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Gene Review

LEFTY2  -  left-right determination factor 2

Homo sapiens

Synonyms: EBAF, Endometrial bleeding-associated factor, LEFTA, LEFTYA, Left-right determination factor 2, ...
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Disease relevance of LEFTY2


High impact information on LEFTY2


Biological context of LEFTY2

  • RESULTS: The human LEFTY locus comprises two functional genes (LEFTY1 and LEFTY2) and a putative pseudogene [6].
  • Analysis of 126 human cases of LR-axis malformations showed one nonsense and one missense mutation in LEFTY A [5].
  • Both mutations lie in the cysteine-knot region of the protein LEFTY A, and the phenotype of affected individuals is very similar to that typically seen in Lefty1-/- mice with LR-axis malformations [5].
  • In fresh tissues, a major increase in MMP-9 mRNA expression occurred at menstruation, after a larger increase in LEFTY-A mRNA [7].
  • We measured LEFTY-A and beta-ACTIN mRNA concentration during the menstrual cycle in vivo and found that their ratio was dramatically ( approximately 100-fold) increased at the perimenstrual phase [8].

Anatomical context of LEFTY2

  • LEFTY A is identical to ebaf, a cDNA previously identified in a search for genes expressed in human endometrium [5].
  • These findings show that ebaf is a secreted product and is released into body fluids [1].
  • These mechanisms appear to converge on highly conserved expression patterns of genes in the transforming growth factor-beta (TGFbeta) family of cell-cell signaling factors, nodal and lefty-2, and subsequently the expression of the transcription regulator Pitx2, in left lateral plate mesoderm [9].
  • The cloning and sequencing of cDNAs corresponding to this chondrocyte RNA demonstrate that it represents a new member of the TGF beta family, which we have named TGF beta 4 [10].

Associations of LEFTY2 with chemical compounds


Regulatory relationships of LEFTY2

  • Addition of recombinant LEFTY-A to explants induced MMP-9 in most samples, a response prevented by ovarian steroids [7].

Other interactions of LEFTY2

  • In addition, when cells are maintained undifferentiated by treatment with the GSK3-inhibitor, BIO, high expression of nodal, lefty-A, and lefty-B also requires activation of ALK4/5/7 [11].
  • EGF-CFC, ACVR2B, and LEFTYA are all members of a transforming growth factor-beta signal transduction pathway that is critical for proper left-right development [12].
  • Transcripts for TGF beta 1 and TGF beta 4 were not detected in any tissue or time frame examined [13].


  1. Dysregulated expression of ebaf, a novel molecular defect in the endometria of patients with infertility. Tabibzadeh, S., Mason, J.M., Shea, W., Cai, Y., Murray, M.J., Lessey, B. J. Clin. Endocrinol. Metab. (2000) [Pubmed]
  2. Distinct tumor specific expression of TGFB4 (ebaf)*, a novel human gene of the TGF-beta superfamily. Tabibzadeh, S., Kothapalli, R., Buyuksal, I. Front. Biosci. (1997) [Pubmed]
  3. Role of EBAF/Lefty in implantation and uterine bleeding. Tabibzadeh, S. Ernst Schering Res. Found. Workshop (2005) [Pubmed]
  4. Detection of ebaf, a novel human gene of the transforming growth factor beta superfamily association of gene expression with endometrial bleeding. Kothapalli, R., Buyuksal, I., Wu, S.Q., Chegini, N., Tabibzadeh, S. J. Clin. Invest. (1997) [Pubmed]
  5. Characterization and mutation analysis of human LEFTY A and LEFTY B, homologues of murine genes implicated in left-right axis development. Kosaki, K., Bassi, M.T., Kosaki, R., Lewin, M., Belmont, J., Schauer, G., Casey, B. Am. J. Hum. Genet. (1999) [Pubmed]
  6. Distinct transcriptional regulation and phylogenetic divergence of human LEFTY genes. Yashiro, K., Saijoh, Y., Sakuma, R., Tada, M., Tomita, N., Amano, K., Matsuda, Y., Monden, M., Okada, S., Hamada, H. Genes Cells (2000) [Pubmed]
  7. Regulation of matrix metalloproteinase-9/gelatinase B expression and activation by ovarian steroids and LEFTY-A/endometrial bleeding-associated factor in the human endometrium. Cornet, P.B., Galant, C., Eeckhout, Y., Courtoy, P.J., Marbaix, E., Henriet, P. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  8. Regulation and function of LEFTY-A/EBAF in the human endometrium. mRNA expression during the menstrual cycle, control by progesterone, and effect on matrix metalloprotineases. Cornet, P.B., Picquet, C., Lemoine, P., Osteen, K.G., Bruner-Tran, K.L., Tabibzadeh, S., Courtoy, P.J., Eeckhout, Y., Marbaix, E., Henriet, P. J. Biol. Chem. (2002) [Pubmed]
  9. Establishment of left-right asymmetry. Yost, H.J. Int. Rev. Cytol. (2001) [Pubmed]
  10. Complementary deoxyribonucleic acid cloning of a messenger ribonucleic acid encoding transforming growth factor beta 4 from chicken embryo chondrocytes. Jakowlew, S.B., Dillard, P.J., Sporn, M.B., Roberts, A.B. Mol. Endocrinol. (1988) [Pubmed]
  11. Expression of nodal, lefty-a, and lefty-B in undifferentiated human embryonic stem cells requires activation of Smad2/3. Besser, D. J. Biol. Chem. (2004) [Pubmed]
  12. DNA mutation analysis in heterotaxy. Ware, S.M. Methods Mol. Med. (2006) [Pubmed]
  13. Expression of transforming growth factor beta in the embryonic avian lens coincides with the presence of mitochondria. Potts, J.D., Bassnett, S., Beebe, D.C. Dev. Dyn. (1995) [Pubmed]
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