Recombinant Human Growth/differentiation factor 11 (GDF11)

Function

Secreted signal that acts globally to regulate anterior/posterior axial patterning during development. May play critical roles in patterning both mesodermal and neural tissues (By similarity). It is required for proper vertebral patterning and orofacial development (PubMed:31215115). Signals through activin receptors type-2, ACVR2A and ACVR2B, and activin receptors type-1, ACVR1B, ACVR1C and TGFBR1 leading to the phosphorylation of SMAD2 and SMAD3 (PubMed:28257634)

Subcellular Location

Secreted

Disease Association

Vertebral hypersegmentation and orofacial anomalies (VHO) : An autosomal dominant disease characterized by supernumerary ribs, supernumerary cervical, thoracic and/or lumbar vertebrae, and orofacial anomalies such as cleft lip with or without cleft palate in most patients. [The disease may be caused by variants affecting the gene represented in this entry]

Tissue Specificity

In the embryo, strong expression is seen in the palatal epithelia, including the medial edge epithelial and midline epithelial seam of the palatal shelves. Less pronounced expression is also seen throughout the palatal shelf and tongue mesenchyme

Subunit

Homodimer; disulfide-linked (PubMed:26919518, PubMed:31215115). Interacts directly with ACVR2B (By similarity). Interacts directly with ACVR2A (By similarity). Interacts with ACVR1B, TGFBR1 and ACVR1C in an ACVR2B-dependent manner (By similarity). Interacts with FST isoform 2/FS-288 (PubMed:28257634)

• Gamer L.W. et al. A novel BMP expressed in developing mouse limb, spinal cord, and tail bud is a potent mesoderm inducer in Xenopus embryos. — Dev. Biol. (1999)
• McPherron A.C. et al. Regulation of anterior/posterior patterning of the axial skeleton by growth/differentiation factor 11. — Nat. Genet. (1999)
• Cox T.C. et al. Mutations in GDF11 and the extracellular antagonist, Follistatin, as a likely cause of Mendelian forms of orofacial clefting in humans. — Hum. Mutat. (2019)
• Padyana A.K. et al. Crystal structure of human GDF11. — Acta Crystallogr. F (2016)
• Walker R.G. et al. Structural basis for potency differences between GDF8 and GDF11. — BMC Biol. (2017)