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O15105

- SMAD7_HUMAN

UniProt

O15105 - SMAD7_HUMAN

Protein

Mothers against decapentaplegic homolog 7

Gene

SMAD7

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 152 (01 Oct 2014)
      Sequence version 1 (01 Jan 1998)
      Previous versions | rss
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    Functioni

    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.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi125 – 1251ZincBy similarity
    Metal bindingi180 – 1801ZincBy similarity
    Metal bindingi192 – 1921ZincBy similarity
    Metal bindingi197 – 1971ZincBy similarity

    GO - Molecular functioni

    1. activin binding Source: BHF-UCL
    2. beta-catenin binding Source: BHF-UCL
    3. I-SMAD binding Source: BHF-UCL
    4. metal ion binding Source: UniProtKB-KW
    5. protein binding Source: UniProtKB
    6. sequence-specific DNA binding transcription factor activity Source: InterPro
    7. transcription regulatory region DNA binding Source: BHF-UCL
    8. transforming growth factor beta receptor, inhibitory cytoplasmic mediator activity Source: BHF-UCL
    9. type I transforming growth factor beta receptor binding Source: BHF-UCL
    10. ubiquitin protein ligase binding Source: BHF-UCL

    GO - Biological processi

    1. adherens junction assembly Source: BHF-UCL
    2. artery morphogenesis Source: BHF-UCL
    3. BMP signaling pathway Source: Reactome
    4. cellular protein complex localization Source: BHF-UCL
    5. cellular response to transforming growth factor beta stimulus Source: BHF-UCL
    6. gene expression Source: Reactome
    7. negative regulation of BMP signaling pathway Source: BHF-UCL
    8. negative regulation of cell migration Source: BHF-UCL
    9. negative regulation of epithelial to mesenchymal transition Source: BHF-UCL
    10. negative regulation of pathway-restricted SMAD protein phosphorylation Source: BHF-UCL
    11. negative regulation of peptidyl-serine phosphorylation Source: BHF-UCL
    12. negative regulation of peptidyl-threonine phosphorylation Source: BHF-UCL
    13. negative regulation of protein ubiquitination Source: BHF-UCL
    14. negative regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
    15. negative regulation of transcription by competitive promoter binding Source: BHF-UCL
    16. negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
    17. negative regulation of transforming growth factor beta receptor signaling pathway Source: BHF-UCL
    18. negative regulation of ubiquitin-protein transferase activity Source: BHF-UCL
    19. pathway-restricted SMAD protein phosphorylation Source: BHF-UCL
    20. positive regulation of cell-cell adhesion Source: BHF-UCL
    21. positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: BHF-UCL
    22. positive regulation of protein ubiquitination Source: BHF-UCL
    23. positive regulation of transcription from RNA polymerase II promoter Source: Reactome
    24. protein stabilization Source: BHF-UCL
    25. regulation of activin receptor signaling pathway Source: BHF-UCL
    26. regulation of cardiac muscle contraction Source: BHF-UCL
    27. regulation of transforming growth factor beta receptor signaling pathway Source: BHF-UCL
    28. regulation of ventricular cardiac muscle cell membrane depolarization Source: BHF-UCL
    29. response to laminar fluid shear stress Source: BHF-UCL
    30. transcription, DNA-templated Source: Reactome
    31. transcription initiation from RNA polymerase II promoter Source: Reactome
    32. transforming growth factor beta receptor signaling pathway Source: Reactome
    33. ureteric bud development Source: Ensembl
    34. ventricular cardiac muscle tissue morphogenesis Source: BHF-UCL
    35. ventricular septum morphogenesis Source: BHF-UCL

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding, Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_12034. Signaling by BMP.
    REACT_120727. Downregulation of TGF-beta receptor signaling.
    REACT_120734. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
    SignaLinkiO15105.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Mothers against decapentaplegic homolog 7
    Short name:
    MAD homolog 7
    Short name:
    Mothers against DPP homolog 7
    Alternative name(s):
    Mothers against decapentaplegic homolog 8
    Short name:
    MAD homolog 8
    Short name:
    Mothers against DPP homolog 8
    SMAD family member 7
    Short name:
    SMAD 7
    Short name:
    Smad7
    Short name:
    hSMAD7
    Gene namesi
    Name:SMAD7
    Synonyms:MADH7, MADH8
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 18

    Organism-specific databases

    HGNCiHGNC:6773. SMAD7.

    Subcellular locationi

    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.

    GO - Cellular componenti

    1. cytoplasm Source: BHF-UCL
    2. cytosol Source: Reactome
    3. nucleoplasm Source: Reactome
    4. nucleus Source: BHF-UCL
    5. plasma membrane Source: BHF-UCL
    6. protein complex Source: MGI
    7. transcription factor complex Source: InterPro

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    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.1 Publication
    Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi64 – 641K → A: Loss of acetylation, and of SMURF1-dependent degradation; when associated with A-70. 2 Publications
    Mutagenesisi70 – 701K → A: Loss of acetylation, and of SMURF1-dependent degradation; when associated with A-64. 2 Publications
    Mutagenesisi207 – 2115Missing: Diminishes interaction with SMURF2. 1 Publication
    Mutagenesisi211 – 2111Y → A: Diminishes interaction with SMURF2 and reduces inhibition of TGF-beta signaling. 2 Publications
    Mutagenesisi409 – 42618Missing: 90% reduction in TGF-beta receptor binding. 1 PublicationAdd
    BLAST

    Organism-specific databases

    MIMi612229. phenotype.
    PharmGKBiPA134875286.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 426426Mothers against decapentaplegic homolog 7PRO_0000090872Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei64 – 641N6-acetyllysine; alternate1 Publication
    Cross-linki64 – 64Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate1 Publication
    Modified residuei70 – 701N6-acetyllysine; alternate1 Publication
    Cross-linki70 – 70Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate1 Publication
    Modified residuei249 – 2491PhosphoserinePROSITE-ProRule annotation

    Post-translational modificationi

    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 PDPK1.By similarity1 Publication
    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 degradation.By similarity
    Acetylation prevents ubiquitination and degradation mediated by SMURF1.1 Publication

    Keywords - PTMi

    Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiO15105.
    PRIDEiO15105.

    PTM databases

    PhosphoSiteiO15105.

    Expressioni

    Tissue specificityi

    Ubiquitous with higher expression in the lung and vascular endothelium.

    Inductioni

    By TGFB1.

    Gene expression databases

    ArrayExpressiO15105.
    BgeeiO15105.
    CleanExiHS_SMAD7.
    GenevestigatoriO15105.

    Organism-specific databases

    HPAiCAB026212.
    HPA028897.

    Interactioni

    Subunit structurei

    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).By similarity13 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ACVR1BP368962EBI-3861591,EBI-1384128
    AXIN1O151698EBI-3861591,EBI-710484
    COPS5Q9290510EBI-3861591,EBI-594661
    FKBP1AP629423EBI-3861591,EBI-1027571
    Rnf111Q99ML92EBI-3861591,EBI-646015From a different organism.
    WWP2O003085EBI-3861591,EBI-743923

    Protein-protein interaction databases

    BioGridi110267. 86 interactions.
    DIPiDIP-42252N.
    IntActiO15105. 26 interactions.
    MINTiMINT-1179821.
    STRINGi9606.ENSP00000262158.

    Structurei

    Secondary structure

    1
    426
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi204 – 2063
    Beta strandi212 – 2143

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2DJYNMR-B203-217[»]
    2KXQNMR-B203-217[»]
    2LTVNMR-B206-217[»]
    2LTWNMR-B205-217[»]
    2LTXNMR-B203-217[»]
    2LTYNMR-B203-217[»]
    2LTZNMR-B203-217[»]
    ProteinModelPortaliO15105.
    SMRiO15105. Positions 112-201, 261-424.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO15105.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini64 – 207144MH1PROSITE-ProRule annotationAdd
    BLAST
    Domaini261 – 426166MH2PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni208 – 21710Important for interaction with SMURF2

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi208 – 2114PY-motif

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi27 – 359Poly-Gly
    Compositional biasi49 – 568Poly-Gly
    Compositional biasi207 – 2104Poly-Pro

    Sequence similaritiesi

    Belongs to the dwarfin/SMAD family.Curated
    Contains 1 MH1 (MAD homology 1) domain.PROSITE-ProRule annotation
    Contains 1 MH2 (MAD homology 2) domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG309572.
    HOGENOMiHOG000060106.
    HOVERGENiHBG053021.
    InParanoidiO15105.
    KOiK04677.
    OMAiGQLCSEN.
    OrthoDBiEOG7GN2PK.
    PhylomeDBiO15105.
    TreeFamiTF314923.

    Family and domain databases

    Gene3Di2.60.200.10. 1 hit.
    3.90.520.10. 2 hits.
    InterProiIPR013790. Dwarfin.
    IPR003619. MAD_homology1_Dwarfin-type.
    IPR013019. MAD_homology_MH1.
    IPR017855. SMAD_dom-like.
    IPR001132. SMAD_dom_Dwarfin-type.
    IPR008984. SMAD_FHA_domain.
    [Graphical view]
    PANTHERiPTHR13703. PTHR13703. 1 hit.
    PfamiPF03165. MH1. 1 hit.
    PF03166. MH2. 1 hit.
    [Graphical view]
    SMARTiSM00523. DWA. 1 hit.
    SM00524. DWB. 1 hit.
    [Graphical view]
    SUPFAMiSSF49879. SSF49879. 1 hit.
    SSF56366. SSF56366. 2 hits.
    PROSITEiPS51075. MH1. 1 hit.
    PS51076. MH2. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: O15105-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MFRTKRSALV RRLWRSRAPG GEDEEEGAGG GGGGGELRGE GATDSRAHGA    50
    GGGGPGRAGC CLGKAVRGAK GHHHPHPPAA GAGAAGGAEA DLKALTHSVL 100
    KKLKERQLEL LLQAVESRGG TRTACLLLPG RLDCRLGPGA PAGAQPAQPP 150
    SSYSLPLLLC KVFRWPDLRH SSEVKRLCCC ESYGKINPEL VCCNPHHLSR 200
    LCELESPPPP YSRYPMDFLK PTADCPDAVP SSAETGGTNY LAPGGLSDSQ 250
    LLLEPGDRSH WCVVAYWEEK TRVGRLYCVQ EPSLDIFYDL PQGNGFCLGQ 300
    LNSDNKSQLV QKVRSKIGCG IQLTREVDGV WVYNRSSYPI FIKSATLDNP 350
    DSRTLLVHKV FPGFSIKAFD YEKAYSLQRP NDHEFMQQPW TGFTVQISFV 400
    KGWGQCYTRQ FISSCPCWLE VIFNSR 426
    Length:426
    Mass (Da):46,426
    Last modified:January 1, 1998 - v1
    Checksum:i5B76EC986776C102
    GO
    Isoform 2 (identifier: O15105-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-215: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:211
    Mass (Da):23,901
    Checksum:i04F71C0D2D257D71
    GO
    Isoform 3 (identifier: O15105-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         223-223: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:425
    Mass (Da):46,355
    Checksum:i881EA3C25C342A91
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti71 – 711G → C in AAB81354. (PubMed:9335507)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 215215Missing in isoform 2. 1 PublicationVSP_045197Add
    BLAST
    Alternative sequencei223 – 2231Missing in isoform 3. 1 PublicationVSP_047540

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF010193 mRNA. Translation: AAB81246.1.
    AF015261 mRNA. Translation: AAB81354.1.
    AF026559
    , AF026556, AF026557, AF026558 Genomic DNA. Translation: AAL68977.1.
    AK301535 mRNA. Translation: BAH13509.1.
    DA882147 mRNA. No translation available.
    AC114684 Genomic DNA. No translation available.
    BC074818 mRNA. Translation: AAH74818.2.
    BC074819 mRNA. Translation: AAH74819.2.
    CCDSiCCDS11936.1. [O15105-1]
    CCDS54186.1. [O15105-2]
    CCDS59317.1. [O15105-3]
    RefSeqiNP_001177750.1. NM_001190821.1. [O15105-3]
    NP_001177751.1. NM_001190822.1. [O15105-2]
    NP_001177752.1. NM_001190823.1.
    NP_005895.1. NM_005904.3. [O15105-1]
    UniGeneiHs.465087.

    Genome annotation databases

    EnsembliENST00000262158; ENSP00000262158; ENSG00000101665. [O15105-1]
    ENST00000589634; ENSP00000467621; ENSG00000101665. [O15105-3]
    ENST00000591805; ENSP00000466902; ENSG00000101665. [O15105-2]
    GeneIDi4092.
    KEGGihsa:4092.
    UCSCiuc002ldg.3. human. [O15105-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF010193 mRNA. Translation: AAB81246.1 .
    AF015261 mRNA. Translation: AAB81354.1 .
    AF026559
    , AF026556 , AF026557 , AF026558 Genomic DNA. Translation: AAL68977.1 .
    AK301535 mRNA. Translation: BAH13509.1 .
    DA882147 mRNA. No translation available.
    AC114684 Genomic DNA. No translation available.
    BC074818 mRNA. Translation: AAH74818.2 .
    BC074819 mRNA. Translation: AAH74819.2 .
    CCDSi CCDS11936.1. [O15105-1 ]
    CCDS54186.1. [O15105-2 ]
    CCDS59317.1. [O15105-3 ]
    RefSeqi NP_001177750.1. NM_001190821.1. [O15105-3 ]
    NP_001177751.1. NM_001190822.1. [O15105-2 ]
    NP_001177752.1. NM_001190823.1.
    NP_005895.1. NM_005904.3. [O15105-1 ]
    UniGenei Hs.465087.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2DJY NMR - B 203-217 [» ]
    2KXQ NMR - B 203-217 [» ]
    2LTV NMR - B 206-217 [» ]
    2LTW NMR - B 205-217 [» ]
    2LTX NMR - B 203-217 [» ]
    2LTY NMR - B 203-217 [» ]
    2LTZ NMR - B 203-217 [» ]
    ProteinModelPortali O15105.
    SMRi O15105. Positions 112-201, 261-424.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 110267. 86 interactions.
    DIPi DIP-42252N.
    IntActi O15105. 26 interactions.
    MINTi MINT-1179821.
    STRINGi 9606.ENSP00000262158.

    PTM databases

    PhosphoSitei O15105.

    Proteomic databases

    PaxDbi O15105.
    PRIDEi O15105.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000262158 ; ENSP00000262158 ; ENSG00000101665 . [O15105-1 ]
    ENST00000589634 ; ENSP00000467621 ; ENSG00000101665 . [O15105-3 ]
    ENST00000591805 ; ENSP00000466902 ; ENSG00000101665 . [O15105-2 ]
    GeneIDi 4092.
    KEGGi hsa:4092.
    UCSCi uc002ldg.3. human. [O15105-1 ]

    Organism-specific databases

    CTDi 4092.
    GeneCardsi GC18M046446.
    HGNCi HGNC:6773. SMAD7.
    HPAi CAB026212.
    HPA028897.
    MIMi 602932. gene.
    612229. phenotype.
    neXtProti NX_O15105.
    PharmGKBi PA134875286.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG309572.
    HOGENOMi HOG000060106.
    HOVERGENi HBG053021.
    InParanoidi O15105.
    KOi K04677.
    OMAi GQLCSEN.
    OrthoDBi EOG7GN2PK.
    PhylomeDBi O15105.
    TreeFami TF314923.

    Enzyme and pathway databases

    Reactomei REACT_12034. Signaling by BMP.
    REACT_120727. Downregulation of TGF-beta receptor signaling.
    REACT_120734. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
    SignaLinki O15105.

    Miscellaneous databases

    EvolutionaryTracei O15105.
    GeneWikii Mothers_against_decapentaplegic_homolog_7.
    GenomeRNAii 4092.
    NextBioi 16046.
    PROi O15105.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O15105.
    Bgeei O15105.
    CleanExi HS_SMAD7.
    Genevestigatori O15105.

    Family and domain databases

    Gene3Di 2.60.200.10. 1 hit.
    3.90.520.10. 2 hits.
    InterProi IPR013790. Dwarfin.
    IPR003619. MAD_homology1_Dwarfin-type.
    IPR013019. MAD_homology_MH1.
    IPR017855. SMAD_dom-like.
    IPR001132. SMAD_dom_Dwarfin-type.
    IPR008984. SMAD_FHA_domain.
    [Graphical view ]
    PANTHERi PTHR13703. PTHR13703. 1 hit.
    Pfami PF03165. MH1. 1 hit.
    PF03166. MH2. 1 hit.
    [Graphical view ]
    SMARTi SM00523. DWA. 1 hit.
    SM00524. DWB. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49879. SSF49879. 1 hit.
    SSF56366. SSF56366. 2 hits.
    PROSITEi PS51075. MH1. 1 hit.
    PS51076. MH2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The MAD-related protein Smad7 associates with the TGFbeta receptor and functions as an antagonist of TGFbeta signaling."
      Hayashi H., Abdollah S., Qiu Y., Cai J., Xu Y.-Y., Grinnell B.W., Richardson M.A., Topper J.N., Gimbrone M.A. Jr., Wrana J.L., Falb D.
      Cell 89:1165-1173(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS OF 409-ARG--ARG-426.
      Tissue: Umbilical vein endothelial cell.
    2. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Umbilical vein endothelial cell.
    3. "Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling."
      Nakao A., Afrakhte M., Moren A., Nakayama T., Christian J.L., Heuchel R., Itoh S., Kawabata M., Heldin N.-E., Heldin C.-H., ten Dijke P.
      Nature 389:631-635(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Brain.
    4. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    5. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 98-271 (ISOFORM 3).
      Tissue: Pulmonary artery.
    6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Lung.
    8. Cited for: REVIEW.
    9. "Remarkable versatility of Smad proteins in the nucleus of transforming growth factor-beta activated cells."
      Verschueren K., Huylebroeck D.
      Cytokine Growth Factor Rev. 10:187-199(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    10. "Roles of pathway-specific and inhibitory Smads in activin receptor signaling."
      Lebrun J.J., Takabe K., Chen Y., Vale W.
      Mol. Endocrinol. 13:15-23(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ACVR1B, FUNCTION.
    11. Cited for: REVIEW.
    12. Cited for: REVIEW.
    13. "Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF-beta receptor for degradation."
      Kavsak P., Rasmussen R.K., Causing C.G., Bonni S., Zhu H., Thomsen G.H., Wrana J.L.
      Mol. Cell 6:1365-1375(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF TYR-211 AND 207-PRO--TYR-211, INTERACTION WITH SMURF2 AND TGFBR1.
    14. "Promoting bone morphogenetic protein signaling through negative regulation of inhibitory Smads."
      Itoh F., Asao H., Sugamura K., Heldin C.-H., ten Dijke P., Itoh S.
      EMBO J. 20:4132-4142(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH STAMBP.
    15. "Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation."
      Ebisawa T., Fukuchi M., Murakami G., Chiba T., Tanaka K., Imamura T., Miyazono K.
      J. Biol. Chem. 276:12477-12480(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SMURF1 AND TGFBR1, PROTEASOMAL DEGRADATION.
    16. "Phosphorylation regulation of the interaction between Smad7 and activin type I receptor."
      Liu X., Nagarajan R.P., Vale W., Chen Y.
      FEBS Lett. 519:93-98(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ACVR1B, FUNCTION.
    17. "Control of Smad7 stability by competition between acetylation and ubiquitination."
      Gronroos E., Hellman U., Heldin C.H., Ericsson J.
      Mol. Cell 10:483-493(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH EP300, ACETYLATION AT LYS-64 AND LYS-70, UBIQUITINATION AT LYS-64 AND LYS-70, MUTAGENESIS OF LYS-64 AND LYS-70.
    18. "Arkadia amplifies TGF-beta superfamily signaling through degradation of Smad7."
      Koinuma D., Shinozaki M., Komuro A., Goto K., Saitoh M., Hanyu A., Ebina M., Nukiwa T., Miyazawa K., Imamura T., Miyazono K.
      EMBO J. 22:6458-6470(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH RNF111, UBIQUITINATION, SUBCELLULAR LOCATION.
    19. "GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I receptor."
      Shi W., Sun C., He B., Xiong W., Shi X., Yao D., Cao X.
      J. Cell Biol. 164:291-300(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH PPP1R15A.
    20. "Jab1/CSN5, a component of the COP9 signalosome, regulates transforming growth factor beta signaling by binding to Smad7 and promoting its degradation."
      Kim B.-C., Lee H.-J., Park S.H., Lee S.R., Karpova T.S., McNally J.G., Felici A., Lee D.K., Kim S.-J.
      Mol. Cell. Biol. 24:2251-2262(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH COPS5.
    21. "Regulation of Smurf2 ubiquitin ligase activity by anchoring the E2 to the HECT domain."
      Ogunjimi A.A., Briant D.J., Pece-Barbara N., Le Roy C., Di Guglielmo G.M., Kavsak P., Rasmussen R.K., Seet B.T., Sicheri F., Wrana J.L.
      Mol. Cell 19:297-308(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SMURF2.
    22. "Axin is a scaffold protein in TGF-beta signaling that promotes degradation of Smad7 by Arkadia."
      Liu W., Rui H., Wang J., Lin S., He Y., Chen M., Li Q., Ye Z., Zhang S., Chan S.C., Chen Y.-G., Han J., Lin S.-C.
      EMBO J. 25:1646-1658(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH AXIN1 AND AXIN2, UBIQUITINATION, SUBCELLULAR LOCATION.
    23. "3-Phosphoinositide-dependent PDK1 negatively regulates transforming growth factor-beta-induced signaling in a kinase-dependent manner through physical interaction with Smad proteins."
      Seong H.A., Jung H., Kim K.T., Ha H.
      J. Biol. Chem. 282:12272-12289(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION BY PDPK1, INTERACTION WITH PDPK1.
    24. "An expanded WW domain recognition motif revealed by the interaction between Smad7 and the E3 ubiquitin ligase Smurf2."
      Chong P.A., Lin H., Wrana J.L., Forman-Kay J.D.
      J. Biol. Chem. 281:17069-17075(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 203-217 IN COMPLEX WITH SMURF2.
    25. Cited for: INVOLVEMENT IN CRCS3.

    Entry informationi

    Entry nameiSMAD7_HUMAN
    AccessioniPrimary (citable) accession number: O15105
    Secondary accession number(s): B7Z773
    , K7EQ10, O14740, Q6DK23
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 4, 2001
    Last sequence update: January 1, 1998
    Last modified: October 1, 2014
    This is version 152 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 18
      Human chromosome 18: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3