GLO2_MACFA
ID GLO2_MACFA Reviewed; 308 AA.
AC Q4R6C1;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-SEP-2009, sequence version 2.
DT 03-AUG-2022, entry version 75.
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; ORFNames=QflA-22824, QtsA-18362;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Frontal cortex, and Testis;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
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=Q4R6C1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q4R6C1-2; Sequence=VSP_037930;
CC -!- TISSUE SPECIFICITY: Testis.
CC -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative splicing. Also
CC produced by alternative initiation at Met-49 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; AB169264; BAE01354.1; -; mRNA.
DR EMBL; AB173495; BAE90557.1; -; mRNA.
DR RefSeq; NP_001270343.1; NM_001283414.1. [Q4R6C1-1]
DR AlphaFoldDB; Q4R6C1; -.
DR SMR; Q4R6C1; -.
DR STRING; 9541.XP_005590961.1; -.
DR GeneID; 102130736; -.
DR CTD; 3029; -.
DR eggNOG; KOG0813; Eukaryota.
DR UniPathway; UPA00619; UER00676.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0004416; F:hydroxyacylglutathione hydrolase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019243; P:methylglyoxal catabolic process to D-lactate via S-lactoyl-glutathione; IEA:InterPro.
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 2: Evidence at transcript level;
KW Acetylation; Alternative initiation; Alternative splicing; Cytoplasm;
KW Hydrolase; Metal-binding; Mitochondrion; Reference proteome;
KW Transit peptide; Zinc.
FT TRANSIT 1..13
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 14..308
FT /note="Hydroxyacylglutathione hydrolase, mitochondrial"
FT /id="PRO_0000278565"
FT BINDING 102
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q16775"
FT BINDING 104
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q16775"
FT BINDING 106
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
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 158
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q16775"
FT BINDING 182
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q16775"
FT BINDING 182
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q16775"
FT BINDING 191..193
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q16775"
FT BINDING 221..223
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q16775"
FT BINDING 221
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q16775"
FT BINDING 297..300
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q16775"
FT MOD_RES 116
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99KB8"
FT MOD_RES 229
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q16775"
FT MOD_RES 229
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99KB8"
FT VAR_SEQ 1..48
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_037930"
SQ SEQUENCE 308 AA; 33905 MW; 0D0AE7D99A87FC9E CRC64;
MVLGRGLLGR RSLAALGAAC ARRGLGPALL GVLHHTDLRK NLTVDEGTMK VEVLPALTDN
YMYLVIDDET KEAAIVDPVQ PQKVLDAARK HGVKLTTVLT THHHWDHAGG NEKLVKLQSG
LKVYGGDDRI GALTHKITHL STLQVGSLNV KCLATPCHTS GHICYFVSRP GGSEPPAVFT
GDTLFVAGCG KFYEGTADEM CKALLEVLGR LPPDTRVYCG HEYTINNLKF ARHVEPGNAA
IQEKLAWAKE KYSIGEPTVP STLAEEFTYN PFMRVREKTV QQHARETDPV TTMRAVRKEK
DEFKMPRD
