Tag Content
SG ID
SG00000151 
UniProt Accession
Theoretical PI
11.35  
Molecular Weight
31031 Da  
Genbank Nucleotide ID
Genbank Protein ID
Gene Name
tra2 
Gene Synonyms/Alias
tra-2 
Protein Name
Transformer-2 sex-determining protein 
Protein Synonyms/Alias
 
Organism
Drosophila melanogaster (Fruit fly) 
NCBI Taxonomy ID
7227 
Chromosome Location
chr:2R;10489509-10491857;-1
View in Ensembl genome browser  
Function in Stage
Function in Cell Type
Description
Temporarily unavailable 
The information of related literatures
1. M. E. McGuffin, D. Chandler, D. Somaiya, B. Dauwalder and W. Mattox (1998) Autoregulation of transformer-2 alternative splicing is necessary for normal male fertility in Drosophila. Genetics 149(3): 1477-86. 

Abstract
In the male germline of Drosophila the transformer-2 protein is required for differential splicing of pre-mRNAs from the exuperantia and att genes and autoregulates alternative splicing of its own pre-mRNA. Autoregulation of TRA-2 splicing results in production of two mRNAs that differ by the splicing/retention of the M1 intron and encode functionally distinct protein isoforms. Splicing of the intron produces an mRNA encoding TRA-2(226), which is necessary and sufficient for both male fertility and regulation of downstream target RNAs. When the intron is retained, an mRNA is produced encoding TRA-2(179), a protein with no known function. We have previously shown that repression of M1 splicing is dependent on TRA-2(226), suggesting that this protein quantitatively limits its own expression through a negative feedback mechanism at the level of splicing. Here we examine this idea, by testing the effect that variations in the level of tra-2 expression have on the splicing of M1 and on male fertility. Consistent with our hypothesis, we observe that as tra-2 gene dosage is increased, smaller proportions of TRA-2(226) mRNA are produced, limiting expression of this isoform. Feedback regulation is critical for male fertility, since it is significantly decreased by a transgene in which repression of M1 splicing cannot occur and TRA-2(226) mRNA is constitutively produced. The effect of this transgene becomes more severe as its dosage is increased, indicating that fertility is sensitive to an excess of TRA-2(226). Our results suggest that autoregulation of TRA-2(226) expression in male germ cells is necessary for normal spermatogenesis. PMID: [9649535] 

2. W. Mattox, M. E. McGuffin and B. S. Baker (1996) A negative feedback mechanism revealed by functional analysis of the alternative isoforms of the Drosophila splicing regulator transformer-2. Genetics 143(1): 303-14. 

Abstract
The Drosophila sex determination gene transformer-2 (tra-2) is a splicing regulator that affects the sex-specific processing of several distinct pre-mRNAs. While the tra-2 gene itself is known to produce alternative mRNAs that together encode three different TRA-2 protein isoforms, the respective roles of these isoforms in affecting individual pre-mRNA targets has remained unclear. We have generated transgenic fly strains with mutations affecting specific TRA-2 isoforms to investigate their individual roles in regulating the alternative processing of doublesex, exuperantia and tra-2 pre-mRNA. Our results indicate that in somatic tissues two different isoforms function redundantly to direct female differentiation and female-specific doublesex pre-mRNA splicing. In the male germline, where tra-2 has an essential role in spermatogenesis, a single isoform was found to uniquely perform all necessary functions. This isoform appears to regulate its own synthesis during spermatogenesis through a negative feedback mechanism involving intron retention. PMID: [8722783] 

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Figures for illustrating the function of this protein/gene
Ref: M. E. McGuffin, D. Chandler, D. Somaiya, B. Dauwalder and W. Mattox (1998) Autoregulation of transformer-2 alternative splicing is necessary for normal male fertility in Drosophila. Genetics 149(3): 1477-86. PMID: [9649535]
Function
Required for female sex determination in somatic cellsand for spermatogenesis in male germ cells. Positive regulator offemale-specific splicing and/or polyadenylation of doublesex (dsx)pre-mRNA. Splicing requires an enhancer complex, dsxRE (dsx repeatelement: which contains six copies of a 13-nucleotide repeat and apurine-rich enhancer (PRE)). DsxRE is formed through cooperativeinteractions between tra, tra2 and the sr proteins, and theseinteractions require both the repeat sequences and PRE. PRE isrequired for specific binding of tra2 to the dsxRE. Protein-RNAand protein-protein interactions are involved in tra-2 dependentactivation and repression of alternative splicing. Together withtra-2, plays a role in switching fru splicing from the male-specific pattern to the female-specific pattern through activationof the female-specific fru 5'-splice site. 
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Subcellular Location
 
Tissue Specificity
Isoform Tmaj and isoform Tmin are expressed inmales and females. Isoform msTmaj and isoform msTmin are presentonly in male germ cells. 
Gene Ontology
GO IDGO termEvidence
GO:0071011 C:precatalytic spliceosome IDA:FlyBase.
GO:0003729 F:mRNA binding ISS:FlyBase.
GO:0000166 F:nucleotide binding IEA:InterPro.
GO:0030154 P:cell differentiation IEA:UniProtKB-KW.
GO:0019101 P:female somatic sex determination TAS:FlyBase.
GO:0019102 P:male somatic sex determination TAS:FlyBase.
GO:0000381 P:regulation of alternative nuclear mRNA splicing, via spliceosome IMP:FlyBase.
GO:0007548 P:sex differentiation IEA:UniProtKB-KW.
GO:0007283 P:spermatogenesis NAS:FlyBase.
GO:0000245 P:spliceosomal complex assembly NAS:FlyBase.
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Interpro
IPR012677;    Nucleotide-bd_a/b_plait.
IPR000504;    RRM_dom.
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Pfam
PF00076;    RRM_1;    1.
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SMART
SM00360;    RRM;    1.
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PROSITE
PS50102;    RRM;    1.
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PRINTS
Created Date
18-Oct-2012 
Record Type
Experiment identified 
Protein sequence Annotation
CHAIN         1    264       Transformer-2 sex-determining protein.
                             /FTId=PRO_0000081986.
DOMAIN       97    175       RRM.
REGION      176    196       Linker.
COMPBIAS     21     90       Arg/Ser-rich (RS1 domain).
COMPBIAS    197    264       Arg/Ser-rich (RS2 domain).
MOD_RES      40     40       Phosphoserine.
MOD_RES     180    180       Phosphothreonine.
MOD_RES     212    212       Phosphoserine.
MOD_RES     214    214       Phosphoserine.
MOD_RES     254    254       Phosphoserine.
VAR_SEQ       1     85       Missing (in isoform MsTmaj).
                             /FTId=VSP_005900.
VAR_SEQ       2     39       Missing (in isoform Tmin).
                             /FTId=VSP_005901.
VAR_SEQ     134    264       TQRSRGFCFIYFEKLSDARAAKDSCSGIEVDGRRIRVDFSI
                             TQRAHTPTPGVYLGRQPRGKAPRSFSPRRGRRVYHDRSASP
                             YDNYRDRYDYRNDRYDRNLRRSPSRNRYTRNRSYSRSRSPQ
                             LRRTSSRY -> INP (in isoform MsTmin).
                             /FTId=VSP_005902.
MUTAGEN      11     82       Missing: In d2; greatly reduced female-
                             specific DSX splicing.
MUTAGEN      49     82       Missing: In d1; greatly reduced female-
                             specific DSX splicing. Retains male
                             fertility.
MUTAGEN     113    123       Missing: In a36; loss of female-specific
                             DSX splicing. Loss of male fertility.
MUTAGEN     138    138       R->L: In pm1; loss of female-specific DSX
                             splicing. Loss of male fertility.
MUTAGEN     140    140       F->A: In pm2; no female-specific DSX
                             splicing. Some low male fertility.
MUTAGEN     151    151       A->V: In ts1; little female-specific DSX
                             splicing. Loss of male fertility and
                             temperature-sensitive phenotype.
MUTAGEN     172    264       Missing: In d5; loss of female-specific
                             DSX splicing. Loss of male fertility.
MUTAGEN     173    173       S->A: In pm3; greatly reduced female-
                             specific DSX splicing. Retains male
                             fertility and temperature-sensitive
                             phenotype.
MUTAGEN     173    173       S->F: In a15, loss of female-specific DSX
                             splicing and male fertility.
MUTAGEN     173    173       S->T: In pm4; loss of female-specific DSX
                             splicing. Retains male fertility and
                             temperature-sensitive phenotype.
MUTAGEN     181    181       P->S: In ts2; temperature-sensitive
                             phenotype.
MUTAGEN     205    264       Missing: In d4; loss of female-specific
                             DSX splicing. Greatly reduced male
                             fertility.
MUTAGEN     236    264       Missing: In d3; greatly reduced female-
                             specific DSX splicing. Retains male
                             fertility.
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Nucleotide Sequence
Length: 1261 bp   Go to nucleotide: FASTA
Protein Sequence
Length: 264 bp   Go to amino acid: FASTA
The verified Protein-Protein interaction information
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SF2IntAct 
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