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Protein

Glutathione S-transferase gliG

Gene

gliG

Organism
Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100) (Aspergillus fumigatus)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Glutathione S-transferase; part of the gene cluster that mediates the biosynthesis of gliotoxin, a member of the epipolythiodioxopiperazine (ETP) class of toxins characterized by a disulfide bridged cyclic dipeptide (PubMed:15979823, PubMed:21612254). The first step in gliotoxin biosynthesis is the condensation of serine and phenylalanine to form the cyclo-L-phenylalanyl-L-serine diketopiperazine (DKP) by the NRPS gliP (PubMed:17154540, PubMed:21612254). GliP is also able to produce the DKP cyclo-L-tryptophanyl-L-serine, suggesting that the substrate specificity of the first adenylation (A) domain in gliP is sufficiently relaxed to accommodate both L-Phe and L-Trp (PubMed:23434416). The cytochrome P450 monooxygenase gliC has been shown to catalyze the subsequent hydroxylation of the alpha-carbon of L-Phe in cyclo-L-phenylalanyl-L-serine whereas the second cytochrome P450 enzyme, gliF, is presumably involved in the modification of the DKP side chain (PubMed:24039048, PubMed:23434416). The glutathione S-transferase (GST) gliG then forms a bis-glutathionylated biosynthetic intermediate which is responsible for the sulfurization of gliotoxin (PubMed:21513890, PubMed:21749092). This bis-glutathionylated intermediate is subsequently processed by the gamma-glutamyl cyclotransferase gliK to remove both gamma-glutamyl moieties (PubMed:22903976, PubMed:24039048). Subsequent processing via gliI yields a biosynthetic intermediate, which is N-methylated via the N-methyltransferase gliN, before the gliotoxin oxidoreductase gliT-mediated disulfide bridge closure (PubMed:20548963, PubMed:22936680, PubMed:24039048, PubMed:25062268). GliN-mediated amide methylation confers stability to ETP, damping the spontaneous formation of tri- and tetrasulfides (PubMed:25062268). Intracellular dithiol gliotoxin oxidized by gliT is subsequently effluxed by gliA (PubMed:26150413). Gliotoxin contributes to pathogenesis during invasive aspergillosis (PubMed:17601876, PubMed:18199036). In macrophages and neutrophils, gliotoxin showed inhibition of various different cell functions including cytokine production, antigen presentation, phagocytosis, and production of reactive oxygen species (PubMed:17601876).11 Publications

Catalytic activityi

RX + glutathione = HX + R-S-glutathione.2 Publications

Pathwayi: Mycotoxin biosynthesis

This protein is involved in Mycotoxin biosynthesis.2 Publications
View all proteins of this organism that are known to be involved in Mycotoxin biosynthesis.

GO - Molecular functioni

  • glutathione transferase activity Source: ASPGD

GO - Biological processi

  • gliotoxin biosynthetic process Source: ASPGD
  • mycotoxin biosynthetic process Source: ASPGD
  • pathogenesis Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Biological processi

Virulence

Names & Taxonomyi

Protein namesi
Recommended name:
Glutathione S-transferase gliG1 Publication (EC:2.5.1.182 Publications)
Alternative name(s):
Gliotoxin biosynthesis protein G1 Publication
Gene namesi
Name:gliG1 Publication
ORF Names:AFUA_6G09690
OrganismiNeosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100) (Aspergillus fumigatus)
Taxonomic identifieri330879 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaPezizomycotinaEurotiomycetesEurotiomycetidaeEurotialesAspergillaceaeAspergillus
Proteomesi
  • UP000002530 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiFungiDB:Afu6g09690.

Pathology & Biotechi

Disruption phenotypei

Abrogates gliotoxin biosynthesis and leads to the accumulation of the shunt metabolite 6-benzyl-6-hydroxy-1-methoxy-3-methylene-piperazine-2,5-dione (PubMed:21513890).1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004377241 – 240Glutathione S-transferase gliGAdd BLAST240

Structurei

3D structure databases

ProteinModelPortaliA4GYZ0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini15 – 98GST N-terminalPROSITE-ProRule annotationAdd BLAST84
Domaini104 – 237GST C-terminalPROSITE-ProRule annotationAdd BLAST134

Sequence similaritiesi

Belongs to the GST superfamily.Curated
Contains 1 GST C-terminal domain.PROSITE-ProRule annotation
Contains 1 GST N-terminal domain.PROSITE-ProRule annotation

Phylogenomic databases

HOGENOMiHOG000187231.
InParanoidiA4GYZ0.
KOiK00799.
OMAiAKYWLYF.
OrthoDBiEOG092C4LON.

Family and domain databases

Gene3Di1.20.1050.10. 1 hit.
3.40.30.10. 1 hit.
InterProiIPR010987. Glutathione-S-Trfase_C-like.
IPR004045. Glutathione_S-Trfase_N.
IPR004046. GST_C.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PfamiPF00043. GST_C. 1 hit.
PF13417. GST_N_3. 1 hit.
[Graphical view]
SUPFAMiSSF47616. SSF47616. 1 hit.
SSF52833. SSF52833. 1 hit.
PROSITEiPS50405. GST_CTER. 1 hit.
PS50404. GST_NTER. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

A4GYZ0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSERPSDLVV NRLVLFVVKG TATSTHNTVK PLILLEELGV PHDIYVVEKV
60 70 80 90 100
SAPWFSEINP HKMVPAILDR SPDGRDTLRA WESTSTLMYI ADAYDKDGTL
110 120 130 140 150
GGRNVQERSE INNWLTLHTA ALGPTAKYWL YFYKLHPEKL PKTIEKLRSN
160 170 180 190 200
ITVQYDILER RLNEPGQQYL ALKDRPTIAD IATLPFAMKS TAELFGLEFE
210 220 230 240
KWPKLQEWSV RMGEREAVKR AWQRVAGFGH GEKEYGMLEA
Length:240
Mass (Da):27,470
Last modified:April 17, 2007 - v1
Checksum:i5352BD3FFD7D1A4B
GO

Sequence cautioni

The sequence AAW03304 differs from that shown. Reason: Erroneous gene model prediction.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY838877 Genomic DNA. Translation: AAW03304.1. Sequence problems.
AAHF01000006 Genomic DNA. Translation: EAL88820.2.
RefSeqiXP_750858.2. XM_745765.2.

Genome annotation databases

EnsemblFungiiCADAFUAT00001942; CADAFUAP00001942; CADAFUAG00001942.
GeneIDi3508163.
KEGGiafm:AFUA_6G09690.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY838877 Genomic DNA. Translation: AAW03304.1. Sequence problems.
AAHF01000006 Genomic DNA. Translation: EAL88820.2.
RefSeqiXP_750858.2. XM_745765.2.

3D structure databases

ProteinModelPortaliA4GYZ0.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblFungiiCADAFUAT00001942; CADAFUAP00001942; CADAFUAG00001942.
GeneIDi3508163.
KEGGiafm:AFUA_6G09690.

Organism-specific databases

EuPathDBiFungiDB:Afu6g09690.

Phylogenomic databases

HOGENOMiHOG000187231.
InParanoidiA4GYZ0.
KOiK00799.
OMAiAKYWLYF.
OrthoDBiEOG092C4LON.

Family and domain databases

Gene3Di1.20.1050.10. 1 hit.
3.40.30.10. 1 hit.
InterProiIPR010987. Glutathione-S-Trfase_C-like.
IPR004045. Glutathione_S-Trfase_N.
IPR004046. GST_C.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PfamiPF00043. GST_C. 1 hit.
PF13417. GST_N_3. 1 hit.
[Graphical view]
SUPFAMiSSF47616. SSF47616. 1 hit.
SSF52833. SSF52833. 1 hit.
PROSITEiPS50405. GST_CTER. 1 hit.
PS50404. GST_NTER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGLIG_ASPFU
AccessioniPrimary (citable) accession number: A4GYZ0
Secondary accession number(s): Q5MBU2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 2, 2016
Last sequence update: April 17, 2007
Last modified: November 30, 2016
This is version 55 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, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

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.