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FLASH GENE
Symbol SMAD7 contributors: mct - updated : 24-06-2015
HGNC name SMAD family member 7
HGNC id 6773
Location 18q21.1      Physical location : 46.446.223 - 46.477.081
Synonym name
  • SMAD, mothers against DPP homolog 7 (Drosophila)
  • MAD, mothers against decapentaplegic homolog 7 (Drosophila)
  • MAD homolog 8
  • Synonym symbol(s) MADH7, MADH8, FLJ16482, CRCS3
    DNA
    TYPE functioning gene
    STRUCTURE 30.86 kb     4 Exon(s)
    regulatory sequence Promoter
    motif
    text structure palindromic Smad binding element
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 3088 - 426 - 2008 18762808
    4 - 3085 - 425 - 2008 18762808
    4 - 2293 - 211 - 2008 18762808
    2 - 2386 - 238 - 2008 18762808
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Endocrinethyroid   highly
    Nervousnerve   highly
    Respiratorylung   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivecartilage  highly
    Epithelialbarrier/lining   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell
    not specificchondrocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • Dwarfin (DWA)/MH1 DNA binding domain
  • a nuclear localization-like signal (NLS-L)
  • a double loop region
  • a linker region
  • a DWB/MH2 heterodimerization and transactivation domain, playing important roles in specific inhibition of TGF-beta superfamily signals through differential interaction with type I receptors
  • C-terminal MH2 region but not MH1 region is critical for interaction with CBL to inhibit the ubiquitination of EGFR
  • mono polymer complex
    HOMOLOGY
    interspecies homolog to Drosophila Mad (mothers against dpp) gene
    Homologene
    FAMILY
  • Dwarfin (DWA/B)/Smad family protein
  • CATEGORY adaptor , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    text ligand induced nuclear translocation; translocation to nucleus induced by TGFB
    basic FUNCTION
  • inhibiting MADH2 and MADH4 action
  • binding TGFB1 receptor and antagonizing TGFB signaling pathway
  • cooperates with MyoD, creating a positive loop to induce Smad7 expression and to promote MyoD driven myogenesis. Taken together, these data implicate Smad7 as a fundamental regulator of differentiation in skeletal muscle cells
  • intracellular mediator of TGFB family of cytokines
  • increasing resistance against TGFB-mediated apoptosis(substantial growth advantage for the tumor)
  • antagonistic SMAD
  • antagonizing activin pathway
  • negative regulator for the signaling of TGFB family members
  • adaptor in an E3 ubiquitin ligase complex targeting TGFBR for degradation
  • cooperates with MYOD1, creating a positive loop to induce SMAD7 expression and to promote MYOD1 driven myogenesis
  • being a fundamental regulator of differentiation in skeletal muscle cells
  • inhibits the phosphorylation of beta-catenin by interacting with Axin, modulating cell-cell adhesion and playing a role in inhibition of tumor metastasis
  • in prechondrogenic cells inhibits chondrocyte differentiation possibly by down-regulating BMP-activated MAPK14 pathways
  • inhibits chondrocyte differentiation and/or proliferation induced by TGFB or BMP
  • may be required for cardiac development in embryonic stage and cardiac function in adult
  • key negative regulator of TGFB signalling
  • TBX1 acts upstream of SMAD7 controlling vascular smooth muscle and extracellular matrix investment of the fourth arch artery
  • cell-intrinsic inhibitor of TGFB1 signaling, is sufficient to directly convert pluripotent hESCs to an anterior neural fate
  • is a negative regulator for TGFB1 signaling pathway through feedback regulation
  • novel role for SMAD7 as a transcriptional coactivator for CASP8 through the interaction with IRF1 in regulation of the cell death pathway
  • may be an important mediator for IFNG-induced CASP8 expression
  • SMAD7 may be required to mediate cell stress responses in the growth plate during development
  • functional role for SMAD7 in sustaining colon cancer cell growth and survival
  • novel key regulator between osteogenesis and osteoclastogenesis
  • enhances cell survival against DNA damage by accelerating ATM dependent DNA repair signaling
  • critical function of SMAD7 in DSB response
  • is a fundamental factor in the maintenance of epithelial growth of epithelial ovarian carcinoma (EOC) cells
  • is an important regulator of muscle growth
  • novel role of SMAD7 as promoter for prolonging the EGFR signal in keratinocyte and skin tissue by reducing its ligand-induced ubiquitination and degradation
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    TGFB
    a component
  • complexing with MADH6 in endothelial INFG
  • SMAD7-APC complex links the TGFBR1 to the microtubule system to regulate directed cellular extension and migratory responses evoked by TGFB1
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • IL1B induced SMAD7 negatively regulates gastrin expression
  • TSC22D1 facilitates TGFB1 signaling by antagonizing SMAD7 activity to increase receptor stability
  • SMAD7 and MAPK14 mitogen-activated protein kinase together regulate the expression of APC and cell migration in prostate cancer cells in response to TGFB1 stimulation
  • USP11 is an interactor of SMAD7, enhances TGFB1 signalling and can override the negative effects of SMAD7
  • TOLLIP interacts with SMAD7, a major modulatory protein involved in the negative regulation of TGFB signaling
  • TOLLIP cooperates with SMAD7 to modulate intracellular trafficking and degradation of ubiquitinated TGFBR1, whereby negatively regulates TGFB signaling pathway
  • SMAD7 was able to activate CASP8 promoter through recruitment of IRF1 transcription factor to the interferon-stimulated response element (ISRE) site
  • transcriptional activator through recruiting IRF1 transcription factor on the ISRE site of CASP8 promoter
  • interplay between the inhibitory SMAD7 and the intracellular mediators SMAD2/3 is likely a control point for pancreatic endocrine development
  • essential and non-redundant role for CBLB in controlling TGFBR signaling by directly targeting SMAD7 for degradation during T cell responses
  • promotes pancreatic beta-cell proliferation by increasing CCND1 and CCND2, and by inducing nuclear exclusion of CDKN1B
  • ITCH-mediated positive regulation of TGFB1 signaling was found to be dependent on SMAD7 ubiquitination and its subsequent degradation
  • inhibitory SMAD that blocks the signal transduction of TGFB1
  • cell & other
    REGULATION
    activated by inhibiting activity enhanced by SMURF2
    induced by IFNG
    can be transcriptionally induced by TGF-&
    946; and other growth factors and serves as an important cross-talk mediator of the TGFB signalling pathway with other signalling pathways
    Other transcription induced by TGF-beta through activation of MADH3 and MADH4 binding to its promoter (in mouse)
    poly-ubiquitinated by RNF111
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in pancreatic carcinomas
    constitutional     --other  
    aberrantly expressed in inflammatory bowel disease
    constitutional     --low  
    and MADH3 upregulated may be responsible of TGF-beta hyperresponsiveness in scleroderma
    tumoral   deletion    
    in colorectal cancers
    constitutional     --low  
    in chronic obstructive pulmonary disease (COPD)by cigarette smocke
    tumoral     --over  
    with ZEB1 downregulation, contribute to resistance to TGF-beta1-mediated growth suppression in ATLL(adult T-cell leukemia/lymphoma) )
    Susceptibility to familial colorectal tumor
    Variant & Polymorphism SNP increasing the risk of familial colorectal tumor
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    induction of SMAD7 expression can be used as a therapeutic approach for some cancers that have defects in CASP8 expression
    neuromuscularmyopathy 
    may be an important therapeutic target for muscle disorders
    ANIMAL & CELL MODELS
  • Smad7 mutant mice died in utero due to multiple defects in cardiovascular development, including ventricular septal defect and non-compaction, as well as outflow tract malformation
  • partial loss of Smad7 function in mice leads to compromised bone formation and enhanced bone resorption
  • Smad7(-/-) mice showed reduced muscle mass, hypotrophy and hypoplasia of muscle fibres, as well as an increase in oxidative fibre types