Q04760 · LGUL_HUMAN
- ProteinLactoylglutathione lyase
- GeneGLO1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids184 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
Involved in the regulation of TNF-induced transcriptional activity of NF-kappa-B (PubMed:19199007).
Required for normal osteoclastogenesis (By similarity).
Catalytic activity
- (R)-S-lactoylglutathione = glutathione + methylglyoxalThis reaction proceeds in the backward direction.
Cofactor
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 mM | methylglyoxal/glutathione (native form) | |||||
0.7 mM | methylglyoxal/glutathione (reduced form) |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
0.335 μmol/min/mg | with methylglyoxal/glutathione as substrate (native form) | ||||
0.7 μmol/min/mg | with 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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 34 | substrate; ligand shared between dimeric partners | ||||
Sequence: Q | ||||||
Binding site | 34 | Zn2+ (UniProtKB | ChEBI); ligand shared between dimeric partners | ||||
Sequence: Q | ||||||
Binding site | 38 | substrate; ligand shared between dimeric partners | ||||
Sequence: R | ||||||
Binding site | 100 | Zn2+ (UniProtKB | ChEBI); ligand shared between dimeric partners | ||||
Sequence: E | ||||||
Binding site | 104 | substrate; ligand shared between dimeric partners | ||||
Sequence: N | ||||||
Binding site | 123 | substrate; ligand shared between dimeric partners; in other chain | ||||
Sequence: R | ||||||
Binding site | 127 | substrate; ligand shared between dimeric partners; in other chain | ||||
Sequence: H | ||||||
Binding site | 127 | Zn2+ (UniProtKB | ChEBI); ligand shared between dimeric partners; in other chain | ||||
Sequence: H | ||||||
Binding site | 157-158 | substrate; ligand shared between dimeric partners; in other chain | ||||
Sequence: KM | ||||||
Active site | 173 | Proton donor/acceptor | ||||
Sequence: E | ||||||
Binding site | 173 | Zn2+ (UniProtKB | ChEBI); ligand shared between dimeric partners; in other chain | ||||
Sequence: E |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | extracellular exosome | |
Cellular Component | nucleoplasm | |
Cellular Component | plasma membrane | |
Molecular Function | lactoylglutathione lyase activity | |
Molecular Function | zinc ion binding | |
Biological Process | carbohydrate metabolic process | |
Biological Process | glutathione metabolic process | |
Biological Process | methylglyoxal metabolic process | |
Biological Process | negative regulation of apoptotic process | |
Biological Process | osteoclast differentiation | |
Biological Process | regulation of transcription by RNA polymerase II |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameLactoylglutathione lyase
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ04760
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_031078 | 19 | in dbSNP:rs17855424 | |||
Sequence: C → Y | ||||||
Mutagenesis | 19 | No effect on NO-mediated modification. Impaired NO-mediated modification; when associated with A-20. Loss of NO-mediated modification; when associated with A-139. | ||||
Sequence: C → A | ||||||
Mutagenesis | 20 | No effect on NO-mediated modification. Impaired NO-mediated modification; when associated with A-19. Loss of NO-mediated modification; when associated with A-139. | ||||
Sequence: C → A | ||||||
Mutagenesis | 34 | Reduces enzyme activity by 99%. | ||||
Sequence: Q → E | ||||||
Mutagenesis | 45 | No effect on phosphorylation. | ||||
Sequence: S → A | ||||||
Mutagenesis | 61 | No effect on NO-mediated modification. | ||||
Sequence: C → A | ||||||
Mutagenesis | 69 | No effect on phosphorylation. | ||||
Sequence: S → A | ||||||
Mutagenesis | 94 | No effect on phosphorylation. | ||||
Sequence: S → A | ||||||
Mutagenesis | 98 | No effect on phosphorylation. | ||||
Sequence: T → A | ||||||
Mutagenesis | 100 | Reduces enzyme activity by over 99%. | ||||
Sequence: E → Q | ||||||
Mutagenesis | 102 | No effect on phosphorylation. | ||||
Sequence: T → A | ||||||
Mutagenesis | 107 | Loss of phosphorylation. | ||||
Sequence: T → A | ||||||
Natural variant | VAR_013481 | 111 | in dbSNP:rs4746 | |||
Sequence: E → A | ||||||
Mutagenesis | 139 | Impaired NO-mediated modification. Loss of NO-mediated modification; when associated with A-19 or A-20. | ||||
Sequence: C → A | ||||||
Mutagenesis | 173 | Abolishes enzyme activity. | ||||
Sequence: E → Q |
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.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylalanine | ||||
Sequence: A | ||||||
Chain | PRO_0000168076 | 2-184 | Lactoylglutathione lyase | |||
Sequence: AEPQPPSGGLTDEAALSCCSDADPSTKDFLLQQTMLRVKDPKKSLDFYTRVLGMTLIQKCDFPIMKFSLYFLAYEDKNDIPKEKDEKIAWALSRKATLELTHNWGTEDDETQSYHNGNSDPRGFGHIGIAVPDVYSACKRFEELGVKFVKKPDDGKMKGLAFIQDPDGYWIEILNPNKMATLM | ||||||
Disulfide bond | 19↔20 | |||||
Sequence: CC | ||||||
Disulfide bond | 61↔139 | Alternate | ||||
Sequence: CDFPIMKFSLYFLAYEDKNDIPKEKDEKIAWALSRKATLELTHNWGTEDDETQSYHNGNSDPRGFGHIGIAVPDVYSAC | ||||||
Modified residue | 88 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 107 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 139 | S-glutathionyl cysteine; alternate | ||||
Sequence: C | ||||||
Modified residue | 148 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 148 | N6-succinyllysine; alternate | ||||
Sequence: K |
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
- PTM
Proteomic databases
2D gel databases
PTM databases
Expression
Interaction
Subunit
Homodimer.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q04760 | PUS10 Q3MIT2 | 3 | EBI-1055525, EBI-11983583 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 31-177 | VOC | ||||
Sequence: LLQQTMLRVKDPKKSLDFYTRVLGMTLIQKCDFPIMKFSLYFLAYEDKNDIPKEKDEKIAWALSRKATLELTHNWGTEDDETQSYHNGNSDPRGFGHIGIAVPDVYSACKRFEELGVKFVKKPDDGKMKGLAFIQDPDGYWIEILNP |
Sequence similarities
Belongs to the glyoxalase I family.
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
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.
- Name1
- Length184
- Mass (Da)20,778
- Last updated2007-03-06 v4
- Checksum46291B7878070028
Q04760-2
- Name2
- Differences from canonical
- 105-119: Missing
Sequence caution
Features
Showing features for alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_041632 | 105-119 | in isoform 2 | |||
Sequence: Missing |
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
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |