Subject: RE: Insect GSTs
Glutathione S-transferases: nomenclature
The glutathione S-transferase (GST) family includes multiple members
in many species. Thus, the early nomenclature was extremely confusing, with
each lab using different naming schemes. Often several names were assigned
to a single protein. In 1992, the major players in the field agreed on a
unifying and systematic nomenclature, initially for human GSTs (1). The
basic principles of that nomenclature are as follows:
(1) Each gene that encodes a GST subunit (cytosolic GSTs are dimeric) has a
unique name.
(2) The subunits are grouped into classes, designated by capital letters.
(Classes have been previously identified on the basis of substrate
specificity, immunological crossreactivity, sequence similarity, and the
ability to form dimers with members of the same class, but not other
classes. Examples of classes are A (also known as Alpha), P (known as Pi),
etc.).
(3) New GST subunits are given systematic names when their full sequence
becomes known. A name consists of the class letter followed by an Arabic
numeral. The numbering is consecutive (in the order of sequence publication)
and has no meaning beyond that.
(4) The name of the protein reflects the dimeric structure of GSTs. For
example, a homodimer of the Alpha subunit that was first to be sequenced is
GSTA1-1, and a heterodimer of two different Alpha subunits could be GSTA1-2
(the name 'GSTA1-A2' is redundant since dimers are formed only within, but
not between classes). The genes encoding the subunits are called GSTA1 and
GSTA2, respectively.
(5) Allelic variants of the same locus receive the same Arabic numeral,
followed by a lowercase letter.
The above nomenclature, which resembles similar schemes established
for other multigene families such as cytochromes P450, ABC transporters, and
others, has been quickly extended to other species, mostly mammals, by using
a prefix denoting the species. Thus, hGSTA1-1 is human, while mGSTA1-1 is
murine etc.
The nomenclature of insect GSTs remains chaotic for historical
reasons and for lack of a generally accepted system. To rectify this,
several of the leading GST researchers suggested an extension of the
mammalian naming convention to invertebrates (2). According to this
proposal, the species designator is typically derived from the systematic
name of the organism, e.g., Dm for Drosophila melanogaster or Ag for
Anopheles gambiae. The major problem is with classes. Some insect GSTs can
be assigned to existing classes, for others, new classes need to be
established. To maintain a unified and conflict-free nomenclature, we
strongly suggest consulting with Dr. Philip Board prior to naming a class or
a single GST.
For Drosophila melanogaster, the systematic nomenclature (2) would
abolish the traditional designations of Class I and Class II. GSTs of Class
I become class Delta; e.g., an enzyme originally described by C.-P. Tu's
group (3) would be named DmGSTD1-1. The previous Class II is heterogeneous.
The Drosophila GST previously named GST-2 (4) belongs to the Sigma class,
and is therefore named DmGSTS1-1. To the recently described GST-3 (5), in
consultation with Dr. Board we assigned the name DmGSTE1-1 (class Epsilon).
Other Drosophila GSTs cloned by Board's group are listed in ref. (2). A
correspondence table of the old and new names is given in reference (2). A
slightly modified and extended version of this table is also shown below.
Although names seemingly don't matter, it is obviously important to
keep them consistent and unequivocal. Since a systematic and generally
accepted nomenclature for vertebrate GSTs already exists, we strongly urge
the adoption of its extension to insect GSTs, as proposed in (2).
References:
1. Mannervik, B., Awasthi, Y.C., Board, P.G., Hayes, J.D., Di Ilio, C.,
Ketterer, B., Listowsky, I., Morgenstern, R., Muramatsu, M., Pearson, W.R.,
Pickett, C.B., Sato, K., Widersten, M. and Wolf, C.R. (1992). Nomenclature
for human glutathione transferases. Biochem. J. 282: 305-308.
2. Chelvanayagam, G., Parker, M.W. and Board, P.G. (2001). Fly fishing for
GSTs: a unified nomenclature for mammalian and insect glutathione
transferases. Chem. Biol. Interact. 133: 256-260.
3. Toung, Y.-P.S., Hsieh, T. and Tu, C.-P.D. (1993). The glutathione
S-transferase D genes. A divergently organized, intronless gene family in
Drosophila melanogaster. J. Biol. Chem. 268: 9737-9746.
4. Beall, C., Fyrberg, C., Song, S. and Fyrberg, E. (1992). Isolation of a
Drosophila gene encoding glutathione S-transferase. Biochem. Genetics 30:
515-527.
5. Singh, M., Silva, E., Schulze, S., Sinclair, D.A.R., Fitzpatrick, K.A.
and Honda, B.M. (2000). Cloning and characterization of a new theta-class
glutathione-S-transferase (GST) gene, gst-3, from Drosophila melanogaster.
Gene 247: 167-173.
\---------------------------------------------------------------------------
|Old name | Proposed | Class | Flybase ID | Other | Comments |
| | systematic | | | identifiers | |
| | gene name | | | | |
\---------------------------------------------------------------------------
| GST-1 | DmGSTD1 | Delta | FBgn0001149 | | |
| DmGST-1 | | | | | |
\---------------------------------------------------------------------------
| DmGST21 | DmGSTD2 | Delta | FBgn0010038 | CG4181 | |
\---------------------------------------------------------------------------
| DmGST22 | DmGSTD3 | Delta | | CG4381 | footnote a |
\---------------------------------------------------------------------------
| DmGST23 | DmGSTD4 | Delta | FBgn0010040 | CG11512 | |
\---------------------------------------------------------------------------
| DmGST24 | DmGSTD5 | Delta | FBgn0010041 | CG12242 | |
\---------------------------------------------------------------------------
| DmGST25 | DmGSTD6 | Delta | FBgn0010042 | CG4423 | |
\---------------------------------------------------------------------------
| DmGST26 | DmGSTD7 | Delta | FBgn0010043 | CG4371 | |
\---------------------------------------------------------------------------
| DmGST27 | DmGSTD8 | Delta | FBgn0010044 | CG4421 | |
\---------------------------------------------------------------------------
| none | DmGSTD9 | Delta | | | |
\---------------------------------------------------------------------------
| none | DmGSTD10 | Delta | | | |
\---------------------------------------------------------------------------
| GST2 | DmGSTS1 | Sigma | FBgn0010226 | | |
\---------------------------------------------------------------------------
| GST3 | DmGSTE1 | Epsilon | FBgn0034335 | CG5164 | footnote b |
\---------------------------------------------------------------------------
| none | DmGSTT1 | Theta | | | footnote c |
\---------------------------------------------------------------------------
| none | DmGSTZ1 | Zeta | | | footnote c |
\---------------------------------------------------------------------------
| none | DmGSTO1 | Omega | | | footnote c |
\---------------------------------------------------------------------------
a DmGSTD3 is listed in Flybase as a pseudogene. However, an EST is listed in
Flybase (clone LP11313) that perfectly matches DmGSTD3, indicating that the
gene is transcribed. We have evidence (manuscript in preparation) that the
open reading frame of DmGSTD3 can be translated and that the resulting
protein is enzymatically active. Thus, DmGSTD3 is probably a functional
gene.
b DmGSTE1 is a member of a gene cluster containing at least ten genes (named
DmGSTE1 to DmGSTE10) (manuscript in preparation).
c Reference (2). No further information (such as sequence) is currently
published.
\------------------------------------------------------------------------------
>DmGSTD1
MVDFYYLPGSSPCRSVIMTAKAVGVELNKKLLNLQAGEHLKPEFLKINPQ
HTIPTLVDNGFALWESRAIQVYLVEKYGKTDSLYPKCPKKRAVINQRLYF
DMGTLYQSFANYYYPQVFAKAPADPEAFKKIEAAFEFLNTFLEGQDYAAG
DSLTVADIALVATVSTFEVAKFEISKYANVNRWYENAKKVTPGWEENWAG
CLEFKKYFE
>DmGSTD2
MDFYYMPGGGGCRTVIMVAKALGLELNKKLLNTMEGEQLKPEFVKLNPQH
TIPTLVDNGFSIWESRAIAVYLVEKYGKDDYLLPNDPKKRAVINQRLYFD
MGTLYESFAKYYYPLFRTGKPGSDEDLKRIETAFGFLDTFLEGQEYVAGD
QLTVADIAILSTVSTFEVSEFDFSKYSNVSRWYDNAKKVTPGWDENWEGL
MAMKALFDARKLAAK
>DmGSTD3
MVGKALGLEFNKKIINTLKGEQMNPDFIKINPQHSIPTLVDNGFTIWESR
AILVYLVEKYGKDDALYPKDIQKQAVINQRLYFDMALMYPTLANYYYKAF
TTGQFGSEEDYKKVQETFDFLNTFLEGQDYVAGDQYTVADIAILANVSNF
DVVGFDISKYPNVARWYDHVKKITPGWEENWAGALDVKKRIEEKQNAAK
>DmGSTD4
MDFYYSPRSSGSRTIIMVAKALGLELNKKQLRITEGEHLKPEFLKLNPQH
TIPTLVDNGFAIWESRAIAVYLVEKYGKDDSLFPNDPQKRALINQRLYFD
MGTLHDSFMKYYYPFIRTGQLGNAENYKKVEAAFEFLDIFLVGQDYVAGS
QLTVADIAILSSVSTFEVVEFDISKYPNVARWYANAKKITPGWDENWKGL
LQMKTMYEAQKASLK
>DmGSTD5
MDFYYSPRGSGCRTVIMVAKALGVKLNMKLLNTLEKDQLKPEFVKLNPQH
TIPTLVDNGFSIWESRAIAVYLVEKYGKDDTLFPKDPKKQALVNQRLYFD
MGTLYDSFAKYYYPLFHTGKPGSDEDFKKIESSFEYLNIFLEGQNYVAGD
HLTVADIAILSTVSTFEIFDFDLNKYPNVARWYANAKKVTPGWEENWKGA
VELKGVFDARQAAAKQ
>DmGSTD6
MDLYNMSGSPSTRAVMMTAKAVGVEFNSIQVNTFVGEQLEPWFVKINPQH
TIPTLVDNLFVIWETRAIVVYLVEQYGKDDSLYPKDPQKQALINQRLYFD
MGTLYDGIAKYFFPLLRTGKPGTQENLEKLNAAFDLLNNFLDGQDYVAGN
QLSVADIVILATVSTTEMVDFDLKKFPNVDRWYKNAQKVTPGWDENLARI
QSAKKFLAENLIEKL
>DmGSTD7
MTNIFIQTLLRLIVLWLFFHKYEHSDSKKSVYFFAFRSSHVSVTMPNLDL
YNFPMAPASRAIQMVAKALGLELNSKLINTMEGDQLKPEFVRINPQHTIP
TLVDNGFVIWESRAIAVYLVEKYGKPDSPLYPNDPQKRALINQRLYFDMG
TLYDALTKYFFLIFRTGKFGDQEALDKVNSAFGFLNTFLEGQDFVAGSQL
TVADIVILATVSTVE
>DmGSTD8
MDFYYHPCSAPCRSVIMTAKALGVDLNMKLLKVMDGEQLKPEFVKLNPQH
CIPTLVDDGFSIWESRAILIYLVEKYGADDSLYPSDPQKKAVVNQRLYFD
MGTLFQSFVEAIYPQIRNNHPADPEAMQKVDSAFGHLDTFLEDQEYVAGD
CLTIADIALLASVSTFEVVDFDIAQYPNVASWYENAKEVTPGWEENWDGV
QLIKKLVQERNE
>DmGSTD9
MLDFYYMLYSAPCRSILMTARALGLELNKKQVDLDAGEHLKPEFVKINPQ
HTIPTLVDDGFAIWESRAILIYLAEKYDKDGSLYPKDPQQRAVINQRLFF
DLSTLYQSYVYYYYPQLFEDVKKPADPDNLKKIDDAFAMFNTLLKGQQYA
ALNKLTLADFALLATVSTFEISEYDFGKYPEVVRWYDNAKKVIPGWEENW
EGCEYYKKLYLGAILNKQ
>DmGSTD10
MDLYYRPGSAPCRSVLMTAKALGVEFDKKTIINTRAREQFTPEYLKINPQ
HTIPTLHDHGFALWESRAIMVYLVEKYGKDDKLFPKDVQKQALINQRLYF
DMGTLYKSFSEYYYPQIFLKKPANEENYKKIEVAFEFLNTFLEGQTYSAG
GDYSLADIAFLATVSTFDVAGFDFKRYANVARWYENAKKLTPGWEENWAG
CQEFRKYF
>DmGSTS1
MADEAQAPPAEGAPPAEGEAPPPAEGAEGAVEGGEAAPPAEPAEPIKHSY
TLFYFNVKALAEPLRYLFAYGNQEYEDVRVTRDEWPALKPTMPMGQMPVL
EVDGKRVHQSISMARFLAKTVGLCGATPWEDLQIDIVVDTINDFRLKIAV
VSYEPEDEIKEKKLVTLNAEVIPFYLEKLEQTVKDNDGHLALGKLTWADV
YFAGITDYMNYMVKRDLLEPYPALRGVVDAVNALEPIKAWIEKRPVTEV
>DmGSTE1
MSSSGIVLYGTDLSPCVRTVKLTLKVLNLDYEYKEVNLQAGEHLSEEYVK
KNPQHTVPMLDDNGTFIWDSHAIAAYLVDKYAKSDELYPKDLAKRAIVNQ
RLFFDASVIYASIANVSRPFWINGVTEVPQEKLDAVHQGLKLLETFLGNS
PYLAGDSLTLADLSTGPTVSAVPAAVDIDPATYPKVTAWLDRLNKLPYYK
EINEAPAQSYVAFLRSKWTKLGDK
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