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O35253 (SMAD7_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Smad7
Synonyms:Madh7, Madh8
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length426 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

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. Ref.6 Ref.7 Ref.8

Subcellular location

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. Ref.5 Ref.8

Tissue specificity

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

Post-translational modification

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. Ref.5

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.

Sequence similarities

Belongs to the dwarfin/SMAD family.

Contains 1 MH1 (MAD homology 1) domain.

Contains 1 MH2 (MAD homology 2) domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   LigandDNA-binding
Metal-binding
Zinc
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadherens junction assembly

Inferred from electronic annotation. Source: Ensembl

artery morphogenesis

Inferred from mutant phenotype PubMed 18952608. Source: BHF-UCL

cellular protein complex localization

Inferred from electronic annotation. Source: Ensembl

cellular response to transforming growth factor beta stimulus

Inferred from mutant phenotype PubMed 18593713. Source: BHF-UCL

negative regulation of BMP signaling pathway

Inferred from direct assay PubMed 19850029. Source: MGI

negative regulation of pathway-restricted SMAD protein phosphorylation

Inferred from electronic annotation. Source: Ensembl

negative regulation of peptidyl-serine phosphorylation

Inferred from mutant phenotype PubMed 18593713. Source: BHF-UCL

negative regulation of peptidyl-threonine phosphorylation

Inferred from mutant phenotype PubMed 18593713. Source: BHF-UCL

negative regulation of sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription by competitive promoter binding

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

negative regulation of transforming growth factor beta receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of ubiquitin-protein ligase activity

Inferred from electronic annotation. Source: Ensembl

pathway-restricted SMAD protein phosphorylation

Inferred from mutant phenotype PubMed 18952608. Source: BHF-UCL

positive regulation of cell-cell adhesion

Inferred from mutant phenotype PubMed 18593713. Source: BHF-UCL

positive regulation of proteasomal ubiquitin-dependent protein catabolic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein ubiquitination

Inferred from electronic annotation. Source: Ensembl

protein stabilization

Inferred from electronic annotation. Source: Ensembl

regulation of activin receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

regulation of cardiac muscle contraction

Inferred from mutant phenotype PubMed 18952608. Source: BHF-UCL

regulation of transforming growth factor beta receptor signaling pathway

Inferred by curator PubMed 18952608. Source: BHF-UCL

regulation of ventricular cardiac muscle cell membrane depolarization

Inferred by curator PubMed 18952608. Source: BHF-UCL

response to laminar fluid shear stress

Inferred from electronic annotation. Source: Ensembl

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

transforming growth factor beta receptor signaling pathway

Inferred from direct assay PubMed 11557747. Source: MGI

ureteric bud development

Inferred from expression pattern PubMed 14656760. Source: UniProtKB

ventricular cardiac muscle tissue morphogenesis

Inferred from mutant phenotype PubMed 18952608. Source: BHF-UCL

ventricular septum morphogenesis

Inferred from mutant phenotype PubMed 18952608. Source: BHF-UCL

   Cellular_componentcatenin complex

Inferred from electronic annotation. Source: Ensembl

cell-cell adherens junction

Inferred from electronic annotation. Source: Ensembl

cytosol

Traceable author statement. Source: Reactome

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay PubMed 16601693PubMed 19796622. Source: MGI

protein complex

Inferred from direct assay PubMed 16601693. Source: MGI

transcription factor complex

Inferred from electronic annotation. Source: InterPro

   Molecular_functioncollagen binding

Inferred from physical interaction PubMed 14559231. Source: MGI

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: InterPro

transcription regulatory region DNA binding

Inferred from electronic annotation. Source: Ensembl

transforming growth factor beta receptor, inhibitory cytoplasmic mediator activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Axin1O356252EBI-5274835,EBI-2365912
Sirt1Q923E46EBI-5274835,EBI-1802585
UBE2OQ9C0C92EBI-5274835,EBI-2339946From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform A (identifier: O35253-1)

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.
Isoform B (identifier: O35253-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 426426Mothers against decapentaplegic homolog 7
PRO_0000090873

Regions

Domain64 – 207144MH1
Domain261 – 426166MH2
Region208 – 21710Important for interaction with SMURF2 By similarity
Motif208 – 2114PY-motif By similarity
Compositional bias27 – 359Poly-Gly
Compositional bias49 – 568Poly-Gly
Compositional bias207 – 2104Poly-Pro

Sites

Metal binding1251Zinc By similarity
Metal binding1801Zinc By similarity
Metal binding1921Zinc By similarity
Metal binding1971Zinc By similarity

Amino acid modifications

Modified residue641N6-acetyllysine; alternate By similarity
Modified residue701N6-acetyllysine; alternate By similarity
Modified residue2491Phosphoserine Ref.5
Cross-link64Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate By similarity
Cross-link70Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate By similarity

Natural variations

Alternative sequence2231Missing in isoform B.
VSP_006181

Experimental info

Mutagenesis2491S → A: No effect on stability, nuclear localization or inhibitory function in TGFB signaling. Abolishes transcriptional activity. Ref.5
Mutagenesis2491S → D: No effect. Ref.5
Sequence conflict2331A → V Ref.3
Sequence conflict2331A → V Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform A [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: BEEE751371C0E0CF

FASTA42646,442
        10         20         30         40         50         60 
MFRTKRSALV RRLWRSRAPG GEDEEEGVGG GGGGGELRGE GATDGRAYGA GGGGAGRAGC 

        70         80         90        100        110        120 
CLGKAVRGAK GHHHPHPPTS GAGAAGGAEA DLKALTHSVL KKLKERQLEL LLQAVESRGG 

       130        140        150        160        170        180 
TRTACLLLPG RLDCRLGPGA PASAQPAQPP SSYSLPLLLC KVFRWPDLRH SSEVKRLCCC 

       190        200        210        220        230        240 
ESYGKINPEL VCCNPHHLSR LCELESPPPP YSRYPMDFLK PTAGCPDAVP SSAETGGTNY 

       250        260        270        280        290        300 
LAPGGLSDSQ LLLEPGDRSH WCVVAYWEEK TRVGRLYCVQ EPSLDIFYDL PQGNGFCLGQ 

       310        320        330        340        350        360 
LNSDNKSQLV QKVRSKIGCG IQLTREVDGV WVYNRSSYPI FIKSATLDNP DSRTLLVHKV 

       370        380        390        400        410        420 
FPGFSIKAFD YEKAYSLQRP NDHEFMQQPW TGFTVQISFV KGWGQCYTRQ FISSCPCWLE 


VIFNSR 

« Hide

Isoform B [UniParc].

Checksum: 2C7975BB14492A53
Show »

FASTA42546,371

References

[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF015260 mRNA. Translation: AAB81353.1.
AJ000550 mRNA. Translation: CAA04182.1.
AJ000551 mRNA. Translation: CAA04183.1.
RefSeqNP_001036125.1. NM_001042660.1.
XP_006525766.1. XM_006525703.1.
UniGeneMm.34407.

3D structure databases

ProteinModelPortalO35253.
SMRO35253. Positions 112-201, 261-424.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201280. 27 interactions.
IntActO35253. 8 interactions.
MINTMINT-261918.

PTM databases

PhosphoSiteO35253.

Proteomic databases

PRIDEO35253.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000026999; ENSMUSP00000026999; ENSMUSG00000025880. [O35253-1]
ENSMUST00000168918; ENSMUSP00000129322; ENSMUSG00000025880. [O35253-1]
GeneID17131.
KEGGmmu:17131.
UCSCuc008fqd.1. mouse. [O35253-1]
uc008fqe.2. mouse. [O35253-2]

Organism-specific databases

CTD4092.
MGIMGI:1100518. Smad7.

Phylogenomic databases

eggNOGNOG309572.
GeneTreeENSGT00600000084353.
HOGENOMHOG000060106.
HOVERGENHBG053021.
InParanoidO35253.
KOK04677.
OMAGQLCSEN.
OrthoDBEOG7GN2PK.
PhylomeDBO35253.
TreeFamTF314923.

Gene expression databases

ArrayExpressO35253.
BgeeO35253.
CleanExMM_SMAD7.
GenevestigatorO35253.

Family and domain databases

Gene3D2.60.200.10. 1 hit.
3.90.520.10. 2 hits.
InterProIPR013790. 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]
PANTHERPTHR13703. PTHR13703. 1 hit.
PfamPF03165. MH1. 1 hit.
PF03166. MH2. 1 hit.
[Graphical view]
SMARTSM00523. DWA. 1 hit.
SM00524. DWB. 1 hit.
[Graphical view]
SUPFAMSSF49879. SSF49879. 1 hit.
SSF56366. SSF56366. 2 hits.
PROSITEPS51075. MH1. 1 hit.
PS51076. MH2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSMAD7. mouse.
NextBio291328.
PROO35253.
SOURCESearch...

Entry information

Entry nameSMAD7_MOUSE
AccessionPrimary (citable) accession number: O35253
Secondary accession number(s): O88709
Entry history
Integrated into UniProtKB/Swiss-Prot: May 4, 2001
Last sequence update: January 1, 1998
Last modified: April 16, 2014
This is version 131 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot