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FLASH GENE
Symbol SMAD6 contributors: mct/pgu - updated : 23-02-2015
HGNC name SMAD family member 6
HGNC id 6772
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
4 - 2886 - 496 - 2008 19032685
  • isoform 1
  • 4 - 1293 - 235 - 2008 19032685
  • isoform 2, SMAD6s
  • possessing a different N-terminus
  • - splicing - - - in human prostatic cell lines 2008 19032685
  • exhibits a truncated C-terminus lacking the entire MH-2 domain and most parts of the linker region
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Reproductivemale systemtestis  highly Homo sapiens
    Respiratorylung   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier/lining   
    Muscularstriatumcardiac  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell
    Reproductivespermatid Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    Text ubiquitous during testis development but becomes cell-specific in the adult
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • Dwarfin (DWA)/MH1 DNA binding domain including a nuclear localization-like signal (NLS-L)
  • a double loop region
  • a linker region and a DWB/MH2 heterodimerization and transactivation domain
  • mono polymer complex
    HOMOLOGY
    interspecies homolog to murine Smad6 (94.3pc)
    homolog to rattus Smad6 (94.7pc)
    Homologene
    FAMILY
  • dwarfin/SMAD family
  • CATEGORY regulatory , transcription factor , receptor membrane serine/threonine
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text ligand induced nuclear translocation
    basic FUNCTION
  • signal transducer and transcriptional modulator that mediate multiple signaling pathways
  • with PRKX are required for PMA-induced cell attachment and spreading
  • signal-transduction protei
  • involved in the inhibition of TGFB/BMP signaling pathway by competing with MADH4 for receptor activated MADH1
  • facilitates the degradation of TBX6 through recruitment of SMURF1, reducing TBX6-mediated Myf5 gene activation
  • associated with a reduced survival in lung cancer patients, playing a critical role in supporting lung cancer cell growth and survival and its targeted inactivation may provide a novel therapeutic strategy for lung cancer expressing SMAD6
  • negatively regulating IL-1R-Toll-like receptor signals and promoting TGB-beta-mediated anti-inflammatory effects
  • enhancing SMURF1-induced RUNX2 degradation in an ubiquitin-proteasome-dependent manner
  • regulating glucocorticoid actions as a corepressor of the glucocorticoid receptor and may contribute to the neuroprotective, anticatabolic and pro wound healing properties of the TGFbeta family of proteins
  • required for promoting neuronal progenitor cells to exit the cell cycle and differentiate into neurons
  • promotes neuronal differentiation by inhibiting both the BMP and the Wnt/beta catenin pathways in the developing dorsal spinal cord
  • indirectly maintains stemness by preventing spontaneous erythropoiesis in hematopoietic stem cells (HSCs)
  • UBE2O and SMAD6 cooperated in the regulation of BMP7-induced adipogenesis
  • is a regulatory molecule which regulates the proliferation, self-renewal and WNT/CTNNB1 signaling in hepatic progenitor cells (HPCs)
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling signal transduction
    TGFB, BMP
    a component
  • complexing with MADH7 in endothelial cells
  • INTERACTION
    DNA binding to regulatory elements in target promoter regions
    RNA
    small molecule
    protein
  • HOXC8, HOXA9
  • playing a modulatory role in the regulation of Dlx3-dependent gene transcription within placental trophoblasts
  • interacting with TBX6
  • interacting with NEDD4L
  • interacting with RNF111 and AXIN1
  • interacting with TGF-beta type I receptor superfamily members SMAD1, HOXC8, HOXC9
  • interacts with STAMBP, PRKX
  • interacting with SMURF1, RUNX2
  • binding to PELI1
  • ADP-ribosylation of SMAD proteins by PARP1 is a key step in controlling the strength and duration of SMAD-mediated transcription
  • RUNX1 in conjunction with FLI1, GATA2, and TAL1, directly regulates the expression of SMAD6 in the aorta-gonad-mesonephros (AGM) region in the developing embryo
  • PIN1 controls SMAD6 function
  • UBE2O is a novel interacting protein of SMAD6 and potentiated BMP7 signalling in a SMAD6-dependent manner
  • inhibits non-canonical TGFB1 signalling by recruiting the deubiquitinase TNFAIP3 to TRAF6
  • melatonin plays a role in the regulation of BMP6 signal intensity for controlling progesterone production in the ovary
  • ZDHHC13 regulates fate specification of ectoderm and mesoderm cell lineages by modulating SMAD6 activity 7)
  • cell & other
    REGULATION
    activated by an OAZ-SMAD1/4 complex upon BMP4 stimulation
    induced by TGFB in cooperation with MADH2,MADH3,MADH4
    Other
  • phosphorylated by BMP type 1 receptor kinase and by PRKX
  • ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in chronic obstructive pulmonary disease (COPD)by cigarette smocke
    constitutional     --low  
    down-regulated in lesional and non lesional psoriatic skin
    Susceptibility
  • to congenital cardiovascular malformation (CVM)
  • Variant & Polymorphism SNP
  • candidate for the genetic determinants of bone mineral density in postmenopausal women, SNP could be useful as a genetic marker for predicting the risk of osteoporosis
  • low-frequency deleterious variants in SMAD6 predispose to CVM
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS