Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

O35253

- SMAD7_MOUSE

UniProt

O35253 - SMAD7_MOUSE

Protein

Mothers against decapentaplegic homolog 7

Gene

Smad7

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 136 (01 Oct 2014)
      Sequence version 1 (01 Jan 1998)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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. collagen binding Source: MGI
    2. metal ion binding Source: UniProtKB-KW
    3. protein binding Source: IntAct
    4. sequence-specific DNA binding transcription factor activity Source: InterPro
    5. transcription regulatory region DNA binding Source: Ensembl
    6. transforming growth factor beta receptor, inhibitory cytoplasmic mediator activity Source: Ensembl

    GO - Biological processi

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

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding, Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_203903. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
    REACT_215733. Downregulation of TGF-beta receptor signaling.
    REACT_220505. Signaling by BMP.

    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
    Gene namesi
    Name:Smad7
    Synonyms:Madh7, Madh8
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 18

    Organism-specific databases

    MGIiMGI:1100518. Smad7.

    Subcellular locationi

    Nucleus. Cytoplasm
    Note: Interaction with NEDD4L or RNF111 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 By similarity.By similarity

    GO - Cellular componenti

    1. catenin complex Source: Ensembl
    2. cell-cell adherens junction Source: Ensembl
    3. cytosol Source: Reactome
    4. nucleoplasm Source: Reactome
    5. nucleus Source: MGI
    6. protein complex Source: MGI
    7. transcription factor complex Source: InterPro

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi249 – 2491S → A: No effect on stability, nuclear localization or inhibitory function in TGFB signaling. Abolishes transcriptional activity. 1 Publication
    Mutagenesisi249 – 2491S → D: No effect. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 426426Mothers against decapentaplegic homolog 7PRO_0000090873Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei64 – 641N6-acetyllysine; alternateBy similarity
    Cross-linki64 – 64Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
    Modified residuei70 – 701N6-acetyllysine; alternateBy similarity
    Cross-linki70 – 70Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
    Modified residuei249 – 2491Phosphoserine1 PublicationPROSITE-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. Phosphorylated by PDPK1 By similarity.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.By similarity
    Acetylation prevents ubiquitination and degradation mediated by SMURF1.By similarity

    Keywords - PTMi

    Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PRIDEiO35253.

    PTM databases

    PhosphoSiteiO35253.

    Expressioni

    Tissue specificityi

    Ubiquitous in various organs, with higher levels in brain and kidney.

    Gene expression databases

    ArrayExpressiO35253.
    BgeeiO35253.
    CleanExiMM_SMAD7.
    GenevestigatoriO35253.

    Interactioni

    Subunit structurei

    Interacts with COPS5. Interacts with STAMBP. Interacts with PPP1R15A By similarity. Interacts with NEDD4L. Interacts with RNF111, AXIN1 and AXIN2. Interacts with ACVR1B, SMURF1, SMURF2 and TGFBR1; SMAD7 recruits SMURF1 and SMURF2 to the TGF-beta receptor and regulates its degradation By similarity. Interacts with WWP1. Interacts with PDPK1 (via PH domain) By similarity. Ubiquitinated by WWP1.By similarity3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Axin1O356252EBI-5274835,EBI-2365912
    Sirt1Q923E46EBI-5274835,EBI-1802585
    UBE2OQ9C0C92EBI-5274835,EBI-2339946From a different organism.

    Protein-protein interaction databases

    BioGridi201280. 27 interactions.
    IntActiO35253. 8 interactions.
    MINTiMINT-261918.

    Structurei

    3D structure databases

    ProteinModelPortaliO35253.
    SMRiO35253. Positions 112-201, 261-424.
    ModBaseiSearch...
    MobiDBiSearch...

    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 SMURF2By similarity

    Motif

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

    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.
    GeneTreeiENSGT00600000084353.
    HOGENOMiHOG000060106.
    HOVERGENiHBG053021.
    InParanoidiO35253.
    KOiK04677.
    OMAiGQLCSEN.
    OrthoDBiEOG7GN2PK.
    PhylomeDBiO35253.
    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 (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform A (identifier: O35253-1) [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 GEDEEEGVGG GGGGGELRGE GATDGRAYGA    50
    GGGGAGRAGC CLGKAVRGAK GHHHPHPPTS GAGAAGGAEA DLKALTHSVL 100
    KKLKERQLEL LLQAVESRGG TRTACLLLPG RLDCRLGPGA PASAQPAQPP 150
    SSYSLPLLLC KVFRWPDLRH SSEVKRLCCC ESYGKINPEL VCCNPHHLSR 200
    LCELESPPPP YSRYPMDFLK PTAGCPDAVP 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):46,442
    Last modified:January 1, 1998 - v1
    Checksum:iBEEE751371C0E0CF
    GO
    Isoform B (identifier: O35253-2) [UniParc]FASTAAdd to Basket

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

    Show »
    Length:425
    Mass (Da):46,371
    Checksum:i2C7975BB14492A53
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti233 – 2331A → V1 PublicationCurated
    Sequence conflicti233 – 2331A → V(PubMed:10828018)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei223 – 2231Missing in isoform B. 2 PublicationsVSP_006181

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF015260 mRNA. Translation: AAB81353.1.
    AJ000550 mRNA. Translation: CAA04182.1.
    AJ000551 mRNA. Translation: CAA04183.1.
    CCDSiCCDS37860.1. [O35253-1]
    RefSeqiNP_001036125.1. NM_001042660.1. [O35253-1]
    XP_006525766.1. XM_006525703.1. [O35253-2]
    UniGeneiMm.34407.

    Genome annotation databases

    EnsembliENSMUST00000026999; ENSMUSP00000026999; ENSMUSG00000025880. [O35253-1]
    ENSMUST00000168918; ENSMUSP00000129322; ENSMUSG00000025880. [O35253-1]
    GeneIDi17131.
    KEGGimmu:17131.
    UCSCiuc008fqd.1. mouse. [O35253-1]
    uc008fqe.2. mouse. [O35253-2]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF015260 mRNA. Translation: AAB81353.1 .
    AJ000550 mRNA. Translation: CAA04182.1 .
    AJ000551 mRNA. Translation: CAA04183.1 .
    CCDSi CCDS37860.1. [O35253-1 ]
    RefSeqi NP_001036125.1. NM_001042660.1. [O35253-1 ]
    XP_006525766.1. XM_006525703.1. [O35253-2 ]
    UniGenei Mm.34407.

    3D structure databases

    ProteinModelPortali O35253.
    SMRi O35253. Positions 112-201, 261-424.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 201280. 27 interactions.
    IntActi O35253. 8 interactions.
    MINTi MINT-261918.

    PTM databases

    PhosphoSitei O35253.

    Proteomic databases

    PRIDEi O35253.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000026999 ; ENSMUSP00000026999 ; ENSMUSG00000025880 . [O35253-1 ]
    ENSMUST00000168918 ; ENSMUSP00000129322 ; ENSMUSG00000025880 . [O35253-1 ]
    GeneIDi 17131.
    KEGGi mmu:17131.
    UCSCi uc008fqd.1. mouse. [O35253-1 ]
    uc008fqe.2. mouse. [O35253-2 ]

    Organism-specific databases

    CTDi 4092.
    MGIi MGI:1100518. Smad7.

    Phylogenomic databases

    eggNOGi NOG309572.
    GeneTreei ENSGT00600000084353.
    HOGENOMi HOG000060106.
    HOVERGENi HBG053021.
    InParanoidi O35253.
    KOi K04677.
    OMAi GQLCSEN.
    OrthoDBi EOG7GN2PK.
    PhylomeDBi O35253.
    TreeFami TF314923.

    Enzyme and pathway databases

    Reactomei REACT_203903. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
    REACT_215733. Downregulation of TGF-beta receptor signaling.
    REACT_220505. Signaling by BMP.

    Miscellaneous databases

    ChiTaRSi SMAD7. mouse.
    NextBioi 291328.
    PROi O35253.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O35253.
    Bgeei O35253.
    CleanExi MM_SMAD7.
    Genevestigatori O35253.

    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. "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 A).
      Tissue: Placenta.
    2. "Characterization of a novel mouse homologue of Mad, Smad7, that can mediate TGF-beta family signalling."
      Kitamura K., Okazaki K.
      Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
      Tissue: Embryo.
    3. "Isolation of cDNAs encoding mouse homologues of Mad (Smad7 and Smad7B) that can mediate TGF-beta family signalling."
      Kitamura K., Okazaki K.
      Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B).
      Tissue: Embryo.
    4. "Smad7 selectively interferes with different pathways of activin signaling and inhibits erythroid leukemia cell differentiation."
      Kitamura K., Aota S., Sakamoto R., Yoshikawa S.I., Okazaki K.
      Blood 95:3371-3379(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B).
    5. "Phosphorylation of Smad7 at Ser-249 does not interfere with its inhibitory role in transforming growth factor-beta-dependent signaling but affects Smad7-dependent transcriptional activation."
      Pulaski L., Landstrom M., Heldin C.-H., Souchelnytskyi S.
      J. Biol. Chem. 276:14344-14349(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-249, MUTAGENESIS OF SER-249, SUBCELLULAR LOCATION.
    6. "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.
    7. "Negative regulation of transforming growth factor-beta (TGF-beta) signaling by WW domain-containing protein 1 (WWP1)."
      Komuro A., Imamura T., Saitoh M., Yoshida Y., Yamori T., Miyazono K., Miyazawa K.
      Oncogene 23:6914-6923(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH WWP1, UBIQUITINATION.
    8. "NEDD4-2 (neural precursor cell expressed, developmentally down-regulated 4-2) negatively regulates TGF-beta (transforming growth factor-beta) signalling by inducing ubiquitin-mediated degradation of Smad2 and TGF-beta type I receptor."
      Kuratomi G., Komuro A., Goto K., Shinozaki M., Miyazawa K., Miyazono K., Imamura T.
      Biochem. J. 386:461-470(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NEDD4L, SUBCELLULAR LOCATION.

    Entry informationi

    Entry nameiSMAD7_MOUSE
    AccessioniPrimary (citable) accession number: O35253
    Secondary accession number(s): O88709
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 4, 2001
    Last sequence update: January 1, 1998
    Last modified: October 1, 2014
    This is version 136 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3