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FLASH GENE
Symbol BMP6 contributors: mct - updated : 26-06-2013
HGNC name bone morphogenetic protein 6
HGNC id 1073
Location 6p24.3      Physical location : 7.727.010 - 7.881.960
Synonym name
  • Vg-related sequence
  • vegetal related growth factor (TGFB-related)
  • Vg1-related sequence
    • Synonym symbol(s) VGR1, VGR
    DNA
    TYPE functioning gene
    STRUCTURE 154.95 kb     7 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence cytosine-phosphate-guanine/HTF
    Binding site
    text structure CpG loci around SP1 binding sites demethylated in the invading and metaslasizing cancer cells
    MAPPING cloned Y linked N status confirmed
    Map pter - D6S1640 - D6S1547 - BMP6 - D6S2257 - D6S1674 - cen
    Authors UCSC (2009)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 3105 - 513 - 1990 2263636
    preproprotein
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivefemale systemuteruscervix highly
     female systemovary  highly Homo sapiens
    Visualeyelens   
     eyeretina    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Connectivebone   
    Epithelialbarrier liningretinal pigment epithelium (RPE)   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Reproductivegranulosa cell Homo sapiens
    Skeletonosteoclast Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text fetal eye
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • TGF-beta-like domain
    • mono polymer homomer , heteromer , dimer
    isoforms Precursor cleaved at a consensus Arg-X-X-Arg to yield a C terminus mature dimer
    HOMOLOGY
    interspecies homolog to Drosophila decapentaplegic-Vg,DVR family
    homolog to murine Bmp6
    homolog to Xenopus Vg-1
    intraspecies paralog to BMP5,BMP7
    Homologene
    FAMILY
  • TGF-beta family
    • CATEGORY protooncogene , signaling growth factor , receptor membrane serine/threonine
    SUBCELLULAR LOCALIZATION extracellular
    text extracellular matrix
    basic FUNCTION
  • involved in enchondral bone formation
  • trophic factor promoting dendritic growth without modifying axonal length or soma area and increasing the number and differentiation of calbindin-positive neurons
  • may play an important role in the pathogenesis of myelofibrosis in primary myelofibrosis and are apparently induced by cytokines such as TGFbeta-1
  • control CDKN1C expression and cell growth arrest/terminal differentiation in normal primary epidermal keratinocytes
  • having a critical role for iron homeostasis and it is functionally nonredundant with other members of the Bmp subfamily
  • having a key role as a ligand for hemojuvelin and an endogenous regulator of hepcidin expression and iron metabolism
  • important mediator to support healthy follicle growth in the human ovary
  • key regulator of hepatic hepcidin expression and iron metabolism, and iron-induced expression of BMP6 in intestinal cells is the main regulator of hepatic hepcidin expression
  • novel role of BMP6/HMOX1 cascade to relieve breast cancer metastasis by regulating the secretion of growth factors in tumor microenvironment
  • BMP6 and iron not only induce hepcidin expression but also induce TMPRSS6, a negative regulator of hepcidin expression)
  • major regulator of systemic iron
  • reduced Ig production by 70p100 in memory B cells and more than 55p100 in naive B cells, whereas the other BMPs were slightly less potent
  • potent suppressor of naive and memory B cells
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development , ossification
    PATHWAY
    metabolism
    signaling
    a component
  • heterodimer BMP2/BMP6 (BMP2/6) compared to the homodimers BMP2 or BMP6 is more potent for inducing differentiation of embryonic stem (hES) cells
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • EEF1D is likely the switch through which BMP6 restores CDH1-mediated cell-to-cell adhesion and prevents breast cancer metastasis
  • interacting with HFE2, resulting in increasing expression of HAMP
  • in memory B cells, BMP6 upregulated expression of DNA-binding protein inhibitor genes, but potently inhibited CD40L/IL21-induced upregulation of the transcription factor XBP1, necessary for the late stages of plasmacytic differentiation
  • CREBZF inhibits the function of BMP6 by interacting with SMAD1, SMAD5, SMAD9
  • melatonin plays a role in the regulation of BMP6 signal intensity for controlling progesterone production in the ovary
    • cell & other
    REGULATION
    activated by cleaved by subtilisin like convertases
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in advanced stages of myelofibrosis
    constitutional germinal mutation      
    might cause iron overload with severe juvenile hemochromatosis
    tumoral     --over  
    in prostate cancer and associated with bone forming skeletal metastasis
    constitutional     --low  
    in RPE cells in early AMD may contribute to iron build-up in age-related macular degeneration (AMD)
    constitutional     --low  
    decreased hepcidin levels, and increased hepatic iron
    Susceptibility to drepanocytosis with reduced gravity (increasing HBF level)
    Variant & Polymorphism SNP SNP associated with paucisymptomatic drepanocyosis
    Candidate gene
    Marker
  • BMP6 activity could be used as a prognostic indicator in prostate, bladder and colorectal cancers
  • BMP6, NOG and SOST could be used in combination as a prognostic indicator in cancer progression
    • Therapy target
    ANIMAL & CELL MODELS
  • despite their severe iron overload, the livers of Bmp6-deficient mice have low levels of phosphorylated Smad1, Smad5 and Smad8, and these Smads are not significantly translocated to the nucleus
  • Bmp6(-/-) mice had age-dependent retinal iron accumulation and degeneration