Q16772 (GSTA3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glutathione S-transferase A3
EC=2.5.1.18

Alternative name(s):
GST class-alpha member 3
Glutathione S-transferase A3-3

Gene names

Name:

GSTA3

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	222 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. Catalyzes isomerization reactions that contribute to the biosynthesis of steroid hormones. Efficiently catalyze obligatory double-bond isomerizations of delta(5)-androstene-3,17-dione and delta(5)-pregnene-3,20-dione, precursors to testosterone and progesterone, respectively. Ref.8 Ref.9
Catalytic activity	RX + glutathione = HX + R-S-glutathione.
Subunit structure	Homodimer. Ref.9
Subcellular location	Cytoplasm.
Sequence similarities	Belongs to the GST superfamily. Alpha family. Contains 1 GST C-terminal domain. Contains 1 GST N-terminal domain.
Biophysicochemical properties	Kinetic parameters: KM=23 µM for delta(5)-androstene-3,17-dione Ref.8 Vmax=99 µmol/min/mg enzyme for delta(5)-androstene-3,17-dione isomerization
Sequence caution	The sequence AAA74634.1 differs from that shown. Reason: Erroneous initiation. The sequence AAD04712.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Molecular function	Transferase
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	glutathione metabolic process Inferred from sequence or structural similarity. Source: UniProtKB xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	glutathione transferase activity Inferred from sequence or structural similarity. 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 By similarity

Chain

2 – 222

221

Glutathione S-transferase A3

PRO_0000185785

Regions

Domain

3 – 83

81

GST N-terminal

Domain

85 – 207

123

GST C-terminal

Region

54 – 55

2

Glutathione binding

Region

67 – 68

2

Glutathione binding

Sites

Binding site

9

1

Glutathione

Binding site

45

1

Glutathione

Amino acid modifications

Modified residue

2

1

N-acetylalanine By similarity

Natural variations

Natural variant

36

1

G → E. Ref.3

VAR_062276

Natural variant

71

1

I → L. Ref.3 Ref.7
Corresponds to variant rs1052661 [ dbSNP | Ensembl ].

VAR_049484

Natural variant

73

1

N → D. Ref.3
Corresponds to variant rs41273858 [ dbSNP | Ensembl ].

VAR_049485

Natural variant

113

1

R → Q. Ref.3

VAR_062277

Natural variant

208

1

A → T. Ref.3

VAR_062278

Experimental info

Sequence conflict

63

1

M → I in AAH20619. Ref.6

Sequence conflict

113 – 114

2

RP → PA in AAA74634. Ref.1

Sequence conflict

128

1

T → I in AAA74634. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

222

Helix Strand Turn

Details...

Beta strand

6 – 9

4

Turn

14 – 16

3

Helix

17 – 25

9

Beta strand

31 – 34

4

Helix

38 – 46

9

Beta strand

57 – 60

4

Beta strand

63 – 67

5

Helix

68 – 78

11

Helix

86 – 108

23

Helix

109 – 111

3

Helix

114 – 130

17

Helix

132 – 143

12

Beta strand

146 – 149

4

Helix

155 – 170

16

Turn

172 – 177

6

Helix

179 – 190

12

Helix

192 – 197

6

Helix

210 – 220

11

Sequences

	Sequence		Length	Mass (Da)
	Q16772 [UniParc]. Last modified May 27, 2002. Version 3. Checksum: 904AA17519B5343C	FASTA	222	25,302
	10 20 30 40 50 60 MAGKPKLHYF NGRGRMEPIR WLLAAAGVEF EEKFIGSAED LGKLRNDGSL MFQQVPMVEI 70 80 90 100 110 120 DGMKLVQTRA ILNYIASKYN LYGKDIKERA LIDMYTEGMA DLNEMILLLP LCRPEEKDAK 130 140 150 160 170 180 IALIKEKTKS RYFPAFEKVL QSHGQDYLVG NKLSRADISL VELLYYVEEL DSSLISNFPL 190 200 210 220 LKALKTRISN LPTVKKFLQP GSPRKPPADA KALEEARKIF RF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure and organization of the human alpha class glutathione S-transferase genes and related pseudogenes." Suzuki T., Johnston P.N., Board P.G. Genomics 18:680-686(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Human glutathione transferase A3-3, a highly efficient catalyst of double-bond isomerization in the biosynthetic pathway of steroid hormones." Johansson A.-S., Mannervik B. J. Biol. Chem. 276:33061-33065(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION.
[3]	NIEHS SNPs program Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLU-36; LEU-71; ASP-73; GLN-113 AND THR-208.
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	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].
[6]	"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]. Tissue: Placenta.
[7]	"Identification of cDNAs encoding two human alpha class glutathione transferases (GSTA3 and GSTA4) and the heterologous expression of GSTA4-4." Board P.G. Biochem. J. 330:827-831(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 30-222, VARIANT LEU-71.
[8]	"Crystal structure of human glutathione S-transferase A3-3 and mechanistic implications for its high steroid isomerase activity." Gu Y., Guo J., Pal A., Pan S.S., Zimniak P., Singh S.V., Ji X. Biochemistry 43:15673-15679(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH GLUTATHIONE, BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION.
[9]	"Structural basis for featuring of steroid isomerase activity in alpha class glutathione transferases." Tars K., Olin B., Mannervik B. J. Mol. Biol. 397:332-340(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH GLUTATHIONE AND DELTA5-ANDROSTENE-3-17-DIONE, FUNCTION, SUBUNIT.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L13275 , L13270, L13271, L13272, L13273, L13274 Genomic DNA. Translation: AAA74634.1. Different initiation.
AF508266 mRNA. Translation: AAM33360.1.
DQ993361 Genomic DNA. Translation: ABI75350.1.
AL121969 Genomic DNA. Translation: CAC10389.1.
CH471081 Genomic DNA. Translation: EAX04391.1.
BC020619 mRNA. Translation: AAH20619.1.
AF020919 mRNA. Translation: AAD04712.1. Different initiation.

IPI

IPI00003929.

PIR

A49365.

RefSeq

NP_000838.3. NM_000847.4.

UniGene

Hs.102484.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1TDI	X-ray	2.40	A/B	1-222	[»]
2VCV	X-ray	1.80	A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P	1-222	[»]

ProteinModelPortal

Q16772.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000211122.

PTM databases

PhosphoSite

Q16772.

Polymorphism databases

DMDM

21264437.

Proteomic databases

PaxDb

Q16772.

PRIDE

Q16772.

Protocols and materials databases

DNASU

2940.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000211122; ENSP00000211122; ENSG00000174156.

GeneID

2940.

KEGG

hsa:2940.

UCSC

uc003pbb.3. human.

Organism-specific databases

CTD

2940.

GeneCards

GC06M052761.

HGNC

HGNC:4628. GSTA3.

HPA

HPA004342.

MIM

605449. gene.

neXtProt

NX_Q16772.

PharmGKB

PA29018.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG266414.

HOGENOM

HOG000115734.

HOVERGEN

HBG053749.

InParanoid

Q16772.

KO

K00799.

OMA

KSRYFPA.

PhylomeDB

Q16772.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

SABIO-RK

Q16772.

Gene expression databases

ArrayExpress

Q16772.

Bgee

Q16772.

CleanEx

HS_GSTA3.

Genevestigator

Q16772.

GermOnline

ENSG00000174156. 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.
IPR003080. GST_alpha.
IPR004046. GST_C.
IPR012336. Thioredoxin-like_fold.
[Graphical view]

PANTHER

PTHR11571:SF4. PTHR11571:SF4. 1 hit.

Pfam

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

PRINTS

PR01266. GSTRNSFRASEA.

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

CHEMBL4866.

DrugBank

DB00143. Glutathione.

EvolutionaryTrace

Q16772.

GenomeRNAi

2940.

NextBio

11651.

SOURCE

Search...

Entry information

Entry name

GSTA3_HUMAN

Accession

Primary (citable) accession number: Q16772
Secondary accession number(s): O43468 , Q068V6, Q8WWA8, Q9H415

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	May 27, 2002
Last modified:	May 1, 2013
This is version 123 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.