LGUL_RAT
ID LGUL_RAT Reviewed; 184 AA.
AC Q6P7Q4;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Lactoylglutathione lyase;
DE EC=4.4.1.5 {ECO:0000269|PubMed:8719777};
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;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pituitary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP PROTEIN SEQUENCE OF 29-38; 44-83; 89-95 AND 124-148, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus, and Spinal cord;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q.;
RL Submitted (APR-2007) to UniProtKB.
RN [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=8719777; DOI=10.1016/0047-6374(95)01632-a;
RA Kawase M., Kondoh C., Matsumoto S., Teshigawara M., Chisaka Y.,
RA Higashiura M., Nakata K., Ohmori S.;
RT "Contents of D-lactate and its related metabolites as well as enzyme
RT activities in the liver, muscle and blood plasma of aging rats.";
RL Mech. Ageing Dev. 84:55-63(1995).
CC -!- FUNCTION: Catalyzes the conversion of hemimercaptal, formed from
CC methylglyoxal and glutathione, to S-lactoylglutathione
CC (PubMed:8719777). Involved in the regulation of TNF-induced
CC transcriptional activity of NF-kappa-B (By similarity). Required for
CC normal osteoclastogenesis (By similarity).
CC {ECO:0000250|UniProtKB:Q04760, ECO:0000250|UniProtKB:Q9CPU0,
CC ECO:0000269|PubMed:8719777}.
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; Evidence={ECO:0000269|PubMed:8719777};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:19071;
CC Evidence={ECO:0000305|PubMed:8719777};
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; BC061570; AAH61570.1; -; mRNA.
DR RefSeq; NP_997477.1; NM_207594.2.
DR AlphaFoldDB; Q6P7Q4; -.
DR SMR; Q6P7Q4; -.
DR BioGRID; 254669; 1.
DR STRING; 10116.ENSRNOP00000000650; -.
DR ChEMBL; CHEMBL2306; -.
DR iPTMnet; Q6P7Q4; -.
DR PhosphoSitePlus; Q6P7Q4; -.
DR SwissPalm; Q6P7Q4; -.
DR jPOST; Q6P7Q4; -.
DR PaxDb; Q6P7Q4; -.
DR PRIDE; Q6P7Q4; -.
DR Ensembl; ENSRNOT00000000650; ENSRNOP00000000650; ENSRNOG00000000541.
DR GeneID; 294320; -.
DR KEGG; rno:294320; -.
DR UCSC; RGD:2702; rat.
DR CTD; 2739; -.
DR RGD; 2702; Glo1.
DR eggNOG; KOG2944; Eukaryota.
DR GeneTree; ENSGT00390000009312; -.
DR HOGENOM; CLU_046006_1_1_1; -.
DR InParanoid; Q6P7Q4; -.
DR OMA; NWGTESY; -.
DR OrthoDB; 1513831at2759; -.
DR PhylomeDB; Q6P7Q4; -.
DR TreeFam; TF105011; -.
DR Reactome; R-RNO-70268; Pyruvate metabolism.
DR SABIO-RK; Q6P7Q4; -.
DR UniPathway; UPA00619; UER00675.
DR PRO; PR:Q6P7Q4; -.
DR Proteomes; UP000002494; Chromosome 20.
DR Bgee; ENSRNOG00000000541; Expressed in quadriceps femoris and 20 other tissues.
DR Genevisible; Q6P7Q4; RN.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0004462; F:lactoylglutathione lyase activity; IDA:RGD.
DR GO; GO:0008270; F:zinc ion binding; ISO:RGD.
DR GO; GO:0005975; P:carbohydrate metabolic process; IDA:RGD.
DR GO; GO:0006749; P:glutathione metabolic process; IDA:RGD.
DR GO; GO:0009438; P:methylglyoxal metabolic process; IDA:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0030316; P:osteoclast differentiation; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD.
DR Gene3D; 3.10.180.10; -; 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 Pfam; PF00903; Glyoxalase; 1.
DR SUPFAM; SSF54593; SSF54593; 1.
DR TIGRFAMs; TIGR00068; glyox_I; 1.
DR PROSITE; PS00934; GLYOXALASE_I_1; 1.
DR PROSITE; PS00935; GLYOXALASE_I_2; 1.
DR PROSITE; PS51819; VOC; 1.
PE 1: Evidence at protein level;
KW Acetylation; Direct protein sequencing; Disulfide bond; Glutathionylation;
KW Lyase; Metal-binding; 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_0000168079"
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 107
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q04760"
FT MOD_RES 139
FT /note="S-glutathionyl cysteine"
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"
SQ SEQUENCE 184 AA; 20820 MW; 1834FA5E9871A1C7 CRC64;
MAEPQPASSG LTDEAALSCC SDPDPSTKDF LLQQTMLRIK DPKKSLDFYT RVLGLTLLQK
LDFPSMKFSL YFLAYEDKND IPKDKTERTA WAFSRKATLE LTHNWGTEDD ETQSYHNGNS
DPRGFGHIGI AVPDVYEACK RFEELGVKFV KKPDDGKMKG LAFVQDPDGY WIEILNPNKM
ATII
