Activin receptor type-1
Also known as: ACVR1, ACVRLK2
Function
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, 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, suppresses TGFbeta/activin pathway signaling by interfering with the binding of activin to its type II receptor. Besides canonical SMAD signaling, can activate non-canonical pathways such as p38 mitogen-activated protein kinases/MAPKs (By similarity). May promote the expression of HAMP, potentially via its interaction with BMP6 (By similarity).
Classification
- Family (Pfam)
- PF01064 Activin_recp, PF07714 PK_Tyr_Ser-Thr, PF08515 TGF_beta_GS
- InterPro
- Activin_recp, GS_dom, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser-Thr/Tyr_kinase_cat_dom, Ser/Thr_kinase_AS, Snake_toxin-like_sf, TGFB_receptor
- Functional cluster
- Zinc-Finger Nucleic-Acid-Binding & Methyltransferases
Experimental structures · PDB · 85
- 3H9R X-ray 2.35A
- 3MTF X-ray 2.15A
- 3OOM X-ray 2.00A
- 3Q4U X-ray 1.82A
- 4BGG X-ray 2.56A
- 4C02 X-ray 2.17A
- 4DYM X-ray 2.42A
- 5OXG X-ray 2.13A
- 5OY6 X-ray 2.56A
- 5S75 X-ray 1.30A
- 5S76 X-ray 1.31A
- 5S77 X-ray 1.31A
- … and 73 more
A predicted model is available from AlphaFold.
Gene Ontology · 52
- GO:0048179 activin receptor complex
- GO:0045177 apical part of cell
- GO:0070724 BMP receptor complex
- GO:0005886 plasma membrane
- GO:0048185 activin binding
- GO:0016361 activin receptor activity, type I
- GO:0005524 ATP binding
- GO:0098821 BMP receptor activity
- GO:0045296 cadherin binding
- GO:0046872 metal ion binding
- GO:0017046 peptide hormone binding
- GO:0042803 protein homodimerization activity
- GO:0004672 protein kinase activity
- GO:0004674 protein serine/threonine kinase activity
- GO:1990782 protein tyrosine kinase binding
- GO:0046332 SMAD binding
- GO:0050431 transforming growth factor beta binding
- GO:0005025 transforming growth factor beta receptor activity, type I
- GO:0004675 transmembrane receptor protein serine/threonine kinase activity
- GO:0032924 activin receptor signaling pathway
- GO:0002526 acute inflammatory response
- GO:0003289 atrial septum primum morphogenesis
- GO:0003181 atrioventricular valve morphogenesis
- GO:0030509 BMP signaling pathway
- GO:0060923 cardiac muscle cell fate commitment
- GO:0030154 cell differentiation
- GO:0071773 cellular response to BMP stimulus
- GO:0071363 cellular response to growth factor stimulus
- GO:0009953 dorsal/ventral pattern formation
- GO:0003143 embryonic heart tube morphogenesis
- GO:0061445 endocardial cushion cell fate commitment
- GO:0003272 endocardial cushion formation
- GO:0003274 endocardial cushion fusion
- GO:0007507 heart development
- GO:0003183 mitral valve morphogenesis
- GO:0032926 negative regulation of activin receptor signaling pathway
- GO:2001237 negative regulation of extrinsic apoptotic signaling pathway
- GO:2000134 negative regulation of G1/S transition of mitotic cell cycle
- GO:0009968 negative regulation of signal transduction
- GO:0001649 osteoblast differentiation
- GO:0030501 positive regulation of bone mineralization
- GO:0062043 positive regulation of cardiac epithelial to mesenchymal transition
- GO:0030335 positive regulation of cell migration
- GO:2000017 positive regulation of determination of dorsal identity
- GO:0045893 positive regulation of DNA-templated transcription
- GO:1902533 positive regulation of intracellular signal transduction
- GO:0045669 positive regulation of osteoblast differentiation
- GO:0060391 positive regulation of SMAD protein signal transduction
- GO:0045944 positive regulation of transcription by RNA polymerase II
- GO:0030278 regulation of ossification
- GO:0007179 transforming growth factor beta receptor signaling pathway
- GO:0060412 ventricular septum morphogenesis
Disease associations
- fibrodysplasia ossificans progressiva MONDO:0007606
Drugs targeting this protein · 2
- PACRITINIB CITRATE inhibitor
- MOMELOTINIB DIHYDROCHLORIDE MONOHYDRATE inhibitor
Related proteins · sequence + function similarity
- Activin receptor type-1 1.00
- Activin receptor type-1 1.00
- Activin receptor type-1 1.00
- Activin receptor type-1 0.99
- Bone morphogenetic protein receptor type-1B 0.95
- Bone morphogenetic protein receptor type-1B 0.95
- Activin receptor type-1B 0.94
- Activin receptor type-1B 0.94
- Activin receptor type-1B 0.94
- Activin receptor type-1C 0.94
- Activin receptor type-1C 0.94
- TGF-beta receptor type-1 0.93
Co-cited proteins · studied together in the literature
- Anti-Muellerian hormone type-2 receptor 1 shared papers
- Growth/differentiation factor 2 1 shared papers
- Bone morphogenetic protein 7 1 shared papers
- Activin receptor type-2A 2 shared papers
- Bone morphogenetic protein 6 2 shared papers
- Activin receptor type-2B 1 shared papers
- Bone morphogenetic protein receptor type-1A 3 shared papers
- TGF-beta receptor type-2 2 shared papers
- Clusterin 1 shared papers
- Activin receptor type-1-like 2 shared papers
- Activin receptor type-1B 2 shared papers
- Activin receptor type-1 1 shared papers
Literature · 18 cited papers
- Erythroferrone lowers hepcidin by sequestering BMP2/6 heterodimer from binding to the BMP type I receptor ALK3. Blood · 2020
- Mutant activin-like kinase 2 in fibrodysplasia ossificans progressiva are activated via T203 by BMP type II receptors. Mol. Endocrinol. · 2015
- Structure of the bone morphogenetic protein receptor ALK2 and implications for fibrodysplasia ossificans progressiva. J. Biol. Chem. · 2012
- Distinct and separable activities of the endocytic clathrin-coat components Fcho1/2 and AP-2 in developmental patterning. Nat. Cell Biol. · 2012
- TSC-22 promotes transforming growth factor beta-mediated cardiac myofibroblast differentiation by antagonizing Smad7 activity. Mol. Cell. Biol. · 2011
- TGFbeta/BMP type I receptors ALK1 and ALK2 are essential for BMP9-induced osteogenic signaling in mesenchymal stem cells. J. Biol. Chem. · 2010
- Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
- Novel mutations in ACVR1 result in atypical features in two fibrodysplasia ossificans progressiva patients. PLoS ONE · 2009
- Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1. Hum. Mutat. · 2009
- Type I receptor binding of bone morphogenetic protein 6 is dependent on N-glycosylation of the ligand. FEBS J. · 2008
- Activin receptor-like kinase-2 inhibits activin signaling by blocking the binding of activin to its type II receptor. J. Endocrinol. · 2007
- Patterns of somatic mutation in human cancer genomes. Nature · 2007
- … and 6 more in the literature graph