LGUL_MOUSE
ID LGUL_MOUSE Reviewed; 184 AA.
AC Q9CPU0; Q543L3; Q8R3T1;
DT 06-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Lactoylglutathione lyase;
DE EC=4.4.1.5 {ECO:0000269|PubMed:18695250};
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RC TISSUE=Embryo, Kidney, Liver, Medulla oblongata, and Spinal cord;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and Czech II; TISSUE=Brain, and Mammary gland;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND EXPRESSION IN CD-1 STRAIN.
RX PubMed=15858064; DOI=10.1523/jneurosci.0115-05.2005;
RA Kroemer S.A., Kessler M.S., Milfay D., Birg I.N., Bunck M., Czibere L.,
RA Panhuysen M., Puetz B., Deussing J.M., Holsboer F., Landgraf R.,
RA Turck C.W.;
RT "Identification of glyoxalase-I as a protein marker in a mouse model of
RT extremes in trait anxiety.";
RL J. Neurosci. 25:4375-4384(2005).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-88 AND LYS-148, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH METHYL-GERFELIN,
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, SUBUNIT, AND
RP ZINC-BINDING SITES.
RX PubMed=18695250; DOI=10.1073/pnas.0712239105;
RA Kawatani M., Okumura H., Honda K., Kanoh N., Muroi M., Dohmae N.,
RA Takami M., Kitagawa M., Futamura Y., Imoto M., Osada H.;
RT "The identification of an osteoclastogenesis inhibitor through the
RT inhibition of glyoxalase I.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:11691-11696(2008).
CC -!- FUNCTION: Catalyzes the conversion of hemimercaptal, formed from
CC methylglyoxal and glutathione, to S-lactoylglutathione
CC (PubMed:18695250). Involved in the regulation of TNF-induced
CC transcriptional activity of NF-kappa-B (By similarity). Required for
CC normal osteoclastogenesis (PubMed:18695250).
CC {ECO:0000250|UniProtKB:Q04760, ECO:0000269|PubMed:18695250}.
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:0000269|PubMed:18695250};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:19071;
CC Evidence={ECO:0000305|PubMed:18695250};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:18695250};
CC Note=Binds 1 zinc ion per subunit. In the homodimer, two zinc ions are
CC bound between subunits. {ECO:0000269|PubMed:18695250};
CC -!- ACTIVITY REGULATION: Subject to competitive inhibition by methyl-
CC gerfelin. {ECO:0000269|PubMed:18695250}.
CC -!- PATHWAY: Secondary metabolite metabolism; methylglyoxal degradation;
CC (R)-lactate from methylglyoxal: step 1/2.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:18695250}.
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 -!- MISCELLANEOUS: Expressed at higher levels in CD-1 mice which have been
CC bred for low-anxiety-related behavior than in those which have been
CC bred for high-anxiety-related behavior.
CC -!- SIMILARITY: Belongs to the glyoxalase I family. {ECO:0000305}.
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DR EMBL; AK002386; BAB22060.1; -; mRNA.
DR EMBL; AK003567; BAB22863.1; -; mRNA.
DR EMBL; AK005055; BAB23781.1; -; mRNA.
DR EMBL; AK031832; BAC27570.1; -; mRNA.
DR EMBL; AK049703; BAC33882.1; -; mRNA.
DR EMBL; BC024663; AAH24663.1; -; mRNA.
DR EMBL; BC081432; AAH81432.1; -; mRNA.
DR CCDS; CCDS28600.1; -.
DR RefSeq; NP_001107032.1; NM_001113560.1.
DR RefSeq; NP_079650.3; NM_025374.3.
DR PDB; 2ZA0; X-ray; 1.70 A; A/B=1-184.
DR PDB; 4KYH; X-ray; 2.50 A; A/B=1-184.
DR PDB; 4KYK; X-ray; 2.00 A; A/B=1-184.
DR PDB; 4OPN; X-ray; 2.10 A; A/B=1-184.
DR PDB; 4PV5; X-ray; 2.30 A; A/B=2-184.
DR PDB; 4X2A; X-ray; 2.00 A; A/B=1-184.
DR PDB; 6L0U; X-ray; 1.95 A; A/B=6-184.
DR PDBsum; 2ZA0; -.
DR PDBsum; 4KYH; -.
DR PDBsum; 4KYK; -.
DR PDBsum; 4OPN; -.
DR PDBsum; 4PV5; -.
DR PDBsum; 4X2A; -.
DR PDBsum; 6L0U; -.
DR AlphaFoldDB; Q9CPU0; -.
DR SMR; Q9CPU0; -.
DR BioGRID; 225051; 3.
DR IntAct; Q9CPU0; 1.
DR STRING; 10090.ENSMUSP00000024823; -.
DR BindingDB; Q9CPU0; -.
DR ChEMBL; CHEMBL2175; -.
DR iPTMnet; Q9CPU0; -.
DR PhosphoSitePlus; Q9CPU0; -.
DR SwissPalm; Q9CPU0; -.
DR REPRODUCTION-2DPAGE; IPI00321734; -.
DR REPRODUCTION-2DPAGE; Q9CPU0; -.
DR UCD-2DPAGE; Q9CPU0; -.
DR CPTAC; non-CPTAC-3926; -.
DR EPD; Q9CPU0; -.
DR jPOST; Q9CPU0; -.
DR MaxQB; Q9CPU0; -.
DR PaxDb; Q9CPU0; -.
DR PRIDE; Q9CPU0; -.
DR ProteomicsDB; 291944; -.
DR Antibodypedia; 29872; 516 antibodies from 38 providers.
DR DNASU; 109801; -.
DR Ensembl; ENSMUST00000167624; ENSMUSP00000126586; ENSMUSG00000024026.
DR Ensembl; ENSMUST00000235547; ENSMUSP00000157858; ENSMUSG00000024026.
DR Ensembl; ENSMUST00000236335; ENSMUSP00000158296; ENSMUSG00000024026.
DR GeneID; 109801; -.
DR KEGG; mmu:109801; -.
DR UCSC; uc012aos.1; mouse.
DR CTD; 2739; -.
DR MGI; MGI:95742; Glo1.
DR VEuPathDB; HostDB:ENSMUSG00000024026; -.
DR eggNOG; KOG2944; Eukaryota.
DR GeneTree; ENSGT00390000009312; -.
DR HOGENOM; CLU_046006_1_1_1; -.
DR InParanoid; Q9CPU0; -.
DR OMA; NWGTESY; -.
DR OrthoDB; 1513831at2759; -.
DR PhylomeDB; Q9CPU0; -.
DR TreeFam; TF105011; -.
DR BRENDA; 4.4.1.5; 3474.
DR Reactome; R-MMU-70268; Pyruvate metabolism.
DR UniPathway; UPA00619; UER00675.
DR BioGRID-ORCS; 109801; 4 hits in 72 CRISPR screens.
DR ChiTaRS; Glo1; mouse.
DR EvolutionaryTrace; Q9CPU0; -.
DR PRO; PR:Q9CPU0; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q9CPU0; protein.
DR Bgee; ENSMUSG00000024026; Expressed in pineal body and 259 other tissues.
DR ExpressionAtlas; Q9CPU0; baseline and differential.
DR Genevisible; Q9CPU0; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0004462; F:lactoylglutathione lyase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0005975; P:carbohydrate metabolic process; ISO:MGI.
DR GO; GO:0006749; P:glutathione metabolic process; ISO:MGI.
DR GO; GO:0019243; P:methylglyoxal catabolic process to D-lactate via S-lactoyl-glutathione; IC:MGI.
DR GO; GO:0009438; P:methylglyoxal metabolic process; ISO:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0030316; P:osteoclast differentiation; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
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 3D-structure; Acetylation; Disulfide bond; Glutathionylation; Lyase;
KW 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_0000168078"
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:0007744|PDB:2ZA0, ECO:0007744|PDB:4OPN,
FT ECO:0007744|PDB:4X2A"
FT BINDING 34
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|PubMed:18695250,
FT ECO:0007744|PDB:4OPN"
FT BINDING 38
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0007744|PDB:4KYH, ECO:0007744|PDB:4OPN"
FT BINDING 100
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|PubMed:18695250,
FT ECO:0007744|PDB:4OPN"
FT BINDING 104
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0007744|PDB:4KYH, ECO:0007744|PDB:4OPN"
FT BINDING 123
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0007744|PDB:4OPN"
FT BINDING 127
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0007744|PDB:4OPN, ECO:0007744|PDB:4X2A"
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:0000269|PubMed:18695250,
FT ECO:0007744|PDB:4OPN"
FT BINDING 157..158
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0007744|PDB:4OPN"
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:0000269|PubMed:18695250,
FT ECO:0007744|PDB:4OPN"
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:0007744|PubMed:23806337"
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:0007744|PubMed:23806337"
FT DISULFID 19..20
FT /evidence="ECO:0000250"
FT CONFLICT 92
FT /note="T -> M (in Ref. 2; AAH24663)"
FT /evidence="ECO:0000305"
FT STRAND 7..9
FT /evidence="ECO:0007829|PDB:4PV5"
FT HELIX 13..18
FT /evidence="ECO:0007829|PDB:2ZA0"
FT HELIX 25..27
FT /evidence="ECO:0007829|PDB:2ZA0"
FT STRAND 31..38
FT /evidence="ECO:0007829|PDB:2ZA0"
FT HELIX 42..51
FT /evidence="ECO:0007829|PDB:2ZA0"
FT STRAND 56..63
FT /evidence="ECO:0007829|PDB:2ZA0"
FT HELIX 64..66
FT /evidence="ECO:0007829|PDB:2ZA0"
FT STRAND 68..75
FT /evidence="ECO:0007829|PDB:2ZA0"
FT HELIX 78..80
FT /evidence="ECO:0007829|PDB:2ZA0"
FT HELIX 85..92
FT /evidence="ECO:0007829|PDB:2ZA0"
FT STRAND 95..104
FT /evidence="ECO:0007829|PDB:2ZA0"
FT HELIX 107..109
FT /evidence="ECO:0007829|PDB:2ZA0"
FT STRAND 118..122
FT /evidence="ECO:0007829|PDB:2ZA0"
FT STRAND 125..131
FT /evidence="ECO:0007829|PDB:2ZA0"
FT HELIX 135..144
FT /evidence="ECO:0007829|PDB:2ZA0"
FT STRAND 149..151
FT /evidence="ECO:0007829|PDB:2ZA0"
FT STRAND 155..158
FT /evidence="ECO:0007829|PDB:2ZA0"
FT STRAND 162..165
FT /evidence="ECO:0007829|PDB:2ZA0"
FT STRAND 171..175
FT /evidence="ECO:0007829|PDB:2ZA0"
FT TURN 177..179
FT /evidence="ECO:0007829|PDB:2ZA0"
FT HELIX 180..182
FT /evidence="ECO:0007829|PDB:2ZA0"
SQ SEQUENCE 184 AA; 20810 MW; F6B5667A65454D18 CRC64;
MAEPQPASSG LTDETAFSCC SDPDPSTKDF LLQQTMLRIK DPKKSLDFYT RVLGLTLLQK
LDFPAMKFSL YFLAYEDKND IPKDKSEKTA WTFSRKATLE LTHNWGTEDD ETQSYHNGNS
DPRGFGHIGI AVPDVYSACK RFEELGVKFV KKPDDGKMKG LAFIQDPDGY WIEILNPNKI
ATII
