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P84022 (SMAD3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | 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 3

Short name=MAD homolog 3
Short name=Mad3
Short name=Mothers against DPP homolog 3
Short name=hMAD-3
Alternative name(s):
JV15-2
SMAD family member 3
Short name=SMAD 3
Short name=Smad3
Short name=hSMAD3
Gene names
Name:SMAD3
Synonyms:MADH3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length425 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.14 Ref.15 Ref.16 Ref.23 Ref.24 Ref.25 Ref.32 Ref.36 Ref.38 Ref.43 Ref.45

Subunit structure

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. Part of a complex consisting of AIP1, ACVR2A, ACVR1B and SMAD3. Interacts with AIP1, TGFB1I1, TTRAP, FOXL2, PML, PRDM16, HGS, WWP1 and SNW1. Interacts (via MH2 domain) with CITED2 (via C-terminus) By similarity. Interacts with NEDD4L; the interaction requires TGF-beta stimulation By similarity. Interacts (via the MH2 domain) with ZFYVE9. Interacts with HDAC1, VDR, TGIF and TGIF2, RUNX3, CREBBP, SKOR1, SKOR2, SNON, ATF2, SMURF2 and TGFB1I1. Interacts with DACH1; the interaction inhibits the TGF-beta signaling. 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 MEN1. Interacts with IL1F7. 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. Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.24 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35 Ref.36 Ref.37 Ref.39 Ref.40 Ref.43 Ref.44 Ref.46 Ref.48 Ref.49 Ref.54

Subcellular location

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. Ref.25 Ref.26 Ref.29 Ref.32 Ref.36 Ref.43 Ref.45 Ref.49

Domain

The MH1 domain is required for DNA binding. Also binds zinc ions which are necessary for the DNA binding. Ref.24

The MH2 domain is required for both homomeric and heteromeric interactions and for transcriptional regulation. Sufficient for nuclear import. Ref.24

The linker region is required for the TGFbeta-mediated transcriptional activity and acts synergistically with the MH2 domain. Ref.24

Post-translational modification

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. Phosphorylated by PDPK1. Ref.1 Ref.12 Ref.20 Ref.23 Ref.24 Ref.25 Ref.32 Ref.36 Ref.40 Ref.45

Acetylation in the nucleus by EP300 in the MH2 domain regulates positively its transcriptional activity and is enhanced by TGF-beta. Ref.38

Ubiquitinated. Monoubiquitinated, leading to prevent DNA-binding. Deubiquitination by USP15 alleviates inhibition and promotes activation of TGF-beta target genes. Ref.40 Ref.48

Involvement in disease

Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
Note: The disease may be caused by mutations affecting the gene represented in this entry.

Loeys-Dietz syndrome 3 (LDS3) [MIM:613795]: An aortic aneurysm syndrome with widespread systemic involvement. The disorder is characterized by the triad of arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. Patients with LDS3 also manifest early-onset osteoarthritis. They lack craniosynostosis and mental retardation.
Note: The disease is caused by mutations affecting the gene represented in this entry. SMAD3 mutations have been reported to be also associated with thoracic aortic aneurysms and dissection (TAAD) (Ref.56). This phenotype is distinguised from LDS3 by having aneurysms restricted to thoracic aorta. As individuals carrying these mutations also exhibit aneurysms of other arteries, including abdominal aorta, iliac, and/or intracranial arteries (Ref.56), they have been classified as LDS3 by the OMIM resource. Ref.56 Ref.57

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
Polymorphism
   DiseaseAortic aneurysm
Disease mutation
   LigandDNA-binding
Metal-binding
Zinc
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processSMAD protein complex assembly

Inferred from direct assay PubMed 10823886PubMed 9111321. Source: BHF-UCL

T cell activation

Inferred from electronic annotation. Source: Ensembl

activation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from mutant phenotype PubMed 15107418. Source: BHF-UCL

activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

activin receptor signaling pathway

Inferred from mutant phenotype PubMed 15150278. Source: BHF-UCL

cell cycle arrest

Inferred from mutant phenotype PubMed 14555988. Source: BHF-UCL

cell-cell junction organization

Inferred from mutant phenotype PubMed 18505915. Source: BHF-UCL

developmental growth

Inferred from electronic annotation. Source: Ensembl

embryonic cranial skeleton morphogenesis

Inferred from electronic annotation. Source: Ensembl

embryonic foregut morphogenesis

Inferred from electronic annotation. Source: Ensembl

embryonic pattern specification

Inferred from electronic annotation. Source: Ensembl

endoderm development

Inferred from electronic annotation. Source: Ensembl

evasion or tolerance of host defenses by virus

Inferred from direct assay PubMed 15334054. Source: BHF-UCL

extrinsic apoptotic signaling pathway

Inferred from mutant phenotype PubMed 15334054. Source: BHF-UCL

gene expression

Traceable author statement. Source: Reactome

heart looping

Inferred from electronic annotation. Source: Ensembl

immune response

Inferred from mutant phenotype PubMed 16886151. Source: BHF-UCL

immune system development

Inferred from electronic annotation. Source: Ensembl

in utero embryonic development

Inferred from electronic annotation. Source: Ensembl

intracellular signal transduction

Inferred from direct assay PubMed 9111321. Source: GOC

lens fiber cell differentiation

Inferred from electronic annotation. Source: Ensembl

liver development

Inferred from electronic annotation. Source: Ensembl

mesoderm formation

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell growth

Inferred from direct assay Ref.1. Source: BHF-UCL

negative regulation of inflammatory response

Inferred from electronic annotation. Source: Ensembl

negative regulation of mitotic cell cycle

Inferred from mutant phenotype PubMed 14555988. Source: BHF-UCL

negative regulation of osteoblast differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of osteoblast proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of protein catabolic process

Inferred from mutant phenotype PubMed 20097766. Source: BHF-UCL

negative regulation of protein phosphorylation

Inferred from mutant phenotype PubMed 20097766. Source: BHF-UCL

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.1. Source: BHF-UCL

negative regulation of transforming growth factor beta receptor signaling pathway

Traceable author statement. Source: Reactome

negative regulation of wound healing

Inferred from electronic annotation. Source: Ensembl

nodal signaling pathway

Inferred from mutant phenotype PubMed 15150278. Source: BHF-UCL

osteoblast development

Inferred from electronic annotation. Source: Ensembl

paraxial mesoderm morphogenesis

Inferred from electronic annotation. Source: Ensembl

pericardium development

Inferred from electronic annotation. Source: Ensembl

positive regulation of alkaline phosphatase activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of bone mineralization

Inferred from electronic annotation. Source: Ensembl

positive regulation of canonical Wnt signaling pathway

Inferred from mutant phenotype PubMed 20097766. Source: BHF-UCL

positive regulation of catenin import into nucleus

Inferred from mutant phenotype PubMed 20097766. Source: BHF-UCL

positive regulation of cell migration

Inferred from electronic annotation. Source: Ensembl

positive regulation of chondrocyte differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of epithelial to mesenchymal transition

Inferred from direct assay PubMed 21307346. Source: BHF-UCL

positive regulation of focal adhesion assembly

Inferred from electronic annotation. Source: Ensembl

positive regulation of gene expression involved in extracellular matrix organization

Inferred from mutant phenotype PubMed 21307346. Source: BHF-UCL

positive regulation of interleukin-1 beta production

Inferred from electronic annotation. Source: Ensembl

positive regulation of positive chemotaxis

Inferred from electronic annotation. Source: Ensembl

positive regulation of stress fiber assembly

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription factor import into nucleus

Inferred from direct assay Ref.29. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 18832382. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 9111321Ref.9Ref.14. Source: BHF-UCL

positive regulation of transforming growth factor beta3 production

Inferred from electronic annotation. Source: Ensembl

primary miRNA processing

Traceable author statement PubMed 19018011. Source: BHF-UCL

protein stabilization

Inferred from mutant phenotype PubMed 20097766. Source: BHF-UCL

regulation of binding

Inferred from electronic annotation. Source: Ensembl

regulation of epithelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

regulation of immune response

Inferred from electronic annotation. Source: Ensembl

regulation of striated muscle tissue development

Inferred from electronic annotation. Source: Ensembl

regulation of transforming growth factor beta receptor signaling pathway

Inferred from mutant phenotype Ref.1. Source: BHF-UCL

regulation of transforming growth factor beta2 production

Inferred from mutant phenotype PubMed 12411310. Source: BHF-UCL

response to hypoxia

Inferred from mutant phenotype PubMed 12411310. Source: BHF-UCL

signal transduction involved in regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

somitogenesis

Inferred from electronic annotation. Source: Ensembl

thyroid gland development

Inferred from electronic annotation. Source: Ensembl

transcription initiation from RNA polymerase II promoter

Traceable author statement. Source: Reactome

transcription, DNA-templated

Traceable author statement. Source: Reactome

transdifferentiation

Inferred from electronic annotation. Source: Ensembl

transforming growth factor beta receptor signaling pathway

Inferred from direct assay Ref.48. Source: UniProtKB

transport

Inferred from direct assay Ref.29. Source: BHF-UCL

ureteric bud development

Inferred from electronic annotation. Source: Ensembl

wound healing

Traceable author statement PubMed 19018011. Source: BHF-UCL

   Cellular_componentSMAD protein complex

Inferred from direct assay PubMed 18832382Ref.48. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.48. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

nuclear inner membrane

Inferred from direct assay Ref.28. Source: UniProtKB

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.48. Source: UniProtKB

plasma membrane

Inferred from electronic annotation. Source: Ensembl

receptor complex

Inferred from mutant phenotype Ref.1. Source: BHF-UCL

transcription factor complex

Inferred from direct assay Ref.48. Source: UniProtKB

   Molecular_functionR-SMAD binding

Inferred from physical interaction Ref.9. Source: BHF-UCL

RNA polymerase II activating transcription factor binding

Inferred from physical interaction PubMed 17251190. Source: BHF-UCL

beta-catenin binding

Inferred from physical interaction PubMed 20097766. Source: BHF-UCL

chromatin DNA binding

Inferred from electronic annotation. Source: Ensembl

co-SMAD binding

Inferred from physical interaction Ref.1PubMed 9111321Ref.9Ref.14. Source: BHF-UCL

core promoter proximal region sequence-specific DNA binding

Inferred from direct assay PubMed 18832382Ref.48. Source: UniProtKB

double-stranded DNA binding

Inferred from electronic annotation. Source: Ensembl

phosphatase binding

Inferred from physical interaction Ref.32. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 10681527Ref.21Ref.24Ref.28Ref.31Ref.30Ref.35Ref.37PubMed 17469184Ref.39PubMed 18832382Ref.44Ref.43Ref.48Ref.10Ref.15. Source: UniProtKB

protein homodimerization activity

Inferred from physical interaction Ref.1. Source: BHF-UCL

protein kinase binding

Inferred from physical interaction PubMed 12874272. Source: UniProtKB

sequence-specific DNA binding

Inferred from direct assay PubMed 10823886. Source: BHF-UCL

sequence-specific DNA binding transcription factor activity

Inferred from direct assay Ref.48. Source: UniProtKB

transcription factor binding

Inferred from physical interaction PubMed 21828274Ref.14. Source: BHF-UCL

transcription regulatory region DNA binding

Inferred from direct assay Ref.14. Source: BHF-UCL

transforming growth factor beta receptor binding

Inferred from physical interaction Ref.9. Source: BHF-UCL

transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity

Inferred from direct assay PubMed 9111321. Source: BHF-UCL

ubiquitin binding

Inferred from direct assay Ref.40. Source: UniProtKB

ubiquitin protein ligase binding

Inferred from physical interaction PubMed 11278251PubMed 19122240. Source: BHF-UCL

zinc ion binding

Inferred from direct assay Ref.53. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P84022-1)

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 2 (identifier: P84022-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-68: MSSILPFTPP...NVNTKCITIP → MSCLHPRQTWKGAALVHRKAWWMG
Note: No experimental confirmation available.
Isoform 3 (identifier: P84022-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-105: Missing.
Isoform 4 (identifier: P84022-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-195: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.42
Chain2 – 425424Mothers against decapentaplegic homolog 3
PRO_0000090856

Regions

Domain10 – 136127MH1
Domain232 – 425194MH2
Region137 – 23195Linker
Region271 – 32454Sufficient for interaction with XPO4

Sites

Metal binding641Zinc
Metal binding1091Zinc
Metal binding1211Zinc
Metal binding1261Zinc
Site401Required for trimerization
Site411Required for interaction with DNA and JUN and for functional cooperation with JUN

Amino acid modifications

Modified residue21N-acetylserine Ref.42 Ref.50
Modified residue81Phosphothreonine; by CDK2 and CDK4 Ref.23
Modified residue1791Phosphothreonine; by CDK2, CDK4 and MAPK Ref.23 Ref.25 Ref.45
Modified residue2041Phosphoserine; by GSK3 and MAPK Ref.23 Ref.25 Ref.45
Modified residue2081Phosphoserine; by MAPK Ref.23 Ref.25 Ref.45
Modified residue2131Phosphoserine; by CDK2 and CDK4 Ref.23
Modified residue3781N6-acetyllysine Ref.38
Modified residue4161Phosphoserine Ref.41
Modified residue4181Phosphoserine; by CK1 Ref.40
Modified residue4221Phosphoserine; by TGFBR1 By similarity
Modified residue4231Phosphoserine; by TGFBR1 By similarity
Modified residue4251Phosphoserine; by TGFBR1 By similarity
Cross-link33Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Probable
Cross-link81Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Probable

Natural variations

Alternative sequence1 – 195195Missing in isoform 4.
VSP_045348
Alternative sequence1 – 105105Missing in isoform 3.
VSP_043793
Alternative sequence1 – 6868MSSIL…CITIP → MSCLHPRQTWKGAALVHRKA WWMG in isoform 2.
VSP_042900
Natural variant1121A → V in LDS3. Ref.56
VAR_067051
Natural variant1701I → V.
Corresponds to variant rs35874463 [ dbSNP | Ensembl ].
VAR_052021
Natural variant2391E → K in LDS3. Ref.56
VAR_067047
Natural variant2611T → I in LDS3. Ref.57
VAR_065578
Natural variant2791R → K in LDS3. Ref.56
VAR_067048
Natural variant2871R → W in LDS3. Ref.57
VAR_065579
Natural variant3931P → L in a colorectal cancer sample; somatic mutation. Ref.55
VAR_036474

Experimental info

Mutagenesis81T → V: Reduced phosphorylation, increased transcriptional and antiproliferative activities. Further increase in transcriptional and antiproliferative activities; when associated with V-179 and A-213. Ref.23
Mutagenesis331K → R: Slightly decreased monoubiquitination. Ref.48
Mutagenesis401K → A: Little effect on interaction with DNA or JUN. Abolishes interaction with DNA and JUN; when associated with A-41; A-43 and A-44. Ref.16
Mutagenesis411K → A: Greatly reduced interaction with DNA and JUN. Abolishes interaction with DNA and JUN; when associated with A-40; A-44 and A-43. Ref.16
Mutagenesis431K → A: Little effect on interaction with DNA or JUN. Abolishes interaction with DNA and JUN; when associated with A-40; A-41 and A-44. Ref.16
Mutagenesis441K → A: Little effect on interaction with DNA or JUN. Abolishes interaction with JUN; when associated with A-40; A-41 and A-43. Ref.16
Mutagenesis531K → R: Slightly decreased monoubiquitination. Ref.48
Mutagenesis741R → D: Reduced interaction with JUN. Loss of transcriptional activity and cooperation with JUN. Ref.16
Mutagenesis811K → R: Decreased monoubiquitination. Ref.48
Mutagenesis1791T → V: Reduced phosphorylation, increased transcriptional and increased antiproliferative activities. Further increase in transcriptional and antiproliferative activities; when associated with V-8 and A-213. Ref.23 Ref.25 Ref.45
Mutagenesis2041S → A: Increased transcriptional activity. Further increased transcriptional activity; when associated with S-208. Ref.23 Ref.25 Ref.45
Mutagenesis2081S → A: Increased transcriptional activity. Further increased transcriptional activity; when associated with S-208. Ref.23 Ref.25 Ref.45
Mutagenesis2131S → A: Reduced phosphorylation. Increased transcriptional and antiproliferative activities. Further increase in transcriptional and antiproliferative activities; when associated with V-8 and V-179. Ref.23
Mutagenesis3331K → R: No effect on acetylation. Completely abolishes acetylation and 97% reduction in transcriptional activity; when associated with R-341; R-378 and R-409. Ref.38
Mutagenesis3411K → R: No effect on acetylation. Completely abolishes acetylation and 97% reduction in transcriptional activity; when associated with R-333; R-378 and R-409. Ref.38
Mutagenesis3781K → Q: Increased transcriptional activity. No further increase in transcriptional activity with EP300. Ref.38
Mutagenesis3781K → R: Greatly reduced acetylation and 85% reduction in transcriptional activity. Completely abolishes acetylation and 97% reduction in transcriptional activity; when associated with R-333; R-341 and R-409. Ref.38
Mutagenesis4091K → R: No effect on acetylation. Completely abolishes acetylation and 97% reduction in transcriptional activity; when associated with R-333; R-341 and R-378. Ref.38
Mutagenesis4181S → A: Increased constitutive activity. Ref.40
Mutagenesis4181S → D: Decreased activity. Ref.40
Mutagenesis422 – 4254SSVS → AAVA: Does not abolish protein nuclear export. Abolishes almost completely acetylation. Ref.20 Ref.34 Ref.38
Mutagenesis422 – 4254SSVS → EEVE: Forms heterotrimers. Ref.20 Ref.34 Ref.38
Mutagenesis422 – 4254SSVS → RRVR: Diminishes cargo protein export. Ref.20 Ref.34 Ref.38
Sequence conflict1781E → EVGTWAAQAGL in BAA22032. Ref.3
Sequence conflict3601F → L in BAH13315. Ref.5

Secondary structure

.................................................................... 425
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 5, 2004. Version 1.
Checksum: 46DF5E8B371321AC

FASTA42548,081
        10         20         30         40         50         60 
MSSILPFTPP IVKRLLGWKK GEQNGQEEKW CEKAVKSLVK KLKKTGQLDE LEKAITTQNV 

        70         80         90        100        110        120 
NTKCITIPRS LDGRLQVSHR KGLPHVIYCR LWRWPDLHSH HELRAMELCE FAFNMKKDEV 

       130        140        150        160        170        180 
CVNPYHYQRV ETPVLPPVLV PRHTEIPAEF PPLDDYSHSI PENTNFPAGI EPQSNIPETP 

       190        200        210        220        230        240 
PPGYLSEDGE TSDHQMNHSM DAGSPNLSPN PMSPAHNNLD LQPVTYCEPA FWCSISYYEL 

       250        260        270        280        290        300 
NQRVGETFHA SQPSMTVDGF TDPSNSERFC LGLLSNVNRN AAVELTRRHI GRGVRLYYIG 

       310        320        330        340        350        360 
GEVFAECLSD SAIFVQSPNC NQRYGWHPAT VCKIPPGCNL KIFNNQEFAA LLAQSVNQGF 

       370        380        390        400        410        420 
EAVYQLTRMC TIRMSFVKGW GAEYRRQTVT STPCWIELHL NGPLQWLDKV LTQMGSPSIR 


CSSVS 

« Hide

Isoform 2 [UniParc].

Checksum: D436B607B2677761
Show »

FASTA38143,237
Isoform 3 [UniParc].

Checksum: CB3D9B2D53AAC9E9
Show »

FASTA32035,895
Isoform 4 [UniParc].

Checksum: AFC64318B5EC08D1
Show »

FASTA23025,722

References

« Hide 'large scale' references
[1]"Receptor-associated Mad homologues synergize as effectors of the TGF-beta response."
Zhang Y., Feng X.-H., Wu R.-Y., Derynck R.
Nature 383:168-172(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PHOSPHORYLATION.
Tissue: Placenta.
[2]"Mad-related genes in the human."
Riggins G.J., Thiagalingam S., Rosenblum E., Weinstein C.L., Kern S.E., Hamilton S.R., Willson J.K.V., Markowitz S.D., Kinzler K.W., Vogelstein B.V.
Nat. Genet. 13:347-349(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]"Genomic structure of the human Smad3 gene and its infrequent alterations in colorectal cancers."
Arai T., Akiyama Y., Okabe S., Ando M., Endo M., Yuasa Y.
Cancer Lett. 122:157-163(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Colon carcinoma.
[4]Hagiwara K., Yang K., McMenamin M.G., Freeman A.H., Bennett W.P., Nagashima M., Minter A.R., Miyazono K., Takenoshita S., Harris C.C.
Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2; 3 AND 4).
Tissue: Brain.
[6]"Analysis of the DNA sequence and duplication history of human chromosome 15."
Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. expand/collapse author list , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"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 1).
Tissue: Pancreas.
[9]"TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4."
Nakao A., Imamura T., Souchelnytskyi S., Kawabata M., Ishisaki A., Oeda E., Tamaki K., Hanai J., Heldin C.H., Miyazono K., ten Dijke P.
EMBO J. 16:5353-5362(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TGFBR1.
[10]"SARA, a FYVE domain protein that recruits Smad2 to the TGFbeta receptor."
Tsukazaki T., Chiang T.A., Davison A.F., Attisano L., Wrana J.L.
Cell 95:779-791(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ZFYVE9.
[11]"Smad proteins exist as monomers in vivo and undergo homo- and hetero-oligomerization upon activation by serine/threonine kinase receptors."
Kawabata M., Inoue H., Hanyu A., Imamura T., Miyazono K.
EMBO J. 17:4056-4065(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[12]"TGF-beta-induced phosphorylation of Smad3 regulates its interaction with coactivator p300/CREB-binding protein."
Shen X., Hu P.P., Liberati N.T., Datto M.B., Frederick J.P., Wang X.F.
Mol. Biol. Cell 9:3309-3319(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, INTERACTION WITH EP300.
[13]"The oncoprotein Evi-1 represses TGF-beta signalling by inhibiting Smad3."
Kurokawa M., Mitani K., Irie K., Matsuyama T., Takahashi T., Chiba S., Yazaki Y., Matsumoto K., Hirai H.
Nature 394:92-96(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MECOM.
[14]"Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced transcription."
Zhang Y., Feng X.H., Derynck R.
Nature 394:909-913(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION AS A COMPONENT OF THE SMAD3/SMAD4/JUN/FOS COMPLEX, INTERACTION WITH JUN AND FOS, DNA-BINDING, FUNCTION.
[15]"Roles of pathway-specific and inhibitory Smads in activin receptor signaling."
Lebrun J.J., Takabe K., Chen Y., Vale W.
Mol. Endocrinol. 13:15-23(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ACVR1B, FUNCTION.
[16]"Structural and functional characterization of the transforming growth factor-beta -induced Smad3/c-Jun transcriptional cooperativity."
Qing J., Zhang Y., Derynck R.
J. Biol. Chem. 275:38802-38812(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH JUN IN THE SMAD3/SMAD4/JUN/FOS COMPLEX, DNA-BINDING, FUNCTION, MUTAGENESIS OF LYS-40; LYS-41; LYS-43; LYS-44 AND ARG-74.
[17]"The adaptor molecule Disabled-2 links the transforming growth factor beta receptors to the Smad pathway."
Hocevar B.A., Smine A., Xu X.X., Howe P.H.
EMBO J. 20:2789-2801(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DAB2.
[18]"Ski-interacting protein interacts with Smad proteins to augment transforming growth factor-beta-dependent transcription."
Leong G.M., Subramaniam N., Figueroa J., Flanagan J.L., Hayman M.J., Eisman J.A., Kouzmenko A.P.
J. Biol. Chem. 276:18243-18248(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SNW1.
[19]"TGIF2 interacts with histone deacetylase 1 and represses transcription."
Melhuish T.A., Gallo C.M., Wotton D.
J. Biol. Chem. 276:32109-32114(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TGIF2.
[20]"The L3 loop and C-terminal phosphorylation jointly define Smad protein trimerization."
Chacko B.M., Qin B., Correia J.J., Lam S.S., de Caestecker M.P., Lin K.
Nat. Struct. Biol. 8:248-253(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, PHOSPHORYLATION, MUTAGENESIS OF 422-SER--SER-425.
[21]"Inactivation of menin, a Smad3-interacting protein, blocks transforming growth factor type beta signaling."
Kaji H., Canaff L., Lebrun J.J., Goltzman D., Hendy G.N.
Proc. Natl. Acad. Sci. U.S.A. 98:3837-3842(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MEN1.
[22]"DACH1 inhibits transforming growth factor-beta signaling through binding Smad4."
Wu K., Yang Y., Wang C., Davoli M.A., D'Amico M., Li A., Cveklova K., Kozmik Z., Lisanti M.P., Russell R.G., Cvekl A., Pestell R.G.
J. Biol. Chem. 278:51673-51684(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DACH1.
[23]"Cyclin-dependent kinases regulate the antiproliferative function of Smads."
Matsuura I., Denissova N.G., Wang G., He D., Long J., Liu F.
Nature 430:226-231(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-8; THR-179; SER-204; SER-208 AND SER-213, FUNCTION, MUTAGENESIS OF THR-8; THR-179; SER-204; SER-208 AND SER-213.
[24]"The Smad3 linker region contains a transcriptional activation domain."
Wang G., Long J., Matsuura I., He D., Liu F.
Biochem. J. 386:29-34(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: TRANSCRIPTIONAL ACTIVATION DOMAIN, FUNCTION, PHOSPHORYLATION, SUBUNIT, INTERACTION WITH EP300.
[25]"Identification and characterization of ERK MAP kinase phosphorylation sites in Smad3."
Matsuura I., Wang G., He D., Liu F.
Biochemistry 44:12546-12553(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-179; SER-204 AND SER-208, SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF THR-179; SER-204 AND SER-208.
[26]"MAN1, an integral protein of the inner nuclear membrane, binds Smad2 and Smad3 and antagonizes transforming growth factor-beta signaling."
Lin F., Morrison J.M., Wu W., Worman H.J.
Hum. Mol. Genet. 14:437-445(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH LEMD3.
[27]"Novel function of androgen receptor-associated protein 55/Hic-5 as a negative regulator of Smad3 signaling."
Wang H., Song K., Sponseller T.L., Danielpour D.
J. Biol. Chem. 280:5154-5162(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TGFB1I1.
[28]"The integral inner nuclear membrane protein MAN1 physically interacts with the R-Smad proteins to repress signaling by the transforming growth factor-{beta} superfamily of cytokines."
Pan D., Estevez-Salmeron L.D., Stroschein S.L., Zhu X., He J., Zhou S., Luo K.
J. Biol. Chem. 280:15992-16001(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LEMD3.
[29]"Nuclear targeting of transforming growth factor-beta-activated Smad complexes."
Chen H.B., Rud J.G., Lin K., Xu L.
J. Biol. Chem. 280:21329-21336(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, SUBCELLULAR LOCATION.
[30]"Cloning and functional characterization of a new Ski homolog, Fussel-18, specifically expressed in neuronal tissues."
Arndt S., Poser I., Schubert T., Moser M., Bosserhoff A.-K.
Lab. Invest. 85:1330-1341(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SKOR2.
[31]"Oligomerization of Evi-1 regulated by the PR domain contributes to recruitment of corepressor CtBP."
Nitta E., Izutsu K., Yamaguchi Y., Imai Y., Ogawa S., Chiba S., Kurokawa M., Hirai H.
Oncogene 24:6165-6173(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MECOM.
[32]"PPM1A functions as a Smad phosphatase to terminate TGFbeta signaling."
Lin X., Duan X., Liang Y.Y., Su Y., Wrighton K.H., Long J., Hu M., Davis C.M., Wang J., Brunicardi F.C., Shi Y., Chen Y.G., Meng A., Feng X.H.
Cell 125:915-928(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PPM1A, DEPHOSPHORYLATION, FUNCTION, SUBCELLULAR LOCATION.
[33]"Hematopoiesis controlled by distinct TIF1gamma and Smad4 branches of the TGFbeta pathway."
He W., Dorn D.C., Erdjument-Bromage H., Tempst P., Moore M.A., Massague J.
Cell 125:929-941(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH SMAD2 AND TRIM33, INTERACTION WITH SMAD2 AND TRIM33.
[34]"The mechanism of nuclear export of Smad3 involves exportin 4 and Ran."
Kurisaki A., Kurisaki K., Kowanetz M., Sugino H., Yoneda Y., Heldin C.-H., Moustakas A.
Mol. Cell. Biol. 26:1318-1332(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH RAN AND XPO4, INTERACTION WITH XPO4, MUTAGENESIS OF 422-SER--SER-425.
[35]"Potentiation of Smad-mediated transcriptional activation by the RNA-binding protein RBPMS."
Sun Y., Ding L., Zhang H., Han J., Yang X., Yan J., Zhu Y., Li J., Song H., Ye Q.
Nucleic Acids Res. 34:6314-6326(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RBPMS.
[36]"3-Phosphoinositide-dependent PDK1 negatively regulates transforming growth factor-beta-induced signaling in a kinase-dependent manner through physical interaction with Smad proteins."
Seong H.A., Jung H., Kim K.T., Ha H.
J. Biol. Chem. 282:12272-12289(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION BY PDPK1, INTERACTION WITH PDPK1.
[37]"Fussel-15, a novel Ski/Sno homolog protein, antagonizes BMP signaling."
Arndt S., Poser I., Moser M., Bosserhoff A.-K.
Mol. Cell. Neurosci. 34:603-611(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SKOR1.
[38]"Smad3 is acetylated by p300/CBP to regulate its transactivation activity."
Inoue Y., Itoh Y., Abe K., Okamoto T., Daitoku H., Fukamizu A., Onozaki K., Hayashi H.
Oncogene 26:500-508(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION AT LYS-378, FUNCTION, MUTAGENESIS OF LYS-333; LYS-341; LYS-378; LYS-409 AND 422-SER--SER-425.
[39]"TAZ controls Smad nucleocytoplasmic shuttling and regulates human embryonic stem-cell self-renewal."
Varelas X., Sakuma R., Samavarchi-Tehrani P., Peerani R., Rao B.M., Dembowy J., Yaffe M.B., Zandstra P.W., Wrana J.L.
Nat. Cell Biol. 10:837-848(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH WWTR1.
[40]"Ligand-dependent ubiquitination of Smad3 is regulated by casein kinase 1 gamma 2, an inhibitor of TGF-beta signaling."
Guo X., Waddell D.S., Wang W., Wang Z., Liberati N.T., Yong S., Liu X., Wang X.-F.
Oncogene 27:7235-7247(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CSNK1G2, UBIQUITINATION, PHOSPHORYLATION AT SER-418 BY CSNK1G2/CK1, MUTAGENESIS OF SER-418.
[41]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-416, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[42]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[43]"Nuclear export of Smad2 and Smad3 by RanBP3 facilitates termination of TGF-beta signaling."
Dai F., Lin X., Chang C., Feng X.H.
Dev. Cell 16:345-357(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RANBP3, SUBCELLULAR LOCATION, FUNCTION.
[44]"SKI and MEL1 cooperate to inhibit transforming growth factor-beta signal in gastric cancer cells."
Takahata M., Inoue Y., Tsuda H., Imoto I., Koinuma D., Hayashi M., Ichikura T., Yamori T., Nagasaki K., Yoshida M., Matsuoka M., Morishita K., Yuki K., Hanyu A., Miyazawa K., Inazawa J., Miyazono K., Imamura T.
J. Biol. Chem. 284:3334-3344(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PRDM16; SKI AND HDAC1.
[45]"Transforming growth factor-{beta}-inducible phosphorylation of Smad3."
Wang G., Matsuura I., He D., Liu F.
J. Biol. Chem. 284:9663-9673(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-179; SER-204 AND SER-208, SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF THR-179; SER-204 AND SER-208.
[46]"IL-37 is a fundamental inhibitor of innate immunity."
Nold M.F., Nold-Petry C.A., Zepp J.A., Palmer B.E., Bufler P., Dinarello C.A.
Nat. Immunol. 11:1014-1022(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IL1F7.
[47]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[48]"USP15 is a deubiquitylating enzyme for receptor-activated SMADs."
Inui M., Manfrin A., Mamidi A., Martello G., Morsut L., Soligo S., Enzo E., Moro S., Polo S., Dupont S., Cordenonsi M., Piccolo S.
Nat. Cell Biol. 13:1368-1375(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, DEUBIQUITINATION BY USP15, DNA-BINDING, INTERACTION WITH USP15, UBIQUITINATION AT LYS-33 AND LYS-81, MUTAGENESIS OF LYS-33; LYS-53 AND LYS-81.
[49]"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.
[50]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[51]"Crystal structure of a Smad MH1 domain bound to DNA: insights on DNA binding in TGF-beta signaling."
Shi Y., Wang Y.-F., Jayaraman L., Yang H., Massague J., Pavletich N.P.
Cell 94:585-594(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-144.
[52]"Smad3 allostery links TGF-beta receptor kinase activation to transcriptional control."
Qin B.Y., Lam S.S., Correia J.J., Lin K.
Genes Dev. 16:1950-1963(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.74 ANGSTROMS) OF 220-425 IN COMPLEX WITH ZFYVE9.
[53]"Features of a Smad3 MH1-DNA complex. Roles of water and zinc in DNA binding."
Chai J., Wu J.W., Yan N., Massague J., Pavletich N.P., Shi Y.
J. Biol. Chem. 278:20327-20331(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1-144 IN COMPLEX WITH DNA, ZINC.
[54]"Structural basis of heteromeric smad protein assembly in TGF-beta signaling."
Chacko B.M., Qin B.Y., Tiwari A., Shi G., Lam S., Hayward L.J., De Caestecker M., Lin K.
Mol. Cell 15:813-823(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 228-424 IN COMPLEX WITH SMAD4, SUBUNIT.
[55]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-393.
[56]"Exome sequencing identifies SMAD3 mutations as a cause of familial thoracic aortic aneurysm and dissection with intracranial and other arterial aneurysms."
Regalado E.S., Guo D.C., Villamizar C., Avidan N., Gilchrist D., McGillivray B., Clarke L., Bernier F., Santos-Cortez R.L., Leal S.M., Bertoli-Avella A.M., Shendure J., Rieder M.J., Nickerson D.A., Milewicz D.M.
Circ. Res. 109:680-686(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LDS3 VAL-112; LYS-239 AND LYS-279.
[57]"Mutations in SMAD3 cause a syndromic form of aortic aneurysms and dissections with early-onset osteoarthritis."
van de Laar I.M., Oldenburg R.A., Pals G., Roos-Hesselink J.W., de Graaf B.M., Verhagen J.M., Hoedemaekers Y.M., Willemsen R., Severijnen L.A., Venselaar H., Vriend G., Pattynama P.M., Collee M., Majoor-Krakauer D., Poldermans D., Frohn-Mulder I.M., Micha D., Timmermans J. expand/collapse author list , Hilhorst-Hofstee Y., Bierma-Zeinstra S.M., Willems P.J., Kros J.M., Oei E.H., Oostra B.A., Wessels M.W., Bertoli-Avella A.M.
Nat. Genet. 43:121-126(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LDS3 ILE-261 AND TRP-287.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U68019 mRNA. Translation: AAB80960.1.
U76622 mRNA. Translation: AAB18967.1.
AB004930 Genomic DNA. Translation: BAA22032.1.
AF025300 expand/collapse EMBL AC list , AF025293, AF025294, AF025295, AF025296, AF025297, AF025298, AF025299 Genomic DNA. Translation: AAL68976.1.
AK290881 mRNA. Translation: BAF83570.1.
AK298139 mRNA. Translation: BAH12731.1.
AK300614 mRNA. Translation: BAH13315.1.
AK316017 mRNA. Translation: BAH14388.1.
AC012568 Genomic DNA. No translation available.
AC087482 Genomic DNA. No translation available.
CH471082 Genomic DNA. Translation: EAW77788.1.
BC050743 mRNA. Translation: AAH50743.1.
CCDSCCDS10222.1. [P84022-1]
CCDS45288.1. [P84022-2]
CCDS53950.1. [P84022-3]
CCDS53951.1. [P84022-4]
PIRS71798.
RefSeqNP_001138574.1. NM_001145102.1. [P84022-3]
NP_001138575.1. NM_001145103.1. [P84022-2]
NP_001138576.1. NM_001145104.1. [P84022-4]
NP_005893.1. NM_005902.3. [P84022-1]
UniGeneHs.727986.
Hs.742270.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1MHDX-ray2.80A/B1-132[»]
1MJSX-ray1.91A229-425[»]
1MK2X-ray2.74A220-425[»]
1OZJX-ray2.40A/B1-144[»]
1U7FX-ray2.60A/C228-425[»]
2LAJNMR-B202-211[»]
2LB2NMR-B178-189[»]
ProteinModelPortalP84022.
SMRP84022. Positions 7-132, 228-425.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110263. 316 interactions.
DIPDIP-29720N.
IntActP84022. 148 interactions.
MINTMINT-193987.

Chemistry

BindingDBP84022.
ChEMBLCHEMBL1293258.

PTM databases

PhosphoSiteP84022.

Polymorphism databases

DMDM51338669.

Proteomic databases

MaxQBP84022.
PaxDbP84022.
PRIDEP84022.

Protocols and materials databases

DNASU4088.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000327367; ENSP00000332973; ENSG00000166949. [P84022-1]
ENST00000439724; ENSP00000401133; ENSG00000166949. [P84022-2]
ENST00000537194; ENSP00000445348; ENSG00000166949. [P84022-4]
ENST00000540846; ENSP00000437757; ENSG00000166949. [P84022-3]
GeneID4088.
KEGGhsa:4088.
UCSCuc002aqj.3. human. [P84022-1]
uc010ujs.2. human. [P84022-2]

Organism-specific databases

CTD4088.
GeneCardsGC15P067358.
GeneReviewsSMAD3.
HGNCHGNC:6769. SMAD3.
HPACAB008094.
MIM114500. phenotype.
603109. gene.
613795. phenotype.
neXtProtNX_P84022.
Orphanet284984. Aneurysm - osteoarthritis syndrome.
91387. Familial thoracic aortic aneurysm and aortic dissection.
PharmGKBPA30526.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG320700.
HOGENOMHOG000286018.
HOVERGENHBG053353.
InParanoidP84022.
KOK04500.
OMAAVELCEY.
PhylomeDBP84022.
TreeFamTF314923.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_71. Gene Expression.
SignaLinkP84022.

Gene expression databases

ArrayExpressP84022.
BgeeP84022.
CleanExHS_SMAD3.
GenevestigatorP84022.

Family and domain databases

Gene3D2.60.200.10. 1 hit.
3.90.520.10. 1 hit.
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. 1 hit.
PROSITEPS51075. MH1. 1 hit.
PS51076. MH2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSMAD3. human.
EvolutionaryTraceP84022.
GeneWikiMothers_against_decapentaplegic_homolog_3.
GenomeRNAi4088.
NextBio16026.
PROP84022.
SOURCESearch...

Entry information

Entry nameSMAD3_HUMAN
AccessionPrimary (citable) accession number: P84022
Secondary accession number(s): A8K4B6 expand/collapse secondary AC list , B7Z4Z5, B7Z6M9, B7Z9Q2, F5H383, O09064, O09144, O14510, O35273, Q92940, Q93002, Q9GKR4
Entry history
Integrated into UniProtKB/Swiss-Prot: July 5, 2004
Last sequence update: July 5, 2004
Last modified: July 9, 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
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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM