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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
Corresponding disease
FOP fibrodysplasia ossificans progressiva
Location 2q24.1      Physical location : 158.592.957 - 158.732.374
Synonym name
  • activin receptor-like kinase 2
  • activin A receptor, type II-like kinase 2
  • TGF-B superfamily receptor type I
  • serine/threonine-protein kinase receptor R1
  • BMP type I receptor ALK2
  • Synonym symbol(s) ALK2, ACTRI, ACVRLK2, SKR1, ACVR1A, FOP, TSRI, FOP
    EC.number 2.7.11.1, 2.7.11.30
    DNA
    TYPE functioning gene
    STRUCTURE 139.45 kb     11 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure
  • several transcription factors such as EGR1, EGR2, ZBTB7A/LRF, and HEY1, regulate the ACVR1 promoter by binding to the -762/-308 region, which is essential to confer maximal transcriptional activity
  • MAPPING cloned Y linked   status provisional
    Map cen - D2S141 - D2S2360 - ACVR1- D2S284 - D2S1353 - qter
    Authors Roijer (1998)
    Text by Southern blot analysis and fluorescence in situ hybridization of DNAs from a somatic cell hybrid mapping panel, the ACVR1 gene has been mapped to chromosome 2q23-q24
    Physical map
    LOC391454 2 similar to ATP synthase alpha chain, mitochondrial precursor NR4A2 2q22-q23 nuclear receptor subfamily 4, group A, member 2 LOC389055 2 LOC389055 GPD2 2q24.1 glycerol-3-phosphate dehydrogenase 2 (mitochondrial) LOC391455 2 similar to Acidic ribosomal phosphoprotein P0 LOC220786 2q24.2 cyclin-dependent kinase 7 pseudogene GALNT5 2q24.1 UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 5 (GalNAc-T5) KIAA1189 2q24.2 KIAA1189 protein PSCDBP 2q11.2 pleckstrin homology, Sec7 and coiled-coil domains, binding protein ACVR1C 2q24-q31 activin A receptor, type IC ACVR1 2q23-q24 activin A receptor, type I UPP2 2q24.2 uridine phosphorylase 2 LOC130940 2q24.2 hypothetical protein BC015395 PKP4 2q23-q31 Plakophilin 4 LOC391456 2 similar to KIAA0181 LOC92196 2q24.2 similar to death-associated protein OR7E89P 2q31.3 olfactory receptor, family 7, subfamily E, member 89 pseudogene LOC391457 2 similar to putative taste receptor HTR2 OR7E90P 2q31.3 olfactory receptor, family 7, subfamily E, member 90 pseudogene MGC23908 2 similar to RNA polymerase B transcription factor 3 KIAA1728 2q24.2 KIAA1728 protein FLJ36175 2q24.2 hypothetical protein FLJ36175 BAZ2B 2q23-q24 bromodomain adjacent to zinc finger domain, 2B AXOT 2q24.2 axotrophin DCL-1 2q24.2 type I transmembrane C-type lectin receptor DCL-1 LY75 2p24 lymphocyte antigen 75 PLA2R1 2q23-q24.1 phospholipase A2 receptor 1, 180kDa ITGB6 2q24-q31 integrin, beta 6
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 3062 65 509 mouse lens epithelium 2009 19733164
    11 - 2881 65 509 - 2009 19733164
    12 - 2951 65 509 - 2009 19733164
    12 - 3011 65 509 - 2009 19733164
    8 - 2918 65 509 - 2009 19733164
    8 - 2983 65 509 - 2009 19733164
    12 - 2954 65 509 - 2009 19733164
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Nervousbrain   highly
    Respiratorylung   highly
    Skeletonappendicular skeleton     Homo sapiens
    Urinarykidney   highly
    Visualeyelens  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone  highly Homo sapiens
    Muscular   highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    not specificchondrocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    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
    Variant & Polymorphism
    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