ID LGUL_MACFA Reviewed; 184 AA.
AC Q4R5F2;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 27-MAR-2024, entry version 91.
DE RecName: Full=Lactoylglutathione lyase;
DE EC=4.4.1.5 {ECO:0000250|UniProtKB:Q04760};
DE AltName: Full=Aldoketomutase;
DE AltName: Full=Glyoxalase I;
DE Short=Glx I;
DE AltName: Full=Ketone-aldehyde mutase;
DE AltName: Full=Methylglyoxalase;
DE AltName: Full=S-D-lactoylglutathione methylglyoxal lyase;
GN Name=GLO1; ORFNames=QnpA-15219;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Parietal cortex;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Catalyzes the conversion of hemimercaptal, formed from
CC methylglyoxal and glutathione, to S-lactoylglutathione (By similarity).
CC Involved in the regulation of TNF-induced transcriptional activity of
CC NF-kappa-B (By similarity). Required for normal osteoclastogenesis (By
CC similarity). {ECO:0000250|UniProtKB:Q04760,
CC ECO:0000250|UniProtKB:Q9CPU0}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-S-lactoylglutathione = glutathione + methylglyoxal;
CC Xref=Rhea:RHEA:19069, ChEBI:CHEBI:17158, ChEBI:CHEBI:57474,
CC ChEBI:CHEBI:57925; EC=4.4.1.5;
CC Evidence={ECO:0000250|UniProtKB:Q04760};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:19071;
CC Evidence={ECO:0000250|UniProtKB:Q04760};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q04760};
CC Note=Binds 1 zinc ion per subunit. In the homodimer, two zinc ions are
CC bound between subunits. {ECO:0000250|UniProtKB:Q04760};
CC -!- PATHWAY: Secondary metabolite metabolism; methylglyoxal degradation;
CC (R)-lactate from methylglyoxal: step 1/2.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q04760}.
CC -!- PTM: Glutathionylation at Cys-139 inhibits enzyme activity.
CC {ECO:0000250|UniProtKB:Q04760}.
CC -!- PTM: Phosphorylated at Thr-107 in the presence of CaMK2. However, this
CC is a consensus site for phosphorylation by CK2 so phosphorylation may
CC be mediated by CK2 rather than CaMK2. Phosphorylation is induced by TNF
CC and suppresses the TNF-induced transcriptional activity of NF-kappa-B
CC (By similarity). {ECO:0000250|UniProtKB:Q04760}.
CC -!- PTM: Exists in a nitric oxide (NO)-modified form. The exact nature of
CC the modification is unknown, but it suppresses the TNF-induced
CC transcriptional activity of NF-kappa-B (By similarity).
CC {ECO:0000250|UniProtKB:Q04760}.
CC -!- SIMILARITY: Belongs to the glyoxalase I family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB169591; BAE01673.1; -; mRNA.
DR RefSeq; NP_001271981.1; NM_001285052.1.
DR AlphaFoldDB; Q4R5F2; -.
DR SMR; Q4R5F2; -.
DR STRING; 9541.ENSMFAP00000039784; -.
DR VEuPathDB; HostDB:ENSMFAG00000046082; -.
DR eggNOG; KOG2944; Eukaryota.
DR OMA; THNWDTP; -.
DR OrthoDB; 245930at2759; -.
DR UniPathway; UPA00619; UER00675.
DR Proteomes; UP000233100; Chromosome 4.
DR GO; GO:0004462; F:lactoylglutathione lyase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR CDD; cd07233; GlxI_Zn; 1.
DR Gene3D; 3.10.180.10; 2,3-Dihydroxybiphenyl 1,2-Dioxygenase, domain 1; 1.
DR InterPro; IPR029068; Glyas_Bleomycin-R_OHBP_Dase.
DR InterPro; IPR004360; Glyas_Fos-R_dOase_dom.
DR InterPro; IPR004361; Glyoxalase_1.
DR InterPro; IPR018146; Glyoxalase_1_CS.
DR InterPro; IPR037523; VOC.
DR NCBIfam; TIGR00068; glyox_I; 1.
DR PANTHER; PTHR10374:SF30; LACTOYLGLUTATHIONE LYASE; 1.
DR PANTHER; PTHR10374; LACTOYLGLUTATHIONE LYASE GLYOXALASE I; 1.
DR Pfam; PF00903; Glyoxalase; 1.
DR SUPFAM; SSF54593; Glyoxalase/Bleomycin resistance protein/Dihydroxybiphenyl dioxygenase; 1.
DR PROSITE; PS00934; GLYOXALASE_I_1; 1.
DR PROSITE; PS00935; GLYOXALASE_I_2; 1.
DR PROSITE; PS51819; VOC; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Disulfide bond; Glutathionylation; Lyase; Metal-binding;
KW Phosphoprotein; Reference proteome; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q04760"
FT CHAIN 2..184
FT /note="Lactoylglutathione lyase"
FT /id="PRO_0000168077"
FT DOMAIN 31..177
FT /note="VOC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01163"
FT ACT_SITE 173
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT BINDING 34
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250"
FT BINDING 34
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:Q04760"
FT BINDING 38
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250"
FT BINDING 100
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:Q04760"
FT BINDING 104
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250"
FT BINDING 123
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250"
FT BINDING 127
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250"
FT BINDING 127
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:Q04760"
FT BINDING 157..158
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250"
FT BINDING 173
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:Q04760"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q04760"
FT MOD_RES 88
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9CPU0"
FT MOD_RES 107
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q04760"
FT MOD_RES 139
FT /note="S-glutathionyl cysteine; alternate"
FT /evidence="ECO:0000250"
FT MOD_RES 148
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q04760"
FT MOD_RES 148
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9CPU0"
FT DISULFID 19..20
FT /evidence="ECO:0000250"
FT DISULFID 61..139
FT /note="Alternate"
FT /evidence="ECO:0000250"
SQ SEQUENCE 184 AA; 20710 MW; 8E8B276CB80EAB34 CRC64;
MAEPQPPSGG LTDEAALSCC SDADPSTKDF LLQQTMLRVK DPKKSLDFYT RVLGMTLIQK
CDFPAMKFSL YFLAYEDKND IPKDKEEKIA WALSRKATLE LTHNWGTEDD ETQSYHNGNS
DPRGFGHIGI AVPDVHSACK RFEELGVKFV KKPDDGKMKG LAFIQDPDGY WIEILNPNKM
ATLM
//
