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
//
