NADR_HAEIN
ID NADR_HAEIN Reviewed; 421 AA.
AC P44308;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Bifunctional NAD biosynthesis protein NadR;
DE Includes:
DE RecName: Full=Nicotinamide mononucleotide adenylyltransferase;
DE Short=NMN adenylyltransferase;
DE Short=NMN-AT;
DE Short=NMNAT;
DE EC=2.7.7.1;
DE AltName: Full=Nicotinamide ribonucleotide adenylyltransferase;
DE AltName: Full=Nicotinamide-nucleotide adenylyltransferase;
DE Includes:
DE RecName: Full=Ribosylnicotinamide kinase;
DE Short=RNK;
DE EC=2.7.1.22;
DE AltName: Full=Nicotinamide riboside kinase;
DE Short=NRK;
DE Short=NmR-K;
GN Name=nadR; OrderedLocusNames=HI_0763;
OS Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Pasteurellales;
OC Pasteurellaceae; Haemophilus.
OX NCBI_TaxID=71421;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 51907 / DSM 11121 / KW20 / Rd;
RX PubMed=7542800; DOI=10.1126/science.7542800;
RA Fleischmann R.D., Adams M.D., White O., Clayton R.A., Kirkness E.F.,
RA Kerlavage A.R., Bult C.J., Tomb J.-F., Dougherty B.A., Merrick J.M.,
RA McKenney K., Sutton G.G., FitzHugh W., Fields C.A., Gocayne J.D.,
RA Scott J.D., Shirley R., Liu L.-I., Glodek A., Kelley J.M., Weidman J.F.,
RA Phillips C.A., Spriggs T., Hedblom E., Cotton M.D., Utterback T.R.,
RA Hanna M.C., Nguyen D.T., Saudek D.M., Brandon R.C., Fine L.D.,
RA Fritchman J.L., Fuhrmann J.L., Geoghagen N.S.M., Gnehm C.L., McDonald L.A.,
RA Small K.V., Fraser C.M., Smith H.O., Venter J.C.;
RT "Whole-genome random sequencing and assembly of Haemophilus influenzae
RT Rd.";
RL Science 269:496-512(1995).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, ALTERNATIVE INITIATION, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=ATCC 51907 / DSM 11121 / KW20 / Rd;
RX PubMed=12446641; DOI=10.1128/jb.184.24.6906-6917.2002;
RA Kurnasov O.V., Polanuyer B.M., Ananta S., Sloutsky R., Tam A., Gerdes S.Y.,
RA Osterman A.L.;
RT "Ribosylnicotinamide kinase domain of NadR protein: identification and
RT implications in NAD biosynthesis.";
RL J. Bacteriol. 184:6906-6917(2002).
RN [3]
RP MUTAGENESIS OF LYS-126; GLY-238; TRP-256; TYR-292; ASP-304 AND ARG-352, AND
RP SUBCELLULAR LOCATION.
RC STRAIN=ATCC 51907 / DSM 11121 / KW20 / Rd;
RX PubMed=15968050; DOI=10.1128/jb.187.13.4410-4420.2005;
RA Merdanovic M., Sauer E., Reidl J.;
RT "Coupling of NAD+ biosynthesis and nicotinamide ribosyl transport:
RT characterization of NadR ribonucleotide kinase mutants of Haemophilus
RT influenzae.";
RL J. Bacteriol. 187:4410-4420(2005).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 57-421 IN COMPLEX WITH NAD, AND
RP SUBUNIT.
RX PubMed=12068016; DOI=10.1074/jbc.m204368200;
RA Singh S.K., Kurnasov O.V., Chen B., Robinson H., Grishin N.V.,
RA Osterman A.L., Zhang H.;
RT "Crystal structure of Haemophilus influenzae NadR protein. A bifunctional
RT enzyme endowed with NMN adenyltransferase and ribosylnicotinimide kinase
RT activities.";
RL J. Biol. Chem. 277:33291-33299(2002).
CC -!- FUNCTION: This enzyme has two activities: nicotinamide mononucleotide
CC (NMN) adenylyltransferase and ribosylnicotinamide (RN) kinase. The RN
CC kinase activity catalyzes the phosphorylation of RN to form
CC nicotinamide ribonucleotide. The NMN adenylyltransferase activity
CC catalyzes the transfer of the AMP moiety of ATP to nicotinamide
CC ribonucleotide to form NAD(+). {ECO:0000269|PubMed:12446641}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + beta-nicotinamide D-ribonucleotide + H(+) = diphosphate
CC + NAD(+); Xref=Rhea:RHEA:21360, ChEBI:CHEBI:14649, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57540; EC=2.7.7.1;
CC Evidence={ECO:0000269|PubMed:12446641};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + beta-nicotinamide D-riboside = ADP + beta-nicotinamide
CC D-ribonucleotide + H(+); Xref=Rhea:RHEA:14017, ChEBI:CHEBI:14649,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15927, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:456216; EC=2.7.1.22;
CC Evidence={ECO:0000269|PubMed:12446641};
CC -!- ACTIVITY REGULATION: Feed-back regulated by NAD. At high levels of NAD
CC the RN kinase activity is inhibited.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.14 mM for NMN {ECO:0000269|PubMed:12446641};
CC -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis [regulation].
CC -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis; NAD(+) from
CC nicotinamide D-ribonucleotide: step 1/1.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:12068016}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15968050};
CC Peripheral membrane protein {ECO:0000269|PubMed:15968050}. Cytoplasm
CC {ECO:0000269|PubMed:15968050}. Note=Found as a soluble cytoplasmic
CC protein as well as a membrane-associated protein. In combination with
CC corepressor (NAD), the cytoplasmic form of NadR would be capable of
CC acting as a transcriptional repressor.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=Long;
CC IsoId=P44308-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P44308-2; Sequence=VSP_040071;
CC -!- MISCELLANEOUS: [Isoform Short]: Shows the same catalytic activity as
CC isoform Long. {ECO:0000305}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the bacterial NMN
CC adenylyltransferase family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the bacterial RNK
CC family. {ECO:0000305}.
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DR EMBL; L42023; AAC22421.1; -; Genomic_DNA.
DR PIR; D64091; D64091.
DR RefSeq; NP_438922.1; NC_000907.1.
DR PDB; 1LW7; X-ray; 2.90 A; A=57-421.
DR PDBsum; 1LW7; -.
DR AlphaFoldDB; P44308; -.
DR SMR; P44308; -.
DR STRING; 71421.HI_0763; -.
DR TCDB; 4.B.1.1.2; the nicotinamide ribonucleoside (nr) uptake permease (pnuc) family.
DR EnsemblBacteria; AAC22421; AAC22421; HI_0763.
DR KEGG; hin:HI_0763; -.
DR PATRIC; fig|71421.8.peg.802; -.
DR eggNOG; COG3172; Bacteria.
DR HOGENOM; CLU_052648_0_1_6; -.
DR OMA; QDPFRYW; -.
DR PhylomeDB; P44308; -.
DR BioCyc; HINF71421:G1GJ1-803-MON; -.
DR BioCyc; MetaCyc:MON-8322; -.
DR SABIO-RK; P44308; -.
DR UniPathway; UPA00253; -.
DR UniPathway; UPA00253; UER00600.
DR EvolutionaryTrace; P44308; -.
DR Proteomes; UP000000579; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0000309; F:nicotinamide-nucleotide adenylyltransferase activity; IBA:GO_Central.
DR GO; GO:0050262; F:ribosylnicotinamide kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0009435; P:NAD biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR CDD; cd02167; NMNAT_NadR; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR Gene3D; 3.40.50.620; -; 1.
DR InterPro; IPR004821; Cyt_trans-like.
DR InterPro; IPR016429; NAD_NadR.
DR InterPro; IPR038727; NadR/Ttd14_AAA_dom.
DR InterPro; IPR006417; NadR_NMN_Atrans.
DR InterPro; IPR041749; NMNAT_NadR.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR Pfam; PF13521; AAA_28; 1.
DR Pfam; PF01467; CTP_transf_like; 1.
DR PIRSF; PIRSF004776; NadR_NMNAT/RNK; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00125; cyt_tran_rel; 1.
DR TIGRFAMs; TIGR01526; nadR_NMN_Atrans; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative initiation; ATP-binding; Cell membrane;
KW Cytoplasm; Kinase; Membrane; Multifunctional enzyme; NAD;
KW Nucleotide-binding; Pyridine nucleotide biosynthesis; Reference proteome;
KW Transferase.
FT CHAIN 1..421
FT /note="Bifunctional NAD biosynthesis protein NadR"
FT /id="PRO_0000096689"
FT REGION 57..224
FT /note="Nicotinamide mononucleotide adenylyltransferase"
FT REGION 225..421
FT /note="Ribosylnicotinamide kinase"
FT BINDING 64..67
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:12068016"
FT BINDING 71
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:12068016"
FT BINDING 98
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:12068016"
FT BINDING 139..152
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:12068016"
FT BINDING 172..174
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:12068016"
FT BINDING 199..201
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:12068016"
FT BINDING 254..256
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:12068016"
FT BINDING 289..292
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:12068016"
FT VAR_SEQ 1..51
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000305"
FT /id="VSP_040071"
FT MUTAGEN 126
FT /note="K->A,T: Significant reduction of RNK activity, also
FT NMN adenylyltransferase activity is impaired."
FT /evidence="ECO:0000269|PubMed:15968050"
FT MUTAGEN 238
FT /note="G->N,S: Complete loss of RNK activity, no effect on
FT NMN adenylyltransferase activity."
FT /evidence="ECO:0000269|PubMed:15968050"
FT MUTAGEN 256
FT /note="W->F: No effect on enzyme activities, but NAD
FT feedback inhibition is almost lost."
FT /evidence="ECO:0000269|PubMed:15968050"
FT MUTAGEN 292
FT /note="Y->I: Almost no effect."
FT /evidence="ECO:0000269|PubMed:15968050"
FT MUTAGEN 304
FT /note="D->C,N,S: Complete loss of RNK activity, no effect
FT on NMN adenylyltransferase activity."
FT /evidence="ECO:0000269|PubMed:15968050"
FT MUTAGEN 352
FT /note="R->A,C,M,N: Complete loss of RNK activity, no effect
FT on NMN adenylyltransferase activity."
FT /evidence="ECO:0000269|PubMed:15968050"
FT STRAND 60..65
FT /evidence="ECO:0007829|PDB:1LW7"
FT HELIX 72..82
FT /evidence="ECO:0007829|PDB:1LW7"
FT STRAND 86..94
FT /evidence="ECO:0007829|PDB:1LW7"
FT HELIX 96..105
FT /evidence="ECO:0007829|PDB:1LW7"
FT HELIX 114..124
FT /evidence="ECO:0007829|PDB:1LW7"
FT TURN 127..131
FT /evidence="ECO:0007829|PDB:1LW7"
FT STRAND 132..138
FT /evidence="ECO:0007829|PDB:1LW7"
FT STRAND 140..142
FT /evidence="ECO:0007829|PDB:1LW7"
FT HELIX 149..162
FT /evidence="ECO:0007829|PDB:1LW7"
FT STRAND 168..171
FT /evidence="ECO:0007829|PDB:1LW7"
FT HELIX 175..177
FT /evidence="ECO:0007829|PDB:1LW7"
FT HELIX 178..184
FT /evidence="ECO:0007829|PDB:1LW7"
FT STRAND 188..190
FT /evidence="ECO:0007829|PDB:1LW7"
FT HELIX 203..208
FT /evidence="ECO:0007829|PDB:1LW7"
FT HELIX 210..216
FT /evidence="ECO:0007829|PDB:1LW7"
FT TURN 219..221
FT /evidence="ECO:0007829|PDB:1LW7"
FT HELIX 222..224
FT /evidence="ECO:0007829|PDB:1LW7"
FT STRAND 227..232
FT /evidence="ECO:0007829|PDB:1LW7"
FT HELIX 238..249
FT /evidence="ECO:0007829|PDB:1LW7"
FT STRAND 253..255
FT /evidence="ECO:0007829|PDB:1LW7"
FT HELIX 260..265
FT /evidence="ECO:0007829|PDB:1LW7"
FT STRAND 266..269
FT /evidence="ECO:0007829|PDB:1LW7"
FT TURN 276..278
FT /evidence="ECO:0007829|PDB:1LW7"
FT HELIX 279..296
FT /evidence="ECO:0007829|PDB:1LW7"
FT STRAND 298..305
FT /evidence="ECO:0007829|PDB:1LW7"
FT HELIX 307..318
FT /evidence="ECO:0007829|PDB:1LW7"
FT HELIX 323..331
FT /evidence="ECO:0007829|PDB:1LW7"
FT STRAND 335..341
FT /evidence="ECO:0007829|PDB:1LW7"
FT HELIX 360..372
FT /evidence="ECO:0007829|PDB:1LW7"
FT HELIX 373..375
FT /evidence="ECO:0007829|PDB:1LW7"
FT STRAND 379..382
FT /evidence="ECO:0007829|PDB:1LW7"
FT HELIX 386..400
FT /evidence="ECO:0007829|PDB:1LW7"
SQ SEQUENCE 421 AA; 49432 MW; D9A4FD4970A6E7E8 CRC64;
MGFTTGREFH PALRMRAKYN AKYLGTKSER EKYFHLAYNK HTQFLRYQEQ IMSKTKEKKV
GVIFGKFYPV HTGHINMIYE AFSKVDELHV IVCSDTVRDL KLFYDSKMKR MPTVQDRLRW
MQQIFKYQKN QIFIHHLVED GIPSYPNGWQ SWSEAVKTLF HEKHFEPSIV FSSEPQDKAP
YEKYLGLEVS LVDPDRTFFN VSATKIRTTP FQYWKFIPKE ARPFFAKTVA ILGGESSGKS
VLVNKLAAVF NTTSAWEYGR EFVFEKLGGD EQAMQYSDYP QMALGHQRYI DYAVRHSHKI
AFIDTDFITT QAFCIQYEGK AHPFLDSMIK EYPFDVTILL KNNTEWVDDG LRSLGSQKQR
QQFQQLLKKL LDKYKVPYIE IESPSYLDRY NQVKAVIEKV LNEEEISELQ NTTFPIKGTS
Q
