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Q16775 (GLO2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Hydroxyacylglutathione hydrolase, mitochondrial

EC=3.1.2.6
Alternative name(s):
Glyoxalase II
Short name=Glx II
Gene names
Name:HAGH
Synonyms:GLO2, HAGH1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length308 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Thiolesterase that catalyzes the hydrolysis of S-D-lactoyl-glutathione to form glutathione and D-lactic acid. HAMAP-Rule MF_01374

Catalytic activity

S-(2-hydroxyacyl)glutathione + H2O = glutathione + a 2-hydroxy carboxylate. HAMAP-Rule MF_01374

Cofactor

Binds 2 zinc ions per subunit.

Pathway

Secondary metabolite metabolism; methylglyoxal degradation; (R)-lactate from methylglyoxal: step 2/2. HAMAP-Rule MF_01374

Subunit structure

Monomer.

Subcellular location

Isoform 1: Mitochondrion matrix Ref.6.

Isoform 2: Cytoplasm Ref.6.

Tissue specificity

Expressed in liver and kidney. Ref.6

Sequence similarities

Belongs to the metallo-beta-lactamase superfamily. Glyoxalase II family.

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.

Sequence caution

The sequence AAH00840.1 differs from that shown. Reason: Erroneous initiation.

The sequence CAA62483.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Cellular componentCytoplasm
Mitochondrion
   Coding sequence diversityAlternative initiation
Alternative splicing
   DomainTransit peptide
   LigandMetal-binding
Zinc
   Molecular functionHydrolase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processglutathione biosynthetic process

Inferred from direct assay Ref.5. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay Ref.6. Source: UniProtKB

mitochondrial matrix

Inferred from direct assay Ref.6. Source: UniProtKB

   Molecular_functionhydroxyacylglutathione hydrolase activity

Inferred from direct assay Ref.5. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing and alternative initiation. [Align] [Select]
Isoform 1 (identifier: Q16775-1)

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.
Isoform 2 (identifier: Q16775-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 1313Mitochondrion Potential
Chain14 – 308295Hydroxyacylglutathione hydrolase, mitochondrial HAMAP-Rule MF_01374
PRO_0000192342

Regions

Region191 – 1933Substrate binding HAMAP-Rule MF_01374
Region221 – 2233Substrate binding HAMAP-Rule MF_01374
Region297 – 3004Substrate binding HAMAP-Rule MF_01374

Sites

Metal binding1021Zinc 1
Metal binding1041Zinc 1
Metal binding1061Zinc 2
Metal binding1071Zinc 2
Metal binding1581Zinc 1
Metal binding1821Zinc 1
Metal binding1821Zinc 2
Metal binding2211Zinc 2

Amino acid modifications

Modified residue1161N6-acetyllysine By similarity
Modified residue2291N6-acetyllysine; alternate Ref.7
Modified residue2291N6-succinyllysine; alternate By similarity

Natural variations

Alternative sequence1 – 4848Missing in isoform 2.
VSP_037929

Experimental info

Sequence conflict1211L → P in BAG61219. Ref.1
Sequence conflict2021K → E in BAF82844. Ref.1

Secondary structure

................................................ 308
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified September 1, 2009. Version 2.
Checksum: 64E5C214B6EC61CB

FASTA30833,806
        10         20         30         40         50         60 
MVVGRGLLGR RSLAALGAAC ARRGLGPALL GVFCHTDLRK NLTVDEGTMK VEVLPALTDN 

        70         80         90        100        110        120 
YMYLVIDDET KEAAIVDPVQ PQKVVDAARK HGVKLTTVLT THHHWDHAGG NEKLVKLESG 

       130        140        150        160        170        180 
LKVYGGDDRI GALTHKITHL STLQVGSLNV KCLATPCHTS GHICYFVSKP GGSEPPAVFT 

       190        200        210        220        230        240 
GDTLFVAGCG KFYEGTADEM CKALLEVLGR LPPDTRVYCG HEYTINNLKF ARHVEPGNAA 

       250        260        270        280        290        300 
IREKLAWAKE KYSIGEPTVP STLAEEFTYN PFMRVREKTV QQHAGETDPV TTMRAVRREK 


DQFKMPRD 

« Hide

Isoform 2 [UniParc].

Checksum: 4C3DEC87FB27A1D2
Show »

FASTA26028,860

References

« Hide 'large scale' references
[1]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Thalamus.
[2]"Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16."
Daniels R.J., Peden J.F., Lloyd C., Horsley S.W., Clark K., Tufarelli C., Kearney L., Buckle V.J., Doggett N.A., Flint J., Higgs D.R.
Hum. Mol. Genet. 10:339-352(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The sequence and analysis of duplication-rich human chromosome 16."
Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. expand/collapse author list , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Cervix and Uterus.
[5]"Molecular cloning, heterologous expression, and characterization of human glyoxalase II."
Ridderstroem M., Saccucci F., Hellman U., Bergman T., Principato G., Mannervik B.
J. Biol. Chem. 271:319-323(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 37-308 (ISOFORMS 1/2).
Tissue: Liver.
[6]"The human hydroxyacylglutathione hydrolase (HAGH) gene encodes both cytosolic and mitochondrial forms of glyoxalase II."
Cordell P.A., Futers T.S., Grant P.J., Pease R.J.
J. Biol. Chem. 279:28653-28661(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, ALTERNATIVE INITIATION, ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), TISSUE SPECIFICITY.
[7]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-229, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"Crystal structure of human glyoxalase II and its complex with a glutathione thiolester substrate analogue."
Cameron A.D., Ridderstroem M., Olin B., Mannervik B.
Structure 7:1067-1077(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 49-308 IN COMPLEX WITH SUBSTRATE ANALOGS AND ZINC IONS.
Tissue: Liver.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK290155 mRNA. Translation: BAF82844.1.
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.
RefSeqNP_001035517.1. NM_001040427.1.
NP_001273178.1. NM_001286249.1.
NP_005317.2. NM_005326.4.
UniGeneHs.157394.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1QH3X-ray1.90A/B49-308[»]
1QH5X-ray1.45A/B49-308[»]
2F50model-A64-225[»]
ProteinModelPortalQ16775.
SMRQ16775. Positions 49-308.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109279. 6 interactions.
IntActQ16775. 1 interaction.
STRING9606.ENSP00000380514.

Chemistry

BindingDBQ16775.
ChEMBLCHEMBL2261.
DrugBankDB00143. Glutathione.

PTM databases

PhosphoSiteQ16775.

Polymorphism databases

DMDM257051015.

Proteomic databases

PaxDbQ16775.
PRIDEQ16775.

Protocols and materials databases

DNASU3029.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000397353; ENSP00000380511; ENSG00000063854. [Q16775-2]
ENST00000397356; ENSP00000380514; ENSG00000063854. [Q16775-1]
GeneID3029.
KEGGhsa:3029.
UCSCuc002cmz.3. human. [Q16775-1]

Organism-specific databases

CTD3029.
GeneCardsGC16M001845.
HGNCHGNC:4805. HAGH.
HPACAB033531.
MIM138760. gene+phenotype.
neXtProtNX_Q16775.
PharmGKBPA29179.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0491.
HOGENOMHOG000058041.
HOVERGENHBG001152.
InParanoidQ16775.
KOK01069.
OMAIGDEKEW.
PhylomeDBQ16775.
TreeFamTF105273.

Enzyme and pathway databases

BRENDA3.1.2.6. 5596.
SABIO-RKQ16775.
UniPathwayUPA00619; UER00676.

Gene expression databases

ArrayExpressQ16775.
BgeeQ16775.
CleanExHS_HAGH.
GenevestigatorQ16775.

Family and domain databases

Gene3D3.60.15.10. 1 hit.
HAMAPMF_01374. Glyoxalase_2.
InterProIPR001279. Beta-lactamas-like.
IPR017782. Hydroxyacylglutathione_Hdrlase.
[Graphical view]
PANTHERPTHR11935:SF7. PTHR11935:SF7. 1 hit.
PfamPF00753. Lactamase_B. 1 hit.
[Graphical view]
PIRSFPIRSF005457. Glx. 1 hit.
SMARTSM00849. Lactamase_B. 1 hit.
[Graphical view]
SUPFAMSSF56281. SSF56281. 1 hit.
TIGRFAMsTIGR03413. GSH_gloB. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ16775.
GeneWikiHAGH.
GenomeRNAi3029.
NextBio11990.
PROQ16775.
SOURCESearch...

Entry information

Entry nameGLO2_HUMAN
AccessionPrimary (citable) accession number: Q16775
Secondary accession number(s): A8K290, B4DRA7
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: September 1, 2009
Last modified: April 16, 2014
This is version 129 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM