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Protein

Lactoylglutathione lyase

Gene

GLO1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione. Involved in the regulation of TNF-induced transcriptional activity of NF-kappa-B. Required for normal osteoclastogenesis.3 Publications

Catalytic activityi

(R)-S-lactoylglutathione = glutathione + methylglyoxal.2 Publications

Cofactori

Zn2+2 PublicationsNote: Binds 1 zinc ion per subunit. In the homodimer, two zinc ions are bound between subunits.2 Publications

Enzyme regulationi

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.1 Publication

Kineticsi

Reduction of GLO1 was carried out by incubation with 20 mM betamercaptoethanol prior to kinetic analysis.

  1. KM=1.3 mM for methylglyoxal/glutathione (native form)1 Publication
  2. KM=0.7 mM for methylglyoxal/glutathione (reduced form)1 Publication
  1. Vmax=0.335 µmol/min/mg enzyme with methylglyoxal/glutathione as substrate (native form)1 Publication
  2. Vmax=0.7 µmol/min/mg enzyme with methylglyoxal/glutathione as substrate (reduced form)1 Publication

Pathwayi: methylglyoxal degradation

This protein is involved in step 1 of the subpathway that synthesizes (R)-lactate from methylglyoxal.
Proteins known to be involved in the 2 steps of the subpathway in this organism are:
  1. Lactoylglutathione lyase (HEL-S-74), Lactoylglutathione lyase (GLO1), Lactoylglutathione lyase (GLO1)
  2. Hydroxyacylglutathione hydrolase, mitochondrial (HAGH)
This subpathway is part of the pathway methylglyoxal degradation, which is itself part of Secondary metabolite metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes (R)-lactate from methylglyoxal, the pathway methylglyoxal degradation and in Secondary metabolite metabolism.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi34 – 341Zinc; shared with dimeric partner3 Publications
Binding sitei34 – 341Substrate; shared with dimeric partner
Binding sitei38 – 381Substrate; shared with dimeric partner
Metal bindingi100 – 1001Zinc; shared with dimeric partner3 Publications
Binding sitei104 – 1041Substrate; shared with dimeric partner
Binding sitei123 – 1231Substrate
Metal bindingi127 – 1271Zinc; via tele nitrogen3 Publications
Binding sitei127 – 1271Substrate
Active sitei173 – 1731Proton donor/acceptor2 Publications
Metal bindingi173 – 1731Zinc3 Publications

GO - Molecular functioni

  • lactoylglutathione lyase activity Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi4.4.1.5. 2681.
ReactomeiR-HSA-70268. Pyruvate metabolism.
SABIO-RKQ04760.
UniPathwayiUPA00619; UER00675.

Names & Taxonomyi

Protein namesi
Recommended name:
Lactoylglutathione lyase (EC:4.4.1.5)
Alternative name(s):
Aldoketomutase
Glyoxalase I
Short name:
Glx I
Ketone-aldehyde mutase
Methylglyoxalase
S-D-lactoylglutathione methylglyoxal lyase
Gene namesi
Name:GLO1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:4323. GLO1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi19 – 191C → A: 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. 2 Publications
Mutagenesisi20 – 201C → A: 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. 2 Publications
Mutagenesisi34 – 341Q → E: Reduces enzyme activity by 99%. 1 Publication
Mutagenesisi45 – 451S → A: No effect on phosphorylation. 1 Publication
Mutagenesisi61 – 611C → A: No effect on NO-mediated modification. 1 Publication
Mutagenesisi69 – 691S → A: No effect on phosphorylation. 1 Publication
Mutagenesisi94 – 941S → A: No effect on phosphorylation. 1 Publication
Mutagenesisi98 – 981T → A: No effect on phosphorylation. 1 Publication
Mutagenesisi100 – 1001E → Q: Reduces enzyme activity by over 99%. 1 Publication
Mutagenesisi102 – 1021T → A: No effect on phosphorylation. 1 Publication
Mutagenesisi107 – 1071T → A: Loss of phosphorylation. 1 Publication
Mutagenesisi139 – 1391C → A: Impaired NO-mediated modification. Loss of NO-mediated modification; when associated with A-19 or A-20. 2 Publications
Mutagenesisi173 – 1731E → Q: Abolishes enzyme activity. 1 Publication

Organism-specific databases

PharmGKBiPA28724.

Chemistry

ChEMBLiCHEMBL2424.
DrugBankiDB00143. Glutathione.
DB00328. Indomethacin.

Polymorphism and mutation databases

BioMutaiGLO1.
DMDMi134039205.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedCombined sources1 Publication
Chaini2 – 184183Lactoylglutathione lyasePRO_0000168076Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineCombined sources1 Publication
Disulfide bondi19 ↔ 201 Publication
Disulfide bondi61 ↔ 139Alternate1 Publication
Modified residuei88 – 881N6-succinyllysineBy similarity
Modified residuei107 – 1071Phosphothreonine1 Publication
Modified residuei139 – 1391S-glutathionyl cysteine; alternate1 Publication
Modified residuei148 – 1481N6-acetyllysine; alternateCombined sources
Modified residuei148 – 1481N6-succinyllysine; alternateBy similarity

Post-translational modificationi

Glutathionylation at Cys-139 inhibits enzyme activity.1 Publication
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.2 Publications
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 - PTMi

Acetylation, Disulfide bond, Glutathionylation, Phosphoprotein

Proteomic databases

EPDiQ04760.
PaxDbiQ04760.
PeptideAtlasiQ04760.
PRIDEiQ04760.

2D gel databases

OGPiQ04760.
REPRODUCTION-2DPAGEIPI00220766.
Q04760.

PTM databases

iPTMnetiQ04760.
PhosphoSiteiQ04760.
SwissPalmiQ04760.

Expressioni

Gene expression databases

BgeeiENSG00000124767.
CleanExiHS_GLO1.
ExpressionAtlasiQ04760. baseline and differential.
GenevisibleiQ04760. HS.

Organism-specific databases

HPAiCAB040541.
CAB040542.
HPA059791.

Interactioni

Subunit structurei

Homodimer.3 Publications

Protein-protein interaction databases

BioGridi109001. 38 interactions.
IntActiQ04760. 4 interactions.
STRINGi9606.ENSP00000362463.

Chemistry

BindingDBiQ04760.

Structurei

Secondary structure

1
184
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi13 – 186Combined sources
Helixi25 – 273Combined sources
Beta strandi31 – 388Combined sources
Helixi42 – 5110Combined sources
Beta strandi56 – 638Combined sources
Turni64 – 674Combined sources
Beta strandi68 – 758Combined sources
Helixi78 – 803Combined sources
Helixi85 – 928Combined sources
Beta strandi95 – 10410Combined sources
Helixi107 – 1093Combined sources
Beta strandi118 – 1225Combined sources
Beta strandi124 – 1318Combined sources
Helixi135 – 14410Combined sources
Beta strandi149 – 1513Combined sources
Beta strandi155 – 1584Combined sources
Beta strandi162 – 1654Combined sources
Beta strandi171 – 1755Combined sources
Helixi177 – 1793Combined sources
Helixi181 – 1833Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1BH5X-ray2.20A/B/C/D2-184[»]
1FROX-ray2.20A/B/C/D2-184[»]
1QINX-ray2.00A/B2-184[»]
1QIPX-ray1.72A/B/C/D2-184[»]
3VW9X-ray1.47A/B1-184[»]
3W0TX-ray1.35A/B/C/D1-184[»]
3W0UX-ray1.70A/B1-184[»]
ProteinModelPortaliQ04760.
SMRiQ04760. Positions 3-184.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ04760.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni157 – 1582Substrate binding

Sequence similaritiesi

Belongs to the glyoxalase I family.Curated

Phylogenomic databases

eggNOGiENOG410IU7X. Eukaryota.
ENOG4111FDV. LUCA.
GeneTreeiENSGT00390000009312.
HOVERGENiHBG025852.
InParanoidiQ04760.
KOiK01759.
OMAiWMKSIPG.
OrthoDBiEOG091G0GMY.
PhylomeDBiQ04760.
TreeFamiTF105011.

Family and domain databases

Gene3Di3.10.180.10. 1 hit.
InterProiIPR029068. Glyas_Bleomycin-R_OHBP_Dase.
IPR004360. Glyas_Fos-R_dOase_dom.
IPR004361. Glyoxalase_1.
IPR018146. Glyoxalase_1_CS.
[Graphical view]
PfamiPF00903. Glyoxalase. 1 hit.
[Graphical view]
SUPFAMiSSF54593. SSF54593. 1 hit.
TIGRFAMsiTIGR00068. glyox_I. 1 hit.
PROSITEiPS00934. GLYOXALASE_I_1. 1 hit.
PS00935. GLYOXALASE_I_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q04760-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAEPQPPSGG LTDEAALSCC SDADPSTKDF LLQQTMLRVK DPKKSLDFYT
60 70 80 90 100
RVLGMTLIQK CDFPIMKFSL YFLAYEDKND IPKEKDEKIA WALSRKATLE
110 120 130 140 150
LTHNWGTEDD ETQSYHNGNS DPRGFGHIGI AVPDVYSACK RFEELGVKFV
160 170 180
KKPDDGKMKG LAFIQDPDGY WIEILNPNKM ATLM
Length:184
Mass (Da):20,778
Last modified:March 6, 2007 - v4
Checksum:i46291B7878070028
GO
Isoform 2 (identifier: Q04760-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     105-119: Missing.

Note: No experimental confirmation available.
Show »
Length:169
Mass (Da):19,043
Checksum:i24175E1D1C817515
GO

Sequence cautioni

The sequence BAD93038 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Mass spectrometryi

Isoform 1 : Molecular mass is 20687.4 Da from positions 2 - 184. Determined by ESI. Variant Glu-111.1 Publication
Isoform 1 : Molecular mass is 20629.7 Da from positions 2 - 184. Determined by ESI. Variant Ala-111.1 Publication

Polymorphismi

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.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti19 – 191C → Y.2 Publications
Corresponds to variant rs17855424 [ dbSNP | Ensembl ].
VAR_031078
Natural varianti111 – 1111E → A.5 Publications
Corresponds to variant rs4746 [ dbSNP | Ensembl ].
VAR_013481

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei105 – 11915Missing in isoform 2. 1 PublicationVSP_041632Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D13315 mRNA. Translation: BAA02572.1.
L07837 mRNA. Translation: AAA52565.1.
S83285 mRNA. Translation: AAB49495.1.
AF146651 Genomic DNA. Translation: AAD38008.1.
AB209801 mRNA. Translation: BAD93038.1. Different initiation.
AK293345 mRNA. Translation: BAG56861.1.
AK312662 mRNA. Translation: BAG35544.1.
BT019987 mRNA. Translation: AAV38790.1.
BT019988 mRNA. Translation: AAV38791.1.
AL391415 Genomic DNA. Translation: CAI21586.1.
BC001741 mRNA. Translation: AAH01741.1.
BC011365 mRNA. Translation: AAH11365.1.
BC015934 mRNA. Translation: AAH15934.1.
CCDSiCCDS4837.1. [Q04760-1]
PIRiA46714.
S63603.
RefSeqiNP_006699.2. NM_006708.2. [Q04760-1]
UniGeneiHs.268849.

Genome annotation databases

EnsembliENST00000373365; ENSP00000362463; ENSG00000124767. [Q04760-1]
GeneIDi2739.
KEGGihsa:2739.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D13315 mRNA. Translation: BAA02572.1.
L07837 mRNA. Translation: AAA52565.1.
S83285 mRNA. Translation: AAB49495.1.
AF146651 Genomic DNA. Translation: AAD38008.1.
AB209801 mRNA. Translation: BAD93038.1. Different initiation.
AK293345 mRNA. Translation: BAG56861.1.
AK312662 mRNA. Translation: BAG35544.1.
BT019987 mRNA. Translation: AAV38790.1.
BT019988 mRNA. Translation: AAV38791.1.
AL391415 Genomic DNA. Translation: CAI21586.1.
BC001741 mRNA. Translation: AAH01741.1.
BC011365 mRNA. Translation: AAH11365.1.
BC015934 mRNA. Translation: AAH15934.1.
CCDSiCCDS4837.1. [Q04760-1]
PIRiA46714.
S63603.
RefSeqiNP_006699.2. NM_006708.2. [Q04760-1]
UniGeneiHs.268849.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1BH5X-ray2.20A/B/C/D2-184[»]
1FROX-ray2.20A/B/C/D2-184[»]
1QINX-ray2.00A/B2-184[»]
1QIPX-ray1.72A/B/C/D2-184[»]
3VW9X-ray1.47A/B1-184[»]
3W0TX-ray1.35A/B/C/D1-184[»]
3W0UX-ray1.70A/B1-184[»]
ProteinModelPortaliQ04760.
SMRiQ04760. Positions 3-184.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109001. 38 interactions.
IntActiQ04760. 4 interactions.
STRINGi9606.ENSP00000362463.

Chemistry

BindingDBiQ04760.
ChEMBLiCHEMBL2424.
DrugBankiDB00143. Glutathione.
DB00328. Indomethacin.

PTM databases

iPTMnetiQ04760.
PhosphoSiteiQ04760.
SwissPalmiQ04760.

Polymorphism and mutation databases

BioMutaiGLO1.
DMDMi134039205.

2D gel databases

OGPiQ04760.
REPRODUCTION-2DPAGEIPI00220766.
Q04760.

Proteomic databases

EPDiQ04760.
PaxDbiQ04760.
PeptideAtlasiQ04760.
PRIDEiQ04760.

Protocols and materials databases

DNASUi2739.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000373365; ENSP00000362463; ENSG00000124767. [Q04760-1]
GeneIDi2739.
KEGGihsa:2739.

Organism-specific databases

CTDi2739.
GeneCardsiGLO1.
HGNCiHGNC:4323. GLO1.
HPAiCAB040541.
CAB040542.
HPA059791.
MIMi138750. gene.
neXtProtiNX_Q04760.
PharmGKBiPA28724.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IU7X. Eukaryota.
ENOG4111FDV. LUCA.
GeneTreeiENSGT00390000009312.
HOVERGENiHBG025852.
InParanoidiQ04760.
KOiK01759.
OMAiWMKSIPG.
OrthoDBiEOG091G0GMY.
PhylomeDBiQ04760.
TreeFamiTF105011.

Enzyme and pathway databases

UniPathwayiUPA00619; UER00675.
BRENDAi4.4.1.5. 2681.
ReactomeiR-HSA-70268. Pyruvate metabolism.
SABIO-RKQ04760.

Miscellaneous databases

ChiTaRSiGLO1. human.
EvolutionaryTraceiQ04760.
GeneWikiiGLO1.
Lactoylglutathione_lyase.
GenomeRNAii2739.
PROiQ04760.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000124767.
CleanExiHS_GLO1.
ExpressionAtlasiQ04760. baseline and differential.
GenevisibleiQ04760. HS.

Family and domain databases

Gene3Di3.10.180.10. 1 hit.
InterProiIPR029068. Glyas_Bleomycin-R_OHBP_Dase.
IPR004360. Glyas_Fos-R_dOase_dom.
IPR004361. Glyoxalase_1.
IPR018146. Glyoxalase_1_CS.
[Graphical view]
PfamiPF00903. Glyoxalase. 1 hit.
[Graphical view]
SUPFAMiSSF54593. SSF54593. 1 hit.
TIGRFAMsiTIGR00068. glyox_I. 1 hit.
PROSITEiPS00934. GLYOXALASE_I_1. 1 hit.
PS00935. GLYOXALASE_I_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLGUL_HUMAN
AccessioniPrimary (citable) accession number: Q04760
Secondary accession number(s): B2R6P7
, B4DDV0, P78375, Q59EL0, Q5TZW3, Q96FC0, Q96J41
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: March 6, 2007
Last modified: September 7, 2016
This is version 175 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

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

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. 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.