Cytogenic Location °2q23-q24 (ACVR1, n.d., Where is ACVR1 located, figure 1) C LILT LILIL W IIIILII II IIID |公 AN
Cytogenic Location (“ACVR1,” n.d., Where is ACVR1 located, figure 1) • 2q23-q24
F0:2 FOP 00H 00^,0 121234 (Feldman et al. 2000)
(Feldman et al. 2000)
ACVR1 Also known as Activin receptor-like kinase-2(ALK2) Gene Codes for Activin receptor type 1 protein ACVRI protein function Controls and regulates growth of bones, muscles and ossification recruit and phosphorylate signaling molecules (Smad) Signaled by bone morphogenic protein(BMP) Effects growth and differentiation of cells Mutation Ligand dependent over responsiveness Ligand independent leakiness
ACVR1 • Also known as Activin receptor-like kinase-2 (ALK2) • Gene ▫ Codes for Activin receptor type 1 protein • ACVR1 protein function ▫ Controls and regulates growth of bones, muscles and ossification recruit and phosphorylate signaling molecules (Smad) ▫ Signaled by bone morphogenic protein (BMP) ▫ Effects growth and differentiation of cells • Mutation: ▫ Ligand dependent over responsiveness ▫ Ligand independent leakiness
How AVCR1 works ONTROL SM-FKBP12 cvR1 SM-FKBP12………ACVR1(R206H ⊥ BMP Basally Leaky Signaling BMP Signaling Blocked in Absence of Ligand ACVR1 ACVR1(R206H) ↓↓↓ BMP per-responsive BMP Signaling (Kaplan et al. 2008) in Presence of Ligand
How AVCR1 works (Kaplan et al. 2008)
AVCR1 schematic diagram Typical mutation on AVCRl Missense mutation at codon 206 of gs region 107124146178208 I Ligand-bindingTM GS Protein kinase domain 509aa W… GTG GCT CGC CAG ATT… - Val-Ala-Arg-GIn-lle GTG GCT CAC CAG ATT FOP Va-Aa-Hs·Gn-|le Codon:204205206207208 (Shore et al. 2008)
AVCR1 schematic diagram • Typical mutation on AVCR1 • Missense mutation at codon 206 of GS region (Shore et al. 2008)