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FLASH GENE
Symbol SMAD2 contributors: mct/npt/pgu - updated : 24-05-2017
HGNC name SMAD family member 2
HGNC id 6768
Location 18q21.1      Physical location : 45.359.466 - 45.457.515
Synonym name
  • MAD, mothers against decapentaplegic homolog 2 (Drosophila)
  • SMAD, mothers against DPP homolog 2 (Drosophila)
  • Mad-related protein 2
  • Sma- and Mad-related protein 2
  • MAD homolog 2
    • Synonym symbol(s) JV18, JV18-1, MADR2, MADH2, MGC22139, MGC34440
    DNA
    TYPE functioning gene
    STRUCTURE 98.05 kb     11 Exon(s)
    regulatory sequence cytosine-phosphate-guanine/HTF
    text structure two alternative exons 1 and two promoters
    MAPPING cloned Y linked N status confirmed
    Map see TSG18A
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 10384 32.3 467 - 1998 9503010
    11 - 10531 52.2 467 lacking exon 3 1998 9503010
    10 - 10444 48.8 437 - 1998 9503010
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Endocrineneuroendocrinepituitary  highly
    Hearing/Equilibriumear   highly
    Reproductivefemale systemuteruscervix highly
    Respiratoryrespiratory tractlarynx  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • Dwarfin (DWA)/MH1 DNA binding domain
  • a nuclear localization-like signal (NLS-L)
  • a double loop region, followed by a linker region
  • a DWB/MH2 heterodimerization and transactivation domain
    • mono polymer complex
    HOMOLOGY
    interspecies homolog to Drosophila Mad (mothers against dpp) gene JV18-1
    Homologene
    FAMILY
  • dwarfin/SMAD family
    • CATEGORY regulatory , transcription factor , receptor membrane serine/threonine
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    text
  • translocating to nucleus after binding to MADH4
  • nuclear when complexed with MADH4
    • basic FUNCTION
  • intracellular mediator of TGFB family of cytokines and activin type 1 receptor (ACVR1C)
  • act as an integrator of multiple signals in the regulation of NOS3 expression
  • key intracellular signal transducer for TGF-beta signaling, and its transcriptional activity is controlled through reversible phosphorylation and nucleocytoplasmic shuttling
  • SMAD2, but not SMAD3, is required to maintain the undifferentiated pluripotent state
  • is an important factor in regulating progenitor-specific Vascular smooth muscle cell (VSMC) development
  • SMAD2 and SMAD3 were redundantly essential for TGFB1 signaling to induce histone modifications for IL9 transcription
  • SMAD2 and SMAD3 cooperate and antagonize simultaneously in vertebrate neurogenesis
  • SMAD2 and SMAD3 are both necessary for the formation of lens posterior capsular opacification (PCO)
  • acts as a repressor upstream of the BECN1 promoter region
  • ENG is a critical mediator of autophagy, demonstrating a new transcriptional mechanism by which SMAD2 inhibits angiogenesis
  • SMAD2/3 transcription factor plays a central role in differentiation and survival of erythroid cells
  • is a critical determinant of mitochondrial dynamics
  • is a key scaffold, allowing RIN1 to act as a GTP exchange factor for MFN2-GTPase activation to promote mitochondrial ATP synthesis and suppress superoxide production
    • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    TGFB
    a component
  • complexing with FAST2, TGIF, RUNX2, CREBBP, EP300, SMURF2
    • INTERACTION
    DNA binding to ASE (asymetric enhancers) of NODAL and LEFTB
    RNA
    small molecule
    protein
  • binding to FOXH1
  • SARA
  • SKIL
  • interaction between SMAD2 and the CDC42 guanine nucleotide exchange factor, and Zizimin1, in response to TGF-beta1
  • ADP-ribosylation of SMAD proteins by PARP1 is a key step in controlling the strength and duration of SMAD-mediated transcription
  • TRIB3 triggering the degradation of SMAD ubiquitin regulatory factor 2 (SMURF2), which resulted in a decrease in the degradation of SMAD2 and phosphorylated SMAD3
  • expression of NPNT is regulated by the TGFBR1-SMAD2 signaling pathway in osteoblasts
  • interplay between the inhibitory SMAD7 and the intracellular mediators SMAD2/3 is likely a control point for pancreatic endocrine development
  • LEMD3 is an integral protein of the inner nuclear membrane, inhibiting TGFB1 signaling by binding to SMAD2 and SMAD3
  • IRF4 was essential for the SMAD2/3-mediated IL9 promoter activation
  • CASR interferes with TGFB1-dependent SMAD2 phosphorylation and induces its proteasomal degradation, resulting in a decrease of TGFB1-dependent transcriptional activity
  • SMAD2 overexpression inhibits the proliferation of junctional epithelium (JE) cells by down-regulating MYC and up-regulating CDKN2B and CDKN1B, which resulted in an increase in RB1, leading to cell-cycle arrest
  • SMAD2 and SMAD3 interact with each other to mediate transforming growth factor-beta (TGFB1)-triggered signaling transduction
  • SMAD2 suppressed the phosphorylation and nuclear translocation of SMAD3, which may protect against SMAD3-mediated fibrotic response
  • TCF3 is necessary to drive transcription of SMAD2/3 target genes, including critical regulators of dorsal cell fate and morphogenesis
  • is the major transcriptional regulator of autophagy that targets beclin1 (BECN1) gene expression
  • SH3KBP1 enhanced TGFB1-stimulated SMAD2 phosphorylation, transcriptional responses, and cell migration
  • FSTL1 attenuates differentiation and survival of erythroid cells through SMAD2/3 signaling
  • inactive cytoplasmic SMAD2 rapidly promotes mitochondrial fusion by recruiting RIN1 into a complex with MFN2
  • SENP1 attenuates the liver fibrosis through down-regulating the expression of SMAD2
  • ZFYVE16 binds to SMAD4 and their binding affects the formation of SMAD2/3-SMAD4 complex in TGFB1 signaling
  • TRIM33 is a modulator of TGFB1 signaling that associates with SMAD2, and regulates the proinflammatory function of Th17 cell
  • TGIF1 is a multifunctional protein that represses TGFB1-activated transcription by interacting with SMAD2-SMAD4 complexes
  • LMNA and EMD modulate KLK10, SMAD2 and BCL2L12 expression levels as well as the spatial positions of gene loci in the interphase nucleus
    • cell & other
    REGULATION
    activated by activin receptors in the NODAL pathway (ACVR2)
    Other undergoing phosphorylation
    post-translational modification of SMAD2 could be a mechanism for the action of PGE2 in the pathogenesis of human pathologies
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    in colorectal, hepatocellular and lung carcinomas
    tumoral   LOH    
    in cervical cancer
    constitutional     --over  
    ER stress in HSCs (Hepatic stellate cells) promotes liver fibrosis by inducing overexpression of SMAD2
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    digestiveliver 
    may be a potential therapeutic target for the treatment of hepatic fibrosis
    ANIMAL & CELL MODELS