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O43541

- SMAD6_HUMAN

UniProt

O43541 - SMAD6_HUMAN

Protein

Mothers against decapentaplegic homolog 6

Gene

SMAD6

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 141 (01 Oct 2014)
      Sequence version 2 (03 Oct 2006)
      Previous versions | rss
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    Functioni

    Acts as a mediator of TGF-beta and BMP antiflammatory activity. Suppresses IL1R-TLR signaling through its direct interaction with PEL1, preventing NF-kappa-B activation, nuclear transport and NF-kappa-B-mediated expression of proinflammatory genes. May block the BMP-SMAD1 signaling pathway by competing with SMAD4 for receptor-activated SMAD1-binding. Binds to regulatory elements in target promoter regions.3 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi205 – 2051ZincBy similarity
    Metal bindingi247 – 2471ZincBy similarity
    Metal bindingi260 – 2601ZincBy similarity
    Metal bindingi265 – 2651ZincBy similarity

    GO - Molecular functioni

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

    GO - Biological processi

    1. BMP signaling pathway Source: UniProtKB
    2. cell-substrate adhesion Source: UniProtKB
    3. fat cell differentiation Source: UniProtKB
    4. immune response Source: BHF-UCL
    5. intracellular signal transduction Source: GOC
    6. negative regulation of apoptotic process Source: BHF-UCL
    7. negative regulation of BMP signaling pathway Source: BHF-UCL
    8. negative regulation of cell proliferation Source: BHF-UCL
    9. negative regulation of pathway-restricted SMAD protein phosphorylation Source: BHF-UCL
    10. negative regulation of SMAD protein complex assembly Source: BHF-UCL
    11. negative regulation of transforming growth factor beta receptor signaling pathway Source: BHF-UCL
    12. response to estrogen Source: Ensembl
    13. response to laminar fluid shear stress Source: BHF-UCL
    14. transcription, DNA-templated Source: UniProtKB-KW
    15. transforming growth factor beta receptor signaling pathway Source: InterPro
    16. ureteric bud development Source: Ensembl
    17. zygotic specification of dorsal/ventral axis 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.
    SignaLinkiO43541.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Mothers against decapentaplegic homolog 6
    Short name:
    MAD homolog 6
    Short name:
    Mothers against DPP homolog 6
    Alternative name(s):
    SMAD family member 6
    Short name:
    SMAD 6
    Short name:
    Smad6
    Short name:
    hSMAD6
    Gene namesi
    Name:SMAD6
    Synonyms:MADH6
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 15

    Organism-specific databases

    HGNCiHGNC:6772. SMAD6.

    Subcellular locationi

    Nucleus 1 Publication

    GO - Cellular componenti

    1. cytoplasm Source: BHF-UCL
    2. cytosol Source: Reactome
    3. nucleus Source: UniProtKB
    4. protein complex Source: MGI
    5. transcription factor complex Source: InterPro

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Aortic valve disease 2 (AOVD2) [MIM:614823]: A common defect in the aortic valve in which two rather than three leaflets are present. It is often associated with aortic valve calcification, stenosis and insufficiency. In extreme cases, the blood flow may be so restricted that the left ventricle fails to grow, resulting in hypoplastic left heart syndrome.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry. SMAD6 variants may contribute to increased risk of congenital cardiovascular malformations (CVM). CVM is a major cause of mortality and morbidity in childhood. In most sporadic cases that cannot be attributed to particular malformation syndromes or teratogenic exposures, there remains a substantial excess familial risk, indicating a significant genetic contribution to disease susceptibility (PubMed:22275001).1 Publication
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti415 – 4151P → L in AOVD2; results in significantly lower activity than wild-type in inhibiting BMP signaling in a transcriptional reporter assay. 1 Publication
    VAR_068075
    Natural varianti484 – 4841C → F in AOVD2; results in significantly lower activity than wild-type in inhibiting BMP signaling in a transcriptional reporter assay. 1 Publication
    VAR_068076

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi173 – 1731K → R: Abolishes monoubiquitination by UBE2O. 1 Publication
    Mutagenesisi435 – 4351S → A: Loss of in vitro phosphorylation by PRKX. 1 Publication
    Mutagenesisi471 – 4711G → S: Loss of SMAD1-binding and of inhibition of BMP-SMAD1 signaling. No effect on interaction with BMPR1B and TGFBR1. 1 Publication
    Mutagenesisi478 – 49619Missing: Loss of interaction with BMPR1B, TGFBR1 and SMAD1. Add
    BLAST

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi614823. phenotype.
    Orphaneti1244. Bicuspid aortic valve.
    PharmGKBiPA30529.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 496496Mothers against decapentaplegic homolog 6PRO_0000090869Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei75 – 751Dimethylated arginine; alternateBy similarity
    Modified residuei75 – 751Omega-N-methylarginine; alternateBy similarity
    Modified residuei82 – 821Dimethylated arginine; alternateBy similarity
    Modified residuei82 – 821Omega-N-methylarginine; alternateBy similarity
    Cross-linki173 – 173Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Modified residuei435 – 4351Phosphoserine; by PRKX; in vitro1 PublicationPROSITE-ProRule annotation

    Post-translational modificationi

    Phosphorylated by BMP type 1 receptor kinase and by PRKX.1 Publication
    Ubiquitinated by WWP1 By similarity. Monoubiquitinated at Lys-173 by the E2/E3 hybrid ubiquitin-protein ligase UBE2O, leading to reduced binding affinity for the activated BMP type I receptor ACVR1/ALK2, thereby enhancing BMP7 and regulating adipocyte differentiation.By similarity1 Publication
    Arginine methylation by PRMT1, which is recruited by BMPR2, initiates BMP-Induced signaling and induces dissociation from the BMPR1B receptor at the cell surface leading to derepress downstream Smad1/Smad5 signaling.By similarity

    Keywords - PTMi

    Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiO43541.
    PaxDbiO43541.
    PRIDEiO43541.

    PTM databases

    PhosphoSiteiO43541.

    Expressioni

    Tissue specificityi

    Ubiquitous in various organs, with higher levels in lung. Isoform B is up-regulated in diseased heart tissue.

    Gene expression databases

    ArrayExpressiO43541.
    BgeeiO43541.
    CleanExiHS_SMAD6.
    GenevestigatoriO43541.

    Interactioni

    Subunit structurei

    Interacts with NEDD4L By similarity. Interacts with WWP1 By similarity. Interacts with STAMBP and PRKX. Interacts with RNF111 and AXIN1. Interacts with TGF-beta type I receptor superfamily members, including ACVR1B, BMPR1B and TGFBR1. In response to BMP2, but not to TGFB treatment, interacts with SMAD1, but not with SMAD2, nor with SMAD4; this interaction may inhibit SMAD1 binding to SMAD4. Interacts with HOXC8 and HOXC9. Interacts with PELI1; this interaction interferes with PELI1 complex formation with TRAF6, IRAK1, IRAK4 and MYD88 in response to IL1B and hence negatively regulates IL1R-TLR signaling.By similarity7 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    PRKXP518175EBI-976374,EBI-4302903
    RUNX2Q139503EBI-976374,EBI-976402
    STAMBPO956302EBI-4324970,EBI-396676

    Protein-protein interaction databases

    BioGridi110266. 48 interactions.
    DIPiDIP-36708N.
    IntActiO43541. 10 interactions.
    MINTiMINT-1198639.
    STRINGi9606.ENSP00000288840.

    Structurei

    3D structure databases

    ProteinModelPortaliO43541.
    SMRiO43541. Positions 192-269, 328-493.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini148 – 275128MH1PROSITE-ProRule annotationAdd
    BLAST
    Domaini331 – 496166MH2PROSITE-ProRule annotationAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi25 – 339Poly-Gly
    Compositional biasi82 – 854Poly-Arg
    Compositional biasi165 – 1684Poly-Leu
    Compositional biasi251 – 2544Poly-Ala
    Compositional biasi275 – 2784Poly-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.
    HOVERGENiHBG053021.
    InParanoidiO43541.
    KOiK04677.
    OMAiWRSRLIP.
    OrthoDBiEOG7GN2PK.
    PhylomeDBiO43541.
    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. 1 hit.
    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 A (identifier: O43541-1) [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

    MFRSKRSGLV RRLWRSRVVP DREEGGSGGG GGGDEDGSLG SRAEPAPRAR    50
    EGGGCGRSEV RPVAPRRPRD AVGQRGAQGA GRRRRAGGPP RPMSEPGAGA 100
    GSSLLDVAEP GGPGWLPESD CETVTCCLFS ERDAAGAPRD ASDPLAGAAL 150
    EPAGGGRSRE ARSRLLLLEQ ELKTVTYSLL KRLKERSLDT LLEAVESRGG 200
    VPGGCVLVPR ADLRLGGQPA PPQLLLGRLF RWPDLQHAVE LKPLCGCHSF 250
    AAAADGPTVC CNPYHFSRLC GPESPPPPYS RLSPRDEYKP LDLSDSTLSY 300
    TETEATNSLI TAPGEFSDAS MSPDATKPSH WCSVAYWEHR TRVGRLYAVY 350
    DQAVSIFYDL PQGSGFCLGQ LNLEQRSESV RRTRSKIGFG ILLSKEPDGV 400
    WAYNRGEHPI FVNSPTLDAP GGRALVVRKV PPGYSIKVFD FERSGLQHAP 450
    EPDAADGPYD PNSVRISFAK GWGPCYSRQF ITSCPCWLEI LLNNPR 496
    Length:496
    Mass (Da):53,497
    Last modified:October 3, 2006 - v2
    Checksum:iA4B928AE2D34EBC2
    GO
    Isoform B (identifier: O43541-2) [UniParc]FASTAAdd to Basket

    Also known as: Smad 6S

    The sequence of this isoform differs from the canonical sequence as follows:
         1-261: Missing.
         262-273: NPYHFSRLCGPE → MSRMGKPIETQK

    Show »
    Length:235
    Mass (Da):26,236
    Checksum:i0847C2C84DC0B2A2
    GO
    Isoform D (identifier: O43541-4) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         318-338: DASMSPDATKPSHWCSVAYWE → AADAGIGSRGNRGLESSVPCS
         339-496: Missing.

    Show »
    Length:338
    Mass (Da):35,467
    Checksum:iC4D02353D7FD76CE
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti21 – 211D → N in AAB94137. (PubMed:9436979)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti325 – 3251A → T Found in a patient with congenital mitral valve prolapse. 1 Publication
    Corresponds to variant rs199822239 [ dbSNP | Ensembl ].
    VAR_068074
    Natural varianti415 – 4151P → L in AOVD2; results in significantly lower activity than wild-type in inhibiting BMP signaling in a transcriptional reporter assay. 1 Publication
    VAR_068075
    Natural varianti484 – 4841C → F in AOVD2; results in significantly lower activity than wild-type in inhibiting BMP signaling in a transcriptional reporter assay. 1 Publication
    VAR_068076

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 261261Missing in isoform B. 1 PublicationVSP_006179Add
    BLAST
    Alternative sequencei262 – 27312NPYHF…LCGPE → MSRMGKPIETQK in isoform B. 1 PublicationVSP_006180Add
    BLAST
    Alternative sequencei318 – 33821DASMS…VAYWE → AADAGIGSRGNRGLESSVPC S in isoform D. 1 PublicationVSP_035489Add
    BLAST
    Alternative sequencei339 – 496158Missing in isoform D. 1 PublicationVSP_035490Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U59914 mRNA. Translation: AAC50792.1.
    AF035528 mRNA. Translation: AAB94137.1.
    AF043640 mRNA. Translation: AAC00497.1.
    AF037469 mRNA. Translation: AAC82331.1.
    AF041065
    , AF041062, AF041063, AF041064 Genomic DNA. Translation: AAF14343.1.
    AM909653 mRNA. Translation: CAP20377.1.
    BC012986 mRNA. Translation: AAH12986.1.
    AF101474 Genomic DNA. Translation: AAF06841.1.
    CCDSiCCDS10221.1. [O43541-1]
    CCDS45287.1. [O43541-2]
    RefSeqiNP_001136333.1. NM_001142861.2. [O43541-2]
    NP_005576.3. NM_005585.4. [O43541-1]
    UniGeneiHs.153863.

    Genome annotation databases

    EnsembliENST00000288840; ENSP00000288840; ENSG00000137834. [O43541-1]
    ENST00000557916; ENSP00000452955; ENSG00000137834. [O43541-4]
    GeneIDi4091.
    KEGGihsa:4091.
    UCSCiuc002aqf.3. human. [O43541-1]
    uc002aqg.3. human. [O43541-2]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U59914 mRNA. Translation: AAC50792.1 .
    AF035528 mRNA. Translation: AAB94137.1 .
    AF043640 mRNA. Translation: AAC00497.1 .
    AF037469 mRNA. Translation: AAC82331.1 .
    AF041065
    , AF041062 , AF041063 , AF041064 Genomic DNA. Translation: AAF14343.1 .
    AM909653 mRNA. Translation: CAP20377.1 .
    BC012986 mRNA. Translation: AAH12986.1 .
    AF101474 Genomic DNA. Translation: AAF06841.1 .
    CCDSi CCDS10221.1. [O43541-1 ]
    CCDS45287.1. [O43541-2 ]
    RefSeqi NP_001136333.1. NM_001142861.2. [O43541-2 ]
    NP_005576.3. NM_005585.4. [O43541-1 ]
    UniGenei Hs.153863.

    3D structure databases

    ProteinModelPortali O43541.
    SMRi O43541. Positions 192-269, 328-493.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 110266. 48 interactions.
    DIPi DIP-36708N.
    IntActi O43541. 10 interactions.
    MINTi MINT-1198639.
    STRINGi 9606.ENSP00000288840.

    PTM databases

    PhosphoSitei O43541.

    Proteomic databases

    MaxQBi O43541.
    PaxDbi O43541.
    PRIDEi O43541.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000288840 ; ENSP00000288840 ; ENSG00000137834 . [O43541-1 ]
    ENST00000557916 ; ENSP00000452955 ; ENSG00000137834 . [O43541-4 ]
    GeneIDi 4091.
    KEGGi hsa:4091.
    UCSCi uc002aqf.3. human. [O43541-1 ]
    uc002aqg.3. human. [O43541-2 ]

    Organism-specific databases

    CTDi 4091.
    GeneCardsi GC15P066994.
    H-InvDB HIX0132566.
    HGNCi HGNC:6772. SMAD6.
    MIMi 602931. gene.
    614823. phenotype.
    neXtProti NX_O43541.
    Orphaneti 1244. Bicuspid aortic valve.
    PharmGKBi PA30529.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG309572.
    HOVERGENi HBG053021.
    InParanoidi O43541.
    KOi K04677.
    OMAi WRSRLIP.
    OrthoDBi EOG7GN2PK.
    PhylomeDBi O43541.
    TreeFami TF314923.

    Enzyme and pathway databases

    Reactomei REACT_12034. Signaling by BMP.
    SignaLinki O43541.

    Miscellaneous databases

    ChiTaRSi SMAD6. human.
    GeneWikii Mothers_against_decapentaplegic_homolog_6.
    GenomeRNAii 4091.
    NextBioi 16042.
    PROi O43541.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O43541.
    Bgeei O43541.
    CleanExi HS_SMAD6.
    Genevestigatori O43541.

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

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
    2. "Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor."
      Hata A., Lagna G., Massague J., Hemmati-Brivanlou A.
      Genes Dev. 12:186-197(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, INTERACTION WITH ACVR1B; BMPR1B; SMAD1 AND TGFBR1, MUTAGENESIS OF GLY-471 AND 478-ARG--ARG-496.
      Tissue: T-cell.
    3. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
      Tissue: Placenta.
    4. Hagiwara K., Freeman A.H., McMenamin M.G., Bennett W.P., Nagashima M., Minter A.R., Yang K., Takenoshita S., Harris C.C.
      Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM A).
    5. "Identification of a new SMAD6 variant in human."
      Konrad L., Scheiber J.A., Brandt H., Eickelberg O., Hofmann R.
      Submitted (NOV-2007) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM D).
      Tissue: Prostatic carcinoma.
    6. "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] (ISOFORM A).
      Tissue: Uterus.
    7. "Determination of the genomic structure of human Smad3, Smad6 and Smad7 and the cloning of the human Smad3 promoter."
      Hagiwara K., Freeman A.A.H., McMenamin M.G., Bennett W.P., Yang K., Takenoshita S., Harris C.C.
      Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases
      Cited for: PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM B).
    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. Cited for: REVIEW.
    11. Cited for: REVIEW.
    12. "Smad6 as a transcriptional corepressor."
      Bai S., Shi X., Yang X., Cao X.
      J. Biol. Chem. 275:8267-8270(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HOXC8.
    13. "Human truncated Smad 6 (Smad 6s) inhibits the BMP pathway in Xenopus laevis."
      Krishnan P., King M.W., Neff A.W., Sandusky G.E., Bierman K.L., Grinnell B., Smith R.C.
      Dev. Growth Differ. 43:115-132(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION (ISOFORM B).
    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. "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.
    16. "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.
    17. "Smad6 negatively regulates interleukin 1-receptor-Toll-like receptor signaling through direct interaction with the adaptor Pellino-1."
      Choi K.C., Lee Y.S., Lim S., Choi H.K., Lee C.H., Lee E.K., Hong S., Kim I.H., Kim S.J., Park S.H.
      Nat. Immunol. 7:1057-1065(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH PELI1.
    18. "Smad6 is a protein kinase X phosphorylation substrate and is required for HL-60 cell differentiation."
      Glesne D., Huberman E.
      Oncogene 25:4086-4098(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PRKX, MUTAGENESIS OF SER-435, PHOSPHORYLATION AT SER-435.
    19. "Nonsynonymous variants in the SMAD6 gene predispose to congenital cardiovascular malformation."
      Tan H.L., Glen E., Topf A., Hall D., O'Sullivan J.J., Sneddon L., Wren C., Avery P., Lewis R.J., ten Dijke P., Arthur H.M., Goodship J.A., Keavney B.D.
      Hum. Mutat. 33:720-727(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN CONGENITAL CARDIOVASCULAR MALFORMATIONS, VARIANT THR-325, VARIANTS AOVD2 LEU-415 AND PHE-484, CHARACTERIZATION OF VARIANTS AOVD2 LEU-415 AND PHE-484.
    20. "Fine-tuning BMP7 signalling in adipogenesis by UBE2O/E2-230K-mediated monoubiquitination of SMAD6."
      Zhang X., Zhang J., Bauer A., Zhang L., Selinger D.W., Lu C.X., Ten Dijke P.
      EMBO J. 32:996-1007(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION AT LYS-173, MUTAGENESIS OF LYS-173.

    Entry informationi

    Entry nameiSMAD6_HUMAN
    AccessioniPrimary (citable) accession number: O43541
    Secondary accession number(s): A9J6M5
    , O43654, Q15799, Q7Z7L4, Q96E31, Q9UKZ3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 4, 2001
    Last sequence update: October 3, 2006
    Last modified: October 1, 2014
    This is version 141 of the entry and version 2 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

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 15
      Human chromosome 15: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3