GLO2_RAT
ID GLO2_RAT Reviewed; 309 AA.
AC O35952; Q4V8M8;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-SEP-2009, sequence version 2.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Hydroxyacylglutathione hydrolase, mitochondrial;
DE EC=3.1.2.6 {ECO:0000269|PubMed:8719777};
DE AltName: Full=Glyoxalase II;
DE Short=Glx II;
DE AltName: Full=Round spermatid protein RSP29;
DE Flags: Precursor;
GN Name=Hagh; Synonyms=Rsp29;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 2), AND TISSUE
RP SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=9434774; DOI=10.1006/bbrc.1997.7880;
RA Ji X., Moore H.D.M., Russell R.G.G., Watts D.J.;
RT "cDNA cloning and characterization of a rat spermatogenesis-associated
RT protein RSP29.";
RL Biochem. Biophys. Res. Commun. 241:714-719(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-179 (ISOFORMS 1 AND 2).
RA Kube M., Klages S., Kuhl H., Thiel J., Beck A., Reinhardt R.;
RT "Euratools EST.";
RL Submitted (SEP-2008) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 6-309 (ISOFORM 1/2).
RC TISSUE=Placenta;
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 [4]
RP PROTEIN SEQUENCE OF 96-114 AND 204-211, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus, and Spinal cord;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q.;
RL Submitted (APR-2007) to UniProtKB.
RN [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=8719777; DOI=10.1016/0047-6374(95)01632-a;
RA Kawase M., Kondoh C., Matsumoto S., Teshigawara M., Chisaka Y.,
RA Higashiura M., Nakata K., Ohmori S.;
RT "Contents of D-lactate and its related metabolites as well as enzyme
RT activities in the liver, muscle and blood plasma of aging rats.";
RL Mech. Ageing Dev. 84:55-63(1995).
CC -!- FUNCTION: Thiolesterase that catalyzes the hydrolysis of S-D-lactoyl-
CC glutathione to form glutathione and D-lactic acid.
CC {ECO:0000269|PubMed:8719777}.
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:0000269|PubMed:8719777};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21865;
CC Evidence={ECO:0000269|PubMed:8719777};
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:0000269|PubMed:8719777};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25246;
CC Evidence={ECO:0000305|PubMed:8719777};
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=O35952-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O35952-2; Sequence=VSP_037932;
CC -!- TISSUE SPECIFICITY: Strongly expressed in testis, skeletal muscle and
CC heart. Weakly expressed in placenta, pancreas, spleen and peripheral
CC blood leukocytes. {ECO:0000269|PubMed:9434774}.
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}.
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DR EMBL; U97667; AAC39944.1; -; Genomic_DNA.
DR EMBL; FM068341; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC097301; AAH97301.1; -; mRNA.
DR PIR; JC5826; JC5826.
DR RefSeq; NP_203500.2; NM_033349.2.
DR AlphaFoldDB; O35952; -.
DR SMR; O35952; -.
DR STRING; 10116.ENSRNOP00000020192; -.
DR BindingDB; O35952; -.
DR ChEMBL; CHEMBL2262; -.
DR CarbonylDB; O35952; -.
DR iPTMnet; O35952; -.
DR PhosphoSitePlus; O35952; -.
DR jPOST; O35952; -.
DR PaxDb; O35952; -.
DR PRIDE; O35952; -.
DR GeneID; 24439; -.
DR KEGG; rno:24439; -.
DR UCSC; RGD:2779; rat. [O35952-1]
DR CTD; 3029; -.
DR RGD; 2779; Hagh.
DR eggNOG; KOG0813; Eukaryota.
DR InParanoid; O35952; -.
DR OrthoDB; 961826at2759; -.
DR PhylomeDB; O35952; -.
DR BRENDA; 3.1.2.6; 5301.
DR Reactome; R-RNO-70268; Pyruvate metabolism.
DR SABIO-RK; O35952; -.
DR UniPathway; UPA00619; UER00676.
DR PRO; PR:O35952; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0004416; F:hydroxyacylglutathione hydrolase activity; IDA:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005975; P:carbohydrate metabolic process; IDA:RGD.
DR GO; GO:0006750; P:glutathione biosynthetic process; ISO:RGD.
DR GO; GO:0006749; P:glutathione metabolic process; IDA:RGD.
DR GO; GO:0019243; P:methylglyoxal catabolic process to D-lactate via S-lactoyl-glutathione; IEA:InterPro.
DR GO; GO:0007283; P:spermatogenesis; NAS:RGD.
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 Direct protein sequencing; Hydrolase; Metal-binding; Mitochondrion;
KW Reference proteome; 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_0000192344"
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:0000250|UniProtKB:Q99KB8"
FT MOD_RES 117
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99KB8"
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:0000250|UniProtKB:Q99KB8"
FT VAR_SEQ 1..49
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9434774, ECO:0000303|Ref.2"
FT /id="VSP_037932"
FT CONFLICT 145
FT /note="E -> Q (in Ref. 2; FM068341 and 3; AAH97301)"
FT /evidence="ECO:0000305"
FT CONFLICT 173
FT /note="S -> N (in Ref. 2; FM068341)"
FT /evidence="ECO:0000305"
FT CONFLICT 219
FT /note="I -> Y (in Ref. 3; AAH97301)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 309 AA; 34109 MW; 625AD975E86E9B72 CRC64;
MVLGRGSLCL RSLSVLGAAC ARRGLGQALL GLSLCHTDFR KNLTVQQDMM KIELLPALTD
NYMYLIIDED TQEAAVVDPV QPQKVIETVK KHRVKLTTVL TTHHHWDHAG GNEKLVKLEP
GLKVYGGDDR IGALTHKVTH LSTLEVGSLS VKCLSTPCHT SGHICYFVSK PGSSEPSAVF
TGDTLFVAGC GKFYEGTADE MYKALLEVLG RLPPDTKVIC GHEYTVNNLK FARHVEPGNT
AVQEKLAWAK EKNAIGEPTV PSTLAEEFTY NPFMRVKEKT VQQHAGETDP VTTMRAIRRE
KDQFKVPRD
