Reviewed, UniProtKB/Swiss-Prot Q04760 (LGUL_HUMAN)

Names and origin

Protein names

Recommended name:
    Lactoylglutathione lyase
    EC=4.4.1.5
Alternative name(s):
    Methylglyoxalase
    Aldoketomutase
    Glyoxalase I
      Short name=Glx I
    Ketone-aldehyde mutase
    S-D-lactoylglutathione methylglyoxal lyase

Gene names

Name:

GLO1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	184 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	Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione.
Catalytic activity	(R)-S-lactoylglutathione = glutathione + methylglyoxal.
Cofactor	Binds 1 zinc ion per subunit.
Pathway	Secondary metabolite metabolism; methylglyoxal degradation; (R)-lactate from methylglyoxal: step 1/2.
Subunit structure	Homodimer.
Polymorphism	Exists in three separable isoforms which originate from two alleles in the genome. These correspond to two homodimers and one heterodimer composed of two subunits showing different electrophoretic properties.
Sequence similarities	Belongs to the glyoxalase I family.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Ligand	Metal-binding Zinc
Molecular function	Lyase
PTM	Acetylation
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	anti-apoptosis Inferred from direct assay. Source: UniProtKB carbohydrate metabolic process Ref.1 Non-traceable author statement. Source: ProtInc
Cellular component	cytoplasm Traceable author statement. Source: UniProtKB
Molecular function	lactoylglutathione lyase activity Ref.1 Inferred from direct assay. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Probable

Chain

2 – 184

183

Lactoylglutathione lyase

PRO_0000168076

Sites

Metal binding

34

1

Zinc

Metal binding

100

1

Zinc

Metal binding

127

1

Zinc

Metal binding

173

1

Zinc

Amino acid modifications

Modified residue

148

1

N6-acetyllysine Ref.10

Natural variations

Natural variant

19

1

C → Y: dbSNP rs17855424. Ref.8

VAR_031078

Natural variant

111

1

E → A: dbSNP rs4746. Ref.8 Ref.1 Ref.2 Ref.4 Ref.5

VAR_013481

Secondary structure

1

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184

Helix Strand Turn

Details...

Helix

13 – 18

6

Helix

25 – 27

3

Beta strand

31 – 38

8

Helix

42 – 51

10

Beta strand

56 – 63

8

Turn

64 – 67

4

Beta strand

68 – 75

8

Helix

78 – 80

3

Helix

85 – 92

8

Beta strand

96 – 104

9

Helix

107 – 109

3

Beta strand

118 – 122

5

Beta strand

125 – 131

7

Helix

135 – 144

10

Beta strand

149 – 151

3

Beta strand

155 – 158

4

Beta strand

162 – 165

4

Beta strand

171 – 175

5

Helix

177 – 179

3

Sequences

	Sequence		Length	Mass (Da)
	Q04760-1 [UniParc]. Last modified March 6, 2007. Version 4. Checksum: 46291B7878070028	FASTA	184	20,778
	10 20 30 40 50 60 MAEPQPPSGG LTDEAALSCC SDADPSTKDF LLQQTMLRVK DPKKSLDFYT RVLGMTLIQK 70 80 90 100 110 120 CDFPIMKFSL YFLAYEDKND IPKEKDEKIA WALSRKATLE LTHNWGTEDD ETQSYHNGNS 130 140 150 160 170 180 DPRGFGHIGI AVPDVYSACK RFEELGVKFV KKPDDGKMKG LAFIQDPDGY WIEILNPNKM ATLM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human glyoxalase I. cDNA cloning, expression, and sequence similarity to glyoxalase I from Pseudomonas putida." Kim N.-S., Umezawa Y., Ohmura S., Kato S. J. Biol. Chem. 268:11217-11221(1993) [PubMed: 7684374] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ALA-111.
[2]	"Cloning and characterization of human colon glyoxalase-I." Ranganathan S., Walsh E.S., Godwin A.K., Tew K.D. J. Biol. Chem. 268:5661-5667(1993) [PubMed: 8449929] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ALA-111. Tissue: Colon.
[3]	"Optimized heterologous expression of the human zinc enzyme glyoxalase I." Ridderstroem M., Mannervik B. Biochem. J. 314:463-467(1996) [PubMed: 8670058] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Genomic sequence of human glyoxalase-I: analysis of promoter activity and its regulation." Ranganathan S., Ciaccio P.J., Walsh E.S., Tew K.D. Gene 240:149-155(1999) [PubMed: 10564821] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ALA-111.
[5]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-111.
[6]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS TYR-19 AND ALA-111. Tissue: Brain, Eye and Uterus.
[9]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[10]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-148, MASS SPECTROMETRY.
[11]	"Crystal structure of human glyoxalase I -- evidence for gene duplication and 3D domain swapping." Cameron A.D., Olin B., Ridderstroem M., Mannervik B., Jones T.A. EMBO J. 16:3386-3395(1997) [PubMed: 9218781] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[12]	"Involvement of an active-site Zn2+ ligand in the catalytic mechanism of human glyoxalase I." Ridderstroem M., Cameron A.D., Jones T.A., Mannervik B. J. Biol. Chem. 273:21623-21628(1998) [PubMed: 9705294] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[13]	"Reaction mechanism of glyoxalase I explored by an X-ray crystallographic analysis of the human enzyme in complex with a transition state analogue." Cameron A.D., Ridderstroem M., Olin B., Kavarana M.J., Creighton D.J., Mannervik B. Biochemistry 38:13480-13490(1999) [PubMed: 10521255] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

D13315 mRNA. Translation: BAA02572.1.
L07837 mRNA. Translation: AAA52565.1.
S83285 mRNA. Translation: AAB49495.1.
AF146651 Genomic DNA. Translation: AAD38008.1.
AK312662 mRNA. Translation: BAG35544.1.
BT019987 mRNA. Translation: AAV38790.1.
BT019988 mRNA. Translation: AAV38791.1.
AL391415 Genomic DNA. Translation: CAI21586.1.
BC001741 mRNA. Translation: AAH01741.1.
BC011365 mRNA. Translation: AAH11365.1.
BC015934 mRNA. Translation: AAH15934.1.

IPI

IPI00220766.

PIR

A46714.
S63603.

RefSeq

NP_006699.2.

UniGene

Hs.268849

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BH5	X-ray	2.20	A/B/C/D	2-184	[»]
1FRO	X-ray	2.20	A/B/C/D	2-184	[»]
1QIN	X-ray	2.00	A/B	2-184	[»]
1QIP	X-ray	1.72	A/B/C/D	2-184	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q04760. 1 interaction.

STRING

Q04760.

PTM databases

PhosphoSite

Q04760.

2-D gel databases

OGP

Q04760.

REPRODUCTION-2DPAGE

IPI00220766.
Q04760.

Proteomic databases

PRIDE

Q04760.

Genome annotation databases

Ensembl

ENST00000373365; ENSP00000362463; ENSG00000124767; Homo sapiens. [Genome view]

GeneID

2739.

KEGG

hsa:2739.

UCSC

uc003ooc.1. human.

Organism-specific databases

CTD

2739.

GeneCards

GC06M038751.

H-InvDB

HIX0005848.

HGNC

HGNC:4323. GLO1.

MIM

138750. gene.

PharmGKB

PA28724.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q04760.

OMA

FAYHNGN.

Enzyme and pathway databases

BRENDA

4.4.1.5. 247.

Gene expression databases

ArrayExpress

Q04760.

Bgee

Q04760.

CleanEx

HS_GLO1.

Genevestigator

Q04760.

GermOnline

ENSG00000124767. Homo sapiens.

Family and domain databases

InterPro

IPR004360. Glyas_bleo-R_dOase.
IPR004361. Glyoxalase_1.
IPR018146. Glyoxalase_1_CS.
[Graphical view]

Pfam

PF00903. Glyoxalase. 1 hit.
[Graphical view]

ProDom

PD002334. Gly_diox. 1 hit.
[Graphical view] [Entries sharing at least one domain]

TIGRFAMs

TIGR00068. glyox_I. 1 hit.

PROSITE

PS00934. GLYOXALASE_I_1. 1 hit.
PS00935. GLYOXALASE_I_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00143. Glutathione.

NextBio

10796.

SOURCE

Search...

Entry information

Entry name

LGUL_HUMAN

Accession

Primary (citable) accession number: Q04760
Secondary accession number(s): B2R6P7 , P78375, Q5TZW3, Q96FC0, Q96J41

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	March 6, 2007
Last modified:	November 3, 2009
This is version 108 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.