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)

O35182

- SMAD6_MOUSE

UniProt

O35182 - SMAD6_MOUSE

Protein

Mothers against decapentaplegic homolog 6

Gene

Smad6

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 127 (01 Oct 2014)
      Sequence version 1 (01 Jan 1998)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    Binds to regulatory elements in target promoter regions By similarity. May block the BMP-SMAD1 signaling pathway by competing with SMAD4 for receptor-activated SMAD1-binding By similarity. 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.By similarity1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi206 – 2061ZincBy similarity
    Metal bindingi248 – 2481ZincBy similarity
    Metal bindingi261 – 2611ZincBy similarity
    Metal bindingi266 – 2661ZincBy similarity

    GO - Molecular functioni

    1. chromatin binding Source: UniProtKB
    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: UniProtKB
    6. transforming growth factor beta receptor, inhibitory cytoplasmic mediator activity Source: Ensembl

    GO - Biological processi

    1. BMP signaling pathway Source: UniProtKB
    2. cardiac vascular smooth muscle cell development Source: DFLAT
    3. cell-substrate adhesion Source: UniProtKB
    4. coronary vasculature morphogenesis Source: DFLAT
    5. fat cell differentiation Source: UniProtKB
    6. immune response Source: Ensembl
    7. negative regulation of apoptotic process Source: Ensembl
    8. negative regulation of BMP signaling pathway Source: Ensembl
    9. negative regulation of cell proliferation Source: Ensembl
    10. negative regulation of pathway-restricted SMAD protein phosphorylation Source: Ensembl
    11. negative regulation of SMAD protein complex assembly Source: Ensembl
    12. negative regulation of transforming growth factor beta receptor signaling pathway Source: Ensembl
    13. negative regulation of vasodilation Source: DFLAT
    14. positive regulation of vasoconstriction Source: DFLAT
    15. response to estrogen Source: Ensembl
    16. response to laminar fluid shear stress Source: Ensembl
    17. transcription, DNA-templated Source: UniProtKB-KW
    18. transforming growth factor beta receptor signaling pathway Source: InterPro
    19. ureteric bud development Source: UniProtKB
    20. zygotic specification of dorsal/ventral axis Source: Ensembl

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding, Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_220505. Signaling by BMP.

    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):
    Mad homolog 7
    SMAD family member 6
    Short name:
    SMAD 6
    Short name:
    Smad6
    Gene namesi
    Name:Smad6
    Synonyms:Madh6, Madh7, Msmad6
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 9

    Organism-specific databases

    MGIiMGI:1336883. Smad6.

    Subcellular locationi

    Nucleus By similarity

    GO - Cellular componenti

    1. nucleus Source: UniProtKB
    2. protein complex Source: MGI
    3. transcription factor complex Source: InterPro

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi74 – 741R → A: Strongly decreased methylation. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 495495Mothers against decapentaplegic homolog 6PRO_0000090870Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei74 – 741Dimethylated arginine; alternate1 Publication
    Modified residuei74 – 741Omega-N-methylarginine; alternate1 Publication
    Modified residuei81 – 811Dimethylated arginine; alternate1 Publication
    Modified residuei81 – 811Omega-N-methylarginine; alternate1 Publication
    Cross-linki174 – 174Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Modified residuei436 – 4361Phosphoserine; by PRKX; in vitroPROSITE-ProRule annotation

    Post-translational modificationi

    Monoubiquitinated at Lys-174 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 similarity. Ubiquitinated by WWP1.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.1 Publication

    Keywords - PTMi

    Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiO35182.
    PRIDEiO35182.

    PTM databases

    PhosphoSiteiO35182.

    Expressioni

    Tissue specificityi

    Ubiquitous in various organs, with higher levels in lung.

    Inductioni

    By TGF-beta and BMP4.1 Publication

    Gene expression databases

    ArrayExpressiO35182.
    BgeeiO35182.
    CleanExiMM_SMAD6.
    GenevestigatoriO35182.

    Interactioni

    Subunit structurei

    Interacts with NEDD4L. Interacts with WWP1. Interacts with STAMBP and PRKX By similarity. Interacts with RNF111 and AXIN1. Interacts with TGF-beta type I receptor superfamily members, including ACVR1B, BMPR1B and TGFBR1. In response to BMP2 treatment, interacts with SMAD1; this interaction may inhibit SMAD1-binding to SMAD4. Interacts with HOXC8 and HOXC9 By similarity. 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 similarity4 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Axin1O356252EBI-4321242,EBI-2365912
    Bmpr1bP368982EBI-4321242,EBI-7107883
    Prmt1Q9JIF03EBI-4321242,EBI-519055
    UBE2OQ9C0C94EBI-4321242,EBI-2339946From a different organism.

    Protein-protein interaction databases

    BioGridi201279. 11 interactions.
    IntActiO35182. 189 interactions.
    MINTiMINT-1899791.

    Structurei

    3D structure databases

    ProteinModelPortaliO35182.
    SMRiO35182. Positions 193-270, 329-492.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini149 – 276128MH1PROSITE-ProRule annotationAdd
    BLAST
    Domaini332 – 495164MH2PROSITE-ProRule annotationAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi25 – 317Poly-Gly
    Compositional biasi81 – 844Poly-Arg
    Compositional biasi166 – 1694Poly-Leu
    Compositional biasi276 – 2794Poly-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.
    InParanoidiO35182.
    KOiK04677.
    OMAiWRSRLIP.
    OrthoDBiEOG7GN2PK.
    PhylomeDBiO35182.
    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]

    Sequencei

    Sequence statusi: Complete.

    O35182-1 [UniParc]FASTAAdd to Basket

    « Hide

    MFRSKRSGLV RRLWRSRVVP DREEGSGGGG GVDEDGSLGS RAEPAPRARE    50
    GGGCSRSEVR SVAPRRPRDA VGPRGAAIAG RRRRTGGLPR PVSESGAGAG 100
    GSPLDVAEPG GPGWLPESDC ETVTCCLFSE RDAAGAPRDS GDPQARQSPE 150
    PEEGGGPRSR EARSRLLLLE QELKTVTYSL LKRLKERSLD TLLEAVESRG 200
    GVPGGCVLVP RADLRLGGQP APPQLLLGRL FRWPDLQHAV ELKPLCGCHS 250
    FTAAADGPTV CCNPYHFSRL CGPESPPPPY SRLSPPDQYK PLDLSDSTLS 300
    YTETEATNSL ITAPGEFSDA SMSPDATKPS HWCSVAYWEH RTRVGRLYAV 350
    YDQAVSIFYD LPQGSGFCLG QLNLEQRSES VRRTRSKIGF GILLSKEPDG 400
    VWAYNRGEHP IFVNSPTLDA PGGRALVVRK VPPGYSIKVF DFERSGLLQH 450
    ADAAHGPYDP HSVRISFAKG WGPCYSRQFI TSCPCWLEIL LNNHR 495
    Length:495
    Mass (Da):53,714
    Last modified:January 1, 1998 - v1
    Checksum:iD9282D42B120C507
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti176 – 1772VT → AQ in BAB23460. (PubMed:16141072)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF010133 mRNA. Translation: AAB81351.1.
    AK004671 mRNA. Translation: BAB23460.1.
    CCDSiCCDS23273.1.
    RefSeqiNP_032568.3. NM_008542.3.
    XP_006510885.1. XM_006510822.1.
    UniGeneiMm.325757.

    Genome annotation databases

    EnsembliENSMUST00000041029; ENSMUSP00000036285; ENSMUSG00000036867.
    GeneIDi17130.
    KEGGimmu:17130.
    UCSCiuc009qbk.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF010133 mRNA. Translation: AAB81351.1 .
    AK004671 mRNA. Translation: BAB23460.1 .
    CCDSi CCDS23273.1.
    RefSeqi NP_032568.3. NM_008542.3.
    XP_006510885.1. XM_006510822.1.
    UniGenei Mm.325757.

    3D structure databases

    ProteinModelPortali O35182.
    SMRi O35182. Positions 193-270, 329-492.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 201279. 11 interactions.
    IntActi O35182. 189 interactions.
    MINTi MINT-1899791.

    PTM databases

    PhosphoSitei O35182.

    Proteomic databases

    PaxDbi O35182.
    PRIDEi O35182.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000041029 ; ENSMUSP00000036285 ; ENSMUSG00000036867 .
    GeneIDi 17130.
    KEGGi mmu:17130.
    UCSCi uc009qbk.2. mouse.

    Organism-specific databases

    CTDi 4091.
    MGIi MGI:1336883. Smad6.

    Phylogenomic databases

    eggNOGi NOG309572.
    GeneTreei ENSGT00600000084353.
    HOGENOMi HOG000060106.
    HOVERGENi HBG053021.
    InParanoidi O35182.
    KOi K04677.
    OMAi WRSRLIP.
    OrthoDBi EOG7GN2PK.
    PhylomeDBi O35182.
    TreeFami TF314923.

    Enzyme and pathway databases

    Reactomei REACT_220505. Signaling by BMP.

    Miscellaneous databases

    NextBioi 291324.
    PROi O35182.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O35182.
    Bgeei O35182.
    CleanExi MM_SMAD6.
    Genevestigatori O35182.

    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].
      Tissue: Lung.
    2. "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] OF 174-495.
      Strain: C57BL/6J.
      Tissue: Lung.
    3. "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.
    4. "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.
    5. "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.
    6. "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, INDUCTION.
    7. Cited for: METHYLATION AT ARG-74 AND ARG-81, MUTAGENESIS OF ARG-74.

    Entry informationi

    Entry nameiSMAD6_MOUSE
    AccessioniPrimary (citable) accession number: O35182
    Secondary accession number(s): Q9CW62
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 4, 2001
    Last sequence update: January 1, 1998
    Last modified: October 1, 2014
    This is version 127 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