Full text data of GLO1
GLO1
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Lactoylglutathione lyase; 4.4.1.5 (Aldoketomutase; Glyoxalase I; Glx I; Ketone-aldehyde mutase; Methylglyoxalase; S-D-lactoylglutathione methylglyoxal lyase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Lactoylglutathione lyase; 4.4.1.5 (Aldoketomutase; Glyoxalase I; Glx I; Ketone-aldehyde mutase; Methylglyoxalase; S-D-lactoylglutathione methylglyoxal lyase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00220766
IPI00220766 Lactoylglutathione lyase Glyoxalase I, Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00220766 Lactoylglutathione lyase Glyoxalase I, Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
Q04760
ID LGUL_HUMAN Reviewed; 184 AA.
AC Q04760; B2R6P7; B4DDV0; P78375; Q59EL0; Q5TZW3; Q96FC0; Q96J41;
read moreDT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 4.
DT 22-JAN-2014, entry version 149.
DE RecName: Full=Lactoylglutathione lyase;
DE EC=4.4.1.5;
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ALA-111.
RX PubMed=7684374;
RA Kim N.-S., Umezawa Y., Ohmura S., Kato S.;
RT "Human glyoxalase I. cDNA cloning, expression, and sequence similarity
RT to 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;
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;
RA Ridderstroem M., Mannervik B.;
RT "Optimized heterologous expression of the human zinc enzyme glyoxalase
RT 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
RT and 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
RP VARIANTS 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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
RT 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.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA 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.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., 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
RP TYR-19 AND 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP PROTEIN SEQUENCE OF 13-18 AND 128-135, ENZYME REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, MASS SPECTROMETRY, CLEAVAGE OF
RP INITIATOR METHIONINE, ACETYLATION AT ALA-2, GLUTATHIONYLATION AT
RP CYS-139, AND DISULFIDE BONDS.
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
RT nitric-oxide-responsive form of glyoxalase I.";
RL Biochem. J. 407:121-128(2007).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
RP FUNCTION, PHOSPHORYLATION AT THR-107, AND MUTAGENESIS OF CYS-19;
RP CYS-20; SER-45; SER-69; SER-94; THR-98; THR-102; THR-107 AND CYS-139.
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
RT suppress 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 MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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.,
RA Buerckstuemmer T., 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 X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH
RP S-BENZYL-GLUTATHIONE AND ZINC.
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
RT duplication and 3D domain swapping.";
RL EMBO J. 16:3386-3395(1997).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH ZINC AND
RP S-HEXYLGLUTATHIONE, CATALYTIC ACTIVITY, FUNCTION, COFACTOR, ACTIVE
RP SITE, SUBUNIT, AND MUTAGENESIS OF GLN-34; GLU-100 AND GLU-173.
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
RT of human glyoxalase I.";
RL J. Biol. Chem. 273:21623-21628(1998).
RN [18]
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
RT crystallographic analysis of the human enzyme in complex with a
RT transition state analogue.";
RL Biochemistry 38:13480-13490(1999).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.47 ANGSTROMS) IN COMPLEX WITH SYNTHETIC
RP INHIBITOR AND ZINC, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND
RP COFACTOR.
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. Involved
CC in the regulation of TNF-induced transcriptional activity of NF-
CC kappa-B. Required for normal osteoclastogenesis.
CC -!- CATALYTIC ACTIVITY: (R)-S-lactoylglutathione = glutathione +
CC methylglyoxal.
CC -!- COFACTOR: Binds 1 zinc ion per subunit. In the homodimer, two zinc
CC ions are bound between subunits.
CC -!- ENZYME REGULATION: Regulated by oxidation of Cys-139 in response
CC to the redox state of the cell. Results in the alternative
CC formation of cystine or glutathione-bound cysteine, the latter
CC modification leading to reduced enzyme activity.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.3 mM for methylglyoxal/glutathione (native form);
CC KM=0.7 mM for methylglyoxal/glutathione (reduced form);
CC Vmax=0.335 umol/min/mg enzyme with methylglyoxal/glutathione as
CC substrate (native form);
CC Vmax=0.7 umol/min/mg enzyme with methylglyoxal/glutathione as
CC substrate (reduced form);
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
CC degradation; (R)-lactate from methylglyoxal: step 1/2.
CC -!- SUBUNIT: Homodimer.
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 Note=No experimental confirmation available;
CC -!- PTM: Glutathionylation at Cys-139 inhibits enzyme activity.
CC -!- PTM: Phosphorylated at Thr-107 in the presence of CaMK2. However,
CC this is a consensus site for phosphorylation by CK2 so
CC phosphorylation may be mediated by CK2 rather than CaMK2.
CC Phosphorylation is induced by TNF and suppresses the TNF-induced
CC transcriptional activity of NF-kappa-B.
CC -!- PTM: Exists in a nitric oxide (NO)-modified form. The exact nature
CC of the modification is unknown, but it suppresses the TNF-induced
CC transcriptional activity of NF-kappa-B.
CC -!- MASS SPECTROMETRY: Mass=20687.4; Method=Electrospray; Range=2-184
CC (Q04760-1); Note=Variant Glu-111; Source=PubMed:20454679;
CC -!- MASS SPECTROMETRY: Mass=20629.7; Method=Electrospray; Range=2-184
CC (Q04760-1); Note=Variant Ala-111; Source=PubMed:20454679;
CC -!- POLYMORPHISM: Exists in three separable isoforms which originate
CC from two alleles in the genome. These correspond to two homodimers
CC and one heterodimer composed of two subunits showing different
CC electrophoretic properties.
CC -!- SIMILARITY: Belongs to the glyoxalase I family.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD93038.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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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; CAI21586.1; -; Genomic_DNA.
DR EMBL; BC001741; AAH01741.1; -; mRNA.
DR EMBL; BC011365; AAH11365.1; -; mRNA.
DR EMBL; BC015934; AAH15934.1; -; mRNA.
DR PIR; A46714; A46714.
DR PIR; S63603; S63603.
DR RefSeq; NP_006699.2; NM_006708.2.
DR UniGene; Hs.268849; -.
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 PDBsum; 1BH5; -.
DR PDBsum; 1FRO; -.
DR PDBsum; 1QIN; -.
DR PDBsum; 1QIP; -.
DR PDBsum; 3VW9; -.
DR PDBsum; 3W0T; -.
DR PDBsum; 3W0U; -.
DR ProteinModelPortal; Q04760; -.
DR SMR; Q04760; 9-184.
DR IntAct; Q04760; 3.
DR STRING; 9606.ENSP00000362463; -.
DR BindingDB; Q04760; -.
DR ChEMBL; CHEMBL2424; -.
DR DrugBank; DB00143; Glutathione.
DR PhosphoSite; Q04760; -.
DR DMDM; 134039205; -.
DR OGP; Q04760; -.
DR REPRODUCTION-2DPAGE; IPI00220766; -.
DR REPRODUCTION-2DPAGE; Q04760; -.
DR PaxDb; Q04760; -.
DR PRIDE; Q04760; -.
DR DNASU; 2739; -.
DR Ensembl; ENST00000373365; ENSP00000362463; ENSG00000124767.
DR GeneID; 2739; -.
DR KEGG; hsa:2739; -.
DR UCSC; uc003ooc.3; human.
DR CTD; 2739; -.
DR GeneCards; GC06M038643; -.
DR HGNC; HGNC:4323; GLO1.
DR HPA; CAB040541; -.
DR HPA; CAB040542; -.
DR MIM; 138750; gene.
DR neXtProt; NX_Q04760; -.
DR PharmGKB; PA28724; -.
DR eggNOG; COG0346; -.
DR HOVERGEN; HBG025852; -.
DR InParanoid; Q04760; -.
DR KO; K01759; -.
DR OMA; YWVEIIQ; -.
DR OrthoDB; EOG7XPZ6W; -.
DR PhylomeDB; Q04760; -.
DR BRENDA; 4.4.1.5; 2681.
DR SABIO-RK; Q04760; -.
DR UniPathway; UPA00619; UER00675.
DR EvolutionaryTrace; Q04760; -.
DR GeneWiki; GLO1; -.
DR GeneWiki; Lactoylglutathione_lyase; -.
DR GenomeRNAi; 2739; -.
DR NextBio; 10796; -.
DR PRO; PR:Q04760; -.
DR Bgee; Q04760; -.
DR CleanEx; HS_GLO1; -.
DR Genevestigator; Q04760; -.
DR GO; GO:0005737; C:cytoplasm; TAS:UniProtKB.
DR GO; GO:0004462; F:lactoylglutathione lyase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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:0006357; P:regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
DR InterPro; IPR004360; Glyas_Fos-R_dOase_dom.
DR InterPro; IPR004361; Glyoxalase_1.
DR InterPro; IPR018146; Glyoxalase_1_CS.
DR Pfam; PF00903; Glyoxalase; 1.
DR TIGRFAMs; TIGR00068; glyox_I; 1.
DR PROSITE; PS00934; GLYOXALASE_I_1; 1.
DR PROSITE; PS00935; GLYOXALASE_I_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Glutathionylation; Lyase;
KW Metal-binding; Phosphoprotein; Polymorphism; Reference proteome; Zinc.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 184 Lactoylglutathione lyase.
FT /FTId=PRO_0000168076.
FT REGION 157 158 Substrate binding.
FT ACT_SITE 173 173 Proton donor/acceptor.
FT METAL 34 34 Zinc; shared with dimeric partner.
FT METAL 100 100 Zinc; shared with dimeric partner.
FT METAL 127 127 Zinc; via tele nitrogen.
FT METAL 173 173 Zinc.
FT BINDING 34 34 Substrate; shared with dimeric partner.
FT BINDING 38 38 Substrate; shared with dimeric partner.
FT BINDING 104 104 Substrate; shared with dimeric partner.
FT BINDING 123 123 Substrate.
FT BINDING 127 127 Substrate.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 107 107 Phosphothreonine.
FT MOD_RES 139 139 S-glutathionyl cysteine; alternate.
FT MOD_RES 148 148 N6-acetyllysine.
FT DISULFID 19 20
FT DISULFID 61 139 Alternate; alternate.
FT VAR_SEQ 105 119 Missing (in isoform 2).
FT /FTId=VSP_041632.
FT VARIANT 19 19 C -> Y (in dbSNP:rs17855424).
FT /FTId=VAR_031078.
FT VARIANT 111 111 E -> A (in dbSNP:rs4746).
FT /FTId=VAR_013481.
FT MUTAGEN 19 19 C->A: No effect on NO-mediated
FT modification. Impaired NO-mediated
FT modification; when associated with A-20.
FT Loss of NO-mediated modification; when
FT associated with A-139.
FT MUTAGEN 20 20 C->A: No effect on NO-mediated
FT modification. Impaired NO-mediated
FT modification; when associated with A-19.
FT Loss of NO-mediated modification; when
FT associated with A-139.
FT MUTAGEN 34 34 Q->E: Reduces enzyme activity by 99%.
FT MUTAGEN 45 45 S->A: No effect on phosphorylation.
FT MUTAGEN 61 61 C->A: No effect on NO-mediated
FT modification.
FT MUTAGEN 69 69 S->A: No effect on phosphorylation.
FT MUTAGEN 94 94 S->A: No effect on phosphorylation.
FT MUTAGEN 98 98 T->A: No effect on phosphorylation.
FT MUTAGEN 100 100 E->Q: Reduces enzyme activity by over
FT 99%.
FT MUTAGEN 102 102 T->A: No effect on phosphorylation.
FT MUTAGEN 107 107 T->A: Loss of phosphorylation.
FT MUTAGEN 139 139 C->A: Impaired NO-mediated modification.
FT Loss of NO-mediated modification; when
FT associated with A-19 or A-20.
FT MUTAGEN 173 173 E->Q: Abolishes enzyme activity.
FT HELIX 13 18
FT HELIX 25 27
FT STRAND 31 38
FT HELIX 42 51
FT STRAND 56 63
FT TURN 64 67
FT STRAND 68 75
FT HELIX 78 80
FT HELIX 85 92
FT STRAND 96 104
FT HELIX 107 109
FT STRAND 118 122
FT STRAND 124 131
FT HELIX 135 144
FT STRAND 149 151
FT STRAND 155 158
FT STRAND 162 165
FT STRAND 171 175
FT HELIX 177 179
FT HELIX 181 183
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
//
ID LGUL_HUMAN Reviewed; 184 AA.
AC Q04760; B2R6P7; B4DDV0; P78375; Q59EL0; Q5TZW3; Q96FC0; Q96J41;
read moreDT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 4.
DT 22-JAN-2014, entry version 149.
DE RecName: Full=Lactoylglutathione lyase;
DE EC=4.4.1.5;
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ALA-111.
RX PubMed=7684374;
RA Kim N.-S., Umezawa Y., Ohmura S., Kato S.;
RT "Human glyoxalase I. cDNA cloning, expression, and sequence similarity
RT to 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;
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;
RA Ridderstroem M., Mannervik B.;
RT "Optimized heterologous expression of the human zinc enzyme glyoxalase
RT 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
RT and 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
RP VARIANTS 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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
RT 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.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA 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.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., 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
RP TYR-19 AND 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP PROTEIN SEQUENCE OF 13-18 AND 128-135, ENZYME REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, MASS SPECTROMETRY, CLEAVAGE OF
RP INITIATOR METHIONINE, ACETYLATION AT ALA-2, GLUTATHIONYLATION AT
RP CYS-139, AND DISULFIDE BONDS.
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
RT nitric-oxide-responsive form of glyoxalase I.";
RL Biochem. J. 407:121-128(2007).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
RP FUNCTION, PHOSPHORYLATION AT THR-107, AND MUTAGENESIS OF CYS-19;
RP CYS-20; SER-45; SER-69; SER-94; THR-98; THR-102; THR-107 AND CYS-139.
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
RT suppress 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 MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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.,
RA Buerckstuemmer T., 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 X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH
RP S-BENZYL-GLUTATHIONE AND ZINC.
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
RT duplication and 3D domain swapping.";
RL EMBO J. 16:3386-3395(1997).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH ZINC AND
RP S-HEXYLGLUTATHIONE, CATALYTIC ACTIVITY, FUNCTION, COFACTOR, ACTIVE
RP SITE, SUBUNIT, AND MUTAGENESIS OF GLN-34; GLU-100 AND GLU-173.
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
RT of human glyoxalase I.";
RL J. Biol. Chem. 273:21623-21628(1998).
RN [18]
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
RT crystallographic analysis of the human enzyme in complex with a
RT transition state analogue.";
RL Biochemistry 38:13480-13490(1999).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.47 ANGSTROMS) IN COMPLEX WITH SYNTHETIC
RP INHIBITOR AND ZINC, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND
RP COFACTOR.
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. Involved
CC in the regulation of TNF-induced transcriptional activity of NF-
CC kappa-B. Required for normal osteoclastogenesis.
CC -!- CATALYTIC ACTIVITY: (R)-S-lactoylglutathione = glutathione +
CC methylglyoxal.
CC -!- COFACTOR: Binds 1 zinc ion per subunit. In the homodimer, two zinc
CC ions are bound between subunits.
CC -!- ENZYME REGULATION: Regulated by oxidation of Cys-139 in response
CC to the redox state of the cell. Results in the alternative
CC formation of cystine or glutathione-bound cysteine, the latter
CC modification leading to reduced enzyme activity.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.3 mM for methylglyoxal/glutathione (native form);
CC KM=0.7 mM for methylglyoxal/glutathione (reduced form);
CC Vmax=0.335 umol/min/mg enzyme with methylglyoxal/glutathione as
CC substrate (native form);
CC Vmax=0.7 umol/min/mg enzyme with methylglyoxal/glutathione as
CC substrate (reduced form);
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
CC degradation; (R)-lactate from methylglyoxal: step 1/2.
CC -!- SUBUNIT: Homodimer.
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 Note=No experimental confirmation available;
CC -!- PTM: Glutathionylation at Cys-139 inhibits enzyme activity.
CC -!- PTM: Phosphorylated at Thr-107 in the presence of CaMK2. However,
CC this is a consensus site for phosphorylation by CK2 so
CC phosphorylation may be mediated by CK2 rather than CaMK2.
CC Phosphorylation is induced by TNF and suppresses the TNF-induced
CC transcriptional activity of NF-kappa-B.
CC -!- PTM: Exists in a nitric oxide (NO)-modified form. The exact nature
CC of the modification is unknown, but it suppresses the TNF-induced
CC transcriptional activity of NF-kappa-B.
CC -!- MASS SPECTROMETRY: Mass=20687.4; Method=Electrospray; Range=2-184
CC (Q04760-1); Note=Variant Glu-111; Source=PubMed:20454679;
CC -!- MASS SPECTROMETRY: Mass=20629.7; Method=Electrospray; Range=2-184
CC (Q04760-1); Note=Variant Ala-111; Source=PubMed:20454679;
CC -!- POLYMORPHISM: Exists in three separable isoforms which originate
CC from two alleles in the genome. These correspond to two homodimers
CC and one heterodimer composed of two subunits showing different
CC electrophoretic properties.
CC -!- SIMILARITY: Belongs to the glyoxalase I family.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD93038.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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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; CAI21586.1; -; Genomic_DNA.
DR EMBL; BC001741; AAH01741.1; -; mRNA.
DR EMBL; BC011365; AAH11365.1; -; mRNA.
DR EMBL; BC015934; AAH15934.1; -; mRNA.
DR PIR; A46714; A46714.
DR PIR; S63603; S63603.
DR RefSeq; NP_006699.2; NM_006708.2.
DR UniGene; Hs.268849; -.
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 PDBsum; 1BH5; -.
DR PDBsum; 1FRO; -.
DR PDBsum; 1QIN; -.
DR PDBsum; 1QIP; -.
DR PDBsum; 3VW9; -.
DR PDBsum; 3W0T; -.
DR PDBsum; 3W0U; -.
DR ProteinModelPortal; Q04760; -.
DR SMR; Q04760; 9-184.
DR IntAct; Q04760; 3.
DR STRING; 9606.ENSP00000362463; -.
DR BindingDB; Q04760; -.
DR ChEMBL; CHEMBL2424; -.
DR DrugBank; DB00143; Glutathione.
DR PhosphoSite; Q04760; -.
DR DMDM; 134039205; -.
DR OGP; Q04760; -.
DR REPRODUCTION-2DPAGE; IPI00220766; -.
DR REPRODUCTION-2DPAGE; Q04760; -.
DR PaxDb; Q04760; -.
DR PRIDE; Q04760; -.
DR DNASU; 2739; -.
DR Ensembl; ENST00000373365; ENSP00000362463; ENSG00000124767.
DR GeneID; 2739; -.
DR KEGG; hsa:2739; -.
DR UCSC; uc003ooc.3; human.
DR CTD; 2739; -.
DR GeneCards; GC06M038643; -.
DR HGNC; HGNC:4323; GLO1.
DR HPA; CAB040541; -.
DR HPA; CAB040542; -.
DR MIM; 138750; gene.
DR neXtProt; NX_Q04760; -.
DR PharmGKB; PA28724; -.
DR eggNOG; COG0346; -.
DR HOVERGEN; HBG025852; -.
DR InParanoid; Q04760; -.
DR KO; K01759; -.
DR OMA; YWVEIIQ; -.
DR OrthoDB; EOG7XPZ6W; -.
DR PhylomeDB; Q04760; -.
DR BRENDA; 4.4.1.5; 2681.
DR SABIO-RK; Q04760; -.
DR UniPathway; UPA00619; UER00675.
DR EvolutionaryTrace; Q04760; -.
DR GeneWiki; GLO1; -.
DR GeneWiki; Lactoylglutathione_lyase; -.
DR GenomeRNAi; 2739; -.
DR NextBio; 10796; -.
DR PRO; PR:Q04760; -.
DR Bgee; Q04760; -.
DR CleanEx; HS_GLO1; -.
DR Genevestigator; Q04760; -.
DR GO; GO:0005737; C:cytoplasm; TAS:UniProtKB.
DR GO; GO:0004462; F:lactoylglutathione lyase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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:0006357; P:regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
DR InterPro; IPR004360; Glyas_Fos-R_dOase_dom.
DR InterPro; IPR004361; Glyoxalase_1.
DR InterPro; IPR018146; Glyoxalase_1_CS.
DR Pfam; PF00903; Glyoxalase; 1.
DR TIGRFAMs; TIGR00068; glyox_I; 1.
DR PROSITE; PS00934; GLYOXALASE_I_1; 1.
DR PROSITE; PS00935; GLYOXALASE_I_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Glutathionylation; Lyase;
KW Metal-binding; Phosphoprotein; Polymorphism; Reference proteome; Zinc.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 184 Lactoylglutathione lyase.
FT /FTId=PRO_0000168076.
FT REGION 157 158 Substrate binding.
FT ACT_SITE 173 173 Proton donor/acceptor.
FT METAL 34 34 Zinc; shared with dimeric partner.
FT METAL 100 100 Zinc; shared with dimeric partner.
FT METAL 127 127 Zinc; via tele nitrogen.
FT METAL 173 173 Zinc.
FT BINDING 34 34 Substrate; shared with dimeric partner.
FT BINDING 38 38 Substrate; shared with dimeric partner.
FT BINDING 104 104 Substrate; shared with dimeric partner.
FT BINDING 123 123 Substrate.
FT BINDING 127 127 Substrate.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 107 107 Phosphothreonine.
FT MOD_RES 139 139 S-glutathionyl cysteine; alternate.
FT MOD_RES 148 148 N6-acetyllysine.
FT DISULFID 19 20
FT DISULFID 61 139 Alternate; alternate.
FT VAR_SEQ 105 119 Missing (in isoform 2).
FT /FTId=VSP_041632.
FT VARIANT 19 19 C -> Y (in dbSNP:rs17855424).
FT /FTId=VAR_031078.
FT VARIANT 111 111 E -> A (in dbSNP:rs4746).
FT /FTId=VAR_013481.
FT MUTAGEN 19 19 C->A: No effect on NO-mediated
FT modification. Impaired NO-mediated
FT modification; when associated with A-20.
FT Loss of NO-mediated modification; when
FT associated with A-139.
FT MUTAGEN 20 20 C->A: No effect on NO-mediated
FT modification. Impaired NO-mediated
FT modification; when associated with A-19.
FT Loss of NO-mediated modification; when
FT associated with A-139.
FT MUTAGEN 34 34 Q->E: Reduces enzyme activity by 99%.
FT MUTAGEN 45 45 S->A: No effect on phosphorylation.
FT MUTAGEN 61 61 C->A: No effect on NO-mediated
FT modification.
FT MUTAGEN 69 69 S->A: No effect on phosphorylation.
FT MUTAGEN 94 94 S->A: No effect on phosphorylation.
FT MUTAGEN 98 98 T->A: No effect on phosphorylation.
FT MUTAGEN 100 100 E->Q: Reduces enzyme activity by over
FT 99%.
FT MUTAGEN 102 102 T->A: No effect on phosphorylation.
FT MUTAGEN 107 107 T->A: Loss of phosphorylation.
FT MUTAGEN 139 139 C->A: Impaired NO-mediated modification.
FT Loss of NO-mediated modification; when
FT associated with A-19 or A-20.
FT MUTAGEN 173 173 E->Q: Abolishes enzyme activity.
FT HELIX 13 18
FT HELIX 25 27
FT STRAND 31 38
FT HELIX 42 51
FT STRAND 56 63
FT TURN 64 67
FT STRAND 68 75
FT HELIX 78 80
FT HELIX 85 92
FT STRAND 96 104
FT HELIX 107 109
FT STRAND 118 122
FT STRAND 124 131
FT HELIX 135 144
FT STRAND 149 151
FT STRAND 155 158
FT STRAND 162 165
FT STRAND 171 175
FT HELIX 177 179
FT HELIX 181 183
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
//
MIM
138750
*RECORD*
*FIELD* NO
138750
*FIELD* TI
*138750 GLYOXALASE I; GLO1
*FIELD* TX
DESCRIPTION
Glyoxalase I (EC 4.4.1.5) is a glutathione-binding protein involved in
read morethe detoxification of methylglyoxal, a byproduct of glycolysis. GLO1 and
glyoxalase II (GLO2; 138760) catalyze successive steps in the pathway.
GLO1 catalyzes condensation of methylglyoxal and reduced glutathione to
form S-lactoyl-glutathione; GLO2 (hydroxyacyl glutathione hydrolase)
converts the latter substance to D-lactic acid and reduced glutathione
(Ranganathan et al., 1999).
CLONING
Kim et al. (1993) isolated a cDNA corresponding to the GLO1 gene from a
human monocyte cDNA library. The cDNA predicts a 184-amino acid protein
with M(r) 20,719.
Ranganathan et al. (1993) isolated a GLO1 cDNA from a human colon cDNA
library. The human enzyme showed 42% amino acid homology with bacterial
Glo1. Northern blot analysis identified a 2.2-kb mRNA transcript in
colon tissue. There was a 12-fold increase of the GLO1 transcript in
colon carcinoma tissue compared to normal colon tissue from the same
patient, and the authors concluded that GLO1 gene expression was induced
in colon carcinoma. Ranganathan et al. (1999) identified an insulin
response element (IRE) and zinc metal response element (MRE) in the
promoter region of the GLO1 gene.
GENE STRUCTURE
Ranganathan et al. (1999) determined that the GLO1 gene contains 5
exons. Using bioinformatics, Gale and Grant (2004) found that the GLO1
gene contains 6 exons with evidence of possible alternative splicing.
MAPPING
Reinsmoen et al. (1977) presented evidence from the family data that GLO
is linked to HLA and that the order of loci on chromosome 6p is HLA-A,
HLA-B, HLA-D, GLO, centromere. Meo et al. (1977) found that in the mouse
glyoxalase I maps approximately 3 cM from the Ss locus, a component of
the major histocompatibility complex, H-2. GLO1 has no known functional
relationship to MHC.
From study of a 3-generation family segregating for variation of the
centromeric heterochromatic region of chromosome 6p11, Bakker et al.
(1979) concluded that the HLA cluster and 6ph are about 6 cM apart (with
peak lod score of 3.466), that GLO is on the centromeric side of HLA,
that PGM3 (172100) is not on the short arm, and that HLA-B is closer to
the centromere than HLA-A.
Hansen and Eriksen (1979) found a maximum lod score of 14.6 at theta =
0.060 for linkage of HLA and GLO1. Goldman et al. (1991) confirmed the
linkage by study of 2-dimensional electrophoresis in CEPH families.
Blanche et al. (1991) presented a genetic map of 6p which involved RFLP
mapping of the GLO1 locus.
MOLECULAR GENETICS
Kompf et al. (1975) found that red cell GLO1 is polymorphic in man.
Junaid et al. (2004) presented evidence suggesting that an ala111-to-glu
polymorphism in the GLO1 gene (A111E; 138750.0001) may be a
susceptibility factor for the development of autism (see 209850). This
suggestion was not confirmed in studies by Rehnstrom et al. (2008) and
Wu et al. (2008) in Finnish and Han Chinese populations, respectively.
POPULATION GENETICS
Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).
ANIMAL MODEL
Chen et al. (2004) found that the Glo1 gene was upregulated
approximately 1.6-fold in brain tissue of a transgenic mouse model of
Alzheimer disease (AD; 104300) and frontotemporal dementia (600274). The
transgenic mice carried the pro301-to-leu mutation in the tau gene
(P301L; 157140.0001) and developed neurofibrillary tangles. GLO1 was
also elevated in human Alzheimer disease brains compared to nondemented
controls, and GLO1 immunohistochemistry detected intensely stained
flame-shaped neurons in AD brains. The data demonstrated the potential
of transcriptomics applied to animal models of human diseases and
suggested a previously unidentified role for glyoxalase I in
neurodegenerative disease.
Using a combination of behavioral analysis of 6 inbred mouse strains
with quantitative gene expression profiling of several brain regions,
Hovatta et al. (2005) identified 17 genes with expression patterns that
correlated with anxiety-like behavioral phenotypes. To determine if 2 of
the genes, glyoxalase-1 and glutathione reductase-1 (138300), have a
causal role in the genesis of anxiety, Hovatta et al. (2005) performed
genetic manipulation using lentivirus-mediated gene transfer. Local
overexpression of these genes in the mouse brain resulted in increased
anxiety-like behavior, while local inhibition of glyoxalase-1 expression
by RNA interference decreased the anxiety-like behavior. Hovatta et al.
(2005) concluded that both of these genes are involved in oxidative
stress metabolism, linking this pathway with anxiety-related behavior.
*FIELD* AV
.0001
RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE
GLO1, ALA111GLU (dbSNP rs4746)
This variant, formerly titled AUTISM, SUSCEPTIBILITY TO, has been
reclassified based on the findings of Rehnstrom et al. (2008) and Wu et
al. (2008).
Using a proteomics method to identify abnormal proteins in autopsied
brains of patients with autism (209850), Junaid et al. (2004) found an
increase in polarity of glyoxalase I by 2-dimensional gel
electrophoresis; direct sequencing of the GLO1 gene identified a 419C-A
transversion in the gene, resulting in an ala111-to-glu (A111E)
substitution. The glu111 enzyme is more acidic than the ala111 enzyme
and has reduced functional activity. Four brains were homozygous for A/A
(glu111), 3 were heterozygous for A/C (ala111/glu111), and 1 was
homozygous for C/C (ala111). Of 9 controls, which included 1 patient
with Down syndrome and 3 patients with mental retardation, 2 were A/A, 3
were A/C, and 4 were C/C. In a larger sample of autism patients and
controls, the frequency of the 419A allele was 0.6 in autism and 0.4 in
controls. Junaid et al. (2004) suggested that a reduction in GLO1 enzyme
activity could result in the accumulation of methylglyoxal, which may be
toxic to the developing brain. The data suggested that homozygosity for
the glu111 allele is a predisposing factor in the development of autism.
Rehnstrom et al. (2008) genotyped 6 polymorphisms in the GLO1 gene,
including A111E, in Finnish families with more than 230 individuals with
autism spectrum disorders and carried out both linkage and association
analyses. They observed no significant linkage or association between
any SNP and ASD.
Wu et al. (2008) performed mutation screening of all exons of the GLO1
gene in 272 Han Chinese patients with autism and 310 healthy controls.
They found no significant differences in the frequency distributions of
A111E between the autism and control groups. Moreover, they did not
identify any other mutations associated with autism in the exon regions.
*FIELD* SA
Bender and Grzeschik (1976); Beretta et al. (1983); Carter et al.
(1978); Giblett and Lewis (1976); Karlsson et al. (1980); Kavathas
and DeMars (1981); Kompf et al. (1975); Kompf et al. (1980); Olaisen
et al. (1976); Parr et al. (1977); Rubinstein and Suciu-Foca (1979);
Schimandle and Vander Jagt (1979); Sparkes et al. (1983); Teng et
al. (1978); Whittington et al. (1980); Ziegler et al. (1985)
*FIELD* RF
1. Bakker, E.; Pearson, P. L.; Meera Khan, P.; Schreuder, G. M. T.;
Madan, K.: Orientation of major histocompatibility (MHC) genes relative
to the centromere of human chromosome 6. Clin. Genet. 15: 198-202,
1979.
2. Bender, K.; Grzeschik, K. H.: Assignment of the genes for human
glyoxalase I to chromosome 6 and for human esterase D to chromosome
13. Cytogenet. Cell Genet. 16: 93-96, 1976.
3. Beretta, M.; Schiliro, G.; Russo, A.; Barbujani, G.; Mazzetti,
P.; Russo, G.; Barrai, I.: A new rare variant of the glyoxalase I
system of the red cell: GLO-Sicily. Am. J. Hum. Genet. 35: 1042-1047,
1983.
4. Blanche, H.; Zoghbi, H. Y.; Jabs, E. W.; de Gouyon, B.; Zunec,
R.; Dausset, J.; Cann, H. M.: A centromere-based genetic map of the
short arm of human chromosome 6. Genomics 9: 420-428, 1991.
5. Carter, N. D.; West, C. M.; Bernard, J. M.; Farid, N. R.; Larsen,
B.; Marshall, W. H.: Linkage of glyoxalase I and HLA in two Newfoundland
communities. Hum. Hered. 28: 397-400, 1978.
6. Chen, F.; Wollmer, M. A.; Hoerndli, F.; Munch, G.; Kuhla, B.; Rogaev,
E. I.; Tsolaki, M.; Papassotiropoulos, A.; Gotz, J.: Role for glyoxalase
I in Alzheimer's disease. Proc. Nat. Acad. Sci. 101: 7687-7692,
2004.
7. Gale, C. P.; Grant, P. J.: The characterisation and functional
analysis of the human glyoxalase-1 gene using methods of bioinformatics. Gene 340:
251-260, 2004.
8. Giblett, E. R.; Lewis, M.: Gene linkage studies on glyoxalase
I. Cytogenet. Cell Genet. 16: 313 only, 1976.
9. Goldman, D.; O'Brien, S. J.; Lucas-Derse, S.; Dean, M.: Linkage
mapping of human polymorphic proteins identified by two-dimensional
electrophoresis. Genomics 11: 875-884, 1991.
10. Hansen, H. E.; Eriksen, B.: HLA-GLO linkage analysis in 57 informative
families. Hum. Hered. 29: 355-360, 1979.
11. Hovatta, I.; Tennant, R. S.; Helton, R.; Marr, R. A.; Singer,
O.; Redwine, J. M.; Ellison, J. A.; Schadt, E. E.; Verma, I. M.; Lockhart,
D. J.; Barlow, C.: Glyoxalase 1 and glutathione reductase 1 regulate
anxiety in mice. Nature 438: 662-666, 2005.
12. Junaid, M. A.; Kowal, D.; Barua, M.; Pullarkat, P. S.; Sklower
Brooks, S.; Pullarkat, R. K.: Proteomic studies identified a single
nucleotide polymorphism in glyoxalase I as autism susceptibility factor. Am.
J. Med. Genet. 131A: 11-17, 2004.
13. Karlsson, S.; Arnason, A.; Jensson, O.: GLO polymorphism in Iceland. Hum.
Hered. 30: 383-385, 1980.
14. Kavathas, P.; DeMars, R.: A new variant glyoxalase I allele that
is readily detectable in stimulated lymphocytes and lymphoblastoid
cell lines but not in circulating lymphocytes or erythrocytes. Am.
J. Hum. Genet. 33: 935-945, 1981.
15. Kim, N. S.; Umezawa, Y.; Ohmura, S.; Kato, S.: Human glyoxalase
I: cDNA cloning, expression, and sequence similarity to glyoxalase
I from Pseudomonas putida. J. Biol. Chem. 268: 11217-11221, 1993.
16. Kompf, J.; Bissbort, S.; Gussmann, S.; Ritter, H.: Polymorphism
of red cell glyoxalase I (E.C.4.4.1.5), a new genetic marker in man:
investigation of 169 mother-child combinations. Humangenetik 27:
141-143, 1975.
17. Kompf, J.; Bissbort, S.; Ritter, H.: Red cell glyoxalase I (E.C.4.4.1.5):
formal genetics and linkage relations. Humangenetik 28: 249-251,
1975.
18. Kompf, J.; Siebert, G.; Ritter, H.; Heilbronner, H.; Schunter,
F.; Wernet, P.; Gupta, D.; Moeller, H.: Data on linkage relations
between GLO and 21-hydroxylase. Hum. Genet. 54: 419-420, 1980.
19. Meo, T.; Douglas, T.; Rijnbeek, A.-M.: Glyoxalase I polymorphism
in the mouse: a new genetic marker linked to H-2. Science 198: 311-313,
1977.
20. Olaisen, B.; Gedde-Dahl, T., Jr.; Thorsby, E.: Localization of
the human GLO gene locus. Hum. Genet. 32: 301-304, 1976.
21. Parr, C. W.; Bagster, I. A.; Welch, S. G.: Human red cell glyoxalase
I polymorphism. Biochem. Genet. 15: 109-114, 1977.
22. Ranganathan, S.; Ciaccio, P. J.; Walsh, E. S.; Tew, K. D.: Genomic
sequence of human glyoxalase-I: analysis of promoter activity and
its regulation. Gene 240: 149-155, 1999.
23. Ranganathan, S.; Walsh, E. S.; Godwin, A. K.; Tew, K. D.: Cloning
and characterization of human colon glyoxalase-I. J. Biol. Chem. 268:
5661-5667, 1993.
24. Rehnstrom, K.; Ylisaukko-oja, T.; Vanhala, R.; von Wendt, L.;
Peltonen, L.; Hovatta, I.: No association between common variants
in glyoxalase 1 and autism spectrum disorders. Am. J. Med. Genet. 147B:
124-127, 2008.
25. Reinsmoen, N. L.; Friend, P. S.; Miller, W. V.; Burgdorf, A.;
Giblett, E. R.; Yunis, E. J.: Inheritance of recombinant HLA-GLO
haplotype suggesting the gene sequence. Nature 267: 276-278, 1977.
26. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press (pub.) 1988.
27. Rubinstein, P.; Suciu-Foca, N.: Glyoxalase 1: a possible 'null'
allele. Hum. Hered. 29: 217-220, 1979.
28. Schimandle, C. M.; Vander Jagt, D. L.: Isolation and kinetic
analysis of the multiple forms of glyoxalase-1 from human erythrocytes. Arch.
Biochem. Biophys. 195: 261-268, 1979.
29. Sparkes, R. S.; Sparkes, M. C.; Crist, M.; Anderson, C. E.: Glyoxalase
I 'null' allele in a new family: identification by abnormal segregation
pattern and quantitative assay. Hum. Genet. 64: 146-147, 1983.
30. Teng, Y. S.; Tan, S. G.; Lopez, C. G.: Red cell glyoxalase I
and placental soluble aconitase polymorphisms in the three major ethnic
groups of Malaysia. Jpn. J. Hum. Genet. 23: 211-215, 1978.
31. Whittington, J. E.; Keats, B. J. B.; Jackson, J. F.; Currier,
R. D.; Terasaki, P. I.: Linkage studies on glyoxalase I (GLO), pepsinogen
(PG), spinocerebellar ataxia (SCA1), and HLA. Cytogenet. Cell Genet. 28:
145-150, 1980.
32. Wu, Y.-Y.; Chien, W.-H.; Huang, Y.-S.; Gau, S. S.-F.; Chen, C.-H.
: Lack of evidence to support the glyoxalase 1 gene (GLO1) as a risk
gene of autism in Han Chinese patients from Taiwan. Prog. Neuropsychopharmacol.
Biol. Psychiatry 32: 1740-1744, 2008.
33. Ziegler, A.; Fonatsch, C.; Kompf, J.: Mapping of the locus for
glyoxalase 1 (GLO1) on human chromosome 6 using mutant cell lines.
(Abstract) Cytogenet. Cell Genet. 40: 787 only, 1985.
*FIELD* CN
Carol A. Bocchini - updated: 1/21/2011
Ada Hamosh - updated: 1/30/2006
Cassandra L. Kniffin - reorganized: 1/19/2005
Cassandra L. Kniffin - updated: 1/3/2005
Victor A. McKusick - updated: 7/2/2004
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
alopez: 05/20/2011
terry: 1/21/2011
carol: 1/21/2011
ckniffin: 3/5/2007
alopez: 2/1/2006
terry: 1/30/2006
tkritzer: 1/19/2005
ckniffin: 1/3/2005
tkritzer: 7/6/2004
terry: 7/2/2004
pfoster: 2/18/1994
supermim: 3/16/1992
carol: 12/5/1991
carol: 3/6/1991
carol: 2/8/1991
supermim: 3/20/1990
*RECORD*
*FIELD* NO
138750
*FIELD* TI
*138750 GLYOXALASE I; GLO1
*FIELD* TX
DESCRIPTION
Glyoxalase I (EC 4.4.1.5) is a glutathione-binding protein involved in
read morethe detoxification of methylglyoxal, a byproduct of glycolysis. GLO1 and
glyoxalase II (GLO2; 138760) catalyze successive steps in the pathway.
GLO1 catalyzes condensation of methylglyoxal and reduced glutathione to
form S-lactoyl-glutathione; GLO2 (hydroxyacyl glutathione hydrolase)
converts the latter substance to D-lactic acid and reduced glutathione
(Ranganathan et al., 1999).
CLONING
Kim et al. (1993) isolated a cDNA corresponding to the GLO1 gene from a
human monocyte cDNA library. The cDNA predicts a 184-amino acid protein
with M(r) 20,719.
Ranganathan et al. (1993) isolated a GLO1 cDNA from a human colon cDNA
library. The human enzyme showed 42% amino acid homology with bacterial
Glo1. Northern blot analysis identified a 2.2-kb mRNA transcript in
colon tissue. There was a 12-fold increase of the GLO1 transcript in
colon carcinoma tissue compared to normal colon tissue from the same
patient, and the authors concluded that GLO1 gene expression was induced
in colon carcinoma. Ranganathan et al. (1999) identified an insulin
response element (IRE) and zinc metal response element (MRE) in the
promoter region of the GLO1 gene.
GENE STRUCTURE
Ranganathan et al. (1999) determined that the GLO1 gene contains 5
exons. Using bioinformatics, Gale and Grant (2004) found that the GLO1
gene contains 6 exons with evidence of possible alternative splicing.
MAPPING
Reinsmoen et al. (1977) presented evidence from the family data that GLO
is linked to HLA and that the order of loci on chromosome 6p is HLA-A,
HLA-B, HLA-D, GLO, centromere. Meo et al. (1977) found that in the mouse
glyoxalase I maps approximately 3 cM from the Ss locus, a component of
the major histocompatibility complex, H-2. GLO1 has no known functional
relationship to MHC.
From study of a 3-generation family segregating for variation of the
centromeric heterochromatic region of chromosome 6p11, Bakker et al.
(1979) concluded that the HLA cluster and 6ph are about 6 cM apart (with
peak lod score of 3.466), that GLO is on the centromeric side of HLA,
that PGM3 (172100) is not on the short arm, and that HLA-B is closer to
the centromere than HLA-A.
Hansen and Eriksen (1979) found a maximum lod score of 14.6 at theta =
0.060 for linkage of HLA and GLO1. Goldman et al. (1991) confirmed the
linkage by study of 2-dimensional electrophoresis in CEPH families.
Blanche et al. (1991) presented a genetic map of 6p which involved RFLP
mapping of the GLO1 locus.
MOLECULAR GENETICS
Kompf et al. (1975) found that red cell GLO1 is polymorphic in man.
Junaid et al. (2004) presented evidence suggesting that an ala111-to-glu
polymorphism in the GLO1 gene (A111E; 138750.0001) may be a
susceptibility factor for the development of autism (see 209850). This
suggestion was not confirmed in studies by Rehnstrom et al. (2008) and
Wu et al. (2008) in Finnish and Han Chinese populations, respectively.
POPULATION GENETICS
Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).
ANIMAL MODEL
Chen et al. (2004) found that the Glo1 gene was upregulated
approximately 1.6-fold in brain tissue of a transgenic mouse model of
Alzheimer disease (AD; 104300) and frontotemporal dementia (600274). The
transgenic mice carried the pro301-to-leu mutation in the tau gene
(P301L; 157140.0001) and developed neurofibrillary tangles. GLO1 was
also elevated in human Alzheimer disease brains compared to nondemented
controls, and GLO1 immunohistochemistry detected intensely stained
flame-shaped neurons in AD brains. The data demonstrated the potential
of transcriptomics applied to animal models of human diseases and
suggested a previously unidentified role for glyoxalase I in
neurodegenerative disease.
Using a combination of behavioral analysis of 6 inbred mouse strains
with quantitative gene expression profiling of several brain regions,
Hovatta et al. (2005) identified 17 genes with expression patterns that
correlated with anxiety-like behavioral phenotypes. To determine if 2 of
the genes, glyoxalase-1 and glutathione reductase-1 (138300), have a
causal role in the genesis of anxiety, Hovatta et al. (2005) performed
genetic manipulation using lentivirus-mediated gene transfer. Local
overexpression of these genes in the mouse brain resulted in increased
anxiety-like behavior, while local inhibition of glyoxalase-1 expression
by RNA interference decreased the anxiety-like behavior. Hovatta et al.
(2005) concluded that both of these genes are involved in oxidative
stress metabolism, linking this pathway with anxiety-related behavior.
*FIELD* AV
.0001
RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE
GLO1, ALA111GLU (dbSNP rs4746)
This variant, formerly titled AUTISM, SUSCEPTIBILITY TO, has been
reclassified based on the findings of Rehnstrom et al. (2008) and Wu et
al. (2008).
Using a proteomics method to identify abnormal proteins in autopsied
brains of patients with autism (209850), Junaid et al. (2004) found an
increase in polarity of glyoxalase I by 2-dimensional gel
electrophoresis; direct sequencing of the GLO1 gene identified a 419C-A
transversion in the gene, resulting in an ala111-to-glu (A111E)
substitution. The glu111 enzyme is more acidic than the ala111 enzyme
and has reduced functional activity. Four brains were homozygous for A/A
(glu111), 3 were heterozygous for A/C (ala111/glu111), and 1 was
homozygous for C/C (ala111). Of 9 controls, which included 1 patient
with Down syndrome and 3 patients with mental retardation, 2 were A/A, 3
were A/C, and 4 were C/C. In a larger sample of autism patients and
controls, the frequency of the 419A allele was 0.6 in autism and 0.4 in
controls. Junaid et al. (2004) suggested that a reduction in GLO1 enzyme
activity could result in the accumulation of methylglyoxal, which may be
toxic to the developing brain. The data suggested that homozygosity for
the glu111 allele is a predisposing factor in the development of autism.
Rehnstrom et al. (2008) genotyped 6 polymorphisms in the GLO1 gene,
including A111E, in Finnish families with more than 230 individuals with
autism spectrum disorders and carried out both linkage and association
analyses. They observed no significant linkage or association between
any SNP and ASD.
Wu et al. (2008) performed mutation screening of all exons of the GLO1
gene in 272 Han Chinese patients with autism and 310 healthy controls.
They found no significant differences in the frequency distributions of
A111E between the autism and control groups. Moreover, they did not
identify any other mutations associated with autism in the exon regions.
*FIELD* SA
Bender and Grzeschik (1976); Beretta et al. (1983); Carter et al.
(1978); Giblett and Lewis (1976); Karlsson et al. (1980); Kavathas
and DeMars (1981); Kompf et al. (1975); Kompf et al. (1980); Olaisen
et al. (1976); Parr et al. (1977); Rubinstein and Suciu-Foca (1979);
Schimandle and Vander Jagt (1979); Sparkes et al. (1983); Teng et
al. (1978); Whittington et al. (1980); Ziegler et al. (1985)
*FIELD* RF
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*FIELD* CN
Carol A. Bocchini - updated: 1/21/2011
Ada Hamosh - updated: 1/30/2006
Cassandra L. Kniffin - reorganized: 1/19/2005
Cassandra L. Kniffin - updated: 1/3/2005
Victor A. McKusick - updated: 7/2/2004
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
alopez: 05/20/2011
terry: 1/21/2011
carol: 1/21/2011
ckniffin: 3/5/2007
alopez: 2/1/2006
terry: 1/30/2006
tkritzer: 1/19/2005
ckniffin: 1/3/2005
tkritzer: 7/6/2004
terry: 7/2/2004
pfoster: 2/18/1994
supermim: 3/16/1992
carol: 12/5/1991
carol: 3/6/1991
carol: 2/8/1991
supermim: 3/20/1990