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}.
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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
//