extracellular domain (ECD) found in activin receptor-like kinase 2 (ALK-2) and similar proteins
ALK-2 (EC 2.7.11.30, also called ACVRLK2, or activin receptor type-1 (ACVR1), or activin receptor type I (ACTR-I), or serine/threonine-protein kinase receptor R1 (SKR1), or TGF-B superfamily receptor type I (TSR-I)) is bone morphogenetic protein (BMP) type I receptor that is involved in a wide variety of biological processes, including bone, heart, cartilage, nervous, and reproductive system development and regulation. As a type I receptor, ALK-2 forms heterotetrameric receptor complexes with the type II receptors AMHR2, ACVR2A, or ACVR2B. Upon binding of ligands such as BMP7 or GDF2/BMP9 to the heteromeric complexes, type II receptors transphosphorylate ACVR1 intracellular domain. In turn, ACVR1 kinase domain is activated and subsequently phosphorylates SMAD1/5/8 proteins that transduce the signal. In addition to its role in mediating BMP pathway-specific signaling, ALK-2 suppresses TGFbeta/activin pathway signaling by interfering with the binding of activin to its type II receptor. Besides canonical SMAD signaling, it can activate non-canonical pathways such as p38 mitogen-activated protein kinases/MAPKs. This model corresponds to the extracellular domain (ECD) of ALK-2, which belongs to Ly-6 antigen/uPA receptor-like (LU) superfamily and exhibits a snake toxin-like fold (also known as three-finger toxin/3FTx fold or three-fingered protein/TFP domain fold).
Jiyao W et al.(2023). "The conserved domain database in 2023.",