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Protein

Mothers against decapentaplegic homolog 3

Gene

Smad3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei40 – 401Required for trimerizationBy similarity
Sitei41 – 411Required for interaction with DNA and JUN and for functional cooperation with JUNBy similarity
Metal bindingi64 – 641ZincBy similarity
Metal bindingi109 – 1091ZincBy similarity
Metal bindingi121 – 1211ZincBy similarity
Metal bindingi126 – 1261ZincBy similarity

GO - Molecular functioni

  1. beta-catenin binding Source: MGI
  2. bHLH transcription factor binding Source: MGI
  3. chromatin binding Source: MGI
  4. chromatin DNA binding Source: BHF-UCL
  5. collagen binding Source: MGI
  6. core promoter proximal region sequence-specific DNA binding Source: UniProtKB
  7. co-SMAD binding Source: MGI
  8. double-stranded DNA binding Source: MGI
  9. identical protein binding Source: MGI
  10. phosphatase binding Source: MGI
  11. protein binding transcription factor activity Source: Ensembl
  12. protein heterodimerization activity Source: MGI
  13. protein homodimerization activity Source: MGI
  14. protein kinase binding Source: MGI
  15. RNA polymerase II activating transcription factor binding Source: MGI
  16. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: MGI
  17. RNA polymerase II core promoter sequence-specific DNA binding transcription factor activity Source: MGI
  18. R-SMAD binding Source: MGI
  19. sequence-specific DNA binding Source: MGI
  20. sequence-specific DNA binding transcription factor activity Source: MGI
  21. transcription factor binding Source: UniProtKB
  22. transcription regulatory region DNA binding Source: MGI
  23. transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity Source: MGI
  24. transforming growth factor beta receptor binding Source: MGI
  25. ubiquitin binding Source: MGI
  26. ubiquitin protein ligase binding Source: MGI
  27. zinc ion binding Source: MGI

GO - Biological processi

  1. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
  2. activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway Source: Ensembl
  3. activin receptor signaling pathway Source: MGI
  4. cell-cell junction organization Source: MGI
  5. cell cycle arrest Source: MGI
  6. developmental growth Source: MGI
  7. embryonic cranial skeleton morphogenesis Source: MGI
  8. embryonic foregut morphogenesis Source: MGI
  9. embryonic pattern specification Source: MGI
  10. endoderm development Source: MGI
  11. evasion or tolerance of host defenses by virus Source: MGI
  12. extrinsic apoptotic signaling pathway Source: MGI
  13. gastrulation Source: MGI
  14. heart looping Source: MGI
  15. immune response Source: MGI
  16. immune system development Source: MGI
  17. intracellular signal transduction Source: MGI
  18. in utero embryonic development Source: MGI
  19. lens fiber cell differentiation Source: MGI
  20. liver development Source: MGI
  21. mesoderm formation Source: MGI
  22. negative regulation of apoptotic process Source: Ensembl
  23. negative regulation of cell growth Source: MGI
  24. negative regulation of inflammatory response Source: UniProtKB
  25. negative regulation of mitotic cell cycle Source: MGI
  26. negative regulation of osteoblast differentiation Source: MGI
  27. negative regulation of osteoblast proliferation Source: UniProtKB
  28. negative regulation of protein catabolic process Source: MGI
  29. negative regulation of protein phosphorylation Source: MGI
  30. negative regulation of transcription from RNA polymerase II promoter Source: MGI
  31. negative regulation of wound healing Source: UniProtKB
  32. nodal signaling pathway Source: MGI
  33. osteoblast development Source: MGI
  34. osteoblast differentiation Source: UniProtKB
  35. paraxial mesoderm morphogenesis Source: MGI
  36. pericardium development Source: MGI
  37. positive regulation of alkaline phosphatase activity Source: Ensembl
  38. positive regulation of bone mineralization Source: Ensembl
  39. positive regulation of canonical Wnt signaling pathway Source: MGI
  40. positive regulation of catenin import into nucleus Source: MGI
  41. positive regulation of cell migration Source: Ensembl
  42. positive regulation of chondrocyte differentiation Source: UniProtKB
  43. positive regulation of epithelial to mesenchymal transition Source: MGI
  44. positive regulation of focal adhesion assembly Source: Ensembl
  45. positive regulation of gene expression Source: MGI
  46. positive regulation of interleukin-1 beta production Source: Ensembl
  47. positive regulation of positive chemotaxis Source: Ensembl
  48. positive regulation of stress fiber assembly Source: Ensembl
  49. positive regulation of transcription, DNA-templated Source: MGI
  50. positive regulation of transcription factor import into nucleus Source: MGI
  51. positive regulation of transcription from RNA polymerase II promoter Source: MGI
  52. positive regulation of transforming growth factor beta3 production Source: Ensembl
  53. protein stabilization Source: MGI
  54. regulation of binding Source: MGI
  55. regulation of epithelial cell proliferation Source: MGI
  56. regulation of immune response Source: UniProtKB
  57. regulation of striated muscle tissue development Source: MGI
  58. regulation of transcription from RNA polymerase II promoter Source: MGI
  59. regulation of transforming growth factor beta2 production Source: MGI
  60. regulation of transforming growth factor beta receptor signaling pathway Source: MGI
  61. response to hypoxia Source: MGI
  62. signal transduction involved in regulation of gene expression Source: Ensembl
  63. skeletal system development Source: MGI
  64. SMAD protein complex assembly Source: MGI
  65. SMAD protein signal transduction Source: MGI
  66. somitogenesis Source: MGI
  67. T cell activation Source: UniProtKB
  68. thyroid gland development Source: MGI
  69. transcription from RNA polymerase II promoter Source: ProtInc
  70. transdifferentiation Source: Ensembl
  71. transforming growth factor beta receptor signaling pathway Source: MGI
  72. transport Source: MGI
  73. ureteric bud development Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_202264. SMAD4 MH2 Domain Mutants in Cancer.
REACT_203510. TGF-beta receptor signaling activates SMADs.
REACT_203903. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
REACT_215733. Downregulation of TGF-beta receptor signaling.
REACT_216258. Signaling by Activin.
REACT_216792. SMAD2/3 MH2 Domain Mutants in Cancer.
REACT_217958. SMAD2/3 Phosphorylation Motif Mutants in Cancer.
REACT_220566. Downregulation of SMAD2/3:SMAD4 transcriptional activity.
REACT_220645. Signaling by NODAL.
REACT_224802. TGFBR1 KD Mutants in Cancer.

Names & Taxonomyi

Protein namesi
Recommended name:
Mothers against decapentaplegic homolog 3
Short name:
MAD homolog 3
Short name:
Mad3
Short name:
Mothers against DPP homolog 3
Short name:
mMad3
Alternative name(s):
SMAD family member 3
Short name:
SMAD 3
Short name:
Smad3
Gene namesi
Name:Smad3
Synonyms:Madh3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 9

Organism-specific databases

MGIiMGI:1201674. Smad3.

Subcellular locationi

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 (By similarity).By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. nuclear chromatin Source: MGI
  3. nuclear inner membrane Source: MGI
  4. nucleoplasm Source: MGI
  5. nucleus Source: UniProtKB
  6. plasma membrane Source: MGI
  7. receptor complex Source: MGI
  8. SMAD2-SMAD3 protein complex Source: MGI
  9. SMAD protein complex Source: UniProtKB
  10. transcription factor complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

SMAD3 null mice exhibit inhibition of proliferation of mammary gland epithelial cells. Fibrobasts are only partially growth inhibited. Defects in osteoblast differentiation are observed. Animals are osteopenic with less cortical and cancellous bone. Facture healing is accelerated. Decreased bone mineral density (BMD) reflects the inability of osteoblasts to balance osteoclast activity. Wound healing is accelerated to about two and a half times that of normal animals. Wound areas are significantly reduced with less quantities of granulation tissue. There is reduced local infiltration of moncytes and keratinocytes show altered patterns of growth and migration. Accelerated wound healing is observed on castration of null male mice, while null female mice exhibited delayed healing following ovariectomy.4 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 425424Mothers against decapentaplegic homolog 3PRO_0000090857Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineBy similarity
Modified residuei8 – 81Phosphothreonine; by CDK2 and CDK4By similarity
Cross-linki33 – 33Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki81 – 81Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei179 – 1791Phosphothreonine; by CDK2, CDK4 and MAPKBy similarity
Modified residuei204 – 2041Phosphoserine; by GSK3 and MAPKPROSITE-ProRule annotation
Modified residuei208 – 2081Phosphoserine; by MAPKPROSITE-ProRule annotation
Modified residuei213 – 2131Phosphoserine; by CDK2 and CDK4PROSITE-ProRule annotation
Modified residuei378 – 3781N6-acetyllysineBy similarity
Modified residuei416 – 4161PhosphoserinePROSITE-ProRule annotation
Modified residuei418 – 4181Phosphoserine; by CK1PROSITE-ProRule annotation
Modified residuei422 – 4221Phosphoserine; by TGFBR11 PublicationPROSITE-ProRule annotation
Modified residuei423 – 4231Phosphoserine; by TGFBR11 PublicationPROSITE-ProRule annotation
Modified residuei425 – 4251Phosphoserine; by TGFBR11 PublicationPROSITE-ProRule annotation

Post-translational modificationi

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 (By similarity). Phosphorylated by PDPK1 (By similarity).By similarity
Acetylation in the nucleus by EP300 in the MH2 domain regulates positively its transcriptional activity and is enhanced by TGF-beta.By similarity
Ubiquitinated. Monoubiquitinated, leading to prevent DNA-binding. Deubiquitination by USP15 alleviates inhibition and promotes activation of TGF-beta target genes (By similarity).By similarity
Poly-ADP-ribosylated by PARP1 and PARP2. ADP-ribosylation negatively regulates SMAD3 transcriptional responses during the course of TGF-beta signaling.By similarity

Keywords - PTMi

Acetylation, ADP-ribosylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ8BUN5.
PaxDbiQ8BUN5.
PRIDEiQ8BUN5.

PTM databases

PhosphoSiteiQ8BUN5.

Expressioni

Tissue specificityi

Highly expressed in the brain and ovary. Detected in the pyramidal cells of the hippocampus, granule cells of the dentate gyrus, granular cells of the cerebral cortex and the granulosa cells of the ovary.1 Publication

Gene expression databases

BgeeiQ8BUN5.
CleanExiMM_SMAD3.
ExpressionAtlasiQ8BUN5. baseline and differential.
GenevestigatoriQ8BUN5.

Interactioni

Subunit structurei

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. Interacts (via MH2 domain) with CITED2 (via C-terminus). Interacts (via the MH2 domain) with ZFYVE9. Interacts with HDAC1, VDR, TGIF and TGIF2, RUNX3, CREBBP, SKOR1, SKOR2, SNON, ATF2, SMURF2 and SNW1. Interacts with DACH1; the interaction inhibits the TGF-beta signaling. Part of a complex consisting of AIP1, ACVR2A, ACVR1B and SMAD3. 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 synergistic 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 AIP1, TGFB1I1, TTRAP, FOXL2, PRDM16, HGS and WWP1. Interacts with NEDD4L; the interaction requires TGF-beta stimulation. Interacts with PML. Interacts with MEN1. 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. Interacts with LDLRAD4 (via the SMAD interaction motif). Interacts with PMEPA1.10 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Axin1O356252EBI-2337983,EBI-2365912
Pou5f1P2026313EBI-2337983,EBI-1606219
Smad4P974715EBI-2337983,EBI-5259270

Protein-protein interaction databases

BioGridi201276. 35 interactions.
DIPiDIP-29717N.
IntActiQ8BUN5. 12 interactions.
MINTiMINT-262056.

Structurei

3D structure databases

ProteinModelPortaliQ8BUN5.
SMRiQ8BUN5. Positions 7-132, 228-425.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini10 – 136127MH1PROSITE-ProRule annotationAdd
BLAST
Domaini232 – 425194MH2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni137 – 23195LinkerAdd
BLAST
Regioni271 – 32454Sufficient for interaction with XPO4By similarityAdd
BLAST

Domaini

The MH1 domain is required for DNA binding (By similarity). Also binds zinc ions which are necessary for the DNA binding.By similarity
The MH2 domain is required for both homomeric and heteromeric interactions and for transcriptional regulation. Sufficient for nuclear import (By similarity).By similarity
The linker region is required for the TGFbeta-mediated transcriptional activity and acts synergistically with the MH2 domain.By similarity

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

eggNOGiNOG320700.
GeneTreeiENSGT00760000119091.
HOVERGENiHBG053353.
InParanoidiQ8BUN5.
KOiK04500.
OMAiAVELCEY.
OrthoDBiEOG7W1540.
PhylomeDBiQ8BUN5.
TreeFamiTF314923.

Family and domain databases

Gene3Di2.60.200.10. 1 hit.
3.90.520.10. 1 hit.
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.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q8BUN5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSSILPFTPP IVKRLLGWKK GEQNGQEEKW CEKAVKSLVK KLKKTGQLDE
60 70 80 90 100
LEKAITTQNV NTKCITIPRS LDGRLQVSHR KGLPHVIYCR LWRWPDLHSH
110 120 130 140 150
HELRAMELCE FAFNMKKDEV CVNPYHYQRV ETPVLPPVLV PRHTEIPAEF
160 170 180 190 200
PPLDDYSHSI PENTNFPAGI EPQSNIPETP PPGYLSEDGE TSDHQMNHSM
210 220 230 240 250
DAGSPNLSPN PMSPAHNNLD LQPVTYCEPA FWCSISYYEL NQRVGETFHA
260 270 280 290 300
SQPSMTVDGF TDPSNSERFC LGLLSNVNRN AAVELTRRHI GRGVRLYYIG
310 320 330 340 350
GEVFAECLSD SAIFVQSPNC NQRYGWHPAT VCKIPPGCNL KIFNNQEFAA
360 370 380 390 400
LLAQSVNQGF EAVYQLTRMC TIRMSFVKGW GAEYRRQTVT STPCWIELHL
410 420
NGPLQWLDKV LTQMGSPSIR CSSVS
Length:425
Mass (Da):48,081
Last modified:July 5, 2004 - v2
Checksum:i46DF5E8B371321AC
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti26 – 261Q → E in BAC38789 (PubMed:16141072).Curated
Sequence conflicti269 – 2691F → L in AAB81755 (Ref. 2) Curated
Sequence conflicti408 – 4081D → V in BAC33398 (PubMed:16141072).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB008192 mRNA. Translation: BAA76956.1.
AF016189 mRNA. Translation: AAB81755.1.
AK048626 mRNA. Translation: BAC33398.1.
AK083158 mRNA. Translation: BAC38789.1.
BC066850 mRNA. Translation: AAH66850.1.
CCDSiCCDS23272.1.
RefSeqiNP_058049.3. NM_016769.4.
UniGeneiMm.7320.

Genome annotation databases

EnsembliENSMUST00000034973; ENSMUSP00000034973; ENSMUSG00000032402.
GeneIDi17127.
KEGGimmu:17127.
UCSCiuc009qbi.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB008192 mRNA. Translation: BAA76956.1.
AF016189 mRNA. Translation: AAB81755.1.
AK048626 mRNA. Translation: BAC33398.1.
AK083158 mRNA. Translation: BAC38789.1.
BC066850 mRNA. Translation: AAH66850.1.
CCDSiCCDS23272.1.
RefSeqiNP_058049.3. NM_016769.4.
UniGeneiMm.7320.

3D structure databases

ProteinModelPortaliQ8BUN5.
SMRiQ8BUN5. Positions 7-132, 228-425.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201276. 35 interactions.
DIPiDIP-29717N.
IntActiQ8BUN5. 12 interactions.
MINTiMINT-262056.

Chemistry

BindingDBiQ8BUN5.

PTM databases

PhosphoSiteiQ8BUN5.

Proteomic databases

MaxQBiQ8BUN5.
PaxDbiQ8BUN5.
PRIDEiQ8BUN5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000034973; ENSMUSP00000034973; ENSMUSG00000032402.
GeneIDi17127.
KEGGimmu:17127.
UCSCiuc009qbi.1. mouse.

Organism-specific databases

CTDi4088.
MGIiMGI:1201674. Smad3.

Phylogenomic databases

eggNOGiNOG320700.
GeneTreeiENSGT00760000119091.
HOVERGENiHBG053353.
InParanoidiQ8BUN5.
KOiK04500.
OMAiAVELCEY.
OrthoDBiEOG7W1540.
PhylomeDBiQ8BUN5.
TreeFamiTF314923.

Enzyme and pathway databases

ReactomeiREACT_202264. SMAD4 MH2 Domain Mutants in Cancer.
REACT_203510. TGF-beta receptor signaling activates SMADs.
REACT_203903. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
REACT_215733. Downregulation of TGF-beta receptor signaling.
REACT_216258. Signaling by Activin.
REACT_216792. SMAD2/3 MH2 Domain Mutants in Cancer.
REACT_217958. SMAD2/3 Phosphorylation Motif Mutants in Cancer.
REACT_220566. Downregulation of SMAD2/3:SMAD4 transcriptional activity.
REACT_220645. Signaling by NODAL.
REACT_224802. TGFBR1 KD Mutants in Cancer.

Miscellaneous databases

NextBioi16026.
PROiQ8BUN5.
SOURCEiSearch...

Gene expression databases

BgeeiQ8BUN5.
CleanExiMM_SMAD3.
ExpressionAtlasiQ8BUN5. baseline and differential.
GenevestigatoriQ8BUN5.

Family and domain databases

Gene3Di2.60.200.10. 1 hit.
3.90.520.10. 1 hit.
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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
    Tissue: Brain.
  2. Yang X., Xu X., Shen S., Deng C.
    Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: C57BL/6.
  3. "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].
    Strain: C57BL/6J.
    Tissue: Head and Hippocampus.
  4. "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].
    Strain: C57BL/6J.
    Tissue: Embryo.
  5. "Transforming growth factor beta-induced phosphorylation of Smad3 is required for growth inhibition and transcriptional induction in epithelial cells."
    Liu X., Sun Y., Constantinescu S.N., Karam E., Weinberg R.A., Lodish H.F.
    Proc. Natl. Acad. Sci. U.S.A. 94:10669-10674(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-422; SER-423 AND SER-425.
  6. "Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response."
    Ashcroft G.S., Yang X., Glick A.B., Weinstein M., Letterio J.L., Mizel D.E., Anzano M., Greenwell-Wild T., Wahl S.M., Deng C., Roberts A.B.
    Nat. Cell Biol. 1:260-266(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  7. "Identification and characterization of a PDZ protein that interacts with activin types II receptors."
    Shoji H., Tsuchida K., Kishi H., Yamakawa N., Matsuzaki T., Liu Z., Nakamura T., Sugino H.
    J. Biol. Chem. 275:5485-5492(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH AIP1, IDENTIFICATION IN A COMPLEX WITH AIP1; ACVR2A AND ACVR1B.
  8. "Hgs (Hrs), a FYVE domain protein, is involved in Smad signaling through cooperation with SARA."
    Miura S., Takeshita T., Asao H., Kimura Y., Murata K., Sasaki Y., Hanai J., Beppu H., Tsukazaki T., Wrana J.L., Miyazono K., Sugamura K.
    Mol. Cell. Biol. 20:9346-9355(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HGS.
  9. "The loss of Smad3 results in a lower rate of bone formation and osteopenia through dysregulation of osteoblast differentiation and apoptosis."
    Borton A.J., Frederick J.P., Datto M.B., Wang X.F., Weinstein R.S.
    J. Bone Miner. Res. 16:1754-1764(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  10. "Role of Smad3 in the hormonal modulation of in vivo wound healing responses."
    Ashcroft G.S., Mills S.J., Flanders K.C., Lyakh L.A., Anzano M.A., Gilliver S.C., Roberts A.B.
    Wound Repair Regen. 11:468-473(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  11. "A LIM protein, Hic-5, functions as a potential coactivator for Sp1."
    Shibanuma M., Kim-Kaneyama J.-R., Sato S., Nose K.
    J. Cell. Biochem. 91:633-645(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TGFB1I1.
  12. "Cytoplasmic PML function in TGF-beta signalling."
    Lin H.K., Bergmann S., Pandolfi P.P.
    Nature 431:205-211(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION, INTERACTION WITH PML AND ZFYVE9/SARA.
  13. "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.
  14. "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.
  15. "PRDM16/MEL1: a novel Smad binding protein expressed in murine embryonic orofacial tissue."
    Warner D.R., Horn K.H., Mudd L., Webb C.L., Greene R.M., Pisano M.M.
    Biochim. Biophys. Acta 1773:814-820(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PRDM16.
  16. "Ttrap is an essential modulator of Smad3-dependent Nodal signaling during zebrafish gastrulation and left-right axis determination."
    Esguerra C.V., Nelles L., Vermeire L., Ibrahimi A., Crawford A.D., Derua R., Janssens E., Waelkens E., Carmeliet P., Collen D., Huylebroeck D.
    Development 134:4381-4393(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TTRAP.
  17. "FoxL2 and Smad3 coordinately regulate follistatin gene transcription."
    Blount A.L., Schmidt K., Justice N.J., Vale W.W., Fischer W.H., Bilezikjian L.M.
    J. Biol. Chem. 284:7631-7645(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FOXL2.
  18. "Loss of Smad3 gives rise to poor soft callus formation and accelerates early fracture healing."
    Kawakatsu M., Kanno S., Gui T., Gai Z., Itoh S., Tanishima H., Oikawa K., Muragaki Y.
    Exp. Mol. Pathol. 90:107-115(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  19. "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.

Entry informationi

Entry nameiSMAD3_MOUSE
AccessioniPrimary (citable) accession number: Q8BUN5
Secondary accession number(s): O09064
, O09144, O14510, O35273, Q8BX84, Q92940, Q93002, Q9GKR4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 5, 2004
Last sequence update: July 5, 2004
Last modified: March 4, 2015
This is version 126 of the entry and version 2 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

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.