ID LGUL_HUMAN Reviewed; 184 AA. AC Q04760; B2R6P7; B4DDV0; P78375; Q59EL0; Q5TZW3; Q96FC0; Q96J41; DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot. DT 06-MAR-2007, sequence version 4. DT 27-MAR-2024, entry version 225. DE RecName: Full=Lactoylglutathione lyase; DE EC=4.4.1.5 {ECO:0000269|PubMed:20454679, ECO:0000269|PubMed:23122816, ECO:0000269|PubMed:9705294}; 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 Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ALA-111. RX PubMed=7684374; DOI=10.1016/s0021-9258(18)82113-5; RA Kim N.-S., Umezawa Y., Ohmura S., Kato S.; RT "Human glyoxalase I. cDNA cloning, expression, and sequence similarity to RT glyoxalase I from Pseudomonas putida."; RL J. Biol. Chem. 268:11217-11221(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ALA-111. RC TISSUE=Colon; RX PubMed=8449929; DOI=10.1016/s0021-9258(18)53370-6; RA Ranganathan S., Walsh E.S., Godwin A.K., Tew K.D.; RT "Cloning and characterization of human colon glyoxalase-I."; RL J. Biol. Chem. 268:5661-5667(1993). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=8670058; DOI=10.1042/bj3140463; RA Ridderstroem M., Mannervik B.; RT "Optimized heterologous expression of the human zinc enzyme glyoxalase I."; RL Biochem. J. 314:463-467(1996). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-111. RX PubMed=10564821; DOI=10.1016/s0378-1119(99)00420-5; RA Ranganathan S., Ciaccio P.J., Walsh E.S., Tew K.D.; RT "Genomic sequence of human glyoxalase-I: analysis of promoter activity and RT its regulation."; RL Gene 240:149-155(1999). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS RP TYR-19 AND ALA-111. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS TYR-19 AND RP ALA-111. RC TISSUE=Brain, Eye, and Uterus; 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 [10] RP PROTEIN SEQUENCE OF 13-18 AND 128-135, ACTIVITY REGULATION, RP BIOPHYSICOCHEMICAL PROPERTIES, MASS SPECTROMETRY, CLEAVAGE OF INITIATOR RP METHIONINE, ACETYLATION AT ALA-2, GLUTATHIONYLATION AT CYS-139, DISULFIDE RP BONDS, FUNCTION, AND CATALYTIC ACTIVITY. RC TISSUE=Erythrocyte; RX PubMed=20454679; DOI=10.1371/journal.pone.0010399; RA Birkenmeier G., Stegemann C., Hoffmann R., Gunther R., Huse K., RA Birkemeyer C.; RT "Posttranslational modification of human glyoxalase 1 indicates redox- RT dependent regulation."; RL PLoS ONE 5:E10399-E10399(2010). RN [11] RP IDENTIFICATION OF NITRIC OXIDE-MODIFIED FORM, PHOSPHORYLATION, AND RP MUTAGENESIS OF CYS-19; CYS-20; CYS-61 AND CYS-139. RX PubMed=17576200; DOI=10.1042/bj20070379; RA de Hemptinne V., Rondas D., Vandekerckhove J., Vancompernolle K.; RT "Tumour necrosis factor induces phosphorylation primarily of the nitric- RT oxide-responsive form of glyoxalase I."; RL Biochem. J. 407:121-128(2007). RN [12] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [13] RP FUNCTION, PHOSPHORYLATION AT THR-107, MUTAGENESIS OF CYS-19; CYS-20; RP SER-45; SER-69; SER-94; THR-98; THR-102; THR-107 AND CYS-139, AND PTM. RX PubMed=19199007; DOI=10.1007/s11010-009-0031-7; RA de Hemptinne V., Rondas D., Toepoel M., Vancompernolle K.; RT "Phosphorylation on Thr-106 and NO-modification of glyoxalase I suppress RT the TNF-induced transcriptional activity of NF-kappaB."; RL Mol. Cell. Biochem. 325:169-178(2009). RN [14] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-148, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [18] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH S-BENZYL-GLUTATHIONE RP AND ZINC, SUBUNIT, AND ZINC-BINDING SITES. RX PubMed=9218781; DOI=10.1093/emboj/16.12.3386; RA Cameron A.D., Olin B., Ridderstroem M., Mannervik B., Jones T.A.; RT "Crystal structure of human glyoxalase I -- evidence for gene duplication RT and 3D domain swapping."; RL EMBO J. 16:3386-3395(1997). RN [19] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH ZINC AND RP S-HEXYLGLUTATHIONE, CATALYTIC ACTIVITY, FUNCTION, COFACTOR, ACTIVE SITE, RP SUBUNIT, MUTAGENESIS OF GLN-34; GLU-100 AND GLU-173, AND ZINC-BINDING RP SITES. RX PubMed=9705294; DOI=10.1074/jbc.273.34.21623; RA Ridderstroem M., Cameron A.D., Jones T.A., Mannervik B.; RT "Involvement of an active-site Zn2+ ligand in the catalytic mechanism of RT human glyoxalase I."; RL J. Biol. Chem. 273:21623-21628(1998). RN [20] RP X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) IN COMPLEXES WITH RP S-(N-HYDROXY-N-IODOPHENYLCARBAMOYL)GLUTATHIONE; RP S-P-NITROBENZYLOXYCARBONYLGLUTATHIONE AND ZINC, AND ACTIVE SITE. RX PubMed=10521255; DOI=10.1021/bi990696c; RA Cameron A.D., Ridderstroem M., Olin B., Kavarana M.J., Creighton D.J., RA Mannervik B.; RT "Reaction mechanism of glyoxalase I explored by an X-ray crystallographic RT analysis of the human enzyme in complex with a transition state analogue."; RL Biochemistry 38:13480-13490(1999). RN [21] RP X-RAY CRYSTALLOGRAPHY (1.47 ANGSTROMS) IN COMPLEX WITH SYNTHETIC INHIBITOR RP AND ZINC, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, COFACTOR, AND ZINC-BINDING RP SITES. RX PubMed=23122816; DOI=10.1016/j.bmcl.2012.10.045; RA Chiba T., Ohwada J., Sakamoto H., Kobayashi T., Fukami T.A., Irie M., RA Miura T., Ohara K., Koyano H.; RT "Design and evaluation of azaindole-substituted N-hydroxypyridones as RT glyoxalase I inhibitors."; RL Bioorg. Med. Chem. Lett. 22:7486-7489(2012). CC -!- FUNCTION: Catalyzes the conversion of hemimercaptal, formed from CC methylglyoxal and glutathione, to S-lactoylglutathione CC (PubMed:20454679, PubMed:9705294, PubMed:23122816). Involved in the CC regulation of TNF-induced transcriptional activity of NF-kappa-B CC (PubMed:19199007). Required for normal osteoclastogenesis (By CC similarity). {ECO:0000250|UniProtKB:Q9CPU0, CC ECO:0000269|PubMed:19199007, ECO:0000269|PubMed:20454679, CC ECO:0000269|PubMed:23122816, ECO:0000269|PubMed:9705294}. 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:20454679, CC ECO:0000269|PubMed:23122816, ECO:0000269|PubMed:9705294}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:19071; CC Evidence={ECO:0000305|PubMed:9705294}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:23122816, ECO:0000269|PubMed:9705294}; CC Note=Binds 1 zinc ion per subunit. In the homodimer, two zinc ions are CC bound between subunits. {ECO:0000269|PubMed:23122816, CC ECO:0000269|PubMed:9705294}; CC -!- ACTIVITY REGULATION: Regulated by oxidation of Cys-139 in response to CC the redox state of the cell. Results in the alternative formation of CC cystine or glutathione-bound cysteine, the latter modification leading CC to reduced enzyme activity. {ECO:0000269|PubMed:20454679}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=1.3 mM for methylglyoxal/glutathione (native form) CC {ECO:0000269|PubMed:20454679}; CC KM=0.7 mM for methylglyoxal/glutathione (reduced form) CC {ECO:0000269|PubMed:20454679}; CC Vmax=0.335 umol/min/mg enzyme with methylglyoxal/glutathione as CC substrate (native form) {ECO:0000269|PubMed:20454679}; CC Vmax=0.7 umol/min/mg enzyme with methylglyoxal/glutathione as CC substrate (reduced form) {ECO:0000269|PubMed:20454679}; CC Note=Reduction of GLO1 was carried out by incubation with 20 mM CC betamercaptoethanol prior to kinetic analysis.; CC -!- PATHWAY: Secondary metabolite metabolism; methylglyoxal degradation; CC (R)-lactate from methylglyoxal: step 1/2. CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:23122816, CC ECO:0000269|PubMed:9218781, ECO:0000269|PubMed:9705294}. CC -!- INTERACTION: CC Q04760; Q3MIT2: PUS10; NbExp=3; IntAct=EBI-1055525, EBI-11983583; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q04760-1; Sequence=Displayed; CC Name=2; CC IsoId=Q04760-2; Sequence=VSP_041632; CC -!- PTM: Glutathionylation at Cys-139 inhibits enzyme activity. CC {ECO:0000269|PubMed:20454679}. 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 {ECO:0000269|PubMed:17576200, ECO:0000269|PubMed:19199007}. 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. {ECO:0000269|PubMed:19199007}. CC -!- MASS SPECTROMETRY: [Isoform 1]: Mass=20687.4; Method=Electrospray; CC Note=Variant Glu-111. The measured range is 2-184.; CC Evidence={ECO:0000269|PubMed:20454679}; CC -!- MASS SPECTROMETRY: [Isoform 1]: Mass=20629.7; Method=Electrospray; CC Note=Variant Ala-111. The measured range is 2-184.; CC Evidence={ECO:0000269|PubMed:20454679}; CC -!- POLYMORPHISM: Exists in three separable isoforms which originate from CC two alleles in the genome. These correspond to two homodimers and one CC heterodimer composed of two subunits showing different electrophoretic CC properties. CC -!- SIMILARITY: Belongs to the glyoxalase I family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAD93038.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={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; D13315; BAA02572.1; -; mRNA. DR EMBL; L07837; AAA52565.1; -; mRNA. DR EMBL; S83285; AAB49495.1; -; mRNA. DR EMBL; AF146651; AAD38008.1; -; Genomic_DNA. DR EMBL; AB209801; BAD93038.1; ALT_INIT; mRNA. DR EMBL; AK293345; BAG56861.1; -; mRNA. DR EMBL; AK312662; BAG35544.1; -; mRNA. DR EMBL; BT019987; AAV38790.1; -; mRNA. DR EMBL; BT019988; AAV38791.1; -; mRNA. DR EMBL; AL391415; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC001741; AAH01741.1; -; mRNA. DR EMBL; BC011365; AAH11365.1; -; mRNA. DR EMBL; BC015934; AAH15934.1; -; mRNA. DR CCDS; CCDS4837.1; -. [Q04760-1] DR PIR; A46714; A46714. DR PIR; S63603; S63603. DR RefSeq; NP_006699.2; NM_006708.2. [Q04760-1] DR PDB; 1BH5; X-ray; 2.20 A; A/B/C/D=2-184. DR PDB; 1FRO; X-ray; 2.20 A; A/B/C/D=2-184. DR PDB; 1QIN; X-ray; 2.00 A; A/B=2-184. DR PDB; 1QIP; X-ray; 1.72 A; A/B/C/D=2-184. DR PDB; 3VW9; X-ray; 1.47 A; A/B=1-184. DR PDB; 3W0T; X-ray; 1.35 A; A/B/C/D=1-184. DR PDB; 3W0U; X-ray; 1.70 A; A/B=1-184. DR PDB; 7WSZ; X-ray; 1.52 A; A/B=1-184. DR PDB; 7WT0; X-ray; 2.00 A; A/B=1-184. DR PDB; 7WT1; X-ray; 1.85 A; A/B=1-184. DR PDB; 7WT2; X-ray; 2.00 A; A/B=1-184. DR PDBsum; 1BH5; -. DR PDBsum; 1FRO; -. DR PDBsum; 1QIN; -. DR PDBsum; 1QIP; -. DR PDBsum; 3VW9; -. DR PDBsum; 3W0T; -. DR PDBsum; 3W0U; -. DR PDBsum; 7WSZ; -. DR PDBsum; 7WT0; -. DR PDBsum; 7WT1; -. DR PDBsum; 7WT2; -. DR AlphaFoldDB; Q04760; -. DR SMR; Q04760; -. DR BioGRID; 109001; 96. DR IntAct; Q04760; 26. DR MINT; Q04760; -. DR STRING; 9606.ENSP00000362463; -. DR BindingDB; Q04760; -. DR ChEMBL; CHEMBL2424; -. DR DrugBank; DB00143; Glutathione. DR DrugBank; DB00328; Indomethacin. DR DrugBank; DB03345; Mercaptoethanol. DR DrugBank; DB08179; methyl 4-(2,3-dihydroxy-5-methylphenoxy)-2-hydroxy-6-methylbenzoate. DR DrugBank; DB03330; S-(N-hydroxy-N-iodophenylcarbamoyl)glutathione. DR DrugBank; DB03602; S-benzylglutathione. DR DrugBank; DB04132; S-Hexylglutathione. DR DrugBank; DB03130; S-P-Nitrobenzyloxycarbonylglutathione. DR DrugCentral; Q04760; -. DR GlyGen; Q04760; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q04760; -. DR MetOSite; Q04760; -. DR PhosphoSitePlus; Q04760; -. DR SwissPalm; Q04760; -. DR BioMuta; GLO1; -. DR DMDM; 134039205; -. DR OGP; Q04760; -. DR REPRODUCTION-2DPAGE; IPI00220766; -. DR REPRODUCTION-2DPAGE; Q04760; -. DR CPTAC; CPTAC-1416; -. DR CPTAC; CPTAC-1417; -. DR CPTAC; CPTAC-1418; -. DR CPTAC; CPTAC-1419; -. DR CPTAC; CPTAC-1420; -. DR EPD; Q04760; -. DR jPOST; Q04760; -. DR MassIVE; Q04760; -. DR MaxQB; Q04760; -. DR PaxDb; 9606-ENSP00000362463; -. DR PeptideAtlas; Q04760; -. DR ProteomicsDB; 58281; -. [Q04760-1] DR ProteomicsDB; 58282; -. [Q04760-2] DR Pumba; Q04760; -. DR Antibodypedia; 29872; 560 antibodies from 38 providers. DR CPTC; Q04760; 3 antibodies. DR DNASU; 2739; -. DR Ensembl; ENST00000373365.5; ENSP00000362463.3; ENSG00000124767.7. [Q04760-1] DR GeneID; 2739; -. DR KEGG; hsa:2739; -. DR MANE-Select; ENST00000373365.5; ENSP00000362463.3; NM_006708.3; NP_006699.2. DR AGR; HGNC:4323; -. DR CTD; 2739; -. DR DisGeNET; 2739; -. DR GeneCards; GLO1; -. DR HGNC; HGNC:4323; GLO1. DR HPA; ENSG00000124767; Low tissue specificity. DR MIM; 138750; gene. DR neXtProt; NX_Q04760; -. DR OpenTargets; ENSG00000124767; -. DR PharmGKB; PA28724; -. DR VEuPathDB; HostDB:ENSG00000124767; -. DR eggNOG; KOG2944; Eukaryota. DR GeneTree; ENSGT00390000009312; -. DR HOGENOM; CLU_046006_1_1_1; -. DR InParanoid; Q04760; -. DR OMA; THNWDTP; -. DR OrthoDB; 245930at2759; -. DR PhylomeDB; Q04760; -. DR TreeFam; TF105011; -. DR BRENDA; 4.4.1.5; 2681. DR PathwayCommons; Q04760; -. DR Reactome; R-HSA-70268; Pyruvate metabolism. DR SABIO-RK; Q04760; -. DR SignaLink; Q04760; -. DR SIGNOR; Q04760; -. DR UniPathway; UPA00619; UER00675. DR BioGRID-ORCS; 2739; 11 hits in 1151 CRISPR screens. DR ChiTaRS; GLO1; human. DR EvolutionaryTrace; Q04760; -. DR GeneWiki; GLO1; -. DR GeneWiki; Lactoylglutathione_lyase; -. DR GenomeRNAi; 2739; -. DR Pharos; Q04760; Tchem. DR PRO; PR:Q04760; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q04760; Protein. DR Bgee; ENSG00000124767; Expressed in corpus epididymis and 215 other cell types or tissues. DR ExpressionAtlas; Q04760; baseline and differential. DR GO; GO:0005737; C:cytoplasm; TAS:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. 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; NAS:ProtInc. DR GO; GO:0006749; P:glutathione metabolic process; IEA:Ensembl. DR GO; GO:0009438; P:methylglyoxal metabolic process; IEA:Ensembl. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0030316; P:osteoclast differentiation; ISS:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IEA:Ensembl. 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. DR Genevisible; Q04760; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Direct protein sequencing; KW Disulfide bond; Glutathionylation; Lyase; Metal-binding; Phosphoprotein; KW Reference proteome; Zinc. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:20454679, FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:25944712" FT CHAIN 2..184 FT /note="Lactoylglutathione lyase" FT /id="PRO_0000168076" 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:0000269|PubMed:10521255, FT ECO:0000269|PubMed:9705294" FT BINDING 34 FT /ligand="substrate" FT /ligand_note="ligand shared between dimeric partners" 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:23122816, FT ECO:0000269|PubMed:9218781, ECO:0000269|PubMed:9705294" FT BINDING 38 FT /ligand="substrate" FT /ligand_note="ligand shared between dimeric partners" 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:23122816, FT ECO:0000269|PubMed:9218781, ECO:0000269|PubMed:9705294" FT BINDING 104 FT /ligand="substrate" FT /ligand_note="ligand shared between dimeric partners" FT BINDING 123 FT /ligand="substrate" FT /ligand_note="ligand shared between dimeric partners" FT /note="in other chain" FT BINDING 127 FT /ligand="substrate" FT /ligand_note="ligand shared between dimeric partners" FT /note="in other chain" 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:23122816, FT ECO:0000269|PubMed:9218781, ECO:0000269|PubMed:9705294" FT BINDING 157..158 FT /ligand="substrate" FT /ligand_note="ligand shared between dimeric partners" FT /note="in other chain" 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:23122816, FT ECO:0000269|PubMed:9218781, ECO:0000269|PubMed:9705294" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000269|PubMed:20454679, FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:25944712" FT MOD_RES 88 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q9CPU0" FT MOD_RES 107 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:19199007" FT MOD_RES 139 FT /note="S-glutathionyl cysteine; alternate" FT /evidence="ECO:0000269|PubMed:20454679" FT MOD_RES 148 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 148 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q9CPU0" FT DISULFID 19..20 FT /evidence="ECO:0000269|PubMed:20454679" FT DISULFID 61..139 FT /note="Alternate" FT /evidence="ECO:0000269|PubMed:20454679" FT VAR_SEQ 105..119 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_041632" FT VARIANT 19 FT /note="C -> Y (in dbSNP:rs17855424)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334" FT /id="VAR_031078" FT VARIANT 111 FT /note="E -> A (in dbSNP:rs4746)" FT /evidence="ECO:0000269|PubMed:10564821, FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:7684374, ECO:0000269|PubMed:8449929" FT /id="VAR_013481" FT MUTAGEN 19 FT /note="C->A: No effect on NO-mediated modification. FT Impaired NO-mediated modification; when associated with FT A-20. Loss of NO-mediated modification; when associated FT with A-139." FT /evidence="ECO:0000269|PubMed:17576200, FT ECO:0000269|PubMed:19199007" FT MUTAGEN 20 FT /note="C->A: No effect on NO-mediated modification. FT Impaired NO-mediated modification; when associated with FT A-19. Loss of NO-mediated modification; when associated FT with A-139." FT /evidence="ECO:0000269|PubMed:17576200, FT ECO:0000269|PubMed:19199007" FT MUTAGEN 34 FT /note="Q->E: Reduces enzyme activity by 99%." FT /evidence="ECO:0000269|PubMed:9705294" FT MUTAGEN 45 FT /note="S->A: No effect on phosphorylation." FT /evidence="ECO:0000269|PubMed:19199007" FT MUTAGEN 61 FT /note="C->A: No effect on NO-mediated modification." FT /evidence="ECO:0000269|PubMed:17576200" FT MUTAGEN 69 FT /note="S->A: No effect on phosphorylation." FT /evidence="ECO:0000269|PubMed:19199007" FT MUTAGEN 94 FT /note="S->A: No effect on phosphorylation." FT /evidence="ECO:0000269|PubMed:19199007" FT MUTAGEN 98 FT /note="T->A: No effect on phosphorylation." FT /evidence="ECO:0000269|PubMed:19199007" FT MUTAGEN 100 FT /note="E->Q: Reduces enzyme activity by over 99%." FT /evidence="ECO:0000269|PubMed:9705294" FT MUTAGEN 102 FT /note="T->A: No effect on phosphorylation." FT /evidence="ECO:0000269|PubMed:19199007" FT MUTAGEN 107 FT /note="T->A: Loss of phosphorylation." FT /evidence="ECO:0000269|PubMed:19199007" FT MUTAGEN 139 FT /note="C->A: Impaired NO-mediated modification. Loss of FT NO-mediated modification; when associated with A-19 or FT A-20." FT /evidence="ECO:0000269|PubMed:17576200, FT ECO:0000269|PubMed:19199007" FT MUTAGEN 173 FT /note="E->Q: Abolishes enzyme activity." FT /evidence="ECO:0000269|PubMed:9705294" FT HELIX 13..18 FT /evidence="ECO:0007829|PDB:3W0T" FT HELIX 25..27 FT /evidence="ECO:0007829|PDB:3W0T" FT STRAND 31..38 FT /evidence="ECO:0007829|PDB:3W0T" FT HELIX 42..51 FT /evidence="ECO:0007829|PDB:3W0T" FT STRAND 56..63 FT /evidence="ECO:0007829|PDB:3W0T" FT TURN 64..67 FT /evidence="ECO:0007829|PDB:3W0T" FT STRAND 68..75 FT /evidence="ECO:0007829|PDB:3W0T" FT HELIX 78..80 FT /evidence="ECO:0007829|PDB:3W0T" FT HELIX 85..92 FT /evidence="ECO:0007829|PDB:3W0T" FT STRAND 95..104 FT /evidence="ECO:0007829|PDB:3W0T" FT HELIX 107..109 FT /evidence="ECO:0007829|PDB:3W0T" FT STRAND 118..122 FT /evidence="ECO:0007829|PDB:3W0T" FT STRAND 124..131 FT /evidence="ECO:0007829|PDB:3W0T" FT HELIX 135..144 FT /evidence="ECO:0007829|PDB:3W0T" FT STRAND 149..151 FT /evidence="ECO:0007829|PDB:3W0T" FT STRAND 155..158 FT /evidence="ECO:0007829|PDB:3W0T" FT STRAND 162..165 FT /evidence="ECO:0007829|PDB:3W0T" FT STRAND 171..175 FT /evidence="ECO:0007829|PDB:3W0T" FT HELIX 177..179 FT /evidence="ECO:0007829|PDB:3W0T" FT HELIX 181..183 FT /evidence="ECO:0007829|PDB:3W0T" SQ SEQUENCE 184 AA; 20778 MW; 46291B7878070028 CRC64; MAEPQPPSGG LTDEAALSCC SDADPSTKDF LLQQTMLRVK DPKKSLDFYT RVLGMTLIQK CDFPIMKFSL YFLAYEDKND IPKEKDEKIA WALSRKATLE LTHNWGTEDD ETQSYHNGNS DPRGFGHIGI AVPDVYSACK RFEELGVKFV KKPDDGKMKG LAFIQDPDGY WIEILNPNKM ATLM //