GLO2_MOUSE
ID GLO2_MOUSE Reviewed; 309 AA.
AC Q99KB8; Q3TMR4; Q3UCF6; Q8WUR9;
DT 25-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-SEP-2009, sequence version 2.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Hydroxyacylglutathione hydrolase, mitochondrial;
DE EC=3.1.2.6 {ECO:0000250|UniProtKB:Q16775};
DE AltName: Full=Glyoxalase II;
DE Short=Glx II;
DE Flags: Precursor;
GN Name=Hagh; Synonyms=Glo2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, Cerebellum, and Heart;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=FVB/N; TISSUE=Liver, and Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-230, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-90 AND LYS-117, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
CC -!- FUNCTION: Thiolesterase that catalyzes the hydrolysis of S-D-lactoyl-
CC glutathione to form glutathione and D-lactic acid.
CC {ECO:0000250|UniProtKB:Q16775}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an S-(2-hydroxyacyl)glutathione + H2O = a 2-hydroxy
CC carboxylate + glutathione + H(+); Xref=Rhea:RHEA:21864,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57925,
CC ChEBI:CHEBI:58896, ChEBI:CHEBI:71261; EC=3.1.2.6;
CC Evidence={ECO:0000250|UniProtKB:Q16775};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21865;
CC Evidence={ECO:0000250|UniProtKB:Q16775};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-S-lactoylglutathione + H2O = (R)-lactate + glutathione +
CC H(+); Xref=Rhea:RHEA:25245, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16004, ChEBI:CHEBI:57474, ChEBI:CHEBI:57925; EC=3.1.2.6;
CC Evidence={ECO:0000250|UniProtKB:Q16775};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25246;
CC Evidence={ECO:0000250|UniProtKB:Q16775};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q16775};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250|UniProtKB:Q16775};
CC -!- PATHWAY: Secondary metabolite metabolism; methylglyoxal degradation;
CC (R)-lactate from methylglyoxal: step 2/2.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q16775}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Mitochondrion matrix
CC {ECO:0000250|UniProtKB:Q16775}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000250|UniProtKB:Q16775}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=2;
CC Name=1;
CC IsoId=Q99KB8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q99KB8-2; Sequence=VSP_037931;
CC -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative splicing. Also
CC produced by alternative initiation at Met-50 of isoform 1. Alternative
CC initiation has been proven in human. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the metallo-beta-lactamase superfamily.
CC Glyoxalase II family. {ECO:0000305}.
CC -!- CAUTION: Only one single gene encoding glyoxalase II has been
CC identified in vertebrates. In yeast and higher plants, separate genes
CC encode the cytosolic and mitochondrial forms of glyoxalase II.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH04749.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAH19817.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAE27615.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAE29657.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAE30223.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAE31462.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK147022; BAE27615.1; ALT_INIT; mRNA.
DR EMBL; AK150557; BAE29657.1; ALT_INIT; mRNA.
DR EMBL; AK151231; BAE30223.1; ALT_INIT; mRNA.
DR EMBL; AK152742; BAE31462.1; ALT_INIT; mRNA.
DR EMBL; AK165777; BAE38377.1; -; mRNA.
DR EMBL; BC004749; AAH04749.1; ALT_INIT; mRNA.
DR EMBL; BC019817; AAH19817.1; ALT_INIT; mRNA.
DR CCDS; CCDS28499.2; -. [Q99KB8-1]
DR CCDS; CCDS50021.1; -. [Q99KB8-2]
DR RefSeq; NP_001153098.1; NM_001159626.1.
DR RefSeq; NP_077246.2; NM_024284.2.
DR RefSeq; XP_006523723.1; XM_006523660.2.
DR RefSeq; XP_006523724.1; XM_006523661.1.
DR AlphaFoldDB; Q99KB8; -.
DR SMR; Q99KB8; -.
DR BioGRID; 199949; 4.
DR STRING; 10090.ENSMUSP00000113051; -.
DR iPTMnet; Q99KB8; -.
DR PhosphoSitePlus; Q99KB8; -.
DR REPRODUCTION-2DPAGE; Q99KB8; -.
DR CPTAC; non-CPTAC-3647; -.
DR EPD; Q99KB8; -.
DR jPOST; Q99KB8; -.
DR MaxQB; Q99KB8; -.
DR PaxDb; Q99KB8; -.
DR PeptideAtlas; Q99KB8; -.
DR PRIDE; Q99KB8; -.
DR ProteomicsDB; 266810; -. [Q99KB8-1]
DR ProteomicsDB; 266811; -. [Q99KB8-2]
DR DNASU; 14651; -.
DR GeneID; 14651; -.
DR KEGG; mmu:14651; -.
DR CTD; 3029; -.
DR MGI; MGI:95745; Hagh.
DR eggNOG; KOG0813; Eukaryota.
DR InParanoid; Q99KB8; -.
DR OrthoDB; 961826at2759; -.
DR PhylomeDB; Q99KB8; -.
DR Reactome; R-MMU-70268; Pyruvate metabolism.
DR SABIO-RK; Q99KB8; -.
DR UniPathway; UPA00619; UER00676.
DR BioGRID-ORCS; 14651; 4 hits in 72 CRISPR screens.
DR ChiTaRS; Hagh; mouse.
DR PRO; PR:Q99KB8; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q99KB8; protein.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005759; C:mitochondrial matrix; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0004416; F:hydroxyacylglutathione hydrolase activity; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005975; P:carbohydrate metabolic process; ISO:MGI.
DR GO; GO:0006750; P:glutathione biosynthetic process; ISO:MGI.
DR GO; GO:0006749; P:glutathione metabolic process; ISO:MGI.
DR GO; GO:0019243; P:methylglyoxal catabolic process to D-lactate via S-lactoyl-glutathione; IC:MGI.
DR CDD; cd07723; hydroxyacylglutathione_hydrolase_MBL-fold; 1.
DR Gene3D; 3.60.15.10; -; 1.
DR HAMAP; MF_01374; Glyoxalase_2; 1.
DR InterPro; IPR035680; Clx_II_MBL.
DR InterPro; IPR032282; HAGH_C.
DR InterPro; IPR017782; Hydroxyacylglutathione_Hdrlase.
DR InterPro; IPR001279; Metallo-B-lactamas.
DR InterPro; IPR036866; RibonucZ/Hydroxyglut_hydro.
DR Pfam; PF16123; HAGH_C; 1.
DR Pfam; PF00753; Lactamase_B; 1.
DR PIRSF; PIRSF005457; Glx; 1.
DR SMART; SM00849; Lactamase_B; 1.
DR SUPFAM; SSF56281; SSF56281; 1.
DR TIGRFAMs; TIGR03413; GSH_gloB; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative initiation; Alternative splicing; Cytoplasm;
KW Hydrolase; Metal-binding; Mitochondrion; Reference proteome;
KW Transit peptide; Zinc.
FT TRANSIT 1..24
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 25..309
FT /note="Hydroxyacylglutathione hydrolase, mitochondrial"
FT /id="PRO_0000192343"
FT BINDING 103
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q16775"
FT BINDING 105
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q16775"
FT BINDING 107
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q16775"
FT BINDING 108
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q16775"
FT BINDING 159
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q16775"
FT BINDING 183
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q16775"
FT BINDING 183
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q16775"
FT BINDING 192..194
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q16775"
FT BINDING 222..224
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q16775"
FT BINDING 222
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q16775"
FT BINDING 298..301
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q16775"
FT MOD_RES 90
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 117
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 230
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q16775"
FT MOD_RES 230
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT VAR_SEQ 1..49
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_037931"
FT CONFLICT 93
FT /note="H -> R (in Ref. 1; BAE27615/BAE29657/BAE30223/
FT BAE31462/BAE38377)"
FT /evidence="ECO:0000305"
FT CONFLICT 147
FT /note="G -> E (in Ref. 1; BAE38377)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 309 AA; 34084 MW; AC2C17D7AB6E4FBA CRC64;
MVLGRGSLCL RSLSALGATC ARRGLGQALL GLSLCHSDFR KNLTVQQDIM KVELLPALTD
NYMYLIIDED TQEAAIVDPV QPQKVIEAAK KHHVKLTTVL TTHHHWDHAG GNEKLVKLEP
GLKVYGGDDR IGALTHKVTH LSTLQVGSLS VKCLSTPCHT SGHICYFVSK PGSSEPSAVF
TGDTLFVAGC GKFYEGTADE MYKALLEVLG RLPPDTKVYC GHEYTVNNLK FARHVEPGNA
AIQEKLAWAK EKYAIGEPTV PSTLAEEFTY NPFMRVKEKT VQQHAGETDP VTTMRAIRRE
KDQFKVPRD
