LGUL_HUMAN
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 03-AUG-2022, entry version 216.
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};
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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; 75.
DR IntAct; Q04760; 21.
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; Q04760; -.
DR PeptideAtlas; Q04760; -.
DR PRIDE; Q04760; -.
DR ProteomicsDB; 58281; -. [Q04760-1]
DR ProteomicsDB; 58282; -. [Q04760-2]
DR Antibodypedia; 29872; 516 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 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; NWGTESY; -.
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 UniPathway; UPA00619; UER00675.
DR BioGRID-ORCS; 2739; 10 hits in 1071 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 213 other tissues.
DR ExpressionAtlas; Q04760; baseline and differential.
DR Genevisible; Q04760; HS.
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 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; 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 A-
FT 20. Loss of NO-mediated modification; when associated with
FT 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 A-
FT 19. Loss of NO-mediated modification; when associated with
FT 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 NO-
FT mediated modification; when associated with A-19 or 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
