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SMAD2 Gene

protein-coding   GIFtS: 70
GCID: GC18M045357

SMAD Family Member 2

(Previous names: MAD, mothers against decapentaplegic homolog 2 (Drosophila),...)
(Previous symbol: MADH2)
  See SMAD2-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
SMAD Family Member 21 2 3     SMAD, Mothers Against DPP Homolog 2 (Drosophila)1
MADH21 2 3 5     Mother Against DPP Homolog 22
JV18-12 3     Mothers Against Decapentaplegic Homolog 22
MADR22 3     Sma- And Mad-Related Protein 22
hMAD-22 3     SMAD, Mothers Against DPP Homolog 22
hSMAD22 3     Smad23
MAD Homolog 22 3     Mad-Related Protein 23
JV182 5     Mothers Against DPP Homolog 23
MAD, Mothers Against Decapentaplegic Homolog 2 (Drosophila)1     SMAD 23

External Ids:    HGNC: 67681   Entrez Gene: 40872   Ensembl: ENSG000001753877   OMIM: 6013665   UniProtKB: Q157963   

Export aliases for SMAD2 gene to outside databases

Previous GC identifers: GC18M043620 GC18M043621 GC18M042208


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for SMAD2 Gene:
The protein encoded by this gene belongs to the SMAD, a family of proteins similar to the gene products of the
Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. SMAD proteins are signal
transducers and transcriptional modulators that mediate multiple signaling pathways. This protein mediates the
signal of the transforming growth factor (TGF)-beta, and thus regulates multiple cellular processes, such as cell
proliferation, apoptosis, and differentiation. This protein is recruited to the TGF-beta receptors through its
interaction with the SMAD anchor for receptor activation (SARA) protein. In response to TGF-beta signal, this
protein is phosphorylated by the TGF-beta receptors. The phosphorylation induces the dissociation of this protein
with SARA and the association with the family member SMAD4. The association with SMAD4 is important for the
translocation of this protein into the nucleus, where it binds to target promoters and forms a transcription
repressor complex with other cofactors. This protein can also be phosphorylated by activin type 1 receptor
kinase, and mediates the signal from the activin. Alternatively spliced transcript variants have been observed
for this gene. (provided by RefSeq, May 2012)

GeneCards Summary for SMAD2 Gene:
SMAD2 (SMAD family member 2) is a protein-coding gene. Diseases associated with SMAD2 include melorheostosis, and osteopoikilosis. GO annotations related to this gene include transcription factor binding and sequence-specific DNA binding transcription factor activity. An important paralog of this gene is SMAD3.

UniProtKB/Swiss-Prot: SMAD2_HUMAN, Q15796
Function: Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional
modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE
element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD2/SMAD4
complex, activates transcription. May act as a tumor suppressor in colorectal carcinoma. Positively regulates
PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative
regulator

Gene Wiki entry for SMAD2 (Mothers against decapentaplegic homolog 2) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000018.9  NT_010966.15  NC_018929.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the SMAD2 gene promoter:
         CREB   deltaCREB   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidSMAD2 promoter sequence
   Search Chromatin IP Primers for SMAD2

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat SMAD2


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 18q21.1   Ensembl cytogenetic band:  18q21.1   HGNC cytogenetic band: 18q21

SMAD2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
SMAD2 gene location

GeneLoc information about chromosome 18         GeneLoc Exon Structure

GeneLoc location for GC18M045357:  view genomic region     (about GC identifiers)

Start:
45,357,922 bp from pter      End:
45,457,515 bp from pter
Size:
99,594 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: SMAD2_HUMAN, Q15796 (See protein sequence)
Recommended Name: Mothers against decapentaplegic homolog 2  
Size: 467 amino acids; 52306 Da
Subunit: Momomer; the absence of TGF-beta. Heterodimer; in the presence of TGF-beta. Forms a heterodimer with
co-SMAD, SMAD4, in the nucleus to form the transactivation complex SMAD2/SMAD4. Interacts with AIP1, HGS, PML and
WWP1 (By similarity). Interacts with NEDD4L in response to TGF-beta (By similarity). Found in a complex with
SMAD3 and TRIM33 upon addition of TGF-beta. Interacts with ACVR1B, SMAD3 and TRIM33. Interacts (via the MH2
domain) with ZFYVE9; may form trimers with the SMAD4 co-SMAD. Interacts with FOXH1, homeobox protein TGIF,
PEBP2-alpha subunit, CREB-binding protein (CBP), EP300, SKI and SNW1. Interacts with SNON; when phosphorylated at
Ser-465/467. Interacts with SKOR1 and SKOR2. Interacts with PRDM16. Interacts (via MH2 domain) with LEMD3.
Interacts with RBPMS. Interacts with WWP1. Interacts (dephosphorylated form, via the MH1 and MH2 domains) with
RANBP3 (via its C-terminal R domain); the interaction results in the export of dephosphorylated SMAD3 out of the
nucleus and termination ot the TGF-beta signaling. Interacts with PDPK1 (via PH domain). Interacts with DAB2; the
interactions are enhanced upon TGF-beta stimulation. Interacts with USP15. Interacts with PPP5C. Interacts with
ZNF580
4 PDB 3D structures from and Proteopedia for SMAD2:
1DEV (3D)        1KHX (3D)        1U7V (3D)        2LB3 (3D)    
Alternative splicing: 2 isoforms:  Q15796-1   Q15796-2   

Explore the universe of human proteins at neXtProt for SMAD2: NX_Q15796

Explore proteomics data for SMAD2 at MOPED

Post-translational modifications: 

  • Phosphorylated on one or several of Thr-220, Ser-245, Ser-250, and Ser-255. In response to TGF-beta,
    phosphorylated on Ser-465/467 by TGF-beta and activin type 1 receptor kinases. TGF-beta-induced Ser-465/467
    phosphorylation declines progressively in a SETD8-dependent manner. Able to interact with SMURF2 when
    phosphorylated on Ser-465/467, recruiting other proteins, such as SNON, for degradation. In response to decorin,
    the naturally occurring inhibitor of TGF-beta signaling, phosphorylated on Ser-240 by CaMK2. Phosphorylated by
    MAPK3 upon EGF stimulation; which increases transcriptional activity and stability, and is blocked by calmodulin.
    Phosphorylated by PDPK11
  • In response to TGF-beta, ubiquitinated by NEDD4L; which promotes its degradation (By similarity).
    Monoubiquitinated, leading to prevent DNA-binding. Deubiquitination by USP15 alleviates inhibition and promotes
    activation of TGF-beta target genes1
  • Acetylated on Lys-19 by coactivators in response to TGF-beta signaling, which increases transcriptional activity.
    Isoform short: Acetylation increases DNA binding activity in vitro and enhances its association with target
    promoters in vivo. Acetylation in the nucleus by EP300 is enhanced by TGF-beta1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See SMAD2 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (3 alternative transcripts): 
    NP_001003652.1  NP_001129409.1  NP_005892.1  

    ENSEMBL proteins: 
     ENSP00000262160   ENSP00000384449   ENSP00000466193   ENSP00000467075   ENSP00000466254  
     ENSP00000465355   ENSP00000468202   ENSP00000465971   ENSP00000468732   ENSP00000349282  
    Reactome Protein details: Q15796

    SMAD2 Human Recombinant Protein Products:

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    Novus Biologicals SMAD2 Proteins
    Novus Biologicals SMAD2 Lysates
    Browse Sino Biological Recombinant Proteins
    Sino Biological Cell Lysate for SMAD2
    ProSpec Recombinant Protein for SMAD2
    Browse Proteins at Cloud-Clone Corp.

     
    Search eBioscience for Proteins for SMAD2 

    SMAD2 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of SMAD2
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    Abcam antibodies for SMAD2 (Q99717, Q15796, P84022)
    Browse Antibodies at Cloud-Clone Corp.
    ThermoFisher Antibody for SMAD2
    LSBio Antibodies in human, mouse, rat for SMAD2

    SMAD2 Assay Products:

    Browse Kits and Assays available from EMD Millipore
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    Browse Enzo Life Sciences for kits & assays
    Browse ELISAs at Cloud-Clone Corp.
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    Search eBioscience for ELISAs for SMAD2 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    SMAD: SMADs

    Selected InterPro protein domains (see all 6):
     IPR013019 MAD_homology_MH1
     IPR008984 SMAD_FHA_domain
     IPR001132 SMAD_dom_Dwarfin-type
     IPR017855 SMAD_dom-like
     IPR013790 Dwarfin

    Graphical View of Domain Structure for InterPro Entry Q15796

    ProtoNet protein and cluster: Q15796

    1 Blocks protein domain: IPB001132 Dwarfin protein

    UniProtKB/Swiss-Prot: SMAD2_HUMAN, Q15796
    Similarity: Belongs to the dwarfin/SMAD family
    Similarity: Contains 1 MH1 (MAD homology 1) domain
    Similarity: Contains 1 MH2 (MAD homology 2) domain


    Find genes that share domains with SMAD2           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: SMAD2_HUMAN, Q15796
    Function: Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional
    modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE
    element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD2/SMAD4
    complex, activates transcription. May act as a tumor suppressor in colorectal carcinoma. Positively regulates
    PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative
    regulator

         Gene Ontology (GO): Selected molecular function terms (see all 17):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003677contributes to DNA binding IDA9389648
    GO:0003682chromatin binding IEA--
    GO:0003690double-stranded DNA binding ISS--
    GO:0003700contributes to sequence-specific DNA binding transcription factor activity IDA17438144
    GO:0005160transforming growth factor beta receptor binding IPI9311995
         
    Find genes that share ontologies with SMAD2           About GenesLikeMe


    Phenotypes:
         3 GenomeRNAi human phenotypes for SMAD2:
     Increased gamma-H2AX phosphory  Increased mitotic index  Upregulation of Wnt/beta-caten 

         Selected MGI mutant phenotypes (inferred from 21 alleles(MGI details for Smad2) (see all 22):
     behavior/neurological  cardiovascular system  cellular  craniofacial  digestive/alimentary 
     embryogenesis  endocrine/exocrine gland  growth/size/body  hematopoietic system  homeostasis/metabolism 
     immune system  integument  liver/biliary system  mortality/aging  nervous system 

    Find genes that share phenotypes with SMAD2           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for SMAD2: Smad2tm2.1Rob Smad2tm1Cxd Smad2tm1.2Epb Smad2tm1Enl Smad2tm3Rob Smad2tm1.2Mwst
                                                         Smad2tm1Kato Smad2tm1.3Mwst Smad2tm1Rob Smad2tm1Rak Smad2tm1.3Epb

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for SMAD2
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       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for SMAD2
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for SMAD2

    Transcription Factor Targeting: 
    Targeting motifs: HOMER Transcription Factor Regulatory Elements motif viewer 
                                          Consensus sequence:  CTGTCTGG 

    miRNA
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    miRTarBase miRNAs that target SMAD2:
    hsa-mir-200a-3p (MIRT007290), hsa-mir-155-5p (MIRT005872), hsa-mir-200b-3p (MIRT007322), hsa-mir-484 (MIRT042141), hsa-mir-324-5p (MIRT043212), hsa-mir-652-3p (MIRT039468)

    Block miRNA regulation of human, mouse, rat SMAD2 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate SMAD2 (see all 180):
    hsa-miR-128 hsa-miR-4305 hsa-miR-4275 hsa-miR-149 hsa-miR-1243 hsa-miR-200b hsa-miR-509-3-5p hsa-miR-520b
    Browse SwitchGear 3'UTR luciferase reporter plasmids
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    GenScript: all cDNA clones in your preferred vector (see all 3): SMAD2 (NM_001135937)
    Sino Biological Human cDNA Clone for SMAD2
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    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat SMAD2
    Addgene plasmids for SMAD2 

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    eBioscience FlowRNA Probe Sets ( VA1-12082) for SMAD2 


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    SMAD2_HUMAN, Q15796: Cytoplasm. Nucleus. Note=Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta
    stimulation, migrates to the nucleus when complexed with SMAD4. On dephosphorylation by phosphatase PPM1A,
    released from the SMAD2/SMAD4 complex, and exported out of the nucleus by interaction with RANBP1
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    nucleus5
    cytosol4
    extracellular3
    cytoskeleton2
    mitochondrion2
    plasma membrane2
    endoplasmic reticulum1
    endosome1
    peroxisome1

    Gene Ontology (GO): Selected cellular component terms (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005622intracellular ----
    GO:0005634nucleus IDA12411310
    GO:0005654nucleoplasm TAS--
    GO:0005667transcription factor complex IDA17438144
    GO:0005737cytoplasm IDA12411310

    Find genes that share ontologies with SMAD2           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for SMAD2 About   (see all 41)  
    See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1Loss of Function of SMAD2/3 in Cancer
    Transcriptional activity of SMAD2/SMAD3-SMAD4 heterotrimer0.72
    TGFBR2 Kinase Domain Mutants in Cancer0.60
    SMAD2/SMAD3-SMAD4 heterotrimer regulates transcription0.72
    Signaling by TGF-beta Receptor Complex0.60
    Loss of Function of SMAD2/3 in Cancer0.60
    TGFBR1 KD Mutants in Cancer0.60
    TGFBR2 MSI Frameshift Mutants in Cancer0.60
    SMAD2/3 MH2 Domain Mutants in Cancer0.60
    2TGF-beta receptor signaling activates SMADs
    Downregulation of TGF-beta receptor signaling0.82
    TGF-beta receptor signaling activates SMADs0.82
    3Gene Expression
    Generic Transcription Pathway0.40
    Gene Expression0.40
    4Signaling by NODAL
    Signaling by NODAL0.39
    Signaling by Activin0.39
    5Prostate Cancer
    Prostate Cancer0.32
    Integrated Cancer pathway0.32


    Find genes that share SuperPaths with SMAD2           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    2 R&D Systems Pathways for SMAD2
        Th17 Differentiation
    TGF-beta Signaling Pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for SMAD2 (see all 10)
        Factors Promoting Cardiogenesis in Vertebrates
    Molecular Mechanisms of Cancer
    JAK-STAT Pathway
    TGF-Beta Pathway
    TOB in T-Cell Signaling

    1 Cell Signaling Technology (CST) Pathway for SMAD2
        TGF-beta/Smad Signaling

    5 GeneGo (Thomson Reuters) Pathways for SMAD2
        Signal transduction Activin A signaling regulation
    Cell cycle Regulation of G1/S transition (part 1)
    Development Role of Activin A in cell differentiation and proliferation
    Cytokine production by Th17 cells in CF (Mouse model)
    Development TGF-beta receptor signaling

    Selected BioSystems Pathways for SMAD2 (see all 13)
        TGF Beta Signaling Pathway
    EGFR1 Signaling Pathway
    Integrated Breast Cancer Pathway
    AGE/RAGE pathway
    TGF-beta Receptor Signaling Pathway

    1 Sino Biological Pathway for SMAD2
        TGF-beta Signaling Pathway

    Selected Reactome Pathways for SMAD2 (see all 10)
        TGF-beta receptor signaling activates SMADs
    SMAD2/3 MH2 Domain Mutants in Cancer
    SMAD4 MH2 Domain Mutants in Cancer
    Signaling by Activin
    Downregulation of SMAD2/3:SMAD4 transcriptional activity


    Selected Kegg Pathways  (Kegg details for SMAD2) (see all 13):
        FoxO signaling pathway
    Cell cycle
    Endocytosis
    TGF-beta signaling pathway
    Hippo signaling pathway

        Pathway & Disease-focused RT2 Profiler PCR Arrays including SMAD2 (see all 8): 
              Osteogenesis in human mouse rat
              Fibrosis in human mouse rat
              Stem Cell Transcription Factors in human mouse rat
              TGFB/BMP Signaling Pathway in human mouse rat
              Stem Cell Signaling in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for SMAD2

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for SMAD2 (Q157961, 2, 3 ENSP000002621604) via UniProtKB, MINT, STRING, and/or I2D (see all 510)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    ENSG00000237724P081073, ENSP000004063594I2D: score=1 STRING: ENSP00000406359
    ENSG00000212866P081073I2D: score=1 
    ENSG00000215328P081073I2D: score=1 
    ENSG00000224501P081073I2D: score=1 
    ENSG00000231555P081073I2D: score=1 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 49):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000122negative regulation of transcription from RNA polymerase II promoter TAS--
    GO:0001657ureteric bud development IEA--
    GO:0001701in utero embryonic development IEA--
    GO:0001706endoderm formation IEA--
    GO:0001707mesoderm formation ISS--

    Find genes that share ontologies with SMAD2           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for SMAD2

    1 DrugBank Compound for SMAD2    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    Phosphonoserine-- --target--10592235

    Selected Novoseek inferred chemical compound relationships for SMAD2 gene (see all 33)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    tgf beta1 77.4 37 16949833 (4), 11424093 (2), 16253118 (2), 17469181 (2) (see all 24)
    asiaticoside 59.2 6 15323444 (2), 18201262 (2), 16557473 (2)
    threonine 58.9 4 15210694 (1), 17270292 (1), 11106403 (1), 15702493 (1)
    sb 203580 56.3 7 17124250 (2), 18471442 (1), 18583311 (1), 19397700 (1) (see all 6)
    pd 98,059 51.9 4 17124250 (2), 10652224 (1), 15372629 (1)
    serine 51.8 15 15210694 (3), 15522964 (1), 17270292 (1), 11278410 (1) (see all 11)
    sphingosylphosphorylcholine 32.9 12 17481939 (3), 17105765 (3)
    tranilast 30.3 4 16528248 (3), 16284627 (1)
    procollagen 23 1 17051103 (1)
    leptomycin b 20.7 2 11074002 (1), 12547835 (1)



    Find genes that share compounds with SMAD2           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for SMAD2 gene (3 alternative transcripts): 
    NM_001003652.3  NM_001135937.2  NM_005901.5  

    Unigene Cluster for SMAD2:

    SMAD family member 2
    Hs.12253  [show with all ESTs]
    Unigene Representative Sequence: NM_001003652
    12 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000262160(uc002lcy.3) ENST00000402690(uc002lcz.3) ENST00000586040
    ENST00000591214 ENST00000587353 ENST00000587269 ENST00000586514 ENST00000587421
    ENST00000586487 ENST00000589877 ENST00000585978 ENST00000356825(uc010xdc.2 uc010xdd.1)

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    Addgene plasmids for SMAD2 
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    Additional mRNA sequence: 

    AF027964.1 AK126373.1 AK312963.1 AY134745.1 BC014840.1 BC025699.1 BT007422.1 U59911.1 
    U65019.1 U68018.1 

    16 DOTS entries:

    DT.454498  DT.97809192  DT.100816065  DT.97822192  DT.95369913  DT.121097527  DT.100022688  DT.65284280 
    DT.100816060  DT.100800384  DT.101973205  DT.121097501  DT.121097530  DT.91996304  DT.95171474  DT.100816063 

    Selected AceView cDNA sequences (see all 247):

    AA418737 BU172569 BX426272 CD517923 BM874660 NM_001003652 AW207900 AA836967 
    BQ639008 AW243896 BM454449 AA594363 AL555419 AA418792 AI360313 BI832799 
    AA877333 BX455722 AA406238 R82670 BM721481 BM823882 AA283890 BM479698 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for SMAD2 (see all 13)    About this scheme

    ExUns: 1a · 1b · 1c · 1d ^ 2a · 2b · 2c · 2d ^ 3 ^ 4 ^ 5a · 5b ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10a · 10b · 10c ^ 11a · 11b · 11c ^ 12 ^ 13 ^ 14 ^
    SP1:                          -     -     -     -     -     -     -     -                 -     -                                         -                     
    SP2:                                            -     -     -     -     -                 -     -                                         -                     
    SP3:                          -     -     -     -     -     -     -     -     -     -     -     -                                         -                     
    SP4:                                                                                      -     -                                                               
    SP5:                                                                                      -     -                                                               

    ExUns: 15 ^ 16 ^ 17a · 17b
    SP1:                        
    SP2:                        
    SP3:                        
    SP4:                        
    SP5:                        


    ECgene alternative splicing isoforms for SMAD2

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

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    SMAD2 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: ATCCAGTATC
    SMAD2 Expression
    About this image


    SMAD2 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 11) fully expand
     
     Primitive Streak (Early Embryo)    fully expand to see all 3 entries
             Primitive Streak Cells Anterior Primitive Streak
     
     Epiblast (Early Embryo)    fully expand to see all 2 entries
             Primitive Streak Cells Anterior Primitive Streak
     
     Endoderm (Gastrulation Derivatives)
             Endoderm Progenitor Cells Anterior Primitive Streak
     
     Brain (Nervous System)    fully expand to see all 2 entries
             Midbrain tegmentum
     
     Neural Tube (Nervous System)
             Mesencephalic Roof Plate
    SMAD2 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    SMAD2 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.12253

    UniProtKB/Swiss-Prot: SMAD2_HUMAN, Q15796
    Tissue specificity: Expressed at high levels in skeletal muscle, endothelial cells, heart and placenta

        Pathway & Disease-focused RT2 Profiler PCR Arrays including SMAD2 (see all 8): 
              Osteogenesis in human mouse rat
              Fibrosis in human mouse rat
              Stem Cell Transcription Factors in human mouse rat
              TGFB/BMP Signaling Pathway in human mouse rat
              Stem Cell Signaling in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals.

    Orthologs for SMAD2 gene from Selected species (see all 17)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Smad21 , 5 MAD homolog 2 (Drosophila)5
    SMAD family member 21
    92.22(n)1
    99.57(a)1
      18 (51.42 cM)5
    171261  NM_010754.51  NP_034884.21 
     762415805 
    chicken
    (Gallus gallus)
    Aves SMAD21 SMAD family member 2 85.3(n)
    99.36(a)
      395247  NM_204561.1  NP_989892.1 
    lizard
    (Anolis carolinensis)
    Reptilia SMAD26
    SMAD family member 2
    74(a)
    1 ↔ 1
    GL343467.1(315873-333517)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.852 Xenopus laevis Mad2 mRNA, complete cds 84.96(n)    L77885.1 
    zebrafish
    (Danio rerio)
    Actinopterygii madh22 MAD homolog 2 (Drosophila) 79.93(n)   30639  AF229022.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta Smox6
    Smad on X
    62(a)
    1 → many
    X(8032424-8036301)
    worm
    (Caenorhabditis elegans)
    Secernentea sma-26
    Protein SMA-2 (sma-2) mRNA, complete cds
    50(a)
    1 → many
    III(8749771-8757069) WBGene00004856


    ENSEMBL Gene Tree for SMAD2 (if available)
    TreeFam Gene Tree for SMAD2 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for SMAD2 gene
    SMAD32  SMAD12  SMAD62  SMAD52  SMAD42  SMAD92  SMAD72  
    6 SIMAP similar genes for SMAD2 using alignment to 7 protein entries:     SMAD2_HUMAN (see all proteins):
    SMAD3    DKFZp781O1323    MADH5    SMAD9    SMAD5    SMAD1

    Find genes that share paralogs with SMAD2           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for SMAD2 (see all 2133)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 18 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0113774
    A colorectal carcinoma sample4--see VAR_0113772 L R mis40--------
    VAR_0364734
    A colorectal cancer sample4--see VAR_0364732 D V mis40--------
    VAR_0113784
    A colorectal carcinoma sample4--see VAR_0113782 P H mis40--------
    VAR_0113754
    A colorectal carcinoma sample4--see VAR_0113752 R C mis40--------
    VAR_0113794
    A colorectal carcinoma sample4--see VAR_0113792 D E mis40--------
    rs2003735871,2
    --42219695(+) GAAGA-/ACAAAAA 3 -- int10--------
    rs178139081,2
    C,F,H--42219696(+) AAGAAC/AAAAAA 3 -- int18Minor allele frequency- A:0.26NA NS EA 498
    rs577463251,2
    C--42219696(+) AAGAA-/CAAAAA 3 -- int10--------
    rs741720781,2
    C--42225207(+) GTATG-/TATA  
     
    /TATATA
    TATAT
    3 -- int11NA 2
    rs779149021,2
    C--42262711(+) ATATGC/AAAAAA 3 -- int11Minor allele frequency- A:0.50NA 2

    HapMap Linkage Disequilibrium report for SMAD2 (45357922 - 45457515 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 8 variations for SMAD2:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2667321CNV Deletion23128226
    esv2717053CNV Deletion23290073
    esv2627568CNV Deletion19546169
    esv1323042CNV Insertion17803354
    nsv2288CNV Insertion18451855
    nsv909615CNV Loss21882294
    nsv132205CNV Loss16902084
    nsv909614CNV Loss21882294

    Human Gene Mutation Database (HGMD): SMAD2
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing SMAD2
    DNA2.0 Custom Variant and Variant Library Synthesis for SMAD2

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 601366    OMIM disorders: --

    5 diseases for SMAD2:    
    About MalaCards
    melorheostosis    osteopoikilosis    ureteral disease    nephrogenic systemic fibrosis
    colorectal cancer

    4 diseases from the University of Copenhagen DISEASES database for SMAD2:
    Ureteral disease     Pulmonary fibrosis     Kidney disease     Carcinoma

    Find genes that share disorders with SMAD2           About GenesLikeMe

    Selected Novoseek inferred disease relationships for SMAD2 gene (see all 50)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    pancreatic cancer 52.3 7 10505717 (5), 15249209 (1), 10781087 (1)
    keloid 49.7 11 17051103 (4), 17144456 (2), 15453837 (1), 15978417 (1) (see all 5)
    tumors 39.9 74 11391794 (4), 12894231 (3), 10781087 (3), 11438451 (3) (see all 45)
    cancer 38.1 29 10505717 (2), 12237237 (2), 9006934 (2), 9264367 (1) (see all 23)
    scars hypertrophic 37.3 7 11955370 (5), 18616749 (1)
    colorectal cancer 34.8 22 15711891 (2), 9635866 (2), 12967141 (2), 9264367 (1) (see all 13)
    pancreatic carcinoma 29.1 9 9892110 (2), 12140283 (1)
    adenocarcinoma clear cell 26.4 2 16820918 (1)
    gastric carcinoma 23.4 4 10073143 (2), 19351925 (1), 15067346 (1)
    sclerosis systemic 21.6 1 20430497 (1)

    Genetic Association Database (GAD): SMAD2
    Human Genome Epidemiology (HuGE) Navigator: SMAD2 (20 documents)

    Export disorders for SMAD2 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for SMAD2 gene, integrated from 10 sources (see all 800):
    (articles sorted by number of sources associating them with SMAD2)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Mad-related genes in the human. (PubMed id 8673135)1, 2, 3 Riggins G.J.... Vogelstein B.V. (Nat. Genet. 1996)
    2. MADR2 maps to 18q21 and encodes a TGFbeta-regulated MAD-related protein that is functionally mutated in colorectal carcinoma. (PubMed id 8752209)1, 2, 3 Eppert K.... Attisano L. (Cell 1996)
    3. Modulation of Smad2-mediated signaling by extracellular signal- regulated kinase. (PubMed id 12193595)1, 2, 9 Funaba M.... Mathews L.S. (J. Biol. Chem. 2002)
    4. Potentiation of Smad-mediated transcriptional activation by the RNA- binding protein RBPMS. (PubMed id 17099224)1, 2, 9 Sun Y.... Ye Q. (Nucleic Acids Res. 2006)
    5. Alternatively spliced variant of Smad2 lacking exon 3. Comparison with wild-type Smad2 and Smad3. (PubMed id 9873005)1, 2, 9 Yagi K.... Miyazono K. (J. Biol. Chem. 1999)
    6. SARA, a FYVE domain protein that recruits Smad2 to the TGFbeta receptor. (PubMed id 9865696)1, 2, 9 Tsukazaki T.... Wrana J.L. (Cell 1998)
    7. Characterization of the MADH2/Smad2 gene, a human Mad homolog responsible for the transforming growth factor-beta and activin signal transduction pathway. (PubMed id 9503010)1, 2, 9 Takenoshita S.... Hagiwara K. (Genomics 1998)
    8. Dual role of the Smad4/DPC4 tumor suppressor in TGFbeta-inducible transcriptional complexes. (PubMed id 9389648)1, 2, 9 Liu F.... Massague J. (Genes Dev. 1997)
    9. MADR2 is a substrate of the TGFbeta receptor and its phosphorylation is required for nuclear accumulation and signaling. (PubMed id 8980228)1, 2, 9 Macias-Silva M....Wrana J.L. (Cell 1996)
    10. Nuclear export of Smad2 and Smad3 by RanBP3 facilitates termination of TGF-beta signaling. (PubMed id 19289081)1, 2, 9 Dai F.... Feng X.H. (Dev. Cell 2009)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 4087 HGNC: 6768 AceView: SMAD2 Ensembl:ENSG00000175387 euGenes: HUgn4087
    ECgene: SMAD2 Kegg: 4087 H-InvDB: SMAD2

    (According to HUGE)
    About This Section

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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for SMAD2 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for SMAD2 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section

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    Patent Information for SMAD2 gene:
    Search GeneIP for patents involving SMAD2

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, eBioscience, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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