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Q8BUN5

- SMAD3_MOUSE

UniProt

Q8BUN5 - SMAD3_MOUSE

Protein

Mothers against decapentaplegic homolog 3

Gene

Smad3

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 122 (01 Oct 2014)
      Sequence version 2 (05 Jul 2004)
      Previous versions | rss
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    Functioni

    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 SMAD3/SMAD4 complex, activates transcription. Also can form a SMAD3/SMAD4/JUN/FOS complex at the AP-1/SMAD site to regulate TGF-beta-mediated transcription. Has an inhibitory effect on wound healing probably by modulating both growth and migration of primary keratinocytes and by altering the TGF-mediated chemotaxis of monocytes. This effect on wound healing appears to be hormone-sensitive. Regulator of chondrogenesis and osteogenesis and inhibits early healing of bone fractures. 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
    Sitei40 – 401Required for trimerizationBy similarity
    Sitei41 – 411Required for interaction with DNA and JUN and for functional cooperation with JUNBy similarity
    Metal bindingi64 – 641ZincBy similarity
    Metal bindingi109 – 1091ZincBy similarity
    Metal bindingi121 – 1211ZincBy similarity
    Metal bindingi126 – 1261ZincBy similarity

    GO - Molecular functioni

    1. chromatin binding Source: MGI
    2. chromatin DNA binding Source: BHF-UCL
    3. collagen binding Source: MGI
    4. core promoter proximal region sequence-specific DNA binding Source: UniProtKB
    5. double-stranded DNA binding Source: MGI
    6. protein binding Source: UniProtKB
    7. protein binding transcription factor activity Source: Ensembl
    8. sequence-specific DNA binding transcription factor activity Source: MGI
    9. transcription factor binding Source: UniProtKB
    10. transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity Source: Ensembl
    11. zinc ion binding Source: Ensembl

    GO - Biological processi

    1. activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway Source: Ensembl
    2. cell-cell junction organization Source: Ensembl
    3. cell cycle arrest Source: Ensembl
    4. developmental growth Source: MGI
    5. embryonic cranial skeleton morphogenesis Source: MGI
    6. embryonic foregut morphogenesis Source: MGI
    7. embryonic pattern specification Source: MGI
    8. endoderm development Source: MGI
    9. evasion or tolerance of host defenses by virus Source: Ensembl
    10. extrinsic apoptotic signaling pathway Source: Ensembl
    11. gastrulation Source: MGI
    12. heart looping Source: MGI
    13. immune response Source: Ensembl
    14. immune system development Source: MGI
    15. in utero embryonic development Source: MGI
    16. lens fiber cell differentiation Source: MGI
    17. liver development Source: MGI
    18. mesoderm formation Source: MGI
    19. negative regulation of apoptotic process Source: Ensembl
    20. negative regulation of cell growth Source: Ensembl
    21. negative regulation of inflammatory response Source: UniProtKB
    22. negative regulation of mitotic cell cycle Source: Ensembl
    23. negative regulation of osteoblast differentiation Source: MGI
    24. negative regulation of osteoblast proliferation Source: UniProtKB
    25. negative regulation of protein catabolic process Source: Ensembl
    26. negative regulation of protein phosphorylation Source: Ensembl
    27. negative regulation of transcription from RNA polymerase II promoter Source: MGI
    28. negative regulation of wound healing Source: UniProtKB
    29. nodal signaling pathway Source: Ensembl
    30. osteoblast development Source: MGI
    31. osteoblast differentiation Source: UniProtKB
    32. paraxial mesoderm morphogenesis Source: MGI
    33. pericardium development Source: MGI
    34. positive regulation of alkaline phosphatase activity Source: Ensembl
    35. positive regulation of bone mineralization Source: Ensembl
    36. positive regulation of canonical Wnt signaling pathway Source: Ensembl
    37. positive regulation of catenin import into nucleus Source: Ensembl
    38. positive regulation of cell migration Source: Ensembl
    39. positive regulation of chondrocyte differentiation Source: UniProtKB
    40. positive regulation of epithelial to mesenchymal transition Source: Ensembl
    41. positive regulation of focal adhesion assembly Source: Ensembl
    42. positive regulation of gene expression involved in extracellular matrix organization Source: Ensembl
    43. positive regulation of interleukin-1 beta production Source: Ensembl
    44. positive regulation of positive chemotaxis Source: Ensembl
    45. positive regulation of stress fiber assembly Source: Ensembl
    46. positive regulation of transcription, DNA-templated Source: MGI
    47. positive regulation of transcription factor import into nucleus Source: Ensembl
    48. positive regulation of transcription from RNA polymerase II promoter Source: MGI
    49. positive regulation of transforming growth factor beta3 production Source: Ensembl
    50. protein stabilization Source: Ensembl
    51. regulation of binding Source: MGI
    52. regulation of epithelial cell proliferation Source: MGI
    53. regulation of immune response Source: UniProtKB
    54. regulation of striated muscle tissue development Source: MGI
    55. regulation of transforming growth factor beta2 production Source: Ensembl
    56. regulation of transforming growth factor beta receptor signaling pathway Source: MGI
    57. response to hypoxia Source: Ensembl
    58. signal transduction involved in regulation of gene expression Source: Ensembl
    59. skeletal system development Source: MGI
    60. SMAD protein complex assembly Source: Ensembl
    61. somitogenesis Source: MGI
    62. T cell activation Source: UniProtKB
    63. thyroid gland development Source: MGI
    64. transcription from RNA polymerase II promoter Source: ProtInc
    65. transdifferentiation Source: Ensembl
    66. transforming growth factor beta receptor signaling pathway Source: MGI
    67. transport Source: Ensembl
    68. ureteric bud development Source: UniProtKB

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_202264. SMAD4 MH2 Domain Mutants in Cancer.
    REACT_203510. TGF-beta receptor signaling activates SMADs.
    REACT_203903. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
    REACT_215733. Downregulation of TGF-beta receptor signaling.
    REACT_216258. Signaling by Activin.
    REACT_216792. SMAD2/3 MH2 Domain Mutants in Cancer.
    REACT_217958. SMAD2/3 Phosphorylation Motif Mutants in Cancer.
    REACT_220566. Downregulation of SMAD2/3:SMAD4 transcriptional activity.
    REACT_220645. Signaling by NODAL.
    REACT_224802. TGFBR1 KD Mutants in Cancer.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Mothers against decapentaplegic homolog 3
    Short name:
    MAD homolog 3
    Short name:
    Mad3
    Short name:
    Mothers against DPP homolog 3
    Short name:
    mMad3
    Alternative name(s):
    SMAD family member 3
    Short name:
    SMAD 3
    Short name:
    Smad3
    Gene namesi
    Name:Smad3
    Synonyms:Madh3
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 9

    Organism-specific databases

    MGIiMGI:1201674. Smad3.

    Subcellular locationi

    Cytoplasm. Nucleus
    Note: Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4. Through the action of the phosphatase PPM1A, released from the SMAD2/SMAD4 complex, and exported out of the nucleus by interaction with RANBP1. Co-localizes with LEMD3 at the nucleus inner membrane. MAPK-mediated phosphorylation appears to have no effect on nuclear import. PDPK1 prevents its nuclear translocation in response to TGF-beta By similarity.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. nuclear inner membrane Source: Ensembl
    3. nucleus Source: UniProtKB
    4. plasma membrane Source: MGI
    5. receptor complex Source: Ensembl
    6. SMAD protein complex Source: UniProtKB
    7. transcription factor complex Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    SMAD3 null mice exhibit inhibition of proliferation of mammary gland epithelial cells. Fibrobasts are only partially growth inhibited. Defects in osteoblast differentiation are observed. Animals are osteopenic with less cortical and cancellous bone. Facture healing is accelerated. Decreased bone mineral density (BMD) reflects the inability of osteoblasts to balance osteoclast activity. Wound healing is accelerated to about two and a half times that of normal animals. Wound areas are significantly reduced with less quantities of granulation tissue. There is reduced local infiltration of moncytes and keratinocytes show altered patterns of growth and migration. Accelerated wound healing is observed on castration of null male mice, while null female mice exhibited delayed healing following ovariectomy.4 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 425424Mothers against decapentaplegic homolog 3PRO_0000090857Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylserineBy similarity
    Modified residuei8 – 81Phosphothreonine; by CDK2 and CDK4By similarity
    Cross-linki33 – 33Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Cross-linki81 – 81Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Modified residuei179 – 1791Phosphothreonine; by CDK2, CDK4 and MAPKBy similarity
    Modified residuei204 – 2041Phosphoserine; by GSK3 and MAPKPROSITE-ProRule annotation
    Modified residuei208 – 2081Phosphoserine; by MAPKPROSITE-ProRule annotation
    Modified residuei213 – 2131Phosphoserine; by CDK2 and CDK4PROSITE-ProRule annotation
    Modified residuei378 – 3781N6-acetyllysineBy similarity
    Modified residuei416 – 4161PhosphoserinePROSITE-ProRule annotation
    Modified residuei418 – 4181Phosphoserine; by CK1PROSITE-ProRule annotation
    Modified residuei422 – 4221Phosphoserine; by TGFBR12 PublicationsPROSITE-ProRule annotation
    Modified residuei423 – 4231Phosphoserine; by TGFBR12 PublicationsPROSITE-ProRule annotation
    Modified residuei425 – 4251Phosphoserine; by TGFBR12 PublicationsPROSITE-ProRule annotation

    Post-translational modificationi

    Phosphorylated on serine and threonine residues. Enhanced phosphorylation in the linker region on Thr-179, Ser-204 and Ser-208 on EGF and TGF-beta treatment. Ser-208 is the main site of MAPK-mediated phosphorylation. CDK-mediated phosphorylation occurs in a cell-cycle dependent manner and inhibits both the transcriptional activity and antiproliferative functions of SMAD3. This phosphorylation is inhibited by flavopiridol. Maximum phosphorylation at the G1/S junction. Also phosphorylated on serine residues in the C-terminal SXS motif by TGFBR1 and ACVR1. TGFBR1-mediated phosphorylation at these C-terminal sites is required for interaction with SMAD4, nuclear location and transactivational activity, and appears to be a prerequisite for the TGF-beta mediated phosphorylation in the linker region. Dephosphorylated in the C-terminal SXS motif by PPM1A. This dephosphorylation disrupts the interaction with SMAD4, promotes nuclear export and terminates TGF-beta-mediated signaling. Phosphorylation at Ser-418 by CSNK1G2/CK1 promotes ligand-dependent ubiquitination and subsequent proteasome degradation, thus inhibiting SMAD3-mediated TGF-beta responses By similarity. Phosphorylated by PDPK1 By similarity.By similarity
    Acetylation in the nucleus by EP300 in the MH2 domain regulates positively its transcriptional activity and is enhanced by TGF-beta.By similarity
    Ubiquitinated. Monoubiquitinated, leading to prevent DNA-binding. Deubiquitination by USP15 alleviates inhibition and promotes activation of TGF-beta target genes By similarity.By similarity

    Keywords - PTMi

    Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiQ8BUN5.
    PRIDEiQ8BUN5.

    PTM databases

    PhosphoSiteiQ8BUN5.

    Expressioni

    Tissue specificityi

    Highly expressed in the brain and ovary. Detected in the pyramidal cells of the hippocampus, granule cells of the dentate gyrus, granular cells of the cerebral cortex and the granulosa cells of the ovary.1 Publication

    Gene expression databases

    ArrayExpressiQ8BUN5.
    BgeeiQ8BUN5.
    CleanExiMM_SMAD3.
    GenevestigatoriQ8BUN5.

    Interactioni

    Subunit structurei

    Monomer; in the absence of TGF-beta. Homooligomer; in the presence of TGF-beta. Heterotrimer; forms a heterotrimer in the presence of TGF-beta consisting of two molecules of C-terminally phosphorylated SMAD2 or SMAD3 and one of SMAD4 to form the transcriptionally active SMAD2/SMAD3-SMAD4 complex. Interacts with TGFBR1. Interacts (via MH2 domain) with CITED2 (via C-terminus). Interacts (via the MH2 domain) with ZFYVE9. Interacts with HDAC1, VDR, TGIF and TGIF2, RUNX3, CREBBP, SKOR1, SKOR2, SNON, ATF2, SMURF2 and SNW1. Interacts with DACH1; the interaction inhibits the TGF-beta signaling. Part of a complex consisting of AIP1, ACVR2A, ACVR1B and SMAD3. Forms a complex with SMAD2 and TRIM33 upon addition of TGF-beta. Found in a complex with SMAD3, RAN and XPO4. Interacts in the complex directly with XPO4. Interacts (via the MH2 domain) with LEMD3; the interaction represses SMAD3 transcriptional activity through preventing the formation of the heteromeric complex with SMAD4 and translocation to the nucleus. Interacts with RBPMS. Interacts (via MH2 domain) with MECOM. Interacts with WWTR1 (via its coiled-coil domain). Interacts (via the linker region) with EP300 (C-terminal); the interaction promotes SMAD3 acetylation and is enhanced by TGF-beta phosphorylation in the C-terminal of SMAD3. This interaction can be blocked by competitive binding of adenovirus oncoprotein E1A to the same C-terminal site on EP300, which then results in partially inhibited SMAD3/SMAD4 transcriptional activity. Interacts with SKI; the interaction represses SMAD3 transcriptional activity. Component of the multimeric complex SMAD3/SMAD4/JUN/FOS which forms at the AP1 promoter site; required for syngernistic transcriptional activity in response to TGF-beta. Interacts (via an N-terminal domain) with JUN (via its basic DNA binding and leucine zipper domains); this interaction is essential for DNA binding and cooperative transcriptional activity in response to TGF-beta. Interacts with PPM1A; the interaction dephosphorylates SMAD3 in the C-terminal SXS motif leading to disruption of the SMAD2/3-SMAD4 complex, nuclear export and termination of TGF-beta signaling. 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 of the TGF-beta signaling. Interacts with AIP1, TGFB1I1, TTRAP, FOXL2, PRDM16, HGS and WWP1. Interacts with NEDD4L; the interaction requires TGF-beta stimulation. Interacts with PML. Interacts with MEN1. Interaction with CSNK1G2. Interacts with PDPK1 (via PH domain). Interacts with DAB2; the interactions are enhanced upon TGF-beta stimulation. Interacts with USP15. Interacts with PPP5C; the interaction decreases SMAD3 phosphorylation and protein levels. Interacts with LDLRAD4 (via the SMAD interaction motif). Interacts with PMEPA1.10 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Axin1O356252EBI-2337983,EBI-2365912
    Pou5f1P2026313EBI-2337983,EBI-1606219
    Smad4P974715EBI-2337983,EBI-5259270

    Protein-protein interaction databases

    BioGridi201276. 34 interactions.
    DIPiDIP-29717N.
    IntActiQ8BUN5. 12 interactions.
    MINTiMINT-262056.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8BUN5.
    SMRiQ8BUN5. Positions 7-132, 228-425.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini10 – 136127MH1PROSITE-ProRule annotationAdd
    BLAST
    Domaini232 – 425194MH2PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni137 – 23195LinkerAdd
    BLAST
    Regioni271 – 32454Sufficient for interaction with XPO4By similarityAdd
    BLAST

    Domaini

    The MH1 domain is required for DNA binding By similarity. Also binds zinc ions which are necessary for the DNA binding.By similarity
    The MH2 domain is required for both homomeric and heteromeric interactions and for transcriptional regulation. Sufficient for nuclear import By similarity.By similarity
    The linker region is required for the TGFbeta-mediated transcriptional activity and acts synergistically with the MH2 domain.By similarity

    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

    eggNOGiNOG320700.
    GeneTreeiENSGT00600000084186.
    HOVERGENiHBG053353.
    InParanoidiQ8BUN5.
    KOiK04500.
    OMAiAVELCEY.
    OrthoDBiEOG7W1540.
    PhylomeDBiQ8BUN5.
    TreeFamiTF314923.

    Family and domain databases

    Gene3Di2.60.200.10. 1 hit.
    3.90.520.10. 1 hit.
    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. 1 hit.
    PROSITEiPS51075. MH1. 1 hit.
    PS51076. MH2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q8BUN5-1 [UniParc]FASTAAdd to Basket

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    MSSILPFTPP IVKRLLGWKK GEQNGQEEKW CEKAVKSLVK KLKKTGQLDE    50
    LEKAITTQNV NTKCITIPRS LDGRLQVSHR KGLPHVIYCR LWRWPDLHSH 100
    HELRAMELCE FAFNMKKDEV CVNPYHYQRV ETPVLPPVLV PRHTEIPAEF 150
    PPLDDYSHSI PENTNFPAGI EPQSNIPETP PPGYLSEDGE TSDHQMNHSM 200
    DAGSPNLSPN PMSPAHNNLD LQPVTYCEPA FWCSISYYEL NQRVGETFHA 250
    SQPSMTVDGF TDPSNSERFC LGLLSNVNRN AAVELTRRHI GRGVRLYYIG 300
    GEVFAECLSD SAIFVQSPNC NQRYGWHPAT VCKIPPGCNL KIFNNQEFAA 350
    LLAQSVNQGF EAVYQLTRMC TIRMSFVKGW GAEYRRQTVT STPCWIELHL 400
    NGPLQWLDKV LTQMGSPSIR CSSVS 425
    Length:425
    Mass (Da):48,081
    Last modified:July 5, 2004 - v2
    Checksum:i46DF5E8B371321AC
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti26 – 261Q → E in BAC38789. (PubMed:16141072)Curated
    Sequence conflicti269 – 2691F → L in AAB81755. 1 PublicationCurated
    Sequence conflicti408 – 4081D → V in BAC33398. (PubMed:16141072)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB008192 mRNA. Translation: BAA76956.1.
    AF016189 mRNA. Translation: AAB81755.1.
    AK048626 mRNA. Translation: BAC33398.1.
    AK083158 mRNA. Translation: BAC38789.1.
    BC066850 mRNA. Translation: AAH66850.1.
    CCDSiCCDS23272.1.
    RefSeqiNP_058049.3. NM_016769.4.
    UniGeneiMm.7320.

    Genome annotation databases

    EnsembliENSMUST00000034973; ENSMUSP00000034973; ENSMUSG00000032402.
    GeneIDi17127.
    KEGGimmu:17127.
    UCSCiuc009qbi.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB008192 mRNA. Translation: BAA76956.1 .
    AF016189 mRNA. Translation: AAB81755.1 .
    AK048626 mRNA. Translation: BAC33398.1 .
    AK083158 mRNA. Translation: BAC38789.1 .
    BC066850 mRNA. Translation: AAH66850.1 .
    CCDSi CCDS23272.1.
    RefSeqi NP_058049.3. NM_016769.4.
    UniGenei Mm.7320.

    3D structure databases

    ProteinModelPortali Q8BUN5.
    SMRi Q8BUN5. Positions 7-132, 228-425.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 201276. 34 interactions.
    DIPi DIP-29717N.
    IntActi Q8BUN5. 12 interactions.
    MINTi MINT-262056.

    Chemistry

    BindingDBi Q8BUN5.

    PTM databases

    PhosphoSitei Q8BUN5.

    Proteomic databases

    PaxDbi Q8BUN5.
    PRIDEi Q8BUN5.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000034973 ; ENSMUSP00000034973 ; ENSMUSG00000032402 .
    GeneIDi 17127.
    KEGGi mmu:17127.
    UCSCi uc009qbi.1. mouse.

    Organism-specific databases

    CTDi 4088.
    MGIi MGI:1201674. Smad3.

    Phylogenomic databases

    eggNOGi NOG320700.
    GeneTreei ENSGT00600000084186.
    HOVERGENi HBG053353.
    InParanoidi Q8BUN5.
    KOi K04500.
    OMAi AVELCEY.
    OrthoDBi EOG7W1540.
    PhylomeDBi Q8BUN5.
    TreeFami TF314923.

    Enzyme and pathway databases

    Reactomei REACT_202264. SMAD4 MH2 Domain Mutants in Cancer.
    REACT_203510. TGF-beta receptor signaling activates SMADs.
    REACT_203903. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
    REACT_215733. Downregulation of TGF-beta receptor signaling.
    REACT_216258. Signaling by Activin.
    REACT_216792. SMAD2/3 MH2 Domain Mutants in Cancer.
    REACT_217958. SMAD2/3 Phosphorylation Motif Mutants in Cancer.
    REACT_220566. Downregulation of SMAD2/3:SMAD4 transcriptional activity.
    REACT_220645. Signaling by NODAL.
    REACT_224802. TGFBR1 KD Mutants in Cancer.

    Miscellaneous databases

    NextBioi 16026.
    PROi Q8BUN5.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q8BUN5.
    Bgeei Q8BUN5.
    CleanExi MM_SMAD3.
    Genevestigatori Q8BUN5.

    Family and domain databases

    Gene3Di 2.60.200.10. 1 hit.
    3.90.520.10. 1 hit.
    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. 1 hit.
    PROSITEi PS51075. MH1. 1 hit.
    PS51076. MH2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
      Tissue: Brain.
    2. Yang X., Xu X., Shen S., Deng C.
      Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: C57BL/6.
    3. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J.
      Tissue: Head and Hippocampus.
    4. "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].
      Strain: C57BL/6J.
      Tissue: Embryo.
    5. "Transforming growth factor beta-induced phosphorylation of Smad3 is required for growth inhibition and transcriptional induction in epithelial cells."
      Liu X., Sun Y., Constantinescu S.N., Karam E., Weinberg R.A., Lodish H.F.
      Proc. Natl. Acad. Sci. U.S.A. 94:10669-10674(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-422; SER-423 AND SER-425.
    6. "Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response."
      Ashcroft G.S., Yang X., Glick A.B., Weinstein M., Letterio J.L., Mizel D.E., Anzano M., Greenwell-Wild T., Wahl S.M., Deng C., Roberts A.B.
      Nat. Cell Biol. 1:260-266(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION.
    7. "Identification and characterization of a PDZ protein that interacts with activin types II receptors."
      Shoji H., Tsuchida K., Kishi H., Yamakawa N., Matsuzaki T., Liu Z., Nakamura T., Sugino H.
      J. Biol. Chem. 275:5485-5492(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH AIP1, IDENTIFICATION IN A COMPLEX WITH AIP1; ACVR2A AND ACVR1B.
    8. "Hgs (Hrs), a FYVE domain protein, is involved in Smad signaling through cooperation with SARA."
      Miura S., Takeshita T., Asao H., Kimura Y., Murata K., Sasaki Y., Hanai J., Beppu H., Tsukazaki T., Wrana J.L., Miyazono K., Sugamura K.
      Mol. Cell. Biol. 20:9346-9355(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HGS.
    9. "The loss of Smad3 results in a lower rate of bone formation and osteopenia through dysregulation of osteoblast differentiation and apoptosis."
      Borton A.J., Frederick J.P., Datto M.B., Wang X.F., Weinstein R.S.
      J. Bone Miner. Res. 16:1754-1764(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION.
    10. "Role of Smad3 in the hormonal modulation of in vivo wound healing responses."
      Ashcroft G.S., Mills S.J., Flanders K.C., Lyakh L.A., Anzano M.A., Gilliver S.C., Roberts A.B.
      Wound Repair Regen. 11:468-473(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION.
    11. "A LIM protein, Hic-5, functions as a potential coactivator for Sp1."
      Shibanuma M., Kim-Kaneyama J.-R., Sato S., Nose K.
      J. Cell. Biochem. 91:633-645(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TGFB1I1.
    12. "Cytoplasmic PML function in TGF-beta signalling."
      Lin H.K., Bergmann S., Pandolfi P.P.
      Nature 431:205-211(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION, INTERACTION WITH PML AND ZFYVE9/SARA.
    13. "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.
    14. "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.
    15. "PRDM16/MEL1: a novel Smad binding protein expressed in murine embryonic orofacial tissue."
      Warner D.R., Horn K.H., Mudd L., Webb C.L., Greene R.M., Pisano M.M.
      Biochim. Biophys. Acta 1773:814-820(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PRDM16.
    16. "Ttrap is an essential modulator of Smad3-dependent Nodal signaling during zebrafish gastrulation and left-right axis determination."
      Esguerra C.V., Nelles L., Vermeire L., Ibrahimi A., Crawford A.D., Derua R., Janssens E., Waelkens E., Carmeliet P., Collen D., Huylebroeck D.
      Development 134:4381-4393(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TTRAP.
    17. "FoxL2 and Smad3 coordinately regulate follistatin gene transcription."
      Blount A.L., Schmidt K., Justice N.J., Vale W.W., Fischer W.H., Bilezikjian L.M.
      J. Biol. Chem. 284:7631-7645(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH FOXL2.
    18. "Loss of Smad3 gives rise to poor soft callus formation and accelerates early fracture healing."
      Kawakatsu M., Kanno S., Gui T., Gai Z., Itoh S., Tanishima H., Oikawa K., Muragaki Y.
      Exp. Mol. Pathol. 90:107-115(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION.
    19. "Protein phosphatase 5 modulates SMAD3 function in the transforming growth factor-? pathway."
      Bruce D.L., Macartney T., Yong W., Shou W., Sapkota G.P.
      Cell. Signal. 24:1999-2006(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PPP5C, SUBCELLULAR LOCATION.

    Entry informationi

    Entry nameiSMAD3_MOUSE
    AccessioniPrimary (citable) accession number: Q8BUN5
    Secondary accession number(s): O09064
    , O09144, O14510, O35273, Q8BX84, Q92940, Q93002, Q9GKR4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 5, 2004
    Last sequence update: July 5, 2004
    Last modified: October 1, 2014
    This is version 122 of the entry and version 2 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