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Protein

Hydroxyacylglutathione hydrolase, mitochondrial

Gene

HAGH

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Thiolesterase that catalyzes the hydrolysis of S-D-lactoyl-glutathione to form glutathione and D-lactic acid.

Catalytic activityi

S-(2-hydroxyacyl)glutathione + H2O = glutathione + a 2-hydroxy carboxylate.

Cofactori

Zn2+1 PublicationNote: Binds 2 Zn2+ ions per subunit.1 Publication

Pathwayi: methylglyoxal degradation

This protein is involved in step 2 of the subpathway that synthesizes (R)-lactate from methylglyoxal.
Proteins known to be involved in the 2 steps of the subpathway in this organism are:
  1. Lactoylglutathione lyase (HEL-S-74), Lactoylglutathione lyase (GLO1), Lactoylglutathione lyase (GLO1)
  2. Hydroxyacylglutathione hydrolase, mitochondrial (HAGH)
This subpathway is part of the pathway methylglyoxal degradation, which is itself part of Secondary metabolite metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes (R)-lactate from methylglyoxal, the pathway methylglyoxal degradation and in Secondary metabolite metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi102Zinc 1; via tele nitrogen1 Publication1
Metal bindingi104Zinc 1; via pros nitrogen1 Publication1
Metal bindingi106Zinc 21 Publication1
Metal bindingi107Zinc 2; via tele nitrogen1 Publication1
Metal bindingi158Zinc 1; via tele nitrogen1 Publication1
Metal bindingi182Zinc 11 Publication1
Metal bindingi182Zinc 21 Publication1
Metal bindingi221Zinc 2; via tele nitrogen1 Publication1

GO - Molecular functioni

  • hydroxyacylglutathione hydrolase activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:HS00787-MONOMER.
BRENDAi3.1.2.6. 2681.
ReactomeiR-HSA-70268. Pyruvate metabolism.
SABIO-RKQ16775.
UniPathwayiUPA00619; UER00676.

Names & Taxonomyi

Protein namesi
Recommended name:
Hydroxyacylglutathione hydrolase, mitochondrial1 Publication (EC:3.1.2.6)
Alternative name(s):
Glyoxalase II
Short name:
Glx II
Gene namesi
Name:HAGH
Synonyms:GLO2, HAGH1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:4805. HAGH.

Subcellular locationi

Isoform 1 :
Isoform 2 :
  • Cytoplasm 1 Publication

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • mitochondrial matrix Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion

Pathology & Biotechi

Organism-specific databases

DisGeNETi3029.
MIMi138760. gene+phenotype.
OpenTargetsiENSG00000063854.
PharmGKBiPA29179.

Chemistry databases

ChEMBLiCHEMBL2261.
DrugBankiDB00143. Glutathione.

Polymorphism and mutation databases

BioMutaiHAGH.
DMDMi257051015.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 13MitochondrionSequence analysisAdd BLAST13
ChainiPRO_000019234214 – 308Hydroxyacylglutathione hydrolase, mitochondrialAdd BLAST295

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei116N6-acetyllysineBy similarity1
Modified residuei229N6-acetyllysine; alternateCombined sources1
Modified residuei229N6-succinyllysine; alternateBy similarity1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ16775.
MaxQBiQ16775.
PaxDbiQ16775.
PeptideAtlasiQ16775.
PRIDEiQ16775.

PTM databases

iPTMnetiQ16775.
PhosphoSitePlusiQ16775.

Expressioni

Tissue specificityi

Expressed in liver and kidney.1 Publication

Gene expression databases

BgeeiENSG00000063854.
CleanExiHS_HAGH.
ExpressionAtlasiQ16775. baseline and differential.
GenevisibleiQ16775. HS.

Organism-specific databases

HPAiCAB033531.
HPA043041.
HPA061143.

Interactioni

Subunit structurei

Monomer.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
TERF2IPQ9NYB02EBI-3905342,EBI-750109

Protein-protein interaction databases

BioGridi109279. 8 interactors.
IntActiQ16775. 2 interactors.
STRINGi9606.ENSP00000380514.

Chemistry databases

BindingDBiQ16775.

Structurei

Secondary structure

1308
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi50 – 56Combined sources7
Turni57 – 59Combined sources3
Beta strandi60 – 67Combined sources8
Turni68 – 71Combined sources4
Beta strandi72 – 77Combined sources6
Helixi81 – 91Combined sources11
Beta strandi94 – 99Combined sources6
Helixi105 – 108Combined sources4
Helixi111 – 117Combined sources7
Beta strandi122 – 126Combined sources5
Beta strandi134 – 136Combined sources3
Beta strandi142 – 145Combined sources4
Beta strandi148 – 154Combined sources7
Beta strandi157 – 159Combined sources3
Beta strandi163 – 168Combined sources6
Beta strandi170 – 174Combined sources5
Beta strandi177 – 181Combined sources5
Helixi197 – 205Combined sources9
Turni206 – 210Combined sources5
Beta strandi216 – 221Combined sources6
Helixi224 – 234Combined sources11
Helixi239 – 254Combined sources16
Helixi263 – 269Combined sources7
Turni271 – 276Combined sources6
Helixi278 – 284Combined sources7
Helixi289 – 302Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1QH3X-ray1.90A/B49-308[»]
1QH5X-ray1.45A/B49-308[»]
2F50model-A64-225[»]
ProteinModelPortaliQ16775.
SMRiQ16775.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ16775.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni191 – 193Substrate binding1 Publication3
Regioni221 – 223Substrate binding1 Publication3
Regioni297 – 300Substrate binding1 Publication4

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG0813. Eukaryota.
COG0491. LUCA.
GeneTreeiENSGT00530000063033.
HOGENOMiHOG000058041.
HOVERGENiHBG001152.
InParanoidiQ16775.
KOiK01069.
OMAiHVKCLST.
OrthoDBiEOG091G0E58.
PhylomeDBiQ16775.
TreeFamiTF105273.

Family and domain databases

Gene3Di3.60.15.10. 1 hit.
HAMAPiMF_01374. Glyoxalase_2. 1 hit.
InterProiIPR032282. HAGH_C.
IPR017782. Hydroxyacylglutathione_Hdrlase.
IPR001279. Metallo-B-lactamas.
[Graphical view]
PfamiPF16123. HAGH_C. 1 hit.
PF00753. Lactamase_B. 1 hit.
[Graphical view]
PIRSFiPIRSF005457. Glx. 1 hit.
SMARTiSM00849. Lactamase_B. 1 hit.
[Graphical view]
SUPFAMiSSF56281. SSF56281. 1 hit.
TIGRFAMsiTIGR03413. GSH_gloB. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basket

Isoform 1 (identifier: Q16775-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MVVGRGLLGR RSLAALGAAC ARRGLGPALL GVFCHTDLRK NLTVDEGTMK
60 70 80 90 100
VEVLPALTDN YMYLVIDDET KEAAIVDPVQ PQKVVDAARK HGVKLTTVLT
110 120 130 140 150
THHHWDHAGG NEKLVKLESG LKVYGGDDRI GALTHKITHL STLQVGSLNV
160 170 180 190 200
KCLATPCHTS GHICYFVSKP GGSEPPAVFT GDTLFVAGCG KFYEGTADEM
210 220 230 240 250
CKALLEVLGR LPPDTRVYCG HEYTINNLKF ARHVEPGNAA IREKLAWAKE
260 270 280 290 300
KYSIGEPTVP STLAEEFTYN PFMRVREKTV QQHAGETDPV TTMRAVRREK

DQFKMPRD
Length:308
Mass (Da):33,806
Last modified:September 1, 2009 - v2
Checksum:i64E5C214B6EC61CB
GO
Isoform 2 (identifier: Q16775-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-48: Missing.

Note: Produced by alternative splicing. Also produced by alternative initiation at Met-49 of isoform 1.
Show »
Length:260
Mass (Da):28,860
Checksum:i4C3DEC87FB27A1D2
GO
Isoform 3 (identifier: Q16775-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     146-236: GSLNVKCLAT...NLKFARHVEP → TPCLWLAAGS...WQRSLPTTPS
     237-308: Missing.

Note: No experimental confirmation available.
Show »
Length:236
Mass (Da):25,455
Checksum:i25A00E2EAD5E9A15
GO

Sequence cautioni

The sequence AAH00840 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAA62483 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti67D → G in BAG60445 (PubMed:14702039).Curated1
Sequence conflicti121L → P in BAG61219 (PubMed:14702039).Curated1
Sequence conflicti202K → E in BAF82844 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0379291 – 48Missing in isoform 2. 1 PublicationAdd BLAST48
Alternative sequenceiVSP_055199146 – 236GSLNV…RHVEP → TPCLWLAAGSSMKGLRMRCV KLCWRSWAGSPRTQESTVAT STPSTTSSLHATWSPAMPPS GRSWPGPRRSTASGSPQCHP PWQRSLPTTPS in isoform 3. 1 PublicationAdd BLAST91
Alternative sequenceiVSP_055200237 – 308Missing in isoform 3. 1 PublicationAdd BLAST72

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK290155 mRNA. Translation: BAF82844.1.
AK298174 mRNA. Translation: BAG60445.1.
AK299173 mRNA. Translation: BAG61219.1.
AE006639 Genomic DNA. Translation: AAK61294.1.
AC012180 Genomic DNA. No translation available.
BC000840 mRNA. Translation: AAH00840.1. Different initiation.
BC002627 mRNA. Translation: AAH02627.2.
X90999 mRNA. Translation: CAA62483.1. Different initiation.
CCDSiCCDS10447.2. [Q16775-1]
CCDS32366.1. [Q16775-2]
CCDS66900.1. [Q16775-3]
RefSeqiNP_001035517.1. NM_001040427.1. [Q16775-2]
NP_001273178.1. NM_001286249.1. [Q16775-3]
NP_005317.2. NM_005326.4. [Q16775-1]
XP_011520772.1. XM_011522470.2. [Q16775-3]
UniGeneiHs.157394.

Genome annotation databases

EnsembliENST00000397353; ENSP00000380511; ENSG00000063854. [Q16775-2]
ENST00000397356; ENSP00000380514; ENSG00000063854. [Q16775-1]
ENST00000455446; ENSP00000406552; ENSG00000063854. [Q16775-3]
GeneIDi3029.
KEGGihsa:3029.
UCSCiuc002cmz.4. human. [Q16775-1]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK290155 mRNA. Translation: BAF82844.1.
AK298174 mRNA. Translation: BAG60445.1.
AK299173 mRNA. Translation: BAG61219.1.
AE006639 Genomic DNA. Translation: AAK61294.1.
AC012180 Genomic DNA. No translation available.
BC000840 mRNA. Translation: AAH00840.1. Different initiation.
BC002627 mRNA. Translation: AAH02627.2.
X90999 mRNA. Translation: CAA62483.1. Different initiation.
CCDSiCCDS10447.2. [Q16775-1]
CCDS32366.1. [Q16775-2]
CCDS66900.1. [Q16775-3]
RefSeqiNP_001035517.1. NM_001040427.1. [Q16775-2]
NP_001273178.1. NM_001286249.1. [Q16775-3]
NP_005317.2. NM_005326.4. [Q16775-1]
XP_011520772.1. XM_011522470.2. [Q16775-3]
UniGeneiHs.157394.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1QH3X-ray1.90A/B49-308[»]
1QH5X-ray1.45A/B49-308[»]
2F50model-A64-225[»]
ProteinModelPortaliQ16775.
SMRiQ16775.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109279. 8 interactors.
IntActiQ16775. 2 interactors.
STRINGi9606.ENSP00000380514.

Chemistry databases

BindingDBiQ16775.
ChEMBLiCHEMBL2261.
DrugBankiDB00143. Glutathione.

PTM databases

iPTMnetiQ16775.
PhosphoSitePlusiQ16775.

Polymorphism and mutation databases

BioMutaiHAGH.
DMDMi257051015.

Proteomic databases

EPDiQ16775.
MaxQBiQ16775.
PaxDbiQ16775.
PeptideAtlasiQ16775.
PRIDEiQ16775.

Protocols and materials databases

DNASUi3029.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000397353; ENSP00000380511; ENSG00000063854. [Q16775-2]
ENST00000397356; ENSP00000380514; ENSG00000063854. [Q16775-1]
ENST00000455446; ENSP00000406552; ENSG00000063854. [Q16775-3]
GeneIDi3029.
KEGGihsa:3029.
UCSCiuc002cmz.4. human. [Q16775-1]

Organism-specific databases

CTDi3029.
DisGeNETi3029.
GeneCardsiHAGH.
HGNCiHGNC:4805. HAGH.
HPAiCAB033531.
HPA043041.
HPA061143.
MIMi138760. gene+phenotype.
neXtProtiNX_Q16775.
OpenTargetsiENSG00000063854.
PharmGKBiPA29179.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0813. Eukaryota.
COG0491. LUCA.
GeneTreeiENSGT00530000063033.
HOGENOMiHOG000058041.
HOVERGENiHBG001152.
InParanoidiQ16775.
KOiK01069.
OMAiHVKCLST.
OrthoDBiEOG091G0E58.
PhylomeDBiQ16775.
TreeFamiTF105273.

Enzyme and pathway databases

UniPathwayiUPA00619; UER00676.
BioCyciZFISH:HS00787-MONOMER.
BRENDAi3.1.2.6. 2681.
ReactomeiR-HSA-70268. Pyruvate metabolism.
SABIO-RKQ16775.

Miscellaneous databases

EvolutionaryTraceiQ16775.
GeneWikiiHAGH.
GenomeRNAii3029.
PROiQ16775.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000063854.
CleanExiHS_HAGH.
ExpressionAtlasiQ16775. baseline and differential.
GenevisibleiQ16775. HS.

Family and domain databases

Gene3Di3.60.15.10. 1 hit.
HAMAPiMF_01374. Glyoxalase_2. 1 hit.
InterProiIPR032282. HAGH_C.
IPR017782. Hydroxyacylglutathione_Hdrlase.
IPR001279. Metallo-B-lactamas.
[Graphical view]
PfamiPF16123. HAGH_C. 1 hit.
PF00753. Lactamase_B. 1 hit.
[Graphical view]
PIRSFiPIRSF005457. Glx. 1 hit.
SMARTiSM00849. Lactamase_B. 1 hit.
[Graphical view]
SUPFAMiSSF56281. SSF56281. 1 hit.
TIGRFAMsiTIGR03413. GSH_gloB. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiGLO2_HUMAN
AccessioniPrimary (citable) accession number: Q16775
Secondary accession number(s): A8K290
, B4DP33, B4DRA7, E7EN93
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: September 1, 2009
Last modified: November 2, 2016
This is version 153 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Caution

Only one single gene encoding glyoxalase II has been identified in vertebrates. In yeast and higher plants, separate genes encode the cytosolic and mitochondrial forms of glyoxalase II.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.