P30711 (GSTT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glutathione S-transferase theta-1
EC=2.5.1.18

Alternative name(s):
GST class-theta-1
Glutathione transferase T1-1

Gene names

Name:

GSTT1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	240 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. Acts on 1,2-epoxy-3-(4-nitrophenoxy)propane, phenethylisothiocyanate 4-nitrobenzyl chloride and 4-nitrophenethyl bromide. Displays glutathione peroxidase activity with cumene hydroperoxide. Ref.10 Ref.11
Catalytic activity	RX + glutathione = HX + R-S-glutathione. Ref.10 Ref.11
Subunit structure	Homodimer. Ref.11
Subcellular location	Cytoplasm.
Tissue specificity	Found in erythrocyte. Expressed at low levels in liver. In lung, expressed at low levels in Clara cells and ciliated cells at the alveolar/bronchiolar junction. Absent from epithelial cells of larger bronchioles. Ref.9
Polymorphism	The GSTT1 gene is absent from 38% of the population. The presence or absence of the GSTT1 gene is coincident with the conjugator (GSST1+) and non-conjugator (GSTT1-) phenotypes respectively. The GSTT1+ phenotype can catalyze the glutathione conjugation of dichloromethane.
Sequence similarities	Belongs to the GST superfamily. Theta family. Contains 1 GST C-terminal domain. Contains 1 GST N-terminal domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	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.10Ref.2. Source: UniProtKB
Cellular component	cytosol Inferred from direct assay. Source: UniProtKB soluble fraction Inferred from direct assay. Source: UniProtKB
Molecular function	glutathione peroxidase activity Inferred from direct assay Ref.2. Source: UniProtKB glutathione transferase activity Inferred from direct assay Ref.10Ref.2. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.8

Chain

2 – 240

239

Glutathione S-transferase theta-1

PRO_0000185938

Regions

Domain

2 – 82

81

GST N-terminal

Domain

88 – 220

133

GST C-terminal

Region

53 – 54

2

Glutathione binding

Region

66 – 67

2

Glutathione binding

Sites

Binding site

40

1

Glutathione

Natural variations

Natural variant

21

1

A → T.
Corresponds to variant rs2266635 [ dbSNP | Ensembl ].

VAR_014501

Natural variant

141

1

D → N.
Corresponds to variant rs2266633 [ dbSNP | Ensembl ].

VAR_014502

Natural variant

169

1

V → I. Ref.5
Corresponds to variant rs2266637 [ dbSNP | Ensembl ].

VAR_014503

Natural variant

173

1

E → K.
Corresponds to variant rs2234953 [ dbSNP | Ensembl ].

VAR_014504

Experimental info

Mutagenesis

176

1

H → Q: Increases activity towards alkylhalogenides, but not hydroperoxides. Ref.11

Mutagenesis

234

1

W → R: Facilitates binding of substrates and increases catalytic activity. Ref.11

Sequence conflict

43 – 44

2

DA → SD AA sequence Ref.8

Sequence conflict

45

1

F → C in AAH07065. Ref.7

Sequence conflict

126

1

E → G in CAA55935. Ref.1

Secondary structure

1

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240

Helix Strand Turn

Details...

Beta strand

3 – 7

5

Helix

12 – 23

12

Beta strand

29 – 32

4

Helix

35 – 37

3

Helix

39 – 41

3

Helix

43 – 48

6

Beta strand

56 – 59

4

Beta strand

62 – 65

4

Helix

67 – 77

11

Helix

82 – 84

3

Helix

89 – 101

13

Helix

102 – 104

3

Helix

106 – 117

12

Helix

118 – 123

6

Helix

130 – 150

21

Turn

151 – 154

4

Beta strand

155 – 162

8

Helix

165 – 179

15

Helix

189 – 202

14

Helix

204 – 210

7

Helix

212 – 215

4

Helix

216 – 219

4

Helix

225 – 239

15

Sequences

	Sequence		Length	Mass (Da)
	P30711 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: BD19F2BFDEF9F619	FASTA	240	27,335
	10 20 30 40 50 60 MGLELYLDLL SQPCRAVYIF AKKNDIPFEL RIVDLIKGQH LSDAFAQVNP LKKVPALKDG 70 80 90 100 110 120 DFTLTESVAI LLYLTRKYKV PDYWYPQDLQ ARARVDEYLA WQHTTLRRSC LRALWHKVMF 130 140 150 160 170 180 PVFLGEPVSP QTLAATLAEL DVTLQLLEDK FLQNKAFLTG PHISLADLVA ITELMHPVGA 190 200 210 220 230 240 GCQVFEGRPK LATWRQRVEA AVGEDLFQEA HEVILKAKDF PPADPTIKQK LMPWVLAMIR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human glutathione S-transferase theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism." Pemble S., Schroeder K.R., Spencer S.R., Meyer D.J., Hallier E., Bolt H.M., Ketterer B., Taylor J.B. Biochem. J. 300:271-276(1994) [PubMed: 8198545] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Kinetic characterization of recombinant human glutathione transferase T1-1, a polymorphic detoxication enzyme." Jemth P., Mannervik B. Arch. Biochem. Biophys. 348:247-254(1997) [PubMed: 9434735] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION.
[3]	"Characterization of the glutathione S-transferase GSTT1 deletion: discrimination of all genotypes by polymerase chain reaction indicates a trimodular genotype-phenotype correlation." Sprenger R., Schlagenhaufer R., Kerb R., Bruhn C., Brockmoeller J., Roots I., Brinkmann U. Pharmacogenetics 10:557-565(2000) [PubMed: 10975610] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Complete genomic structure of human glutathione S-transferase TT1." Iida A., Kondo K., Kitamura Y., Mishima C., Osawa S., Kitamoto T., Harigae C., Nakamura Y. Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Thymus.
[5]	"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], VARIANT ILE-169.
[6]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed: 10591208] [Abstract] 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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Urinary bladder.
[8]	"Theta, a new class of glutathione transferases purified from rat and man." Meyer D.J., Coles B., Pemble S.E., Gilmore K.S., Fraser G.M., Ketterer B. Biochem. J. 274:409-414(1991) [PubMed: 1848757] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-47. Tissue: Liver.
[9]	"The distribution of theta-class glutathione S-transferases in the liver and lung of mouse, rat and human." Mainwaring G.W., Williams S.M., Foster J.R., Tugwood J., Green T. Biochem. J. 318:297-303(1996) [PubMed: 8761485] [Abstract] Cited for: TISSUE SPECIFICITY. Tissue: Liver and Lung.
[10]	"Residue 234 is a master switch of the alternative-substrate activity profile of human and rodent theta class glutathione transferase T1-1." Shokeer A., Mannervik B. Biochim. Biophys. Acta 1800:466-473(2010) [PubMed: 20097269] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY.
[11]	"Structural basis of the suppressed catalytic activity of wild-type human glutathione transferase T1-1 compared to its W234R mutant." Tars K., Larsson A.K., Shokeer A., Olin B., Mannervik B., Kleywegt G.J. J. Mol. Biol. 355:96-105(2006) [PubMed: 16298388] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF WILD-TYPE AND MUTANT ARG-234 IN COMPLEX WITH HEXYLGLUTATHIONE, CATALYTIC ACTIVITY, FUNCTION, SUBUNIT, MUTAGENESIS OF HIS-176 AND TRP-234.
+	Additional computationally mapped references.

Web resources

SHMPD

The Singapore human mutation and polymorphism database

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X79389 mRNA. Translation: CAA55935.1.
AF435971 mRNA. Translation: AAL31549.1.
AF240786 Genomic DNA. Translation: AAG02374.1.
AB057594 Genomic DNA. Translation: BAB39498.1.
BT019951 mRNA. Translation: AAV38754.1.
Z84718 Genomic DNA. No translation available.
BC007065 mRNA. Translation: AAH07065.1.

IPI

IPI00741097.

PIR

S44358.

RefSeq

NP_000844.2. NM_000853.2.

UniGene

Hs.268573.
Hs.720100.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2C3N	X-ray	1.50	A/B/C/D	2-239	[»]
2C3Q	X-ray	1.85	A/B/C/D	2-239	[»]
2C3T	X-ray	2.40	A/B/C/D	2-239	[»]

ProteinModelPortal

P30711.

SMR

P30711. Positions 2-240.

ModBase

Search...

Protein-protein interaction databases

STRING

P30711.

Polymorphism databases

DMDM

21264427.

Proteomic databases

PRIDE

P30711.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000248935; ENSP00000248935; ENSG00000184674.

GeneID

2952.

KEGG

hsa:2952.

UCSC

uc002zze.2. human.

Organism-specific databases

CTD

2952.

GeneCards

GC22M024378.

H-InvDB

HIX0019638.
HIX0203188.

HGNC

HGNC:4641. GSTT1.

MIM

600436. gene.

neXtProt

NX_P30711.

PharmGKB

PA183.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG13436.

HOVERGEN

HBG051854.

InParanoid

P30711.

OMA

KQKLMPR.

OrthoDB

EOG43N7F8.

PhylomeDB

P30711.

Gene expression databases

ArrayExpress

P30711.

Bgee

P30711.

CleanEx

HS_GSTT1.

Genevestigator

P30711.

GermOnline

ENSG00000184674. Homo sapiens.

Family and domain databases

InterPro

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

Gene3D

G3DSA:1.20.1050.10. GST_C_like. 1 hit.
G3DSA:3.40.30.10. Thioredoxin_fold. 1 hit.

KO

K00799.

Pfam

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

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

DrugBank

DB00143. Glutathione.

NextBio

11698.

SOURCE

Search...

Entry information

Entry name

GSTT1_HUMAN

Accession

Primary (citable) accession number: P30711
Secondary accession number(s): O00226 , Q5TZY2, Q969K8, Q96IY3

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
This is version 133 of the entry and version 4 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.