NPPNK_METJA
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 03-AUG-2022, entry version 129.
DE RecName: Full=Bifunctional NADP phosphatase/NAD kinase;
DE Includes:
DE RecName: Full=NAD kinase {ECO:0000255|HAMAP-Rule:MF_00361};
DE EC=2.7.1.23 {ECO:0000255|HAMAP-Rule:MF_00361};
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;
DE Short=NADPase;
DE Short=pNPPase;
DE EC=3.1.3.-;
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 -!- 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 -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:16192277};
CC Note=Mg(2+). NAD and pNPPase kinase show maximum activities at 50 and
CC 20 mM magnesium, respectively. {ECO:0000269|PubMed:16192277};
CC -!- ACTIVITY REGULATION: Phosphatase activity is slightly inhibited by ADP,
CC NADPH and ATP, and moderately inhibited by NAD and 5'-AMP. Kinase
CC activity is slightly inhibited by ADP and NADP.
CC {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 1,6-
CC bisphosphate and NADP as substrates. kcat is 1007 sec(-1) for
CC phosphatase activity with NADPH as substrate.;
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 (PubMed:16192277).
CC {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 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 OMA; VIVPICP; -.
DR PhylomeDB; Q58327; -.
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: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:0046855; P:inositol phosphate dephosphorylation; IEA:InterPro.
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 Gene3D; 2.60.200.30; -; 1.
DR Gene3D; 3.40.50.10330; -; 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 Pfam; PF00459; Inositol_P; 2.
DR Pfam; PF01513; NAD_kinase; 1.
DR PIRSF; PIRSF036641; Bifunctional_PpnK_predicted; 1.
DR PRINTS; PR00377; IMPHPHTASES.
DR SUPFAM; SSF111331; SSF111331; 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 REGION 302..574
FT /note="NAD kinase"
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"
FT BINDING 87
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 87
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 90
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 90
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 243
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
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 474
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
