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ACVR1 — SMAD5

Pathways - manually collected, often from reviews:

• OpenBEL Selventa BEL large corpus: SMAD5 → ACVR1 (increases, ACVR1 Activity, SMAD5 Activity)
  Evidence: BMP receptors activate Smad1, Smad5, and Smad8 (called BR-Smads in this review) whereas Smad2 and Smad3 are phosphorylated by the activin of Tgfbeta recepetors ALK3 and ALK6 can activate all three BR-Smads but ALK2 only phophorylates SMAD1 and SMAD5
• OpenBEL Selventa BEL large corpus: SMAD5 → ACVR1 (directlyIncreases, SMAD5 Activity)
  Evidence: Phosphorylation of the C-terminal serine residues in R-Smads by type I receptor kinases is a crucial step in TGF-b family signalling (Abdollah et al., 1997; Macias-Silva et al., 1996; Souchelnytskyi et al., 1997). The two most C-terminal serine residues become phosphorylated and, together with a third, non-phosphorylated serine residue, form an evolutionarily conserved SSXS motif in all R-Smads.... TGF-b and activin receptors phosphorylate Smad2 and Smad3, and BMP receptors phosphorylate Smad1, ...
• NCI Pathway Database ALK2 signaling events: MIS/MISR2/ALK2 (dimer) complex (AMH-ACVR1-AMHR2) → SMAD1-5-8 (SMAD1/SMAD9/SMAD5) (modification, activates)
  Visser et al., Mol Endocrinol 2001, Clarke et al., Mol Endocrinol 2001
  Evidence: mutant phenotype, assay
• NCI Pathway Database ALK2 signaling events: BMP7/BMPR2/ALK2 (dimer) complex (BMP7-ACVR1-BMPR2) → SMAD1-5-8 (SMAD1/SMAD9/SMAD5) (modification, activates)
  Macías-Silva et al., J Biol Chem 1998, Chen et al., J Biol Chem 1999
  Evidence: assay, physical interaction

Protein-Protein interactions - manually collected from original source literature:

Studies that report less than 10 interactions are marked with *

• IRef Biogrid Interaction: SMAD5 — ACVR1 (physical association, affinity chromatography technology) Macías-Silva et al., J Biol Chem 1998
• IRef Biogrid Interaction: SMAD5 — ACVR1 (physical association, affinity chromatography technology) Pardali et al., J Biol Chem 2000
• IRef Hprd Interaction: SMAD5 — ACVR1 (in vivo) Nishita et al., Genes Cells 1999*, Pardali et al., J Biol Chem 2000, Macías-Silva et al., J Biol Chem 1998
• IRef Ophid Interaction: SMAD5 — ACVR1 (aggregation, confirmational text mining) Macías-Silva et al., J Biol Chem 1998
• IRef Ophid Interaction: SMAD5 — ACVR1 (aggregation, interologs mapping) Brown et al., Bioinformatics 2005

Text-mined interactions from Literome

Besser et al., J Biol Chem 2004 : Conversely, BMP signaling leading to Smad1/5/8 activation via ALK2/3/6 is blocked in undifferentiated cells and becomes activated upon differentiation
Luo et al., J Biol Chem 2010 : Likewise, RNAi silencing of ALK1 and ALK2 expression inhibits BMP9 induced BMPR-Smad activity and osteogenic differentiation in MSCs both in vitro and in vivo
Macías-Silva et al., J Biol Chem 1998 : Biochemical analysis revealed that constitutively active ALK2 associated with and phosphorylated Smad1 on the COOH-terminal SSXS motif, and also regulated Smad5 and Smad8 phosphorylation