ACVRL1

Serine/threonine-protein kinase receptor R3 is an enzyme that in humans is encoded by the ACVRL1 gene.^[5][6][7]

ACVRL1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2LCR, 3MY0, 4FAO
Identifiers
Aliases	ACVRL1, ACVRLK1, ALK-1, ALK1, HHT, HHT2, ORW2, SKR3, TSR-I, activin A receptor like type 1
External IDs	OMIM: 601284; MGI: 1338946; HomoloGene: 20058; GeneCards: ACVRL1; OMA:ACVRL1 - orthologs
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q13.13 Start 51,906,908 bp[1] End 51,923,361 bp[1]
Gene location (Mouse) Chr. Chromosome 15 (mouse)[2] Band 15|15 F1 Start 101,026,403 bp[2] End 101,043,217 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lung upper lobe of left lung tendon of biceps brachii apex of heart mucosa of transverse colon left uterine tube lower lobe of lung right lobe of thyroid gland subcutaneous adipose tissue canal of the cervix Top expressed in granulocyte right lung left lung right lung lobe left lung lobe cardiac muscle tissue of left ventricle extensor digitorum longus muscle extraocular muscle plantaris muscle choroid plexus of fourth ventricle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity nucleotide binding protein kinase activity activin binding transforming growth factor beta-activated receptor activity metal ion binding kinase activity protein serine/threonine kinase activity transmembrane receptor protein serine/threonine kinase activity protein binding BMP receptor activity ATP binding protein kinase binding transforming growth factor beta binding transforming growth factor beta receptor activity, type I activin receptor activity, type I SMAD binding growth factor binding Cellular component integral component of membrane membrane integral component of plasma membrane soma dendrite plasma membrane cell surface receptor complex activin receptor complex Biological process cellular response to transforming growth factor beta stimulus negative regulation of cell adhesion regulation of transcription, DNA-templated positive regulation of endothelial cell differentiation positive regulation of endothelial cell proliferation blood vessel morphogenesis negative regulation of blood vessel endothelial cell migration lymphangiogenesis regulation of DNA replication phosphorylation endothelial tube morphogenesis retina vasculature development in camera-type eye wound healing, spreading of epidermal cells lymphatic endothelial cell differentiation positive regulation of pathway-restricted SMAD protein phosphorylation cellular response to BMP stimulus negative regulation of endothelial cell differentiation in utero embryonic development blood vessel endothelial cell proliferation involved in sprouting angiogenesis blood circulation positive regulation of angiogenesis venous blood vessel development negative regulation of endothelial cell migration negative regulation of endothelial cell proliferation regulation of blood vessel endothelial cell migration regulation of blood pressure positive regulation of transcription, DNA-templated protein phosphorylation blood vessel remodeling negative regulation of cell migration transmembrane receptor protein serine/threonine kinase signaling pathway negative regulation of cell growth positive regulation of chondrocyte differentiation angiogenesis artery development regulation of endothelial cell proliferation positive regulation of BMP signaling pathway transforming growth factor beta receptor signaling pathway negative regulation of focal adhesion assembly negative regulation of DNA biosynthetic process signal transduction negative regulation of cell population proliferation blood vessel maturation activin receptor signaling pathway response to hypoxia endocardial cushion to mesenchymal transition endocardial cushion morphogenesis negative regulation of gene expression dorsal aorta morphogenesis positive regulation of transcription by RNA polymerase II BMP signaling pathway pattern specification process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 94 11482 Ensembl ENSG00000139567 ENSMUSG00000000530 UniProt P37023 Q61288 RefSeq (mRNA) NM_000020 NM_001077401 NM_001277255 NM_001277257 NM_001277258 NM_001277259 NM_009612 RefSeq (protein) NP_000011 NP_001070869 NP_001264184 NP_001264186 NP_001264187 NP_001264188 NP_033742 Location (UCSC) Chr 12: 51.91 – 51.92 Mb Chr 15: 101.03 – 101.04 Mb PubMed search [3] [4]
Wikidata
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ACVRL1 is a receptor in the TGF beta signaling pathway. It is also known as activin receptor-like kinase 1, or ALK1.

Function

This gene encodes a type I cell-surface receptor for the TGF-beta superfamily of ligands. It shares with other type I receptors a high degree of similarity in serine-threonine kinase subdomains, a glycine- and serine-rich region (called the GS domain) preceding the kinase domain, and a short C-terminal tail. The encoded protein, sometimes termed ALK1, shares similar domain structures with other closely related ALK or activin receptor-like kinase proteins that form a subfamily of receptor serine/threonine kinases. Mutations in this gene are associated with hereditary hemorrhagic telangiectasia (HHT) type 2, also known as Rendu-Osler-Weber syndrome 2.^[7]

Pathology

Germline mutations of ACVRL1 are associated with:

• hereditary hemorrhagic telangiectasia type 2 (Rendu-Osler-Weber syndrome 2)^[8]
• Pulmonary arteriovenous malformations^[9]

Somatic mosaicism in ACVRL1 are associated with severe pulmonary arterial hypertension.^[10]

ACVRL1 directly interacts with low-density lipoprotein (LDL), which implies that it might initiate the early phases of atherosclerosis.^[11]

Abnormal activity of ACVRL1 has been found to be closely associated with idiopathic pulmonary arterial hypertension.

As a drug target

• Dalantercept is an experimental ALK1 inhibitor.^[12]

Closely/family related kinases

(Not to be confused with anaplastic lymphoma kinase (ALK) )
ALK4 is ACVR1B, ALK7 is ACVR1C, and ALK5 is [part of] the TGF-β type I receptor.^[13]

See also

• TGF beta signaling pathway, see summary table for ALK*