Q03013 (GSTM4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glutathione S-transferase Mu 4
EC=2.5.1.18

Alternative name(s):
GST class-mu 4
GST-Mu2
GSTM4-4

Gene names

Name:

GSTM4

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. Active on 1-chloro-2,4-dinitrobenzene.
Catalytic activity	RX + glutathione = HX + R-S-glutathione.
Subunit structure	Homodimer.
Subcellular location	Cytoplasm.
Tissue specificity	Expressed in a wide variety of tissues.
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	glutathione metabolic process Inferred from direct assay Ref.3. Source: BHF-UCL xenobiotic catabolic process Inferred from direct assay Ref.3. Source: BHF-UCL
Cellular_component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome
Molecular_function	glutathione binding Inferred from direct assay Ref.3. Source: BHF-UCL glutathione transferase activity Inferred from direct assay Ref.3. Source: BHF-UCL
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q03013-1)

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: Q03013-2)

The sequence of this isoform differs from the canonical sequence as follows:
     190-195: GLEKIS → VSCGIM
     196-218: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 218

217

Glutathione S-transferase Mu 4

PRO_0000185824

Regions

Domain

2 – 88

87

GST N-terminal

Domain

90 – 208

119

GST C-terminal

Region

7 – 8

2

Glutathione binding By similarity

Region

46 – 50

5

Glutathione binding By similarity

Region

59 – 60

2

Glutathione binding By similarity

Region

72 – 73

2

Glutathione binding By similarity

Sites

Binding site

116

1

Substrate By similarity

Natural variations

Alternative sequence

190 – 195

6

GLEKIS → VSCGIM in isoform 2.

VSP_011773

Alternative sequence

196 – 218

23

Missing in isoform 2.

VSP_011774

Natural variant

2

1

S → P.
Corresponds to variant rs3211190 [ dbSNP | Ensembl ].

VAR_033979

Natural variant

160

1

A → V.
Corresponds to variant rs17838158 [ dbSNP | Ensembl ].

VAR_033980

Natural variant

208

1

L → V.
Corresponds to variant rs2229052 [ dbSNP | Ensembl ].

VAR_049487

Natural variant

209

1

Y → F.
Corresponds to variant rs2229053 [ dbSNP | Ensembl ].

VAR_049488

Natural variant

211

1

R → K.
Corresponds to variant rs2229054 [ dbSNP | Ensembl ].

VAR_049489

Natural variant

212

1

V → M. Ref.2
Corresponds to variant rs1051113 [ dbSNP | Ensembl ].

VAR_049490

Experimental info

Sequence conflict

2 – 4

3

SMT → PMI in CAA48637. Ref.2

Sequence conflict

17

1

I → M in AAA57346. Ref.1

Sequence conflict

37

1

D → G in CAA48637. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

218

Helix Strand Turn

Details...

Beta strand

3 – 10

8

Helix

14 – 23

10

Beta strand

28 – 33

6

Turn

38 – 41

4

Helix

44 – 50

7

Helix

51 – 53

3

Beta strand

60 – 64

5

Beta strand

69 – 72

4

Helix

73 – 83

11

Helix

91 – 114

24

Helix

120 – 142

23

Beta strand

150 – 152

3

Helix

155 – 170

16

Helix

179 – 190

12

Helix

192 – 198

7

Turn

214 – 216

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 35E96FA54D566B1E	FASTA	218	25,561
	10 20 30 40 50 60 MSMTLGYWDI RGLAHAIRLL LEYTDSSYEE KKYTMGDAPD YDRSQWLNEK FKLGLDFPNL 70 80 90 100 110 120 PYLIDGAHKI TQSNAILCYI ARKHNLCGET EEEKIRVDIL ENQAMDVSNQ LARVCYSPDF 130 140 150 160 170 180 EKLKPEYLEE LPTMMQHFSQ FLGKRPWFVG DKITFVDFLA YDVLDLHRIF EPNCLDAFPN 190 200 210 LKDFISRFEG LEKISAYMKS SRFLPKPLYT RVAVWGNK
	Isoform 2 [UniParc]. Checksum: 32F3BEF15BB378D3	FASTA	195	22,829
	10 20 30 40 50 60 MSMTLGYWDI RGLAHAIRLL LEYTDSSYEE KKYTMGDAPD YDRSQWLNEK FKLGLDFPNL 70 80 90 100 110 120 PYLIDGAHKI TQSNAILCYI ARKHNLCGET EEEKIRVDIL ENQAMDVSNQ LARVCYSPDF 130 140 150 160 170 180 EKLKPEYLEE LPTMMQHFSQ FLGKRPWFVG DKITFVDFLA YDVLDLHRIF EPNCLDAFPN 190 LKDFISRFEV SCGIM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and analysis of the gene and cDNA for a human Mu class glutathione S-transferase, GSTM4." Comstock K.E., Johnson K.J., Rifenbery D., Henner W.D. J. Biol. Chem. 268:16958-16965(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
[2]	"Deduced amino acid sequence, gene structure and chromosomal location of a novel human class Mu glutathione S-transferase, GSTM4." Zhong S., Spurr N.K., Hayes J.D., Wolf C.R. Biochem. J. 291:41-50(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT MET-212.
[3]	"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: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEIN SEQUENCE OF N-TERMINUS. Tissue: Testis.
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Skeletal muscle.
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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: Eye and Lung.
[8]	"Structure of human glutathione S-transferase class Mu genes." Taylor J.B., Oliver J., Sherrington R., Pemble S.E. Biochem. J. 274:587-593(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 39-160. Tissue: Lymphocyte.
[9]	"A comparison of the enzymatic and physicochemical properties of human glutathione transferase M4-4 and three other human Mu class enzymes." Comstock K.E., Widersten M., Hao X.Y., Henner W.D., Mannervik B. Arch. Biochem. Biophys. 311:487-495(1994) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[10]	"An asparagine-phenylalanine substitution accounts for catalytic differences between hGSTM3-3 and other human class mu glutathione S-transferases." Patskovsky Y.V., Patskovska L.N., Listowsky I. Biochemistry 38:16187-16194(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M96234 mRNA. Translation: AAA57347.1.
M96233 Genomic DNA. Translation: AAA57346.1.
X68677 Genomic DNA. Translation: CAA48637.1.
M99422 mRNA. Translation: AAA58623.1.
CR541869 mRNA. Translation: CAG46667.1.
AK291880 mRNA. Translation: BAF84569.1.
CH471122 Genomic DNA. Translation: EAW56405.1.
BC015513 mRNA. Translation: AAH15513.1.
BC108729 mRNA. Translation: AAI08730.1.
X56837 Genomic DNA. Translation: CAA40167.1.

IPI

IPI00008770.
IPI00470739.

PIR

A47486.
S32425.

RefSeq

NP_000841.1. NM_000850.4.
NP_671489.1. NM_147148.2.

UniGene

Hs.348387.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4GTU	X-ray	3.30	A/B/C/D/E/F/G/H	2-218	[»]

ProteinModelPortal

Q03013.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q03013. 9 interactions.

MINT

MINT-1368381.

STRING

9606.ENSP00000358851.

PTM databases

PhosphoSite

Q03013.

Polymorphism databases

DMDM

1170096.

2D gel databases

REPRODUCTION-2DPAGE

IPI00008770.

Proteomic databases

PaxDb

Q03013.

PRIDE

Q03013.

Protocols and materials databases

DNASU

2948.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000326729; ENSP00000316471; ENSG00000168765.
ENST00000369836; ENSP00000358851; ENSG00000168765.

GeneID

2948.

KEGG

hsa:2948.

UCSC

uc001dyf.3. human.
uc001dyh.2. human.

Organism-specific databases

CTD

2948.

GeneCards

GC01P110198.

HGNC

HGNC:4636. GSTM4.

MIM

138333. gene.

neXtProt

NX_Q03013.

PharmGKB

PA29026.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG300089.

HOGENOM

HOG000115735.

HOVERGEN

HBG106842.

InParanoid

Q03013.

KO

K00799.

OMA

VATWGNK.

OrthoDB

EOG47D9H2.

PhylomeDB

Q03013.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

SABIO-RK

Q03013.

Gene expression databases

ArrayExpress

Q03013.

Bgee

Q03013.

CleanEx

HS_GSTM4.

Genevestigator

Q03013.

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

ChEMBL

CHEMBL2100.

DrugBank

DB00143. Glutathione.

EvolutionaryTrace

Q03013.

GenomeRNAi

2948.

NextBio

11682.

SOURCE

Search...

Entry information

Entry name

GSTM4_HUMAN

Accession

Primary (citable) accession number: Q03013
Secondary accession number(s): A8K765 , Q05465, Q32NC1, Q6FH87

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 138 of the entry and version 3 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.