Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Thiamine thiazole synthase

Gene

THI4

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in biosynthesis of the thiamine precursor thiazole. Catalyzes the conversion of NAD and glycine to adenosine diphosphate 5-(2-hydroxyethyl)-4-methylthiazole-2-carboxylic acid (ADT), an adenylated thiazole intermediate. The reaction includes an iron-dependent sulfide transfer from a conserved cysteine residue of the protein to a thiazole intermediate. The enzyme can only undergo a single turnover, which suggests it is a suicide enzyme. May have additional roles in adaptation to various stress conditions and in DNA damage tolerance.UniRule annotation7 Publications

Cofactori

Fe cationNote: Binds 1 Fe cation per subunit.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei76 – 761Substrate; via amide nitrogen
Binding sitei105 – 1051Substrate; via amide nitrogen
Binding sitei170 – 1701Substrate; via amide nitrogen and carbonyl oxygen
Binding sitei207 – 2071Substrate
Binding sitei237 – 2371Substrate
Binding sitei291 – 2911Substrate; via amide nitrogen

GO - Molecular functioni

  • ferrous iron binding Source: SGD
  • identical protein binding Source: IntAct
  • oxidoreductase activity Source: InterPro

GO - Biological processi

  • mitochondrial genome maintenance Source: SGD
  • response to stress Source: InterPro
  • thiamine biosynthetic process Source: SGD
  • thiazole biosynthetic process Source: SGD
Complete GO annotation...

Keywords - Biological processi

Thiamine biosynthesis

Keywords - Ligandi

Iron, Metal-binding, NAD

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER3O-153.
YEAST:G3O-30848-MONOMER.
YEAST:MONOMER3O-153.
BRENDAi2.8.1.10. 984.

Names & Taxonomyi

Protein namesi
Recommended name:
Thiamine thiazole synthaseUniRule annotation
Alternative name(s):
Thiazole biosynthetic enzymeUniRule annotation
Gene namesi
Name:THI4UniRule annotation
Synonyms:ESP35, MOL1
Ordered Locus Names:YGR144W
ORF Names:G6620
OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Taxonomic identifieri559292 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
Proteomesi
  • UP000002311 Componenti: Chromosome VII

Organism-specific databases

EuPathDBiFungiDB:YGR144W.
SGDiS000003376. THI4.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: SGD
  • nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi97 – 971E → A or Q: No activity. 1 Publication
Mutagenesisi200 – 2001H → N: Partially active, trapping the enzyme at an advanced intermediate, just before the sulfide transfer reaction. 1 Publication
Mutagenesisi204 – 2041C → A: Partially active, trapping the enzyme at an advanced intermediate, just before the sulfide transfer reaction. 1 Publication
Mutagenesisi205 – 2051C → S: Partially active, with very weak activity toward NAD. 1 Publication
Mutagenesisi207 – 2071D → A: No activity. 1 Publication
Mutagenesisi237 – 2371H → A or N: No activity. 1 Publication
Mutagenesisi238 – 2381D → A: Partially active, with very weak activity toward NAD. 1 Publication
Mutagenesisi301 – 3011R → A or Q: No activity. 1 Publication
Mutagenesisi304 – 3041P → A: No activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 326326Thiamine thiazole synthasePRO_0000034058Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei205 – 20512,3-didehydroalanine (Cys)

Post-translational modificationi

During the catalytic reaction, a sulfide is transferred from Cys-205 to a reaction intermediate, generating a dehydroalanine residue.

Expressioni

Inductioni

Repressed by thiamine.2 Publications

Interactioni

Subunit structurei

Homooctamer.UniRule annotation1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-19215,EBI-19215

GO - Molecular functioni

  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi33392. 13 interactions.
DIPiDIP-1703N.
IntActiP32318. 5 interactions.
MINTiMINT-408091.

Structurei

Secondary structure

1
326
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi17 – 193Combined sources
Turni25 – 295Combined sources
Helixi45 – 6218Combined sources
Beta strandi65 – 717Combined sources
Helixi75 – 8713Combined sources
Beta strandi93 – 964Combined sources
Beta strandi98 – 1014Combined sources
Turni104 – 1074Combined sources
Beta strandi116 – 1194Combined sources
Turni120 – 1223Combined sources
Helixi123 – 1286Combined sources
Beta strandi137 – 1437Combined sources
Helixi145 – 15713Combined sources
Beta strandi162 – 1654Combined sources
Beta strandi168 – 17811Combined sources
Beta strandi180 – 1834Combined sources
Beta strandi185 – 1939Combined sources
Helixi194 – 1974Combined sources
Turni198 – 2014Combined sources
Beta strandi209 – 2146Combined sources
Beta strandi220 – 2223Combined sources
Beta strandi230 – 2334Combined sources
Beta strandi239 – 2413Combined sources
Helixi244 – 2529Combined sources
Helixi266 – 27611Combined sources
Beta strandi286 – 2883Combined sources
Helixi291 – 2977Combined sources
Helixi307 – 32519Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3FPZX-ray1.82A/B1-326[»]
4Y4LX-ray2.00A/B/C/D1-326[»]
ProteinModelPortaliP32318.
SMRiP32318. Positions 16-326.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP32318.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni97 – 982Substrate binding
Regioni301 – 3033Substrate binding

Sequence similaritiesi

Belongs to the THI4 family.UniRule annotation

Phylogenomic databases

HOGENOMiHOG000106048.
InParanoidiP32318.
KOiK03146.
OMAiGIVMNWT.
OrthoDBiEOG7ZKSN0.

Family and domain databases

Gene3Di3.50.50.60. 1 hit.
HAMAPiMF_03158. THI4.
InterProiIPR023753. FAD/NAD-binding_dom.
IPR027495. Sti35.
IPR002922. Thi4_fam.
[Graphical view]
SUPFAMiSSF51905. SSF51905. 1 hit.
TIGRFAMsiTIGR00292. TIGR00292. 1 hit.

Sequencei

Sequence statusi: Complete.

P32318-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSATSTATST SASQLHLNST PVTHCLSDIV KKEDWSDFKF APIRESTVSR
60 70 80 90 100
AMTSRYFKDL DKFAVSDVII VGAGSSGLSA AYVIAKNRPD LKVCIIESSV
110 120 130 140 150
APGGGSWLGG QLFSAMVMRK PAHLFLQELE IPYEDEGDYV VVKHAALFIS
160 170 180 190 200
TVLSKVLQLP NVKLFNATCV EDLVTRPPTE KGEVTVAGVV TNWTLVTQAH
210 220 230 240 250
GTQCCMDPNV IELAGYKNDG TRDLSQKHGV ILSTTGHDGP FGAFCAKRIV
260 270 280 290 300
DIDQNQKLGG MKGLDMNHAE HDVVIHSGAY AGVDNMYFAG MEVAELDGLN
310 320
RMGPTFGAMA LSGVHAAEQI LKHFAA
Length:326
Mass (Da):34,991
Last modified:October 1, 1993 - v1
Checksum:i843790F2CE00BF02
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X61669 Genomic DNA. Translation: CAA43843.1.
Z72929 Genomic DNA. Translation: CAA97157.1.
Z72930 Genomic DNA. Translation: CAA97159.1.
X85807 Genomic DNA. Translation: CAA59802.1.
BK006941 Genomic DNA. Translation: DAA08235.1.
PIRiS25321.
RefSeqiNP_011660.1. NM_001181273.1.

Genome annotation databases

EnsemblFungiiYGR144W; YGR144W; YGR144W.
GeneIDi853047.
KEGGisce:YGR144W.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X61669 Genomic DNA. Translation: CAA43843.1.
Z72929 Genomic DNA. Translation: CAA97157.1.
Z72930 Genomic DNA. Translation: CAA97159.1.
X85807 Genomic DNA. Translation: CAA59802.1.
BK006941 Genomic DNA. Translation: DAA08235.1.
PIRiS25321.
RefSeqiNP_011660.1. NM_001181273.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3FPZX-ray1.82A/B1-326[»]
4Y4LX-ray2.00A/B/C/D1-326[»]
ProteinModelPortaliP32318.
SMRiP32318. Positions 16-326.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi33392. 13 interactions.
DIPiDIP-1703N.
IntActiP32318. 5 interactions.
MINTiMINT-408091.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblFungiiYGR144W; YGR144W; YGR144W.
GeneIDi853047.
KEGGisce:YGR144W.

Organism-specific databases

EuPathDBiFungiDB:YGR144W.
SGDiS000003376. THI4.

Phylogenomic databases

HOGENOMiHOG000106048.
InParanoidiP32318.
KOiK03146.
OMAiGIVMNWT.
OrthoDBiEOG7ZKSN0.

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER3O-153.
YEAST:G3O-30848-MONOMER.
YEAST:MONOMER3O-153.
BRENDAi2.8.1.10. 984.

Miscellaneous databases

EvolutionaryTraceiP32318.
PROiP32318.

Family and domain databases

Gene3Di3.50.50.60. 1 hit.
HAMAPiMF_03158. THI4.
InterProiIPR023753. FAD/NAD-binding_dom.
IPR027495. Sti35.
IPR002922. Thi4_fam.
[Graphical view]
SUPFAMiSSF51905. SSF51905. 1 hit.
TIGRFAMsiTIGR00292. TIGR00292. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "MOL1, a Saccharomyces cerevisiae gene that is highly expressed in early stationary phase during growth on molasses."
    Praekelt U.M., Meacock P.A.
    Yeast 8:699-710(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "The nucleotide sequence of Saccharomyces cerevisiae chromosome VII."
    Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J., Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M., Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L., Coblenz A., Coglievina M., Coissac E.
    , Defoor E., Del Bino S., Delius H., Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P., Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M., Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A., Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K., Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P., Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E., Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K., Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A., Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S., Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M., Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C., Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M., Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M., Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y., Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L., Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D., Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F., Zaccaria P., Zimmermann M., Zollner A., Kleine K.
    Nature 387:81-84(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.
  4. "Neurospora crassa CyPBP37: a cytosolic stress protein that is able to replace yeast Thi4p function in the synthesis of vitamin B1."
    Faou P., Tropschug M.
    J. Mol. Biol. 344:1147-1157(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 3-10 AND 12-16, FUNCTION, SUBCELLULAR LOCATION, INDUCTION.
  5. "The sequence of a 27 kb segment on the right arm of chromosome VII from Saccharomyces cerevisiae reveals MOL1, NAT2, RPL30B, RSR1, CYS4, PEM1/CHO2, NSR1 genes and ten new open reading frames."
    Skala J., Nawrocki A., Goffeau A.
    Yeast 11:1421-1427(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 205-326.
    Strain: ATCC 204508 / S288c.
  6. "Regulation of THI4 (MOL1), a thiamine-biosynthetic gene of Saccharomyces cerevisiae."
    Praekelt U.M., Byrne K.L., Meacock P.A.
    Yeast 10:481-490(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: THIAMINE REGULATION.
  7. "Dual role for the yeast THI4 gene in thiamine biosynthesis and DNA damage tolerance."
    Machado C.R., Praekelt U.M., de Oliveira R.C., Barbosa A.C., Byrne K.L., Meacock P.A., Menck C.F.
    J. Mol. Biol. 273:114-121(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN DNA DAMAGE TOLERANCE.
  8. "Thiamin biosynthesis in eukaryotes: characterization of the enzyme-bound product of thiazole synthase from Saccharomyces cerevisiae and its implications in thiazole biosynthesis."
    Chatterjee A., Jurgenson C.T., Schroeder F.C., Ealick S.E., Begley T.P.
    J. Am. Chem. Soc. 128:7158-7159(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "Pdc2 coordinates expression of the THI regulon in the yeast Saccharomyces cerevisiae."
    Mojzita D., Hohmann S.
    Mol. Genet. Genomics 276:147-161(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, INDUCTION.
  10. "Heat stress promotes mitochondrial instability and oxidative responses in yeast deficient in thiazole biosynthesis."
    Medina-Silva R., Barros M.P., Galhardo R.S., Netto L.E., Colepicolo P., Menck C.F.
    Res. Microbiol. 157:275-281(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN STRESS TOLERANCE.
  11. "Biosynthesis of thiamin thiazole in eukaryotes: conversion of NAD to an advanced intermediate."
    Chatterjee A., Jurgenson C.T., Schroeder F.C., Ealick S.E., Begley T.P.
    J. Am. Chem. Soc. 129:2914-2922(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF GLU-97; HIS-200; CYS-204; CYS-205; ASP-207; HIS-237; ASP-238; ARG-301 AND PRO-304.
  12. "Biosynthesis of the thiamin-thiazole in eukaryotes: identification of a thiazole tautomer intermediate."
    Chatterjee A., Schroeder F.C., Jurgenson C.T., Ealick S.E., Begley T.P.
    J. Am. Chem. Soc. 130:11394-11398(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  13. "Structural insights into the function of the thiamin biosynthetic enzyme Thi4 from Saccharomyces cerevisiae."
    Jurgenson C.T., Chatterjee A., Begley T.P., Ealick S.E.
    Biochemistry 45:11061-11070(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.82 ANGSTROMS) IN COMPLEX WITH ADT, SUBUNIT.
  14. "Saccharomyces cerevisiae THI4p is a suicide thiamine thiazole synthase."
    Chatterjee A., Abeydeera N.D., Bale S., Pai P.J., Dorrestein P.C., Russell D.H., Ealick S.E., Begley T.P.
    Nature 478:542-546(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.82 ANGSTROMS), IRON-BINDING, FUNCTION, DIDEHYDROALANINE FORMATION AT CYS-205.

Entry informationi

Entry nameiTHI4_YEAST
AccessioniPrimary (citable) accession number: P32318
Secondary accession number(s): D6VUS4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: October 1, 1993
Last modified: June 8, 2016
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

Miscellaneous

Expressed at high levels in the early stationary phase of batch cultures growing on molasses, an industrial medium.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  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 VII
    Yeast (Saccharomyces cerevisiae) chromosome VII: entries and gene names

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 one 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.