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FLASH GENE
Symbol ACVR1 contributors: shn/npt/pgu - updated : 03-04-2018
HGNC name activin A receptor, type I
HGNC id 171
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a small cysteine-rich extracellular region
  • a juxtamembrane region of phosphorylation, glycine and serine rich (GS)
  • a cytoplasmic serine/threonine kinase domain
    • HOMOLOGY
    interspecies ortholog to murine Acvr1
    intraspecies homolog to ALK3, ALK4
    Homologene
    FAMILY
  • type I bone morphogenetic protein (BMP) receptor family
  • TKL Ser/Thr protein kinase family
  • TGFB receptor subfamily
    • CATEGORY enzyme , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • functioning as a BMP type I receptor and inducing Indian hedgehog in chondrocytes during skeletal development
  • Acvr1 is involved in the proper specification of the left-right axis in mice and in promoting cell proliferation in the neural crest-derived cells of Meckel cartilage
  • Acvr1 plays a role in mouse lens development by regulating lens cell proliferation
  • transmembrane serine/threonine kinase receptor that activates intracellular signaling pathways via Smad1/5, Erk1/2, and MAPK14 in response to BMP binding
  • BMPR1A and ACVR1, activate multiple signaling pathways to regulate lens formation
  • induction of the osteoblastic differentiation of myoblasts by ALK2 seems to be dependent on its kinase activity, which phosphorylates Smad1/5 at its C- termini
  • can repress osteogenesis and Wnt signaling via SOST/DKK1
  • signaling via ACVR1 is required for appropriate aortic valve development in utero, and defects in this process lead to indirect secondary complications later in life
  • is required for chondrocyte proliferation and differentiation, particularly in craniofacial and axial elements, but exerts coordinated functions with both BMPR1A and BMPR1B throughout the developing endochondral skeleton
  • exerts key and non-redundant roles in numerous developmental processes, including the specification, growth and morphogenesis of endochondral skeletal elements
  • plays an important role in bone development
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • forming a stable complex with type II receptor after ligand binding
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • not binding activin
  • inhibiting TGFB1, TGFB2, BMP2
  • cell quiescence controlled by BMP signaling via ACVR1 is required for transient formation of nodal cilia
  • key receptor of BMP7
  • BMP7 signaling through ACVR1 can reduce Wnt signaling via SOST/DKK1 and then inhibits osteogenesis
  • GIPC1, ACVR1, BMPR1A, and TGFBR1 are signaling components required for TGFBR3-mediated endothelial cell epithelial-mesenchymal transformation
  • bone morphogenetic protein signaling mediated by ACVR1 and DLX2 regulates apoptosis in glioma-initiating cells
  • GDF2 and BMP10 enhance TNF-induced monocyte recruitment to the vascular endothelium mainly via ACVR1
  • FKBP1A preferentially targets the BMP receptor ACVR1
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) FOP
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    epiblast-specific deletion of ACVR1 compromised potentially development of nodal cilia, which results in defects in leftward fluid flow and, thus, abnormalities in left-right patterning
    constitutional     --low  
    loss of ACVR1 in osteoblasts increases bone density
    tumoral germinal mutation     gain of function
    in Diffuse Intrinsic Pontine Gliomas (DIPGs)
    Susceptibility to orofacial cleft
    Variant & Polymorphism other
  • variants in SHH, RORA, MRPL53, ACVR1, and GDF11 may contribute to risk of orofacial clefts
    • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    osteoarticularbone 
    small molecule inhibition of BMP type I receptor activity may be useful in treating FOP and heterotopic ossification syndromes associated with excessive BMP signaling
    osteoarticularbone 
    as a plausible therapeutic target during early chondrogenic stages of lesion formation for preventing heterotopic bone formation in FOP and other conditions
    ANIMAL & CELL MODELS
  • Postnatal overexpression of constitutively active Q207D-mutant Alk2 in the left hindlimbs of mice led development of ectopic endochondral bone formation, joint fusion, and functional impairment, thus phenocopying key aspects of human FOP .
  • Acvr1 conditional mouse knockout leads to an increase in apoptosis of lens epithelial and fiber cells resulting in smaller sizes of Acvr1 CKO mouse lenses
  • Acvr1 deficiency in mouse embryonic fibroblasts (MEFs) resulted in severe defects in their quiescence-induced primary cilia
  • bone mass was increased in the Acvr1-null mice
  • Acvr1(CKO) mice are viable but exhibit defects in the development of cranial and axial structures