ID   THIDN_METJA             Reviewed;         417 AA.
AC   Q57688;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   25-JAN-2012, sequence version 2.
DT   27-MAR-2024, entry version 113.
DE   RecName: Full=Bifunctional thiamine biosynthesis protein ThiDN;
DE   Includes:
DE     RecName: Full=Hydroxymethylpyrimidine/phosphomethylpyrimidine kinase;
DE              EC=2.7.1.49 {ECO:0000250|UniProtKB:P76422};
DE              EC=2.7.4.7 {ECO:0000250|UniProtKB:P76422};
DE     AltName: Full=Hydroxymethylpyrimidine kinase;
DE              Short=HMP kinase;
DE     AltName: Full=Hydroxymethylpyrimidine phosphate kinase;
DE              Short=HMP-P kinase;
DE              Short=HMP-phosphate kinase;
DE              Short=HMPP kinase;
DE   Includes:
DE     RecName: Full=Thiamine-phosphate synthase ThiN;
DE              Short=TP synthase;
DE              Short=TPS;
DE              EC=2.5.1.3;
DE     AltName: Full=Thiamine-phosphate pyrophosphorylase;
DE              Short=TMP pyrophosphorylase;
DE              Short=TMP-PPase;
GN   Name=thiDN; OrderedLocusNames=MJ0236;
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   X-RAY CRYSTALLOGRAPHY (2.03 ANGSTROMS) OF 236-416.
RG   New York structural genomix research consortium (NYSGXRC);
RT   "Crystal structure of the C-terminal domain of protein MJ0236
RT   (Y236_METJA).";
RL   Submitted (FEB-2009) to the PDB data bank.
CC   -!- FUNCTION: Catalyzes the phosphorylation of hydroxymethylpyrimidine
CC       phosphate (HMP-P) to HMP-PP, and of HMP to HMP-P.
CC       {ECO:0000250|UniProtKB:P76422}.
CC   -!- FUNCTION: Condenses 4-methyl-5-(beta-hydroxyethyl)thiazole
CC       monophosphate (THZ-P) and 4-amino-5-hydroxymethyl pyrimidine
CC       pyrophosphate (HMP-PP) to form thiamine monophosphate (TMP).
CC       {ECO:0000250|UniProtKB:Q9WZP7}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=4-amino-5-hydroxymethyl-2-methylpyrimidine + ATP = 4-amino-2-
CC         methyl-5-(phosphooxymethyl)pyrimidine + ADP + H(+);
CC         Xref=Rhea:RHEA:23096, ChEBI:CHEBI:15378, ChEBI:CHEBI:16892,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:58354, ChEBI:CHEBI:456216;
CC         EC=2.7.1.49; Evidence={ECO:0000250|UniProtKB:P76422};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine + ATP = 4-
CC         amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + ADP;
CC         Xref=Rhea:RHEA:19893, ChEBI:CHEBI:30616, ChEBI:CHEBI:57841,
CC         ChEBI:CHEBI:58354, ChEBI:CHEBI:456216; EC=2.7.4.7;
CC         Evidence={ECO:0000250|UniProtKB:P76422};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl
CC         phosphate + 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + 2
CC         H(+) = CO2 + diphosphate + thiamine phosphate; Xref=Rhea:RHEA:47844,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:33019,
CC         ChEBI:CHEBI:37575, ChEBI:CHEBI:57841, ChEBI:CHEBI:62899; EC=2.5.1.3;
CC         Evidence={ECO:0000250|UniProtKB:Q9WZP7};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-(2-carboxy-4-methylthiazol-5-yl)ethyl phosphate + 4-amino-2-
CC         methyl-5-(diphosphooxymethyl)pyrimidine + 2 H(+) = CO2 + diphosphate
CC         + thiamine phosphate; Xref=Rhea:RHEA:47848, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16526, ChEBI:CHEBI:33019, ChEBI:CHEBI:37575,
CC         ChEBI:CHEBI:57841, ChEBI:CHEBI:62890; EC=2.5.1.3;
CC         Evidence={ECO:0000250|UniProtKB:Q9WZP7};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + 4-methyl-
CC         5-(2-phosphooxyethyl)-thiazole + H(+) = diphosphate + thiamine
CC         phosphate; Xref=Rhea:RHEA:22328, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:33019, ChEBI:CHEBI:37575, ChEBI:CHEBI:57841,
CC         ChEBI:CHEBI:58296; EC=2.5.1.3;
CC         Evidence={ECO:0000250|UniProtKB:Q9WZP7};
CC   -!- PATHWAY: Cofactor biosynthesis; thiamine diphosphate biosynthesis; 4-
CC       amino-2-methyl-5-diphosphomethylpyrimidine from 5-amino-1-(5-phospho-D-
CC       ribosyl)imidazole.
CC   -!- PATHWAY: Cofactor biosynthesis; thiamine diphosphate biosynthesis;
CC       thiamine phosphate from 4-amino-2-methyl-5-diphosphomethylpyrimidine
CC       and 4-methyl-5-(2-phosphoethyl)-thiazole: step 1/1.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the ThiD family.
CC       {ECO:0000305}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the ThiN family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAB98222.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; L77117; AAB98222.1; ALT_INIT; Genomic_DNA.
DR   PIR; E64329; E64329.
DR   RefSeq; WP_064496432.1; NC_000909.1.
DR   PDB; 2PHP; X-ray; 2.03 A; A/B/D/E=236-416.
DR   PDBsum; 2PHP; -.
DR   AlphaFoldDB; Q57688; -.
DR   SMR; Q57688; -.
DR   STRING; 243232.MJ_0236; -.
DR   PaxDb; 243232-MJ_0236; -.
DR   EnsemblBacteria; AAB98222; AAB98222; MJ_0236.
DR   GeneID; 1451089; -.
DR   KEGG; mja:MJ_0236; -.
DR   eggNOG; arCOG00020; Archaea.
DR   HOGENOM; CLU_035788_0_0_2; -.
DR   InParanoid; Q57688; -.
DR   OrthoDB; 43786at2157; -.
DR   UniPathway; UPA00060; UER00141.
DR   EvolutionaryTrace; Q57688; -.
DR   Proteomes; UP000000805; Chromosome.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0008902; F:hydroxymethylpyrimidine kinase activity; IBA:GO_Central.
DR   GO; GO:0008972; F:phosphomethylpyrimidine kinase activity; IBA:GO_Central.
DR   GO; GO:0004789; F:thiamine-phosphate diphosphorylase activity; IEA:UniProtKB-EC.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0009228; P:thiamine biosynthetic process; IBA:GO_Central.
DR   GO; GO:0009229; P:thiamine diphosphate biosynthetic process; IEA:UniProtKB-UniPathway.
DR   CDD; cd01169; HMPP_kinase; 1.
DR   Gene3D; 3.40.1190.20; -; 1.
DR   Gene3D; 3.40.225.10; Class II aldolase/adducin N-terminal domain; 1.
DR   InterPro; IPR036409; Aldolase_II/adducin_N_sf.
DR   InterPro; IPR004399; HMP/HMP-P_kinase_dom.
DR   InterPro; IPR013749; PM/HMP-P_kinase-1.
DR   InterPro; IPR029056; Ribokinase-like.
DR   InterPro; IPR019293; ThiN.
DR   PANTHER; PTHR20858:SF17; HYDROXYMETHYLPYRIMIDINE_PHOSPHOMETHYLPYRIMIDINE KINASE THI20-RELATED; 1.
DR   PANTHER; PTHR20858; PHOSPHOMETHYLPYRIMIDINE KINASE; 1.
DR   Pfam; PF08543; Phos_pyr_kin; 1.
DR   Pfam; PF10120; ThiP_synth; 1.
DR   SUPFAM; SSF53639; AraD/HMP-PK domain-like; 1.
DR   SUPFAM; SSF53613; Ribokinase-like; 1.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; Kinase; Multifunctional enzyme;
KW   Nucleotide-binding; Reference proteome; Thiamine biosynthesis; Transferase.
FT   CHAIN           1..417
FT                   /note="Bifunctional thiamine biosynthesis protein ThiDN"
FT                   /id="PRO_0000106755"
FT   REGION          1..235
FT                   /note="Hydroxymethylpyrimidine/phosphomethylpyrimidine
FT                   kinase"
FT   REGION          236..417
FT                   /note="Thiamine-phosphate synthase"
FT   BINDING         41
FT                   /ligand="4-amino-5-hydroxymethyl-2-methylpyrimidine"
FT                   /ligand_id="ChEBI:CHEBI:16892"
FT                   /evidence="ECO:0000250"
FT   HELIX           240..255
FT                   /evidence="ECO:0007829|PDB:2PHP"
FT   STRAND          269..272
FT                   /evidence="ECO:0007829|PDB:2PHP"
FT   HELIX           279..281
FT                   /evidence="ECO:0007829|PDB:2PHP"
FT   STRAND          282..287
FT                   /evidence="ECO:0007829|PDB:2PHP"
FT   STRAND          289..291
FT                   /evidence="ECO:0007829|PDB:2PHP"
FT   STRAND          295..299
FT                   /evidence="ECO:0007829|PDB:2PHP"
FT   STRAND          303..305
FT                   /evidence="ECO:0007829|PDB:2PHP"
FT   HELIX           309..319
FT                   /evidence="ECO:0007829|PDB:2PHP"
FT   STRAND          327..331
FT                   /evidence="ECO:0007829|PDB:2PHP"
FT   HELIX           335..341
FT                   /evidence="ECO:0007829|PDB:2PHP"
FT   TURN            342..344
FT                   /evidence="ECO:0007829|PDB:2PHP"
FT   STRAND          347..349
FT                   /evidence="ECO:0007829|PDB:2PHP"
FT   HELIX           352..354
FT                   /evidence="ECO:0007829|PDB:2PHP"
FT   HELIX           361..373
FT                   /evidence="ECO:0007829|PDB:2PHP"
FT   STRAND          378..382
FT                   /evidence="ECO:0007829|PDB:2PHP"
FT   STRAND          391..398
FT                   /evidence="ECO:0007829|PDB:2PHP"
FT   HELIX           399..414
FT                   /evidence="ECO:0007829|PDB:2PHP"
SQ   SEQUENCE   417 AA;  47056 MW;  810246AD46805E27 CRC64;
     MVILAIGGYD PTSGAGISAD IKTAHTLGVY CPTITTSVIP QNNKMVYEKF DLPEENIKNQ
     FKAVFEEFDI EYVKTGVLTK PAIDTLLKYI DKYDLKVICD PVLASTTKFS FVDEKLMEKY
     IELFNKSFLI TPNKEEYKKI MEFIKNNNLM IRNDLYILAT GIDDILMKNF KPIKTFKGFR
     VDKEVHGTGC VYSTAITAFL SKGYDLEEAI KEAKRFVLSS VIYAKKSKFG YNSNPTYINK
     EKVIKNLSYA IYLLKKMNFT LIPEVGSNIA ESLPFPKDFK DVAALTGRII KNKLGGFYIV
     GDIEFGASEH IAKIILSASK FNPEIRACMN IKYDGGLIKL LKDKFAVSSF DRKEEPPNVS
     TMEWGTKIAC EKFGGVPDII YDRGGEGKEP MIRVLGRDAI EVVKKVEVIQ KIYNTLM
//