Q04760 · LGUL_HUMAN

  • Protein
    Lactoylglutathione lyase
  • Gene
    GLO1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione (PubMed:20454679, PubMed:23122816, PubMed:9705294).
Involved in the regulation of TNF-induced transcriptional activity of NF-kappa-B (PubMed:19199007).
Required for normal osteoclastogenesis (By similarity).

Catalytic activity

Cofactor

Zn2+ (UniProtKB | Rhea| CHEBI:29105 )

Note: Binds 1 zinc ion per subunit. In the homodimer, two zinc ions are bound between subunits.

Activity regulation

Regulated by oxidation of Cys-139 in response to the redox state of the cell. Results in the alternative formation of cystine or glutathione-bound cysteine, the latter modification leading to reduced enzyme activity.

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
1.3 mMmethylglyoxal/glutathione (native form)
0.7 mMmethylglyoxal/glutathione (reduced form)
Vmax pH TEMPERATURE[C] NOTES EVIDENCE
0.335 μmol/min/mgwith methylglyoxal/glutathione as substrate (native form)
0.7 μmol/min/mgwith methylglyoxal/glutathione as substrate (reduced form)
Reduction of GLO1 was carried out by incubation with 20 mM betamercaptoethanol prior to kinetic analysis.

Pathway

Secondary metabolite metabolism; methylglyoxal degradation; (R)-lactate from methylglyoxal: step 1/2.

Features

Showing features for binding site, active site.

TypeIDPosition(s)Description
Binding site34substrate; ligand shared between dimeric partners
Binding site34Zn2+ (UniProtKB | ChEBI); ligand shared between dimeric partners
Binding site38substrate; ligand shared between dimeric partners
Binding site100Zn2+ (UniProtKB | ChEBI); ligand shared between dimeric partners
Binding site104substrate; ligand shared between dimeric partners
Binding site123substrate; ligand shared between dimeric partners; in other chain
Binding site127substrate; ligand shared between dimeric partners; in other chain
Binding site127Zn2+ (UniProtKB | ChEBI); ligand shared between dimeric partners; in other chain
Binding site157-158substrate; ligand shared between dimeric partners; in other chain
Active site173Proton donor/acceptor
Binding site173Zn2+ (UniProtKB | ChEBI); ligand shared between dimeric partners; in other chain

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular Componentextracellular exosome
Cellular Componentnucleoplasm
Cellular Componentplasma membrane
Molecular Functionlactoylglutathione lyase activity
Molecular Functionzinc ion binding
Biological Processcarbohydrate metabolic process
Biological Processglutathione metabolic process
Biological Processmethylglyoxal metabolic process
Biological Processnegative regulation of apoptotic process
Biological Processosteoclast differentiation
Biological Processregulation of transcription by RNA polymerase II

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Lactoylglutathione lyase
  • EC number
  • Alternative names
    • Aldoketomutase
    • Glyoxalase I (Glx I)
    • Ketone-aldehyde mutase
    • Methylglyoxalase
    • S-D-lactoylglutathione methylglyoxal lyase

Gene names

    • Name
      GLO1

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    Q04760
  • Secondary accessions
    • B2R6P7
    • B4DDV0
    • P78375
    • Q59EL0
    • Q5TZW3

Proteomes

Organism-specific databases

Disease & Variants

Features

Showing features for natural variant, mutagenesis.

TypeIDPosition(s)Description
Natural variantVAR_03107819in dbSNP:rs17855424
Mutagenesis19No effect on NO-mediated modification. Impaired NO-mediated modification; when associated with A-20. Loss of NO-mediated modification; when associated with A-139.
Mutagenesis20No effect on NO-mediated modification. Impaired NO-mediated modification; when associated with A-19. Loss of NO-mediated modification; when associated with A-139.
Mutagenesis34Reduces enzyme activity by 99%.
Mutagenesis45No effect on phosphorylation.
Mutagenesis61No effect on NO-mediated modification.
Mutagenesis69No effect on phosphorylation.
Mutagenesis94No effect on phosphorylation.
Mutagenesis98No effect on phosphorylation.
Mutagenesis100Reduces enzyme activity by over 99%.
Mutagenesis102No effect on phosphorylation.
Mutagenesis107Loss of phosphorylation.
Natural variantVAR_013481111in dbSNP:rs4746
Mutagenesis139Impaired NO-mediated modification. Loss of NO-mediated modification; when associated with A-19 or A-20.
Mutagenesis173Abolishes enzyme activity.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 214 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for initiator methionine, modified residue, chain, disulfide bond.

TypeIDPosition(s)Description
Initiator methionine1Removed
Modified residue2N-acetylalanine
ChainPRO_00001680762-184Lactoylglutathione lyase
Disulfide bond19↔20
Disulfide bond61↔139Alternate
Modified residue88N6-succinyllysine
Modified residue107Phosphothreonine
Modified residue139S-glutathionyl cysteine; alternate
Modified residue148N6-acetyllysine; alternate
Modified residue148N6-succinyllysine; alternate

Post-translational modification

Glutathionylation at Cys-139 inhibits enzyme activity.
Phosphorylated at Thr-107 in the presence of CaMK2. However, this is a consensus site for phosphorylation by CK2 so phosphorylation may be mediated by CK2 rather than CaMK2. Phosphorylation is induced by TNF and suppresses the TNF-induced transcriptional activity of NF-kappa-B.
Exists in a nitric oxide (NO)-modified form. The exact nature of the modification is unknown, but it suppresses the TNF-induced transcriptional activity of NF-kappa-B.

Keywords

Proteomic databases

2D gel databases

PTM databases

Expression

Gene expression databases

Organism-specific databases

Interaction

Subunit

Homodimer.

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
BINARY Q04760PUS10 Q3MIT23EBI-1055525, EBI-11983583

Protein-protein interaction databases

Chemistry

Miscellaneous

Family & Domains

Features

Showing features for domain.

TypeIDPosition(s)Description
Domain31-177VOC

Sequence similarities

Belongs to the glyoxalase I family.

Phylogenomic databases

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete

This entry describes 2 isoforms produced by Alternative splicing.

Q04760-1

This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

  • Length
    184
  • Mass (Da)
    20,778
  • Last updated
    2007-03-06 v4
  • Checksum
    46291B7878070028
MAEPQPPSGGLTDEAALSCCSDADPSTKDFLLQQTMLRVKDPKKSLDFYTRVLGMTLIQKCDFPIMKFSLYFLAYEDKNDIPKEKDEKIAWALSRKATLELTHNWGTEDDETQSYHNGNSDPRGFGHIGIAVPDVYSACKRFEELGVKFVKKPDDGKMKGLAFIQDPDGYWIEILNPNKMATLM

Q04760-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Sequence caution

The sequence BAD93038.1 differs from that shown. Reason: Erroneous initiation Extended N-terminus.

Features

Showing features for alternative sequence.

TypeIDPosition(s)Description
Alternative sequenceVSP_041632105-119in isoform 2

Mass Spectrometry

Isoform 1

Molecular mass is 20,687.4 Da. Determined by Electrospray. Variant Glu-111. The measured range is 2-184.

Isoform 1

Molecular mass is 20,629.7 Da. Determined by Electrospray. Variant Ala-111. The measured range is 2-184.

Polymorphism

Exists in three separable isoforms which originate from two alleles in the genome. These correspond to two homodimers and one heterodimer composed of two subunits showing different electrophoretic properties.

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
D13315
EMBL· GenBank· DDBJ
BAA02572.1
EMBL· GenBank· DDBJ
mRNA
L07837
EMBL· GenBank· DDBJ
AAA52565.1
EMBL· GenBank· DDBJ
mRNA
S83285
EMBL· GenBank· DDBJ
AAB49495.1
EMBL· GenBank· DDBJ
mRNA
AF146651
EMBL· GenBank· DDBJ
AAD38008.1
EMBL· GenBank· DDBJ
Genomic DNA
AB209801
EMBL· GenBank· DDBJ
BAD93038.1
EMBL· GenBank· DDBJ
mRNA Different initiation
AK293345
EMBL· GenBank· DDBJ
BAG56861.1
EMBL· GenBank· DDBJ
mRNA
AK312662
EMBL· GenBank· DDBJ
BAG35544.1
EMBL· GenBank· DDBJ
mRNA
BT019987
EMBL· GenBank· DDBJ
AAV38790.1
EMBL· GenBank· DDBJ
mRNA
BT019988
EMBL· GenBank· DDBJ
AAV38791.1
EMBL· GenBank· DDBJ
mRNA
AL391415
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
BC001741
EMBL· GenBank· DDBJ
AAH01741.1
EMBL· GenBank· DDBJ
mRNA
BC011365
EMBL· GenBank· DDBJ
AAH11365.1
EMBL· GenBank· DDBJ
mRNA
BC015934
EMBL· GenBank· DDBJ
AAH15934.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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