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Gene Review

tra-1  -  Protein TRA-1

Caenorhabditis elegans

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Disease relevance of tra-1

  • The functional importance of the TRA-1-TRA-2 physical interaction is supported by genetic interactions between tra-1(0) and tra-2(mx) mutations: a reduction of tra-1 gene dose from two copies to one copy enhances the tra-2(mx) feminization phenotype, but has no apparent somatic effect [1].
  • Using the Caenorhabditis elegans sex determining tra-1 gene as a probe we have identified two tra-1 related genes in the genome of O. volvulus [2].

High impact information on tra-1

  • The transcription pattern reveals that alternative mRNA processing governs the number of zinc fingers in the resulting tra-1 protein [3].
  • The tra-1 gene determines sexual phenotype cell-autonomously in C. elegans [4].
  • By analyzing a large number of tra-1 genetic mosaics we have shown that, with the expected exception of vulval induction by the hermaphrodite gonad, tra-1 functions cell-autonomously, consistent with a role as an intracellular component of a signaling pathway [4].
  • Epistasis analysis is most consistent with a model in which mab-3 is controlled by tra-1, the last switch gene known to act in the somatic sex determination pathway [5].
  • In these strains the autosomes carrying the tra-1 locus are in effect homomorphic Z and W sex chromosomes, and the sexes are homogametic ZZ males and heterogametic ZW females, in contrast to the wild-type arrangement of homogametic XX hermaphrodites and heterogametic X0 males [6].

Biological context of tra-1

  • By analyzing double mutants it has been shown that fem-1(+) is part of the sex-determination pathway and has two distinct functions: (1) in the soma it prevents the action of tra-1, thereby allowing male development to occur, and (2) in the germline it is necessary for spermatogenesis in both sexes [7].
  • Two alleles of tra-1 produce almost complete transformation, to a fertile male phenotype; such transformed animals are useful for analyzing sex-linked genes [8].
  • Mab-3 is a direct tra-1 target gene regulating diverse aspects of C. elegans male sexual development and behavior [9].
  • Twenty-three mutations were isolated after chemical mutagenesis and found to fall into both expected classes (four dominant tra-1 mutations and eight recessive xol-1 mutations) and novel classes [10].
  • A low level of both spermatogenesis and oogenesis can occur in the absence of tra-1 activity [11].

Anatomical context of tra-1

  • Paradoxically, tra-2(mx) mutations feminize the XX germ line, as do tra-1 mutations mapping to the TRA-2 binding domain [12].

Regulatory relationships of tra-1

  • All dpy-21 alleles show hermaphroditization effects in XO males that carry a duplication of part of the X chromosome and also partially suppress a transformer (tra-1) mutation that converts XX animals into males [13].

Other interactions of tra-1

  • These fall into three autosomal complementation groups, termed tra-1, tra-2, and tra-3 [8].
  • All alleles of tra-1 and tra-2 are recessive; the one known allele of tra-3 is both recessive and maternal in effect [8].
  • The same mutations also suppress certain alleles of another sex determination gene, tra-1, and of a morphogenetic gene, dpy-5 [14].
  • Furthermore, after transformation into fertile hermaphrodites by a her-1 mutation, XO animals were more radiosensitive than XX her-1 animals; and XX animals transformed into fertile males by a tra-1 mutation did not show increased radiosensitivity [15].
  • The feminization phenotype induced by deletion of the rpn-10 gene was rescued by knockdown of tra-2, one of sexual fate decision genes promoting female development, and its downstream target tra-1, indicating that the TRA-2-mediated sex determination pathway is crucial for the Deltarpn-10-induced sterile phenotype [16].

Analytical, diagnostic and therapeutic context of tra-1


  1. The TRA-1 transcription factor binds TRA-2 to regulate sexual fates in Caenorhabditis elegans. Wang, S., Kimble, J. EMBO J. (2001) [Pubmed]
  2. Identification of a zinc finger encoding gene in Onchocerca volvulus. Holst, C., Zipfel, P.F. Trop. Med. Parasitol. (1993) [Pubmed]
  3. Molecular analysis of the C. elegans sex-determining gene tra-1: a gene encoding two zinc finger proteins. Zarkower, D., Hodgkin, J. Cell (1992) [Pubmed]
  4. The tra-1 gene determines sexual phenotype cell-autonomously in C. elegans. Hunter, C.P., Wood, W.B. Cell (1990) [Pubmed]
  5. mab-3, a gene required for sex-specific yolk protein expression and a male-specific lineage in C. elegans. Shen, M.M., Hodgkin, J. Cell (1988) [Pubmed]
  6. Two types of sex determination in a nematode. Hodgkin, J. Nature (1983) [Pubmed]
  7. A sex-determining gene, fem-1, required for both male and hermaphrodite development in Caenorhabditis elegans. Doniach, T., Hodgkin, J. Dev. Biol. (1984) [Pubmed]
  8. Mutations causing transformation of sexual phenotype in the nematode Caenorhabditis elegans. Hodgkin, J.A., Brenner, S. Genetics (1977) [Pubmed]
  9. Mab-3 is a direct tra-1 target gene regulating diverse aspects of C. elegans male sexual development and behavior. Yi, W., Ross, J.M., Zarkower, D. Development (2000) [Pubmed]
  10. Isolation of dominant XO-feminizing mutations in Caenorhabditis elegans: new regulatory tra alleles and an X chromosome duplication with implications for primary sex determination. Hodgkin, J., Albertson, D.G. Genetics (1995) [Pubmed]
  11. A genetic analysis of the sex-determining gene, tra-1, in the nematode Caenorhabditis elegans. Hodgkin, J. Genes Dev. (1987) [Pubmed]
  12. Direct protein-protein interaction between the intracellular domain of TRA-2 and the transcription factor TRA-1A modulates feminizing activity in C. elegans. Lum, D.H., Kuwabara, P.E., Zarkower, D., Spence, A.M. Genes Dev. (2000) [Pubmed]
  13. An autosomal gene that affects X chromosome expression and sex determination in Caenorhabditis elegans. Meneely, P.M., Wood, W.B. Genetics (1984) [Pubmed]
  14. A new kind of informational suppression in the nematode Caenorhabditis elegans. Hodgkin, J., Papp, A., Pulak, R., Ambros, V., Anderson, P. Genetics (1989) [Pubmed]
  15. Somatic damage to the X chromosome of the nematode Caenorhabditis elegans induced by gamma radiation. Hartman, P.S., Herman, R.K. Mol. Gen. Genet. (1982) [Pubmed]
  16. Proteasomal Ubiquitin Receptor RPN-10 Controls Sex Determination in Caenorhabditis elegans. Shimada, M., Kanematsu, K., Tanaka, K., Yokosawa, H., Kawahara, H. Mol. Biol. Cell (2006) [Pubmed]
  17. TRA-1A regulates transcription of fog-3, which controls germ cell fate in C. elegans. Chen, P., Ellis, R.E. Development (2000) [Pubmed]
  18. Molecular cloning and duplication of the nematode sex-determining gene tra-1. Hodgkin, J. Genetics (1993) [Pubmed]
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