P28161 (GSTM2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glutathione S-transferase Mu 2
EC=2.5.1.18

Alternative name(s):
GST class-mu 2
GSTM2-2

Gene names

Name:	GSTM2
Synonyms:	GST4

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	218 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	Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Ref.10
Catalytic activity	RX + glutathione = HX + R-S-glutathione. Ref.10
Subunit structure	Homodimer. Ref.9
Subcellular location	Cytoplasm.
Tissue specificity	Muscle.
Sequence similarities	Belongs to the GST superfamily. Mu family. Contains 1 GST C-terminal domain. Contains 1 GST N-terminal domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Transferase
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular detoxification of nitrogen compound Inferred from direct assay Ref.1Ref.6. Source: BHF-UCL cellular response to caffeine Inferred from direct assay PubMed 22406107. Source: BHF-UCL glutathione metabolic process Inferred from direct assay Ref.10. Source: UniProtKB negative regulation of ryanodine-sensitive calcium-release channel activity Inferred from direct assay PubMed 17023043PubMed 22406107. Source: BHF-UCL nitrobenzene metabolic process Inferred from direct assay Ref.1Ref.6. Source: BHF-UCL positive regulation of ryanodine-sensitive calcium-release channel activity Inferred from direct assay PubMed 17023043. Source: BHF-UCL regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion Inferred by curator PubMed 17023043PubMed 22406107. Source: BHF-UCL regulation of skeletal muscle contraction by regulation of release of sequestered calcium ion Inferred by curator PubMed 17023043. Source: BHF-UCL relaxation of cardiac muscle Traceable author statement PubMed 21323602. Source: BHF-UCL xenobiotic catabolic process Inferred from direct assay Ref.10. Source: UniProtKB
Cellular_component	sarcoplasmic reticulum Inferred from direct assay PubMed 22406107. Source: BHF-UCL
Molecular_function	glutathione binding Inferred from direct assay Ref.1Ref.6. Source: BHF-UCL glutathione transferase activity Inferred from direct assay Ref.10. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P28161-1)

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: P28161-2)

The sequence of this isoform differs from the canonical sequence as follows:
     190-218: GLEKISAYMKSSRFLPRPVFTKMAVWGNK → HS

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 218

217

Glutathione S-transferase Mu 2

PRO_0000185818

Regions

Domain

2 – 88

87

GST N-terminal

Domain

90 – 208

119

GST C-terminal

Region

7 – 8

2

Glutathione binding

Region

46 – 50

5

Glutathione binding

Region

59 – 60

2

Glutathione binding

Region

72 – 73

2

Glutathione binding

Sites

Binding site

116

1

Substrate By similarity

Site

210

1

Important for substrate specificity

Natural variations

Alternative sequence

190 – 218

29

GLEKI…VWGNK → HS in isoform 2.

VSP_045614

Natural variant

173

1

S → N.
Corresponds to variant rs2229050 [ dbSNP | Ensembl ].

VAR_049486

Experimental info

Mutagenesis

210

1

T → C, F, H, I, K, L, R, Y or W: Reduced enzyme activity. Ref.10

Sequence conflict

2

1

P → S in AAV38750. Ref.3

Sequence conflict

9

1

N → D in AAV38750. Ref.3

Sequence conflict

51

1

F → L in BAG61446. Ref.2

Secondary structure

1

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218

Helix Strand Turn

Details...

Beta strand

3 – 11

9

Helix

12 – 14

3

Helix

15 – 23

9

Beta strand

28 – 33

6

Turn

38 – 41

4

Helix

44 – 47

4

Turn

48 – 51

4

Beta strand

60 – 65

6

Beta strand

68 – 72

5

Helix

73 – 83

11

Helix

91 – 116

26

Helix

120 – 142

23

Beta strand

150 – 152

3

Helix

155 – 170

16

Turn

172 – 177

6

Helix

179 – 190

12

Helix

192 – 199

8

Beta strand

200 – 202

3

Beta strand

205 – 207

3

Turn

208 – 212

5

Beta strand

214 – 216

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 15203709D4A63789	FASTA	218	25,745
	10 20 30 40 50 60 MPMTLGYWNI RGLAHSIRLL LEYTDSSYEE KKYTMGDAPD YDRSQWLNEK FKLGLDFPNL 70 80 90 100 110 120 PYLIDGTHKI TQSNAILRYI ARKHNLCGES EKEQIREDIL ENQFMDSRMQ LAKLCYDPDF 130 140 150 160 170 180 EKLKPEYLQA LPEMLKLYSQ FLGKQPWFLG DKITFVDFIA YDVLERNQVF EPSCLDAFPN 190 200 210 LKDFISRFEG LEKISAYMKS SRFLPRPVFT KMAVWGNK
	Isoform 2 [UniParc]. Checksum: 9267243C014F878F	FASTA	191	22,644
	10 20 30 40 50 60 MPMTLGYWNI RGLAHSIRLL LEYTDSSYEE KKYTMGDAPD YDRSQWLNEK FKLGLDFPNL 70 80 90 100 110 120 PYLIDGTHKI TQSNAILRYI ARKHNLCGES EKEQIREDIL ENQFMDSRMQ LAKLCYDPDF 130 140 150 160 170 180 EKLKPEYLQA LPEMLKLYSQ FLGKQPWFLG DKITFVDFIA YDVLERNQVF EPSCLDAFPN 190 LKDFISRFEH S

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, expression, and characterization of a class-mu glutathione transferase from human muscle, the product of the GST4 locus." Vorachek W.R., Pearson W.R., Rule G.S. Proc. Natl. Acad. Sci. U.S.A. 88:4443-4447(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Muscle.
[2]	"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]. Tissue: Brain.
[3]	"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] (ISOFORM 1).
[4]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] (ISOFORM 1). Tissue: Brain.
[6]	"Molecular cloning and heterologous expression of an alternatively spliced human Mu class glutathione S-transferase transcript." Ross V.L., Board P.G. Biochem. J. 294:373-380(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF N-TERMINUS. Tissue: Testis.
[7]	Lubec G., Vishwanath V. Submitted (MAR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 53-69 AND 153-182, MASS SPECTROMETRY. Tissue: Brain and Cajal-Retzius cell.
[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 class mu glutathione transferase GSTM2-2. Effects of lattice packing on conformational heterogeneity." Raghunathan S., Chandross R.J., Kretsinger R.H., Allison T.J., Penington C.J., Rule G.S. J. Mol. Biol. 238:815-832(1994) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) IN COMPLEX WITH GLUTATHIONE, SUBUNIT.
[10]	"Alternative mutations of a positively selected residue elicit gain or loss of functionalities in enzyme evolution." Norrgard M.A., Ivarsson Y., Tars K., Mannervik B. Proc. Natl. Acad. Sci. U.S.A. 103:4876-4881(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) IN COMPLEX WITH GLUTATHIONE, FUNCTION, MUTAGENESIS OF THR-210, CATALYTIC ACTIVITY.
[11]	"Structural basis for the binding of the anticancer compound 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol to human glutathione s-transferases." Federici L., Lo Sterzo C., Pezzola S., Di Matteo A., Scaloni F., Federici G., Caccuri A.M. Cancer Res. 69:8025-8034(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH NBDHEX.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M63509 mRNA. Translation: AAA60963.1.
AK299482 mRNA. Translation: BAG61446.1.
BT019947 mRNA. Translation: AAV38750.1.
AC000031 Genomic DNA. No translation available.
AC000032 Genomic DNA. No translation available.
BC105038 mRNA. Translation: AAI05039.1.
BC105066 mRNA. Translation: AAI05067.1.

IPI

IPI00219067.
IPI00984060.

PIR

A39375.

RefSeq

NP_000839.1. NM_000848.3.
NP_001135840.1. NM_001142368.1.

UniGene

Hs.279837.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HNA	X-ray	1.85	A	2-218	[»]
1HNB	X-ray	3.50	A/B	2-218	[»]
1HNC	X-ray	3.00	A/B/C/D	2-218	[»]
1XW5	X-ray	1.80	A/B	2-217	[»]
1YKC	X-ray	2.10	A/B	2-217	[»]
2AB6	X-ray	2.50	A/B/C/D	2-217	[»]
2C4J	X-ray	1.35	A/B/C/D	2-217	[»]
2GTU	X-ray	2.55	A/B	2-217	[»]
3GTU	X-ray	2.80	A/C	2-217	[»]
3GUR	X-ray	2.50	A/B/C/D	2-218	[»]

ProteinModelPortal

P28161.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-129N.

STRING

9606.ENSP00000241337.

PTM databases

PhosphoSite

P28161.

Polymorphism databases

DMDM

232204.

2D gel databases

OGP

P28161.

REPRODUCTION-2DPAGE

P28161.

Proteomic databases

PaxDb

P28161.

PRIDE

P28161.

Protocols and materials databases

DNASU

2946.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000241337; ENSP00000241337; ENSG00000213366.
ENST00000442650; ENSP00000416883; ENSG00000213366.
ENST00000460717; ENSP00000435910; ENSG00000213366.

GeneID

2946.

KEGG

hsa:2946.

UCSC

uc001dyi.3. human.
uc010ovt.2. human.

Organism-specific databases

CTD

2946.

GeneCards

GC01P110210.

HGNC

HGNC:4634. GSTM2.

HPA

CAB040547.

MIM

138380. gene.

neXtProt

NX_P28161.

PharmGKB

PA29023.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG300089.

HOGENOM

HOG000115735.

HOVERGEN

HBG106842.

KO

K00799.

OMA

RVNILEN.

PhylomeDB

P28161.

Enzyme and pathway databases

SABIO-RK

P28161.

Gene expression databases

ArrayExpress

P28161.

Bgee

P28161.

CleanEx

HS_GSTM2.

Genevestigator

P28161.

GermOnline

ENSG00000168765. Homo sapiens.

Family and domain databases

Gene3D

1.20.1050.10. 1 hit.
3.40.30.10. 1 hit.

InterPro

IPR010987. Glutathione-S-Trfase_C-like.
IPR004045. Glutathione_S-Trfase_N.
IPR017933. Glutathione_S_Trfase/Cl_chnl_C.
IPR004046. GST_C.
IPR003081. GST_mu.
IPR012336. Thioredoxin-like_fold.
[Graphical view]

Pfam

PF00043. GST_C. 1 hit.
PF02798. GST_N. 1 hit.
[Graphical view]

PRINTS

PR01267. GSTRNSFRASEM.

SUPFAM

SSF47616. GST_C_like. 1 hit.
SSF52833. Thiordxn-like_fd. 1 hit.

PROSITE

PS50405. GST_CTER. 1 hit.
PS50404. GST_NTER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P28161.

ChEMBL

CHEMBL4589.

ChiTaRS

GSTM2. human.

DrugBank

DB00143. Glutathione.

EvolutionaryTrace

P28161.

GenomeRNAi

2946.

NextBio

11674.

SOURCE

Search...

Entry information

Entry name

GSTM2_HUMAN

Accession

Primary (citable) accession number: P28161
Secondary accession number(s): B4DRY4 , E9PEM9, Q2M318, Q5TZY5, Q8WWE1

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	January 23, 2007
Last modified:	May 29, 2013
This is version 140 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.