E9R9Y3 · GLIK_ASPFU

Function

function

Gamma-glutamyl cyclotransferase-like protein; 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:23434416, PubMed:24039048).
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).

Catalytic activity

Pathway

Mycotoxin biosynthesis.

GO annotations

AspectTerm
Cellular Componentmembrane
Molecular Functiongamma-glutamylcyclotransferase activity
Biological Processgliotoxin biosynthetic process
Biological Processmycotoxin biosynthetic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Gamma-glutamyl cyclotransferase gliK
  • EC number
  • Short names
    GGCT gliK
  • Alternative names
    • Gliotoxin biosynthesis protein K

Gene names

    • Name
      gliK
    • ORF names
      AFUA_6G09700

Organism names

Accessions

  • Primary accession
    E9R9Y3
  • Secondary accessions
    • Q4WMJ3
    • Q5MBU3

Proteomes

Organism-specific databases

Subcellular Location

Membrane
; Single-pass membrane protein

Features

Showing features for transmembrane.

TypeIDPosition(s)Description
Transmembrane227-243Helical

Keywords

Phenotypes & Variants

Disruption phenotype

Impairs gliotoxin biosynthesis and accumulates ergothioneine (PubMed:22903976, PubMed:26150413).
Leads also to attenuated gliT abundance (PubMed:22903976, PubMed:26150413).

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00004377271-273Gamma-glutamyl cyclotransferase gliK

Interaction

Protein-protein interaction databases

Structure

Family & Domains

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    273
  • Mass (Da)
    30,501
  • Last updated
    2011-04-05 v1
  • Checksum
    61A9C0A798094BA1
MGKAALQDPHGGIWYFAYGSNLRLSVLENRGIKALDIKAVIVPSHYLTFDIFGIPYAEPSFASVAPFAREKKTTLRLGDSPASRDVPPVQGLAYLLNPRDYRQLVISEGGGVAYDEVEVHASILDKDGKPDPGATLIARTLQAKYPWRPNGAPSARYLGLISTGCKQNEPLTAYSDYIDSLPAYEPPTSLHAKVGGLLFLMFWRPPLRLLIRLIRVNTDQDGHCPQWLGWIILTLYGLMWSYHDNIHSKIWGRGDGRKLHFEETPAKEVPVRH

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AY838877
EMBL· GenBank· DDBJ
AAW03303.1
EMBL· GenBank· DDBJ
Genomic DNA
AAHF01000006
EMBL· GenBank· DDBJ
EAL88821.2
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

Disclaimer

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