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O35253

- SMAD7_MOUSE

UniProt

O35253 - SMAD7_MOUSE

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Protein
Mothers against decapentaplegic homolog 7
Gene
Smad7, Madh7, Madh8
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi125 – 1251Zinc By similarity
Metal bindingi180 – 1801Zinc By similarity
Metal bindingi192 – 1921Zinc By similarity
Metal bindingi197 – 1971Zinc By 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
Complete GO annotation...

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
Complete GO annotation...

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.2 Publications

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
Complete GO annotation...

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 7
PRO_0000090873Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei64 – 641N6-acetyllysine; alternate By similarity
Cross-linki64 – 64Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate By similarity
Modified residuei70 – 701N6-acetyllysine; alternate By similarity
Cross-linki70 – 70Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate By similarity
Modified residuei249 – 2491Phosphoserine1 Publication

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.1 Publication
Polyubiquitinated by RNF111, which is enhanced by AXIN1 and promotes proteasomal degradation. In response to TGF-beta, ubiquitinated by SMURF1; which promotes its degradation By similarity.
Acetylation prevents ubiquitination and degradation mediated by SMURF1 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 WWP1.3 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.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini64 – 207144MH1
Add
BLAST
Domaini261 – 426166MH2
Add
BLAST

Region

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

Motif

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

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

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei223 – 2231Missing in isoform B.
VSP_006181

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti233 – 2331A → V1 Publication
Sequence conflicti233 – 2331A → V1 Publication

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...

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: September 3, 2014
This is version 135 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

Similar proteinsi