The DAN family: modulators of TGF-β signaling and beyond

Protein Sci. 2014 Aug;23(8):999-1012. doi: 10.1002/pro.2485. Epub 2014 Jun 2.


Extracellular binding proteins or antagonists are important factors that modulate ligands in the transforming growth factor (TGF-β) family. While the interplay between antagonists and ligands are essential for developmental and normal cellular processes, their imbalance can lead to the pathology of several disease states. In particular, recent studies have implicated members of the differential screening-selected gene in neuroblastoma (DAN) family in disease such as renal fibrosis, pulmonary arterial hypertension, and reactivation of metastatic cancer stem cells. DAN family members are known to inhibit the bone morphogenetic proteins (BMP) of the TGF-β family. However, unlike other TGF-β antagonist families, DAN family members have roles beyond ligand inhibition and can modulate Wnt and vascular endothelial growth factor (VEGF) signaling pathways. This review describes recent structural and functional advances that have expanded our understanding of DAN family proteins with regards to BMP inhibition and also highlights their emerging roles in the modulation of Wnt and VEGF signaling pathways.

Keywords: BMP; Keywords DAN; TGF-β; VEGF; Wnt; extracellular antagonists.

Publication types

  • Review

MeSH terms

  • Bone Morphogenetic Proteins / antagonists & inhibitors
  • Bone Morphogenetic Proteins / metabolism
  • Cell Cycle Proteins
  • Humans
  • Models, Molecular
  • Proteins / metabolism*
  • Signal Transduction*
  • Transforming Growth Factor beta / metabolism*


  • Bone Morphogenetic Proteins
  • Cell Cycle Proteins
  • NBL1 protein, human
  • Proteins
  • Transforming Growth Factor beta