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FLASH GENE
Symbol ACVRL1 contributors: mct/pgu - updated : 27-02-2015
HGNC name activin A receptor type II-like 1
HGNC id 175
Corresponding disease
ORW2 Rendu-Osler-Weber disease 2
Location 12q13.13      Physical location : 52.301.201 - 52.317.144
Synonym name
  • serine/threonine-protein kinase receptor R3
  • TGF-B superfamily receptor type I
    • Synonym symbol(s) ACVRLK1, ALK1, ARLK1, HHT2, SKR3, HHT, TSR-I, ORW2
    EC.number 2.7.11.30
    DNA
    TYPE functioning gene
    STRUCTURE 16.45 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    text Variants 1 and 2 encode the same protein
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 4263 56 503 - 1996 8640225
    9 - 4126 56 503 - 1996 8640225
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessels     Mus musculusFetal
    Digestiveintestine    
     liver     Homo sapiens
    Respiratorylung    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveloosesubmucosal layer  
    Epithelialabsorptive excretorydigestive epithelium  
    Muscularsmooth    Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmonocyte Homo sapiens
    Cardiovascularendothelial cell Mus musculusFetal
    Lymphoid/Immunemacrophage Homo sapiens
    not specificchondrocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, pregnancy
    Text placenta, mesenchyme of the lung
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a small cysteine-rich extracellular region
  • a single transmembrane segment (TM)
  • a GS domain
  • a cytoplasmic serine/threonine kinase domain with three ligands (TGFB1, TGFB3 and one unknown)
    • secondary structure a beta-strand framework highly similar to BMPR1A, yet there are significant differences in loops shown previously to be important for binding
    HOMOLOGY
    interspecies homolog to murine Acvrl1
    Homologene
    FAMILY
  • protein kinase superfamily
  • TKL Ser/Thr protein kinase family
  • TGFB receptor subfamily
    • CATEGORY enzyme , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • modulator of TGFB1 signaling in the regulation of
  • contributing with BMPR2 to growth inhibition of human pulmonary artery endothelial cells
  • plays a role in transducing hemodynamic forces into a biochemical signal required to limit nascent vessel caliber, and through interaction with blood flow is involved in the development of arteriovenous malformations
  • TGFBR1/ACVRL1 balance regulates leptin expression in mesenchymal stem cells (MSC)
  • TMEM100 may play indispensable roles downstream of GDF2/BMP10-ACVRL1 signaling during endothelial differentiation and vascular morphogenesis
  • play an important role in cardiovascular remodeling
  • ENG and and ACVRL1 contribute to several novel networks, including TGFB1 dependent and independent ones, critical for vascular function and potentially defective in hereditary hemorrhagic telangiectasia
  • ACVRL1 and TGFBR1 play antagonistic roles in transforming growth factor beta-induced podosome formation in aortic endothelial cells
  • type I BMP/TGFBR that mediates signalling in endothelial cells via phosphorylation of SMAD1/5/8
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    TGFB signaling pathway
    a component
  • component of a complex with TGFB1 and TGFB3
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • GDF2 and BMP10 are specific ligands for ACVRL1 that potently inhibit microvascular endothelial cell migration and growth
  • ACVRL1/CSNK2B interaction specifically enhanced SMAD1/5/8 phosphorylation
  • high specificity of ACVRL1 for GDF2/BMP10 is determined by a novel orientation of ACVRL1 with respect to GDF2, which leads to a unique set of receptor-ligand interactions
  • type I cell surface receptor for the transforming growth factor-beta (TGFB) family of proteins
  • BMP9 and BMP10 are the physiological, functionally equivalent ligands of ACVRL1 in vascular development
  • BMP10 is the crucial ligand for ACVRL1 in embryonic vascular development, and circulating BMP10 acts through endothelial ACVRL1 to limit endothelial cell number in and thereby stabilize the caliber of nascent arteries
  • GDF2 inhibits lymphatic vessel formation via ACVRL1 during development and cancer progression
  • PPP2R2B protein interacts with the ACVRL1/TGFBR2/ENG complex and recruits PP2A to nitric oxide synthase 3 (NOS3)
  • synergises with NOTCH1 in stalk cells to induce expression of the NOTCH1 targets HEY1 and HEY2 and thereby represses tip cell formation and angiogenic sprouting
    • cell & other
    REGULATION
    repressed by UBR5 (negative regulation of ACVRL1 gene expression by UBR5 that is exerted at the promoter)
    Other signaling regulated by NR1H2 (LXRB)
    ASSOCIATED DISORDERS
    corresponding disease(s) ORW2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    with EGFL7 showed lower expression in early-onset pre-eclampsia versus late-onset pre-eclampsia
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • deletion of Alk1 in endothelial cell (EC) in adult mice leads to an increased local EC proliferation during brain angiogenesis and de novo brain arteriovenous malformations (AVMs)