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SMAD7 Gene

protein-coding   GIFtS: 64
GCID: GC18M046446

SMAD Family Member 7

(Previous names: MAD, mothers against decapentaplegic homolog 7 (Drosophila),...)
(Previous symbols: MADH8, MADH7)
  See SMAD7-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 71 2 3     MAD (Mothers Against Decapentaplegic, Drosophila) Homolog 72
MADH71 2 3 5     Mothers Against Decapentaplegic Homolog 72
MADH81 2 3     Mothers Against Decapentaplegic, Drosophila, Homolog Of, 72
Mothers Against DPP Homolog 82 3     SMAD, Mothers Against DPP Homolog 72
hSMAD72 3     Smad73
MAD Homolog 82 3     MAD Homolog 73
CRCS32 5     Mothers Against Decapentaplegic Homolog 83
MAD, Mothers Against Decapentaplegic Homolog 7 (Drosophila)1     Mothers Against DPP Homolog 73
SMAD, Mothers Against DPP Homolog 7 (Drosophila)1     SMAD 73

External Ids:    HGNC: 67731   Entrez Gene: 40922   Ensembl: ENSG000001016657   OMIM: 6029325   UniProtKB: O151053   

Export aliases for SMAD7 gene to outside databases

Previous GC identifers: GC18M044699 GC18M044700 GC18M043299


(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 SMAD7 Gene:
The protein encoded by this gene is a nuclear protein that binds the E3 ubiquitin ligase SMURF2. Upon binding,
this complex translocates to the cytoplasm, where it interacts with TGF-beta receptor type-1 (TGFBR1), leading to
the degradation of both the encoded protein and TGFBR1. Expression of this gene is induced by TGFBR1. Variations
in this gene are a cause of susceptibility to colorectal cancer type 3 (CRCS3). Several transcript variants
encoding different isoforms have been found for this gene. (provided by RefSeq, Jun 2010)

GeneCards Summary for SMAD7 Gene:
SMAD7 (SMAD family member 7) is a protein-coding gene. Diseases associated with SMAD7 include colorectal cancer 3, and localized scleroderma. GO annotations related to this gene include sequence-specific DNA binding transcription factor activity and ubiquitin protein ligase binding. An important paralog of this gene is SMAD3.

UniProtKB/Swiss-Prot: SMAD7_HUMAN, O15105
Function: Antagonist of signaling by TGF-beta (transforming growth factor) type 1 receptor superfamily members;
has been shown to inhibit TGF-beta (Transforming growth factor) and activin signaling by associating with their
receptors thus preventing SMAD2 access. Functions as an adapter to recruit SMURF2 to the TGF-beta receptor
complex. Also acts by recruiting the PPP1R15A-PP1 complex to TGFBR1, which promotes its dephosphorylation.
Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which
acts as a negative regulator (By similarity)

Gene Wiki entry for SMAD7 (Mothers against decapentaplegic homolog 7) 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  NC_018929.2  NT_010966.15  
Regulatory elements:
   Regulatory transcription factor binding sites in the SMAD7 gene promoter:
         AhR   STAT1   Pax-5   HFH-1   p300   MyoD   HNF-4alpha1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidSMAD7 promoter sequence
   Search Chromatin IP Primers for SMAD7

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat SMAD7


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: 18q21.1

SMAD7 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
SMAD7 gene location

GeneLoc information about chromosome 18         GeneLoc Exon Structure

GeneLoc location for GC18M046446:  view genomic region     (about GC identifiers)

Start:
46,446,223 bp from pter      End:
46,477,081 bp from pter
Size:
30,859 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., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: SMAD7_HUMAN, O15105 (See protein sequence)
Recommended Name: Mothers against decapentaplegic homolog 7  
Size: 426 amino acids; 46426 Da
Subunit: Interacts with WWP1 (By similarity). Interacts with COPS5. Interacts with NEDD4L. Interacts with STAMBP.
Interacts with RNF111, AXIN1 and AXIN2. Interacts with PPP1R15A. Interacts (via MH2 domain) with EP300. Interacts
with ACVR1B, SMURF1, SMURF2 and TGFBR1; SMAD7 recruits SMURF1 and SMURF2 to the TGF-beta receptor and regulates
its degradation. Interacts with PDPK1 (via PH domain)
Selected PDB 3D structures from and Proteopedia for SMAD7 (see all 7):
2DJY (3D)        2KXQ (3D)        2LTV (3D)        2LTW (3D)        2LTX (3D)        2LTY (3D)    
Secondary accessions: B7Z773 K7EQ10 O14740 Q6DK23
Alternative splicing: 3 isoforms:  O15105-1   O15105-2   O15105-3   (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for SMAD7: NX_O15105

Explore proteomics data for SMAD7 at MOPED

Post-translational modifications: 

  • Phosphorylation on Ser-249 does not affect its stability, nuclear localization or inhibitory function in TGFB
    signaling; however it affects its ability to regulate transcription (By similarity). Phosphorylated by PDPK11
  • Ubiquitinated by WWP1 (By similarity). Polyubiquitinated by RNF111, which is enhanced by AXIN1 and promotes
    proteasomal degradation. In response to TGF-beta, ubiquitinated by SMURF1; which promotes its degradation1
  • Acetylation prevents ubiquitination and degradation mediated by SMURF11
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See SMAD7 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (4 alternative transcripts): 
    NP_001177750.1  NP_001177751.1  NP_001177752.1  NP_005895.1  

    ENSEMBL proteins: 
     ENSP00000262158   ENSP00000466902   ENSP00000467621   ENSP00000465590  
    Reactome Protein details: O15105

    SMAD7 Human Recombinant Protein Products:

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    Browse ProSpec Recombinant Proteins
    Browse Proteins at Cloud-Clone Corp.

     
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    antibodies-online proteins for SMAD7 (5 products) 

     
    antibodies-online peptides for SMAD7

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    antibodies-online antibodies for SMAD7 (46 products) 

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    (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 O15105

    ProtoNet protein and cluster: O15105

    1 Blocks protein domain: IPB001132 Dwarfin protein

    UniProtKB/Swiss-Prot: SMAD7_HUMAN, O15105
    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 SMAD7           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, 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: SMAD7_HUMAN, O15105
    Function: Antagonist of signaling by TGF-beta (transforming growth factor) type 1 receptor superfamily members;
    has been shown to inhibit TGF-beta (Transforming growth factor) and activin signaling by associating with their
    receptors thus preventing SMAD2 access. Functions as an adapter to recruit SMURF2 to the TGF-beta receptor
    complex. Also acts by recruiting the PPP1R15A-PP1 complex to TGFBR1, which promotes its dephosphorylation.
    Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which
    acts as a negative regulator (By similarity)
    Induction: By TGFB1

         Gene Ontology (GO): Selected molecular function terms (see all 11):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003700sequence-specific DNA binding transcription factor activity IEA--
    GO:0005515protein binding IPI14993265
    GO:0005518collagen binding IEA--
    GO:0008013beta-catenin binding IPI18593713
    GO:0030617transforming growth factor beta receptor, inhibitory cytoplasmic mediator activity IDA9256479
         
    Find genes that share ontologies with SMAD7           About GenesLikeMe


    Phenotypes:
         1 GenomeRNAi human phenotype for SMAD7:
     Proliferating cells 

         11 MGI mutant phenotypes (inferred from 5 alleles(MGI details for Smad7):
     behavior/neurological  cardiovascular system  cellular  growth/size/body  hematopoietic system 
     homeostasis/metabolism  immune system  integument  mortality/aging  muscle 
     reproductive system 

    Find genes that share phenotypes with SMAD7           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for SMAD7: Smad7tm1.1Shou Smad7tm1Rheu Smad7tm1.2Ink

       genOway: Develop your customized and physiologically relevant rodent model for SMAD7

    miRNA
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    miRTarBase miRNAs that target SMAD7:
    hsa-mir-25-3p (MIRT007242), hsa-mir-15b-5p (MIRT046499), hsa-mir-16-5p (MIRT031521), hsa-mir-26b-5p (MIRT028980), hsa-mir-217 (MIRT007153), hsa-mir-21-5p (MIRT007362), hsa-mir-98-5p (MIRT027482), hsa-mir-216a-5p (MIRT007154), hsa-mir-92a-3p (MIRT049511), hsa-mir-103a-3p (MIRT027015), hsa-mir-100-5p (MIRT048391)

    Block miRNA regulation of human, mouse, rat SMAD7 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate SMAD7 (see all 77):
    hsa-miR-579 hsa-miR-106a hsa-miR-15a hsa-miR-578 hsa-miR-138-2* hsa-miR-519a hsa-miR-371-5p hsa-miR-1244
    SwitchGear 3'UTR luciferase reporter plasmidSMAD7 3' UTR sequence
    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat SMAD7

    Gene Editing
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    GenScript: all cDNA clones in your preferred vector (see all 4): SMAD7 (NM_005904)
    Browse Sino Biological Human cDNA Clones
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    Addgene plasmids for SMAD7 

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    eBioscience FlowRNA Probe Sets ( VA1-12080) for SMAD7 


    (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
    SMAD7_HUMAN, O15105: Nucleus. Cytoplasm. Note=Interaction with NEDD4L or RNF111 or induces translocation from the
    nucleus to the cytoplasm. TGF-beta stimulates its translocation from the nucleus to the cytoplasm. PDPK1 inhibits
    its translocation from the nucleus to the cytoplasm in response to TGF-beta
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    nucleus5
    cytosol4
    plasma membrane4
    extracellular3
    cytoskeleton1
    mitochondrion1
    peroxisome1

    Gene Ontology (GO): Selected cellular component terms (see all 10):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005622intracellular ----
    GO:0005634nucleus IDA11278251
    GO:0005654nucleoplasm TAS--
    GO:0005667transcription factor complex IEA--
    GO:0005737cytoplasm IDA11278251

    Find genes that share ontologies with SMAD7           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 SMAD7 About   (see all 20)  
    See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1Immune response IFN gamma signaling pathway
    IFN-gamma pathway0.43
    Immune response IFN gamma signaling pathway0.43
    2Signaling by BMP
    Signaling by BMP0.35
    BMP receptor signaling0.31
    3Loss of Function of SMAD2/3 in Cancer
    Transcriptional activity of SMAD2/SMAD3-SMAD4 heterotrimer0.72
    Signaling by TGF-beta Receptor Complex0.60
    SMAD2/SMAD3-SMAD4 heterotrimer regulates transcription0.72
    TGFBR1 KD Mutants in Cancer0.60
    Loss of Function of SMAD2/3 in Cancer0.60
    SMAD2/3 MH2 Domain Mutants in Cancer0.60
    Loss of Function of SMAD4 in Cancer0.60
    SMAD2/3 Phosphorylation Motif Mutants in Cancer0.60
    4TGF-beta receptor signaling activates SMADs
    Downregulation of TGF-beta receptor signaling0.82
    TGF-beta receptor signaling activates SMADs0.82
    5Gene Expression
    Generic Transcription Pathway0.40
    Gene Expression0.40


    Find genes that share SuperPaths with SMAD7           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 R&D Systems Pathway for SMAD7
        TGF-beta Signaling Pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for SMAD7 (see all 6)
        SMAD Signaling Network
    BMP Pathway
    Molecular Mechanisms of Cancer
    JAK-STAT Pathway
    TGF-Beta Pathway

    3 GeneGo (Thomson Reuters) Pathways for SMAD7
        Signal transduction Activin A signaling regulation
    Immune response IFN gamma signaling pathway
    Development TGF-beta receptor signaling

    Selected BioSystems Pathways for SMAD7 (see all 9)
        TGF Beta Signaling Pathway
    Integrated Breast Cancer Pathway
    TGF-beta Receptor Signaling Pathway
    BMP receptor signaling
    Regulation of nuclear SMAD2/3 signaling

    3 Reactome Pathways for SMAD7
        Downregulation of TGF-beta receptor signaling
    Signaling by BMP
    SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription


    3 Kegg Pathways  (Kegg details for SMAD7):
        Endocytosis
    TGF-beta signaling pathway
    Hippo signaling pathway

        Pathway & Disease-focused RT2 Profiler PCR Arrays including SMAD7: 
              Fibrosis in human mouse rat
              TGFB/BMP Signaling Pathway in human mouse rat
              Stem Cell Signaling in human mouse rat
              Liver Cancer in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for SMAD7

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

    Selected Interacting proteins for SMAD7 (O151051, 2, 3 ENSP000002621584) via UniProtKB, MINT, STRING, and/or I2D (see all 133)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    AXIN1O151691, 2, 3, ENSP000002623204EBI-3861591,EBI-710484 MINT-1899832 MINT-1953771 MINT-1953921 MINT-1953720 MINT-1953902 MINT-1953874 MINT-2779077 MINT-1953967 I2D: score=4 STRING: ENSP00000262320
    ACVR1BP368961, 3, ENSP000002579634EBI-3861591,EBI-1384128 I2D: score=4 STRING: ENSP00000257963
    HEYLQ9NQ872, 3, ENSP000003619434MINT-61810 I2D: score=3 STRING: ENSP00000361943
    MYOD1P151722, 3, ENSP000002500034MINT-61815 I2D: score=3 STRING: ENSP00000250003
    PIAS1O759252, 3, ENSP000002496364MINT-61806 I2D: score=3 STRING: ENSP00000249636
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 38):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000122negative regulation of transcription from RNA polymerase II promoter IDA17438144
    GO:0001657ureteric bud development IEA--
    GO:0006351transcription, DNA-templated TAS--
    GO:0006355regulation of transcription, DNA-templated ----
    GO:0006367transcription initiation from RNA polymerase II promoter TAS--

    Find genes that share ontologies with SMAD7           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 SMAD7

    Selected Novoseek inferred chemical compound relationships for SMAD7 gene (see all 18)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    tgf beta1 71.9 6 17469181 (2), 16871886 (1), 17763417 (1), 20196115 (1) (see all 5)
    sb 203580 40.9 2 15905080 (1)
    hydroxyproline 24.6 3 18430418 (2), 18992195 (1)
    matrigel 17.9 2 16407850 (1), 16007121 (1)
    bleomycin 16.4 9 10393693 (5), 16187293 (1), 12761881 (1)
    oligonucleotide 10.8 3 19079231 (1), 12464953 (1), 14586410 (1)
    pd 98,059 7.52 1 12615364 (1)
    cycloheximide 4.21 2 10896788 (1)
    glucose 2.78 4 12753288 (2), 19674192 (1)
    vegf 1.85 5 16902401 (2), 15492278 (1), 19450457 (1), 20006606 (1)



    Find genes that share compounds with SMAD7           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 SMAD7 gene (4 alternative transcripts): 
    NM_001190821.1  NM_001190822.1  NM_001190823.1  NM_005904.3  

    Unigene Cluster for SMAD7:

    SMAD family member 7
    Hs.465087  [show with all ESTs]
    Unigene Representative Sequence: AF010193
    8 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000262158(uc002ldg.3 uc021ujr.1) ENST00000545051(uc002ldf.3 uc010xde.2)
    ENST00000591805 ENST00000589634 ENST00000587336 ENST00000585986 ENST00000586093
    ENST00000588190
    miRNA
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    hsa-miR-579 hsa-miR-106a hsa-miR-15a hsa-miR-578 hsa-miR-138-2* hsa-miR-519a hsa-miR-371-5p hsa-miR-1244
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    Additional mRNA sequence: 

    AF010193.1 AF015261.1 AK131394.1 AK301535.1 BC074818.2 BC074819.2 

    6 DOTS entries:

    DT.313061  DT.99955302  DT.100745695  DT.121083990  DT.40212194  DT.121083988 

    Selected AceView cDNA sequences (see all 69):

    AA683504 AA347448 BQ189164 BU731315 AA347306 CD679259 AW339682 CD671921 
    AA347449 AW614916 BC074819 CK903955 AI215892 AW170511 AF015261 AI635141 
    BC074818 BI907541 BQ898984 BX111807 AI880894 BM479978 BM694805 AK131394 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for SMAD7 (see all 6)    About this scheme

    ExUns: 1 ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6a · 6b · 6c · 6d · 6e
    SP1:                          -     -                                 
    SP2:        -     -           -     -                                 
    SP3:        -     -           -     -                                 
    SP4:                          -     -                                 
    SP5:                                -                                 


    ECgene alternative splicing isoforms for SMAD7

    (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)
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    SMAD7 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TTTAGACTTT
    SMAD7 Expression
    About this image


    SMAD7 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 13) fully expand
     
     Brain (Nervous System)    fully expand to see all 6 entries
             Myelinating Oligodendrocyte Cells Forebrain White Matter
             Cerebral Cortex
     
     Spinal Cord (Nervous System)
             Myelinating Oligodendrocyte Cells Spinal Cord White Matter
     
     Thymus (Hematopoietic System)
             T Helper Cells Thymus
     
     Smooth Muscle (Muscoskeletal System)
             Mural Cells Splanchnic Mesoderm
     
     Primitive Streak (Early Embryo)
             Extraembryonic Mural Cells Extraembryonic Mesoderm
    SMAD7 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    SMAD7 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.465087

    UniProtKB/Swiss-Prot: SMAD7_HUMAN, O15105
    Tissue specificity: Ubiquitous with higher expression in the lung and vascular endothelium

        Pathway & Disease-focused RT2 Profiler PCR Arrays including SMAD7: 
              Fibrosis in human mouse rat
              TGFB/BMP Signaling Pathway in human mouse rat
              Stem Cell Signaling in human mouse rat
              Liver Cancer 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 SMAD7 gene from Selected species (see all 15)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Smad71 , 5 MAD homolog 7 (Drosophila)5
    SMAD family member 71
    95.38(n)1
    98.12(a)1
      18 (51.06 cM)5
    171311  NM_001042660.11  NP_001036125.11 
     753675295 
    chicken
    (Gallus gallus)
    Aves SMAD71 SMAD family member 7 78.12(n)
    80.36(a)
      429683  XM_427238.4  XP_427238.2 
    lizard
    (Anolis carolinensis)
    Reptilia SMAD76
    SMAD family member 7
    95(a)
    1 ↔ 1
    2(517733-573383)
    African clawed frog
    (Xenopus laevis)
    Amphibia madh72 MAD, mothers against decapentaplegic homolog 7 (Drosophila) 81.46(n)    BC059286.1 
    zebrafish
    (Danio rerio)
    Actinopterygii madh72 MAD, mothers against decapentaplegic homolog 7 (Drosophila) 81.68(n)   326282  AY134491.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta Dad6
    Daughters against dpp
    21(a)
    1 → many
    3R(12879729-12896135)
    worm
    (Caenorhabditis elegans)
    Secernentea daf-86
    Protein DAF-8 (daf-8) mRNA, complete cds
    16(a)
    many ↔ many
    I(8584542-8587507) WBGene00000904


    ENSEMBL Gene Tree for SMAD7 (if available)
    TreeFam Gene Tree for SMAD7 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for SMAD7 gene
    SMAD32  SMAD22  SMAD12  SMAD62  SMAD52  SMAD42  SMAD92  
    3 SIMAP similar genes for SMAD7 using alignment to 2 protein entries:     SMAD7_HUMAN (see all proteins):
    SMAD3    SMAD4    SMAD6

    Find genes that share paralogs with SMAD7           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 SMAD7 (see all 729)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 18 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1911528871,2
    --46445071(+) ATCACA/CCTTCC 4 -- ds50010--------
    rs1822788601,2
    --46445135(+) GTAGGC/TTTAGG 4 -- ds50010--------
    rs1867559781,2
    --46445171(+) AAGAAA/CCAGAT 4 -- ds50010--------
    rs1928822281,2
    --46445423(+) CCCACA/GTCTCC 4 -- ds50010--------
    rs1849405831,2
    --46445588(+) ACTCCC/TTTAGA 4 -- ut310--------
    rs169501121,2
    C,F,H--46445837(+) TCAGGT/GTTTTT 4 -- ut317Minor allele frequency- G:0.01NA NS EA 558
    rs169501131,2
    C,F,H--46445911(+) GTTCAT/CTTAAA 4 -- ut3119Minor allele frequency- C:0.08NA NS EA CSA WA 2478
    rs1423414291,2
    C--46445982(+) AGTGTC/TGAAGT 4 -- ut310--------
    rs1900537341,2
    --46446127(+) TCCCCA/GCTTGC 4 -- ut310--------
    rs80882971,2
    C,F,A,H--46446162(+) ACAGGA/CTGGGA 4 -- ut3115Minor allele frequency- C:0.24NS EA NA CSA WA 1447

    HapMap Linkage Disequilibrium report for SMAD7 (46446223 - 46477081 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 2 variations for SMAD7:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv833645CNV Loss17160897
    nsv833644CNV Gain17160897

    Human Gene Mutation Database (HGMD): SMAD7
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing SMAD7
    DNA2.0 Custom Variant and Variant Library Synthesis for SMAD7

    (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: 602932   
    OMIM disorders: 612229  
    UniProtKB/Swiss-Prot: SMAD7_HUMAN, O15105
  • Colorectal cancer 3 (CRCS3) [MIM:612229]: A complex disease characterized by malignant lesions arising
    from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated
    with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the
    colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. Note=Disease
    susceptibility is associated with variations affecting the gene represented in this entry

  • 4 diseases for SMAD7:    
    About MalaCards
    colorectal cancer 3    localized scleroderma    pernicious anemia    colorectal cancer

    1 disease from the University of Copenhagen DISEASES database for SMAD7:
    Ureteral obstruction

    Find genes that share disorders with SMAD7           About GenesLikeMe

    Selected Novoseek inferred disease relationships for SMAD7 gene (see all 38)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    renal fibrosis 51.5 2 18508563 (1), 15193216 (1)
    keloid 46.9 7 17144456 (4), 19781253 (2), 16156269 (1)
    pancreatic cancer 46.2 19 15150118 (4), 10498890 (3), 16714330 (3), 15811853 (2) (see all 7)
    scars hypertrophic 45.6 1 18616749 (1)
    pulmonary fibrosis 38.8 7 10393693 (3)
    liver fibrosis 35.5 3 19878580 (2), 19861282 (1)
    diabetic nephropathies 27.2 2 19959709 (1), 12397035 (1)
    aggressiveness 21.4 1 12952364 (1)
    pancreatic carcinoma 21.3 2 12140283 (1), 9892110 (1)
    colon adenocarcinoma 21 2 15922743 (1), 18781153 (1)

    Genetic Association Database (GAD): SMAD7
    Human Genome Epidemiology (HuGE) Navigator: SMAD7 (32 documents)

    Export disorders for SMAD7 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 SMAD7 gene, integrated from 10 sources (see all 439):
    (articles sorted by number of sources associating them with SMAD7)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Vascular MADs: two novel MAD-related genes selectively inducible by flow in human vascular endothelium. (PubMed id 9256479)1, 2, 3, 9 Topper J.N.... Falb D. (Proc. Natl. Acad. Sci. U.S.A. 1997)
    2. A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk. (PubMed id 17934461)1, 2, 4 Broderick P.... Houlston R.S. (Nat. Genet. 2007)
    3. Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling. (PubMed id 9335507)1, 2, 9 Nakao A....ten Dijke P. (Nature 1997)
    4. Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation. (PubMed id 11278251)1, 2, 9 Ebisawa T....Miyazono K. (J. Biol. Chem. 2001)
    5. Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF-beta receptor for degradation. (PubMed id 11163210)1, 2, 9 Kavsak P.... Wrana J.L. (Mol. Cell 2000)
    6. Increased risk of colon cancer associated with a genetic polymorphism of SMAD7. (PubMed id 20124488)1, 4, 9 Slattery M.L....Peters U. (Cancer Res. 2010)
    7. Axin is a scaffold protein in TGF-beta signaling that promotes degradation of Smad7 by Arkadia. (PubMed id 16601693)1, 2, 9 Liu W.... Lin S.-C. (EMBO J. 2006)
    8. Jab1/CSN5, a component of the COP9 signalosome, regulates transforming growth factor beta signaling by binding to Smad7 and promoting its degradation. (PubMed id 14993265)1, 2, 9 Kim B.-C.... Kim S.-J. (Mol. Cell. Biol. 2004)
    9. GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I receptor. (PubMed id 14718519)1, 2, 9 Shi W.... Cao X. (J. Cell Biol. 2004)
    10. Arkadia amplifies TGF-beta superfamily signaling through degradation of Smad7. (PubMed id 14657019)1, 2, 9 Koinuma D.... Miyazono K. (EMBO J. 2003)

    (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: 4092 HGNC: 6773 AceView: SMAD7 Ensembl:ENSG00000101665 euGenes: HUgn4092
    ECgene: SMAD7 Kegg: 4092 H-InvDB: SMAD7

    (According to HUGE)
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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 SMAD7 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for SMAD7 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for SMAD7 gene:
    Search GeneIP for patents involving SMAD7

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



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