ID   NPPNK_METJA             Reviewed;         574 AA.
AC   Q58327;
DT   04-MAY-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-1998, sequence version 2.
DT   27-MAR-2024, entry version 136.
DE   RecName: Full=Bifunctional NADP phosphatase/NAD kinase {ECO:0000305};
DE   Includes:
DE     RecName: Full=NAD kinase {ECO:0000255|HAMAP-Rule:MF_00361, ECO:0000303|PubMed:16192277};
DE              EC=2.7.1.23 {ECO:0000255|HAMAP-Rule:MF_00361, ECO:0000269|PubMed:16192277};
DE     AltName: Full=ATP-dependent NAD kinase {ECO:0000255|HAMAP-Rule:MF_00361};
DE     AltName: Full=Poly(P)-dependent NAD kinase;
DE              Short=PPNK;
DE   Includes:
DE     RecName: Full=NADP phosphatase {ECO:0000303|PubMed:16192277};
DE              Short=NADPase {ECO:0000303|PubMed:16192277};
DE              Short=pNPPase {ECO:0000303|PubMed:16192277};
DE              EC=3.1.3.- {ECO:0000269|PubMed:16192277};
GN   OrderedLocusNames=MJ0917;
OS   Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM
OS   10045 / NBRC 100440) (Methanococcus jannaschii).
OC   Archaea; Euryarchaeota; Methanomada group; Methanococci; Methanococcales;
OC   Methanocaldococcaceae; Methanocaldococcus.
OX   NCBI_TaxID=243232;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440;
RX   PubMed=8688087; DOI=10.1126/science.273.5278.1058;
RA   Bult C.J., White O., Olsen G.J., Zhou L., Fleischmann R.D., Sutton G.G.,
RA   Blake J.A., FitzGerald L.M., Clayton R.A., Gocayne J.D., Kerlavage A.R.,
RA   Dougherty B.A., Tomb J.-F., Adams M.D., Reich C.I., Overbeek R.,
RA   Kirkness E.F., Weinstock K.G., Merrick J.M., Glodek A., Scott J.L.,
RA   Geoghagen N.S.M., Weidman J.F., Fuhrmann J.L., Nguyen D., Utterback T.R.,
RA   Kelley J.M., Peterson J.D., Sadow P.W., Hanna M.C., Cotton M.D.,
RA   Roberts K.M., Hurst M.A., Kaine B.P., Borodovsky M., Klenk H.-P.,
RA   Fraser C.M., Smith H.O., Woese C.R., Venter J.C.;
RT   "Complete genome sequence of the methanogenic archaeon, Methanococcus
RT   jannaschii.";
RL   Science 273:1058-1073(1996).
RN   [2]
RP   PROTEIN SEQUENCE OF 1-8, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP   PROPERTIES, COFACTOR, SUBSTRATE SPECIFICITY, ACTIVITY REGULATION, AND
RP   SUBUNIT.
RX   PubMed=16192277; DOI=10.1074/jbc.m506426200;
RA   Kawai S., Fukuda C., Mukai T., Murata K.;
RT   "MJ0917 in archaeon Methanococcus jannaschii is a novel NADP
RT   phosphatase/NAD kinase.";
RL   J. Biol. Chem. 280:39200-39207(2005).
CC   -!- FUNCTION: Involved in the regulation of the intracellular balance
CC       between NAD(H) and NADP(H), and is a key enzyme in the biosynthesis of
CC       NADP. Catalyzes the phosphorylation and dephosphorylation of NAD and
CC       NADP, respectively. Although it shows conflicting dual activities and
CC       is able to supply NADP, it seems that its physiological role is to
CC       prevent excess accumulation of NADP. Kinase can use ATP and other
CC       nucleoside triphosphates (UTP, TTP, CTP, GTP) as well as inorganic
CC       polyphosphate (poly(P)) as phosphoryl donors, however poly(P) is not
CC       considered to be the physiological phosphoryl donor. NAD is the
CC       preferred substrate for the kinase, but NADH can also be used as
CC       phosphoryl acceptor. Phosphatase can use NADP or NADPH as phosphoryl
CC       donor, but NADP is the preferred substrate. Phosphatase also has an
CC       activity toward the terminal phosphate group at C-2 of adenosine in 2'-
CC       AMP and toward the phosphate group at C-1 of fructose 1,6-bisphosphate,
CC       but not toward inositol 1-phosphate. {ECO:0000269|PubMed:16192277}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + NAD(+) = ADP + H(+) + NADP(+); Xref=Rhea:RHEA:18629,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:58349, ChEBI:CHEBI:456216; EC=2.7.1.23;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_00361,
CC         ECO:0000269|PubMed:16192277};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18630;
CC         Evidence={ECO:0000269|PubMed:16192277};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + NADP(+) = NAD(+) + phosphate; Xref=Rhea:RHEA:28050,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:58349; Evidence={ECO:0000269|PubMed:16192277};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:28051;
CC         Evidence={ECO:0000269|PubMed:16192277};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=NAD(+) + UTP = H(+) + NADP(+) + UDP; Xref=Rhea:RHEA:75163,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:46398, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:58223, ChEBI:CHEBI:58349;
CC         Evidence={ECO:0000269|PubMed:16192277};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75164;
CC         Evidence={ECO:0000269|PubMed:16192277};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=NAD(+) + TTP = H(+) + NADP(+) + TDP; Xref=Rhea:RHEA:75159,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:58349,
CC         ChEBI:CHEBI:61417, ChEBI:CHEBI:63527;
CC         Evidence={ECO:0000269|PubMed:16192277};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75160;
CC         Evidence={ECO:0000269|PubMed:16192277};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=CTP + NAD(+) = CDP + H(+) + NADP(+); Xref=Rhea:RHEA:75167,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:37563, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:58069, ChEBI:CHEBI:58349;
CC         Evidence={ECO:0000269|PubMed:16192277};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75168;
CC         Evidence={ECO:0000269|PubMed:16192277};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=GTP + NAD(+) = GDP + H(+) + NADP(+); Xref=Rhea:RHEA:75171,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:58189, ChEBI:CHEBI:58349;
CC         Evidence={ECO:0000269|PubMed:16192277};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75172;
CC         Evidence={ECO:0000269|PubMed:16192277};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=dATP + NAD(+) = dADP + H(+) + NADP(+); Xref=Rhea:RHEA:75175,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57667,
CC         ChEBI:CHEBI:58349, ChEBI:CHEBI:61404;
CC         Evidence={ECO:0000269|PubMed:16192277};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75176;
CC         Evidence={ECO:0000269|PubMed:16192277};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + NADPH = NADH + phosphate; Xref=Rhea:RHEA:60664,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57783,
CC         ChEBI:CHEBI:57945; Evidence={ECO:0000269|PubMed:16192277};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60665;
CC         Evidence={ECO:0000269|PubMed:16192277};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=adenosine 2'-phosphate + H2O = adenosine + phosphate;
CC         Xref=Rhea:RHEA:37343, ChEBI:CHEBI:15377, ChEBI:CHEBI:16335,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:77740;
CC         Evidence={ECO:0000269|PubMed:16192277};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37344;
CC         Evidence={ECO:0000269|PubMed:16192277};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=beta-D-fructose 1,6-bisphosphate + H2O = beta-D-fructose 6-
CC         phosphate + phosphate; Xref=Rhea:RHEA:11064, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:32966, ChEBI:CHEBI:43474, ChEBI:CHEBI:57634;
CC         Evidence={ECO:0000269|PubMed:16192277};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11065;
CC         Evidence={ECO:0000269|PubMed:16192277};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:16192277};
CC       Note=NAD kinase and pNPPase show maximum activities at 50 and 20 mM
CC       magnesium, respectively. {ECO:0000269|PubMed:16192277};
CC   -!- ACTIVITY REGULATION: Phosphatase activity is slightly inhibited by ADP,
CC       NADH and ATP, and moderately inhibited by NAD and 5'-AMP
CC       (PubMed:16192277). Kinase activity is slightly inhibited by ADP and
CC       NADP (PubMed:16192277). {ECO:0000269|PubMed:16192277}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.35 mM for ATP (for kinase activity at pH 8.5 and at 85 degrees
CC         Celsius) {ECO:0000269|PubMed:16192277};
CC         KM=3 mM for NAD (for kinase activity at pH 8.5 and at 85 degrees
CC         Celsius) {ECO:0000269|PubMed:16192277};
CC         Vmax=93.4 umol/min/mg enzyme toward ATP (for kinase activity at pH
CC         8.5 and at 85 degrees Celsius) {ECO:0000269|PubMed:16192277};
CC         Vmax=99.2 umol/min/mg enzyme toward NAD (for kinase activity at pH
CC         8.5 and at 85 degrees Celsius) {ECO:0000269|PubMed:16192277};
CC         Vmax=212 umol/min/mg enzyme toward NADP (for phosphatase activity at
CC         pH 8.5 and at 85 degrees Celsius) {ECO:0000269|PubMed:16192277};
CC         Vmax=212 umol/min/mg enzyme toward fructose 1,6-bisphosphate (for
CC         phosphatase activity at pH 8.5 and at 85 degrees Celsius)
CC         {ECO:0000269|PubMed:16192277};
CC         Vmax=236 umol/min/mg enzyme toward NADPH (for phosphatase activity at
CC         pH 8.5 and at 85 degrees Celsius) {ECO:0000269|PubMed:16192277};
CC         Note=kcat is 399 sec(-1) for kinase activity with ATP as substrate.
CC         kcat is 424 sec(-1) for kinase activity with NAD as substrate. kcat
CC         is 906 sec(-1) for phosphatase activity with fructose
CC         1,6-bisphosphate and NADP as substrates. kcat is 1007 sec(-1) for
CC         phosphatase activity with NADPH as substrate.
CC         {ECO:0000269|PubMed:16192277};
CC       Temperature dependence:
CC         Optimum temperature is 100 degrees Celsius for phosphatase and kinase
CC         activities. Both are inactive below 60 degrees Celsius.
CC         {ECO:0000269|PubMed:16192277};
CC   -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:16192277}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00361}.
CC   -!- MISCELLANEOUS: The phosphatase is inert toward the substrates of NAD
CC       kinase (NAD, NADH, ATP, and poly(P)). This demonstrates that the
CC       phosphatase activity never interferes with the NAD kinase activity by
CC       degrading its substrates. {ECO:0000305|PubMed:16192277}.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the inositol
CC       monophosphatase superfamily. {ECO:0000305}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the NAD kinase
CC       family. {ECO:0000305}.
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DR   EMBL; L77117; AAB98922.1; -; Genomic_DNA.
DR   PIR; E64414; E64414.
DR   AlphaFoldDB; Q58327; -.
DR   SMR; Q58327; -.
DR   STRING; 243232.MJ_0917; -.
DR   PaxDb; 243232-MJ_0917; -.
DR   EnsemblBacteria; AAB98922; AAB98922; MJ_0917.
DR   KEGG; mja:MJ_0917; -.
DR   eggNOG; arCOG01348; Archaea.
DR   HOGENOM; CLU_445249_0_0_2; -.
DR   InParanoid; Q58327; -.
DR   PhylomeDB; Q58327; -.
DR   BioCyc; MetaCyc:MONOMER-21978; -.
DR   BRENDA; 2.7.1.23; 3260.
DR   BRENDA; 3.1.3.108; 3260.
DR   BRENDA; 3.1.3.11; 3260.
DR   SABIO-RK; Q58327; -.
DR   Proteomes; UP000000805; Chromosome.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR   GO; GO:0042132; F:fructose 1,6-bisphosphate 1-phosphatase activity; IEA:RHEA.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0051287; F:NAD binding; IDA:UniProtKB.
DR   GO; GO:0003951; F:NAD+ kinase activity; IDA:UniProtKB.
DR   GO; GO:0019178; F:NADP phosphatase activity; IDA:UniProtKB.
DR   GO; GO:0102757; F:NADPH phosphatase activity; IEA:RHEA.
DR   GO; GO:0006553; P:lysine metabolic process; IEA:InterPro.
DR   GO; GO:0019674; P:NAD metabolic process; IEA:InterPro.
DR   GO; GO:0006741; P:NADP biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   CDD; cd01515; Arch_FBPase_1; 1.
DR   Gene3D; 3.40.190.80; -; 1.
DR   Gene3D; 3.30.540.10; Fructose-1,6-Bisphosphatase, subunit A, domain 1; 1.
DR   HAMAP; MF_00361; NAD_kinase; 1.
DR   InterPro; IPR017438; ATP-NAD_kinase_N.
DR   InterPro; IPR017437; ATP-NAD_kinase_PpnK-typ_C.
DR   InterPro; IPR021175; Bifunctional_PpnK_predicted.
DR   InterPro; IPR020583; Inositol_monoP_metal-BS.
DR   InterPro; IPR000760; Inositol_monophosphatase-like.
DR   InterPro; IPR016064; NAD/diacylglycerol_kinase_sf.
DR   InterPro; IPR002504; NADK.
DR   PANTHER; PTHR20275:SF43; BIFUNCTIONAL NADP PHOSPHATASE_NAD KINASE; 1.
DR   PANTHER; PTHR20275; NAD KINASE; 1.
DR   Pfam; PF00459; Inositol_P; 2.
DR   Pfam; PF01513; NAD_kinase; 1.
DR   Pfam; PF20143; NAD_kinase_C; 1.
DR   PIRSF; PIRSF036641; Bifunctional_PpnK_predicted; 1.
DR   PRINTS; PR00377; IMPHPHTASES.
DR   SUPFAM; SSF56655; Carbohydrate phosphatase; 1.
DR   SUPFAM; SSF111331; NAD kinase/diacylglycerol kinase-like; 1.
DR   PROSITE; PS00629; IMP_1; 1.
PE   1: Evidence at protein level;
KW   ATP-binding; Cytoplasm; Direct protein sequencing; Hydrolase; Kinase;
KW   Magnesium; Metal-binding; Multifunctional enzyme; NAD; NADP;
KW   Nucleotide-binding; Reference proteome; Transferase.
FT   CHAIN           1..574
FT                   /note="Bifunctional NADP phosphatase/NAD kinase"
FT                   /id="PRO_0000120700"
FT   REGION          1..297
FT                   /note="NADP phosphatase"
FT                   /evidence="ECO:0000305|PubMed:16192277"
FT   REGION          302..574
FT                   /note="NAD kinase"
FT                   /evidence="ECO:0000305|PubMed:16192277"
FT   ACT_SITE        362
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00361"
FT   BINDING         69
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q57573"
FT   BINDING         87
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q57573"
FT   BINDING         87
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q57573"
FT   BINDING         89
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q57573"
FT   BINDING         90
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q57573"
FT   BINDING         243
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q57573"
FT   BINDING         362..363
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00361"
FT   BINDING         367
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00361"
FT   BINDING         436..437
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00361"
FT   BINDING         447
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00361"
FT   BINDING         464
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00361"
FT   BINDING         466
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00361"
FT   BINDING         477..482
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00361"
SQ   SEQUENCE   574 AA;  64119 MW;  89A1AF944BD99DB1 CRC64;
     MVIMEGFKIA MKVIDEIDKK IKPLIGWEKA DEVVKIGADG TPTKRIDVIA ENMAINILEK
     FSGGILISEE IGLKVVGDEL EYIFILDPID GTYNALKSIP IYSTSIAVAK IKGEDKKLIR
     ENINNIDWIK SFIANKYTIN DLYVGIVKNL ATGDLYYAIK GEGSFLEKDG EKIKIETKNI
     KDLKEASVGL FVYGLSNDLL EFLKERKVRR VRLFGSMALE MCYVVSGALD AYINVNENSR
     LCDIAGAYVI CREGNAIVTN KNGKPLNMKL HLMERTSLIV SNKYLHKKLI ALFGNRWIIK
     PVKFGIVVRE DKEEAINLAI EICKYLKDKN IPFCVEDFLR ERVGGDKFDI SAISHIIAIG
     GDGTILRASR LVNGETIPII AVNMGKVGFL AEFCKDEVFE IIDKVIYGEY EIEKRSKLSC
     KIIKDNRVIK TPSALNEMVV ITKNPAKILE FDVYVNDTLV ENVRADGIIV STPTGSTAYS
     LSAGGPIVEP NVDCFIISPI CPFKLSSRPL VISASNRIKL KLKLEKPALL VIDGSVEYEI
     NKDDELIFEK SDSYAYFVKG QSFYNKLSRC LGIK
//