Lefty2 (Lefty A)

Left-right determination factor 2 (Lefty2), also known as Left-right determination factor A (Lefty A), endometrial bleeding associated factor (left-right determination, factor A transforming growth factor beta superfamily), and Transforming growth factor beta-4, is a member of the TGF-beta family of proteins. This protein is secreted and plays a role in left-right asymmetry determination of organ systems during development. Lefty2/Lefty A may also play a role in endometrial bleeding. Mutations in Lefty2/Lefty A have been associated with left-right axis malformations, particularly in the heart and lungs. Some types of infertility have been associated with dysregulated expression of this gene in the endometrium. Alternative processing of this protein can yield three different products. Depletion of both Lefty1 and Lefty2 causes unchecked Nodal signaling, expansion of mesendoderm, and loss of ectoderm. The expansion of mesendoderm correlates with an extended period of rapid cellular internalization and a failure of deep-cell epiboly. The gastrulation defects of embryos depleted of Lefty1 and Lefty2 result from the deregulation of Squint signaling.

Lefty2 (Lefty A) Related Areas

Stem Cell>>Embryonic Stem Cell (ESC)>>Embryonic Stem Cell Marker>>Lefty2/Lefty A

Cancer>>Growth Factor & Receptor>>TGF-beta Superfamily>>Other>>Lefty2/Lefty A

Immunology>>Cytokine & Receptor>>TGF-beta Superfamily>>Other>>Lefty2/Lefty A

Lefty2 (Lefty A) Alternative Names

Lefty2, LEFTYA, LEFTA, EBAF, MGC46222, TGFB4 [Homo sapiens]

Lefty2, Lefta, Leftb, 6030463A22Rik, AV214969, Ebaf, MGC98569 [Mus musculus]

Summaries for Lefty2 (Lefty A)

Entrez Gene summary for Lefty2:

This Lefty2 gene encodes a member of the TGF-beta family of proteins. Lefty2 is secreted and plays a role in left-right asymmetry determination of organ systems during development. Lefty2 may also play a role in endometrial bleeding. Mutations in this gene have been associated with left-right axis malformations, particularly in the heart and lungs. Some types of infertility have been associated with dysregulated expression of this gene in the endometrium. Alternative processing of Lefty2 can yield three different products. This gene is closely linked to both a related family member and a related pseudogene. Alternate splicing of this Lefty2 gene results in multiple transcript variants.

Human Lefty2 (Lefty A) Protein General Information

 

• Protein names: Protein lefty-2
• Sequence length: 366 AA.
• Sequence caution: The sequence AAB53269.1 differs from that shown. Reason: Authors have revised their sequence, but have not submitted the revised DNA sequence.
• Sequence similarities: Lefty2 belongs to the TGF-beta family.
• Post-translational modification: The processing of the protein may also occur at the second R-X-X-R site located at AA 132-135. Processing appears to be regulated in a cell-type specific manner.
• Developmental stage: Lefty2 is transiently expressed before and during menstrual bleeding.
• Subcellular location: Secreted.
• Tissue specificity: Mesenchymal cells of the endometrial stroma.
• Involvement in disease: Defects in LEFTY2 are the cause of left-right axis malformations (LRAM) [MIM:601877]. The defect includes left pulmonary isomerism, with cardiac anomalies characterized by complete atrioventricular canal defect and hypoplastic left ventricle, and interrupted inferior vena cava.

General information above from UniProt

Function for Lefty2 (Lefty A) Protein

UniProtKB:

Lefty2 is required for left-right (L-R) asymmetry determination of organ systems in mammals. Lefty2 may play a role in endometrial bleeding.

Genatlas:

• Lefty2 plays a role with LEFTYB, NODAL and PITX2 in left-right asymmetry determination of organ systems during development
• Lefty2 may also play a role in endometrial bleeding
• Lefty2 antagonizes NODAL
• Lefty2's expression controlled by NODAL appears to have a substantial role in mesodermal origin cell population establishment, since inhibition of NODAL activity downregulated expression not only of LEFTY1 and LEFTY2 but also of BRACHYURY, an early mesodermal marker (Dvash 2007)
• Lefty2 regulates endometrial MMP9
• Lefty2 acts as a molecular switch that modulates both the induction of decidual differentiation and the maintenance of a decidualized state (Tang 2010)

Homology for human Lefty2 (Lefty A)

• homolog to murine Lefty2

Phenotype Information for Lefty2 (Lefty A)

• Gene/Locus: EBAF, TGFB4, LEFTY2, LEFTA, LEFTYA
• Phenotype: Left-right axis malformations

Phenotype Information for Lefty2 from OMIM (Online Mendelian Inheritance in Man)