Activin receptor type-1-like
Also known as: ACVRL1, ACVRLK1, ALK1
Function
Type I receptor for TGF-beta family ligands BMP9/GDF2 and BMP10 and important regulator of normal blood vessel development. On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. May bind activin as well.
Classification
- Family (Pfam)
- PF07714 PK_Tyr_Ser-Thr, PF08515 TGF_beta_GS
- InterPro
- 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
- Secreted Growth Factors & Cytokines
Experimental structures · PDB · 7
- 2LCR NMR
- 3MY0 X-ray 2.65A
- 4FAO X-ray 3.36A
- 6SF1 X-ray 2.80A
- 6SF2 X-ray 3.30A
- 6SF3 X-ray 2.30A
- 7PPC X-ray 3.60A
A predicted model is available from AlphaFold.
Gene Ontology · 63
- GO:0070724 BMP receptor complex
- GO:0009986 cell surface
- 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:0046872 metal ion binding
- GO:0019901 protein kinase binding
- GO:0004674 protein serine/threonine kinase activity
- GO:0046332 SMAD binding
- GO:0050431 transforming growth factor beta binding
- GO:0005024 transforming growth factor beta receptor activity
- GO:0005025 transforming growth factor beta receptor activity, type I
- GO:0004675 transmembrane receptor protein serine/threonine kinase activity
- GO:0001525 angiogenesis
- GO:0060840 artery development
- GO:0008015 blood circulation
- GO:0002043 blood vessel endothelial cell proliferation involved in sprouting angiogenesis
- GO:0001955 blood vessel maturation
- GO:0001974 blood vessel remodeling
- GO:0030509 BMP signaling pathway
- GO:0030154 cell differentiation
- GO:0071773 cellular response to BMP stimulus
- GO:0071363 cellular response to growth factor stimulus
- GO:0071560 cellular response to transforming growth factor beta stimulus
- GO:0035912 dorsal aorta morphogenesis
- GO:0009953 dorsal/ventral pattern formation
- GO:0003203 endocardial cushion morphogenesis
- GO:0061154 endothelial tube morphogenesis
- GO:0007507 heart development
- GO:0001946 lymphangiogenesis
- GO:0060836 lymphatic endothelial cell differentiation
- GO:0043537 negative regulation of blood vessel endothelial cell migration
- GO:0007162 negative regulation of cell adhesion
- GO:0030308 negative regulation of cell growth
- GO:0030336 negative regulation of cell migration
- GO:0008285 negative regulation of cell population proliferation
- GO:0045602 negative regulation of endothelial cell differentiation
- GO:0010596 negative regulation of endothelial cell migration
- GO:0001937 negative regulation of endothelial cell proliferation
- GO:0051895 negative regulation of focal adhesion assembly
- GO:0010629 negative regulation of gene expression
- GO:1903348 positive regulation of bicellular tight junction assembly
- GO:0030513 positive regulation of BMP signaling pathway
- GO:0032332 positive regulation of chondrocyte differentiation
- GO:0045893 positive regulation of DNA-templated transcription
- GO:0045603 positive regulation of endothelial cell differentiation
- GO:0001938 positive regulation of endothelial cell proliferation
- GO:0030858 positive regulation of epithelial cell differentiation
- GO:0045747 positive regulation of Notch signaling pathway
- GO:0060391 positive regulation of SMAD protein signal transduction
- GO:0045944 positive regulation of transcription by RNA polymerase II
- GO:0008217 regulation of blood pressure
- GO:0043535 regulation of blood vessel endothelial cell migration
- GO:0006275 regulation of DNA replication
- GO:0006355 regulation of DNA-templated transcription
- GO:0001936 regulation of endothelial cell proliferation
- GO:0061298 retina vasculature development in camera-type eye
- GO:0007165 signal transduction
- GO:0007179 transforming growth factor beta receptor signaling pathway
- GO:0060841 venous blood vessel development
- GO:0035313 wound healing, spreading of epidermal cells
Disease associations
- telangiectasia, hereditary hemorrhagic, type 2 MONDO:0010880
Drugs targeting this protein · 1
- PANULISIB inhibitor
Related proteins · sequence + function similarity
- Activin receptor type-1-like 1.00
- Activin receptor type-1-like 0.99
- Activin receptor type-1-like 0.99
- Activin receptor type-2B 0.88
- Activin receptor type-2B 0.86
- Activin receptor type-1B 0.86
- Activin receptor type-2B 0.86
- Activin receptor type-1B 0.85
- Activin receptor type-2B 0.85
- Activin receptor type-1B 0.85
- Activin receptor type-2B 0.85
- Bone morphogenetic protein receptor type-1B 0.85
Co-cited proteins · studied together in the literature
- Endoglin 5 shared papers
- Growth/differentiation factor 2 2 shared papers
- Potassium voltage-gated channel subfamily A member 5 1 shared papers
- Bone morphogenetic protein receptor type-1A 3 shared papers
- Activin receptor type-2B 1 shared papers
- Bone morphogenetic protein receptor type-2 2 shared papers
- Activin receptor type-1 2 shared papers
- Activin receptor type-1B 2 shared papers
- SMAD family member 2 1 shared papers
- TSC22 domain family protein 1 1 shared papers
- SMAD family member 3 1 shared papers
- Activin receptor type-2A 1 shared papers
Literature · 21 cited papers
- Functional and splicing defect analysis of 23 ACVRL1 mutations in a cohort of patients affected by hereditary hemorrhagic telangiectasia. PLoS ONE · 2015
- Novel mutations in BMPR2, ACVRL1 and KCNA5 genes and hemodynamic parameters in patients with pulmonary arterial hypertension. PLoS ONE · 2014
- Structure of the Alk1 extracellular domain and characterization of its bone morphogenetic protein (BMP) binding properties. Biochemistry · 2012
- Specificity and structure of a high affinity activin receptor-like kinase 1 (ALK1) signaling complex. J. Biol. Chem. · 2012
- TSC-22 promotes transforming growth factor beta-mediated cardiac myofibroblast differentiation by antagonizing Smad7 activity. Mol. Cell. Biol. · 2011
- Update on molecular diagnosis of hereditary hemorrhagic telangiectasia. Hum. Genet. · 2010
- Novel mutations in ENG and ACVRL1 identified in a series of 200 individuals undergoing clinical genetic testing for hereditary hemorrhagic telangiectasia (HHT): correlation of genotype with phenotype. Hum. Mutat. · 2006
- The finished DNA sequence of human chromosome 12. Nature · 2006
- Novel mutations in the ENG and ACVRL1 genes causing hereditary hemorrhagic teleangiectasia. Int. J. Mol. Med. · 2006
- Hepatic manifestation is associated with ALK1 in hereditary hemorrhagic telangiectasia: identification of five novel ALK1 and one novel ENG mutations. Hum. Mutat. · 2005
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- Molecular screening of ALK1/ACVRL1 and ENG genes in hereditary hemorrhagic telangiectasia in France. Hum. Mutat. · 2004
- … and 9 more in the literature graph
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