8 CRC64;
MMTSWSDRLQ NAADVPANMD KHALKKYRRE AYHRVFVNRS LAMEKIKCFG FDMDYTLAVY
KSPEYESLGF ELTVERLVSI GYPQELLNFA YDSTFPTRGL VFDTLYGNLL KVDAYGNLLV
CAHGFNFIRG PETREQYPNK FIQRDDTERF YILNTLFNLP ETYLLACLVD FFTNCPRYTS
CDTGFKDGDL 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
