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Protein

Thiamine biosynthetic bifunctional enzyme

Gene

THI6

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Protein inferred from homologyi

Functioni

Essential for thiamine biosynthesis. The kinase activity is involved in the salvage synthesis of TH-P from the thiazole.
Condenses 4-methyl-5-(beta-hydroxyethyl)thiazole monophosphate (THZ-P) and 2-methyl-4-amino-5-hydroxymethyl pyrimidine pyrophosphate (HMP-PP) to form thiamine monophosphate (TMP).By similarity

Catalytic activityi

2-methyl-4-amino-5-hydroxymethylpyrimidine diphosphate + 4-methyl-5-(2-phosphono-oxyethyl)thiazole = diphosphate + thiamine phosphate.
ATP + 4-methyl-5-(2-hydroxyethyl)thiazole = ADP + 4-methyl-5-(2-phosphonooxyethyl)thiazole.

Cofactori

Mg2+By similarityNote: Binds 1 Mg2+ ion per subunit.By similarity

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei75 – 751HMP-PPBy similarity
Metal bindingi76 – 761MagnesiumBy similarity
Metal bindingi95 – 951MagnesiumBy similarity
Binding sitei114 – 1141HMP-PPBy similarity
Binding sitei146 – 1461HMP-PPBy similarity
Binding sitei181 – 1811THZ-P; via amide nitrogenBy similarity
Binding sitei290 – 29014-methyl-5-(2-hydroxyethyl)thiazole; via amide nitrogenBy similarity
Binding sitei365 – 3651ATPBy similarity
Binding sitei415 – 4151ATPBy similarity
Binding sitei462 – 46214-methyl-5-(2-hydroxyethyl)thiazole; via amide nitrogenBy similarity
Active sitei465 – 4651Proton acceptor; for hydroxyethylthiazole kinase activityBy similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. hydroxyethylthiazole kinase activity Source: SGD
  3. metal ion binding Source: UniProtKB-KW
  4. thiamine-phosphate diphosphorylase activity Source: SGD

GO - Biological processi

  1. thiamine biosynthetic process Source: SGD
  2. thiamine diphosphate biosynthetic process Source: UniProtKB-UniPathway
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Biological processi

Thiamine biosynthesis

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:YPL214C-MONOMER.
YEAST:YPL214C-MONOMER.
UniPathwayiUPA00060; UER00139.
UPA00060; UER00141.

Names & Taxonomyi

Protein namesi
Recommended name:
Thiamine biosynthetic bifunctional enzyme
Including the following 2 domains:
Thiamine-phosphate synthase (EC:2.5.1.3)
Short name:
TP synthase
Short name:
TPS
Alternative name(s):
Thiamine-phosphate pyrophosphorylase
Short name:
TMP pyrophosphorylase
Short name:
TMP-PPase
Hydroxyethylthiazole kinase (EC:2.7.1.50)
Alternative name(s):
4-methyl-5-beta-hydroxyethylthiazole kinase
Short name:
TH kinase
Short name:
THZ kinase
Gene namesi
Name:THI6
Ordered Locus Names:YPL214C
OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Taxonomic identifieri559292 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
ProteomesiUP000002311: Chromosome XVI

Organism-specific databases

CYGDiYPL214c.
SGDiS000006135. THI6.

Subcellular locationi

GO - Cellular componenti

  1. cytosol Source: SGD
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 540540Thiamine biosynthetic bifunctional enzymePRO_0000157090Add
BLAST

Proteomic databases

MaxQBiP41835.
PaxDbiP41835.

Expressioni

Gene expression databases

GenevestigatoriP41835.

Interactioni

Subunit structurei

Homooctamer.

Protein-protein interaction databases

BioGridi35971. 47 interactions.
DIPiDIP-1666N.
IntActiP41835. 1 interaction.
MINTiMINT-403731.
STRINGi4932.YPL214C.

Structurei

3D structure databases

ProteinModelPortaliP41835.
SMRiP41835. Positions 3-536.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 238238Thiamine-phosphate synthaseAdd
BLAST
Regioni43 – 475HMP-PP bindingBy similarity
Regioni143 – 1453THZ-P bindingBy similarity
Regioni209 – 2102THZ-P bindingBy similarity
Regioni239 – 540302Hydroxyethylthiazole kinaseAdd
BLAST

Sequence similaritiesi

In the N-terminal section; belongs to the thiamine-phosphate synthase family.Curated
In the C-terminal section; belongs to the Thz kinase family.Curated

Phylogenomic databases

eggNOGiCOG0352.
HOGENOMiHOG000214306.
InParanoidiP41835.
KOiK14154.
OMAiNLVVQNF.
OrthoDBiEOG7KDFMZ.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
3.40.1190.20. 1 hit.
HAMAPiMF_00097. TMP_synthase.
InterProiIPR013785. Aldolase_TIM.
IPR000417. Hyethyz_kinase.
IPR029056. Ribokinase-like.
IPR022998. ThiaminP_synth_SF.
IPR003733. TMP_synthase.
[Graphical view]
PfamiPF02110. HK. 1 hit.
PF02581. TMP-TENI. 1 hit.
[Graphical view]
PRINTSiPR01099. HYETHTZKNASE.
SUPFAMiSSF51391. SSF51391. 1 hit.
SSF53613. SSF53613. 1 hit.
TIGRFAMsiTIGR00693. thiE. 1 hit.
TIGR00694. thiM. 1 hit.

Sequencei

Sequence statusi: Complete.

P41835-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVFTKEEVDY SLYLVTDSTM LPPGTTLCSQ VEAGLKNGVT LVQIREKDIE
60 70 80 90 100
TKNFVAEALE VQKICKKYNV PLIINDRIDV AMAIDADGVH VGQDDMPIPM
110 120 130 140 150
VRKLLGPSKI LGWSVGKPSE VETLAKWGPD MVDYIGVGTL FPTSTKKNPK
160 170 180 190 200
KSPMGPQGAI AILDALEEFK ATWCRTVGIG GLHPDNIQRV LCQCVASNGK
210 220 230 240 250
RSLDGISLVS DIMAAPDACA ATKRLRGLLD ATRYQFVECE LNNTFPTTTS
260 270 280 290 300
IQNVISQVSN NRPLVQHITN KVHQNFGANV TLALGSSPIM SEIESEVSEL
310 320 330 340 350
ARIPNASLLL NTGSVAPIEM LKAAINAYNE VNRPITFDPV GYSATETRLC
360 370 380 390 400
LNNTLLTYGQ FACIKGNCSE ILSLAKLNNH KMKGVDSSSG KTNIDTLVRA
410 420 430 440 450
TQIVAFQYRT VAVCTGEFDC VADGTFGGEY KLSSGTEGIT AEDLPCVIIE
460 470 480 490 500
DGPIPIMGDI TASGCSLGST IASFIGGLDS TGKLFDAVVG AVLLYKSAGK
510 520 530 540
LASTRCQGSG SFHVELIDAL YQLFHENKPE KWSASLKKFK
Length:540
Mass (Da):58,059
Last modified:November 1, 1995 - v1
Checksum:iF34FA1E0B76E3930
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti370 – 3701E → K in THI6-3; possesses TMP-PPASE activity only.
Natural varianti476 – 4761G → D in THI6-2; both enzyme activities greatly decreased.
Natural varianti510 – 5101G → D in THI6-1; both enzyme activities greatly decreased.

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D31908 Genomic DNA. Translation: BAA06703.1.
Z73570 Genomic DNA. Translation: CAA97929.1.
BK006949 Genomic DNA. Translation: DAA11222.1.
PIRiA55145.
RefSeqiNP_015110.1. NM_001184028.1.

Genome annotation databases

EnsemblFungiiYPL214C; YPL214C; YPL214C.
GeneIDi855887.
KEGGisce:YPL214C.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D31908 Genomic DNA. Translation: BAA06703.1.
Z73570 Genomic DNA. Translation: CAA97929.1.
BK006949 Genomic DNA. Translation: DAA11222.1.
PIRiA55145.
RefSeqiNP_015110.1. NM_001184028.1.

3D structure databases

ProteinModelPortaliP41835.
SMRiP41835. Positions 3-536.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi35971. 47 interactions.
DIPiDIP-1666N.
IntActiP41835. 1 interaction.
MINTiMINT-403731.
STRINGi4932.YPL214C.

Proteomic databases

MaxQBiP41835.
PaxDbiP41835.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblFungiiYPL214C; YPL214C; YPL214C.
GeneIDi855887.
KEGGisce:YPL214C.

Organism-specific databases

CYGDiYPL214c.
SGDiS000006135. THI6.

Phylogenomic databases

eggNOGiCOG0352.
HOGENOMiHOG000214306.
InParanoidiP41835.
KOiK14154.
OMAiNLVVQNF.
OrthoDBiEOG7KDFMZ.

Enzyme and pathway databases

UniPathwayiUPA00060; UER00139.
UPA00060; UER00141.
BioCyciMetaCyc:YPL214C-MONOMER.
YEAST:YPL214C-MONOMER.

Miscellaneous databases

NextBioi980553.

Gene expression databases

GenevestigatoriP41835.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
3.40.1190.20. 1 hit.
HAMAPiMF_00097. TMP_synthase.
InterProiIPR013785. Aldolase_TIM.
IPR000417. Hyethyz_kinase.
IPR029056. Ribokinase-like.
IPR022998. ThiaminP_synth_SF.
IPR003733. TMP_synthase.
[Graphical view]
PfamiPF02110. HK. 1 hit.
PF02581. TMP-TENI. 1 hit.
[Graphical view]
PRINTSiPR01099. HYETHTZKNASE.
SUPFAMiSSF51391. SSF51391. 1 hit.
SSF53613. SSF53613. 1 hit.
TIGRFAMsiTIGR00693. thiE. 1 hit.
TIGR00694. thiM. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Isolation and characterization of the THI6 gene encoding a bifunctional thiamin-phosphate pyrophosphorylase/hydroxyethylthiazole kinase from Saccharomyces cerevisiae."
    Nosaka K., Nishimura H., Kawasaki Y., Tsujihara T., Iwashima A.
    J. Biol. Chem. 269:30510-30516(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: ND5-5A.
  2. "The nucleotide sequence of Saccharomyces cerevisiae chromosome XVI."
    Bussey H., Storms R.K., Ahmed A., Albermann K., Allen E., Ansorge W., Araujo R., Aparicio A., Barrell B.G., Badcock K., Benes V., Botstein D., Bowman S., Brueckner M., Carpenter J., Cherry J.M., Chung E., Churcher C.M.
    , Coster F., Davis K., Davis R.W., Dietrich F.S., Delius H., DiPaolo T., Dubois E., Duesterhoeft A., Duncan M., Floeth M., Fortin N., Friesen J.D., Fritz C., Goffeau A., Hall J., Hebling U., Heumann K., Hilbert H., Hillier L.W., Hunicke-Smith S., Hyman R.W., Johnston M., Kalman S., Kleine K., Komp C., Kurdi O., Lashkari D., Lew H., Lin A., Lin D., Louis E.J., Marathe R., Messenguy F., Mewes H.-W., Mirtipati S., Moestl D., Mueller-Auer S., Namath A., Nentwich U., Oefner P., Pearson D., Petel F.X., Pohl T.M., Purnelle B., Rajandream M.A., Rechmann S., Rieger M., Riles L., Roberts D., Schaefer M., Scharfe M., Scherens B., Schramm S., Schroeder M., Sdicu A.-M., Tettelin H., Urrestarazu L.A., Ushinsky S., Vierendeels F., Vissers S., Voss H., Walsh S.V., Wambutt R., Wang Y., Wedler E., Wedler H., Winnett E., Zhong W.-W., Zollner A., Vo D.H., Hani J.
    Nature 387:103-105(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: ATCC 204508 / S288c.
  3. Cited for: GENOME REANNOTATION.
    Strain: ATCC 204508 / S288c.

Entry informationi

Entry nameiTHI6_YEAST
AccessioniPrimary (citable) accession number: P41835
Secondary accession number(s): D6W3F6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: January 7, 2015
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families
  3. Yeast
    Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
  4. Yeast chromosome XVI
    Yeast (Saccharomyces cerevisiae) chromosome XVI: entries and gene names

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.