Q16775 (GLO2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	308 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Thiolesterase that catalyzes the hydrolysis of S-D-lactoyl-glutathione to form glutathione and D-lactic acid.
Catalytic activity	S-(2-hydroxyacyl)glutathione + H2O = glutathione + a 2-hydroxy carboxylate.
Cofactor	Binds 2 zinc ions per subunit.
Pathway	Secondary metabolite metabolism; methylglyoxal degradation; (R)-lactate from methylglyoxal: step 2/2.
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 component	Cytoplasm Mitochondrion
Coding sequence diversity	Alternative initiation Alternative splicing
Domain	Transit peptide
Ligand	Metal-binding Zinc
Molecular function	Hydrolase
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	glutathione biosynthetic process Inferred from direct assay Ref.5. Source: UniProtKB
Cellular_component	cytoplasm Inferred from direct assay Ref.6. Source: UniProtKB mitochondrial matrix Inferred from direct assay Ref.6. Source: UniProtKB
Molecular_function	hydroxyacylglutathione 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 13

13

Mitochondrion Potential

Chain

14 – 308

295

Hydroxyacylglutathione hydrolase, mitochondrial

PRO_0000192342

Regions

Region

191 – 193

3

Substrate

Region

221 – 223

3

Substrate

Region

297 – 300

4

Substrate

Sites

Metal binding

102

1

Zinc 1

Metal binding

104

1

Zinc 1

Metal binding

106

1

Zinc 2

Metal binding

107

1

Zinc 2

Metal binding

158

1

Zinc 1

Metal binding

182

1

Zinc 1

Metal binding

182

1

Zinc 2

Metal binding

221

1

Zinc 2

Amino acid modifications

Modified residue

229

1

N6-acetyllysine Ref.7

Natural variations

Alternative sequence

1 – 48

48

Missing in isoform 2.

VSP_037929

Experimental info

Sequence conflict

121

1

L → P in BAG61219. Ref.1

Sequence conflict

202

1

K → E in BAF82844. Ref.1

Secondary structure

1

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308

Helix Strand Turn

Details...

Beta strand

50 – 56

7

Turn

57 – 59

3

Beta strand

60 – 67

8

Turn

68 – 71

4

Beta strand

72 – 77

6

Helix

81 – 91

11

Beta strand

94 – 99

6

Helix

105 – 108

4

Helix

111 – 117

7

Beta strand

122 – 126

5

Beta strand

134 – 136

3

Beta strand

142 – 145

4

Beta strand

148 – 154

7

Beta strand

157 – 159

3

Beta strand

163 – 168

6

Beta strand

170 – 174

5

Beta strand

177 – 181

5

Helix

197 – 205

9

Turn

206 – 210

5

Beta strand

216 – 221

6

Helix

224 – 234

11

Helix

239 – 254

16

Helix

263 – 269

7

Turn

271 – 276

6

Helix

278 – 284

7

Helix

289 – 302

14

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 1, 2009. Version 2. Checksum: 64E5C214B6EC61CB	FASTA	308	33,806
	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
	Isoform 2 [UniParc]. Checksum: 4C3DEC87FB27A1D2	FASTA	260	28,860
	10 20 30 40 50 60 MKVEVLPALT DNYMYLVIDD ETKEAAIVDP VQPQKVVDAA RKHGVKLTTV LTTHHHWDHA 70 80 90 100 110 120 GGNEKLVKLE SGLKVYGGDD RIGALTHKIT HLSTLQVGSL NVKCLATPCH TSGHICYFVS 130 140 150 160 170 180 KPGGSEPPAV FTGDTLFVAG CGKFYEGTAD EMCKALLEVL GRLPPDTRVY CGHEYTINNL 190 200 210 220 230 240 KFARHVEPGN AAIREKLAWA KEKYSIGEPT VPSTLAEEFT YNPFMRVREK TVQQHAGETD 250 260 PVTTMRAVRR EKDQFKMPRD

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, MASS SPECTROMETRY.
[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.

IPI

IPI00003933.
IPI00745553.

RefSeq

NP_001035517.1. NM_001040427.1.
NP_005317.2. NM_005326.4.

UniGene

Hs.157394.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1QH3	X-ray	1.90	A/B	49-308	[»]
1QH5	X-ray	1.45	A/B	49-308	[»]
2F50	model	-	A	64-225	[»]

ProteinModelPortal

Q16775.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q16775. 1 interaction.

STRING

9606.ENSP00000380514.

PTM databases

PhosphoSite

Q16775.

Polymorphism databases

DMDM

257051015.

Proteomic databases

PaxDb

Q16775.

PRIDE

Q16775.

Protocols and materials databases

DNASU

3029.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000397353; ENSP00000380511; ENSG00000063854.
ENST00000397356; ENSP00000380514; ENSG00000063854.

GeneID

3029.

KEGG

hsa:3029.

UCSC

uc002cmz.3. human.

Organism-specific databases

CTD

3029.

GeneCards

GC16M001845.

HGNC

HGNC:4805. HAGH.

HPA

CAB033531.

MIM

138760. gene+phenotype.

neXtProt

NX_Q16775.

PharmGKB

PA29179.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0491.

HOGENOM

HOG000058041.

HOVERGEN

HBG001152.

InParanoid

Q16775.

KO

K01069.

OMA

PFMRVHE.

OrthoDB

EOG4B5P5Q.

Enzyme and pathway databases

BRENDA

3.1.2.6. 5596.

SABIO-RK

Q16775.

UniPathway

UPA00619; UER00676.

Gene expression databases

ArrayExpress

Q16775.

Bgee

Q16775.

CleanEx

HS_HAGH.

Genevestigator

Q16775.

GermOnline

ENSG00000063854. Homo sapiens.

Family and domain databases

Gene3D

3.60.15.10. 1 hit.

InterPro

IPR001279. Beta-lactamas-like.
IPR017782. Hydroxyacylglutathione_Hdrlase.
[Graphical view]

PANTHER

PTHR11935:SF7. PTHR11935:SF7. 1 hit.

Pfam

PF00753. Lactamase_B. 1 hit.
[Graphical view]

PIRSF

PIRSF005457. Glx. 1 hit.

SMART

SM00849. Lactamase_B. 1 hit.
[Graphical view]

TIGRFAMs

TIGR03413. GSH_gloB. 1 hit.

ProtoNet

Search...

Other

BindingDB

Q16775.

ChEMBL

CHEMBL2261.

DrugBank

DB00143. Glutathione.

EvolutionaryTrace

Q16775.

GenomeRNAi

3029.

NextBio

11990.

SOURCE

Search...

Entry information

Entry name

GLO2_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 121 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.