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Q8BUN5 (SMAD3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 118. 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·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=mMad3
Alternative name(s):
SMAD family member 3
Short name=SMAD 3
Short name=Smad3
Gene names
Name:Smad3
Synonyms:Madh3
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

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 By similarity. Ref.6 Ref.9 Ref.10 Ref.12 Ref.18

Subunit structure

Monomer; in the absence of TGF-beta By similarity. Homooligomer; in the presence of TGF-beta By similarity. 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 By similarity. Interacts (via MH2 domain) with CITED2 (via C-terminus) By similarity. 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 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 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. Ref.7 Ref.8 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.19

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 By similarity. Ref.12 Ref.19

Tissue specificity

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. Ref.1

Domain

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

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

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

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 By similarity. Phosphorylated by PDPK1 By similarity. Ref.5 Ref.12

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.

Disruption phenotype

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. Ref.6 Ref.9 Ref.10 Ref.18

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
   LigandMetal-binding
Zinc
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processSMAD protein complex assembly

Inferred from electronic annotation. Source: Ensembl

T cell activation

Inferred from mutant phenotype PubMed 10064594. Source: UniProtKB

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

Inferred from electronic annotation. Source: Ensembl

cell cycle arrest

Inferred from electronic annotation. Source: Ensembl

cell-cell junction organization

Inferred from electronic annotation. Source: Ensembl

developmental growth

Inferred from genetic interaction PubMed 15183723. Source: MGI

embryonic cranial skeleton morphogenesis

Inferred from genetic interaction PubMed 15183723. Source: MGI

embryonic foregut morphogenesis

Inferred from genetic interaction PubMed 15183723. Source: MGI

embryonic pattern specification

Inferred from genetic interaction PubMed 15183723. Source: MGI

endoderm development

Inferred from genetic interaction PubMed 15183723. Source: MGI

evasion or tolerance of host defenses by virus

Inferred from electronic annotation. Source: Ensembl

extrinsic apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

gastrulation

Inferred from genetic interaction PubMed 15183723. Source: MGI

heart looping

Inferred from genetic interaction PubMed 15183723. Source: MGI

immune response

Inferred from electronic annotation. Source: Ensembl

immune system development

Inferred from genetic interaction PubMed 15183723. Source: MGI

in utero embryonic development

Inferred from genetic interaction PubMed 15183723. Source: MGI

lens fiber cell differentiation

Inferred from mutant phenotype PubMed 17215516. Source: MGI

liver development

Inferred from genetic interaction PubMed 15183723. Source: MGI

mesoderm formation

Inferred from mutant phenotype PubMed 15084457. Source: MGI

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell growth

Inferred from electronic annotation. Source: Ensembl

negative regulation of inflammatory response

Inferred from mutant phenotype Ref.6. Source: UniProtKB

negative regulation of mitotic cell cycle

Inferred from electronic annotation. Source: Ensembl

negative regulation of osteoblast differentiation

Inferred from genetic interaction PubMed 15150273. Source: MGI

negative regulation of osteoblast proliferation

Inferred from mutant phenotype Ref.18. Source: UniProtKB

negative regulation of protein catabolic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of protein phosphorylation

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 11711431PubMed 9702197. Source: MGI

negative regulation of wound healing

Inferred from mutant phenotype Ref.6Ref.10Ref.18. Source: UniProtKB

nodal signaling pathway

Inferred from electronic annotation. Source: Ensembl

osteoblast development

Inferred from genetic interaction PubMed 15150273. Source: MGI

osteoblast differentiation

Inferred from mutant phenotype Ref.9. Source: UniProtKB

paraxial mesoderm morphogenesis

Inferred from mutant phenotype PubMed 15084457. Source: MGI

pericardium development

Inferred from genetic interaction PubMed 15183723. Source: MGI

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 electronic annotation. Source: Ensembl

positive regulation of catenin import into nucleus

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell migration

Inferred from electronic annotation. Source: Ensembl

positive regulation of chondrocyte differentiation

Inferred from mutant phenotype Ref.18. Source: UniProtKB

positive regulation of epithelial to mesenchymal transition

Inferred from electronic annotation. Source: Ensembl

positive regulation of focal adhesion assembly

Inferred from electronic annotation. Source: Ensembl

positive regulation of gene expression involved in extracellular matrix organization

Inferred from electronic annotation. Source: Ensembl

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 electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 12943993PubMed 15150273PubMed 16619037. Source: MGI

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 15282343PubMed 15464984. Source: MGI

positive regulation of transforming growth factor beta3 production

Inferred from electronic annotation. Source: Ensembl

protein stabilization

Inferred from electronic annotation. Source: Ensembl

regulation of binding

Inferred from direct assay PubMed 15282343. Source: MGI

regulation of epithelial cell proliferation

Inferred from mutant phenotype PubMed 12845704. Source: MGI

regulation of immune response

Inferred from mutant phenotype PubMed 10064594. Source: UniProtKB

regulation of striated muscle tissue development

Inferred from direct assay PubMed 11711431. Source: MGI

regulation of transforming growth factor beta receptor signaling pathway

Inferred from direct assay PubMed 11711431. Source: MGI

regulation of transforming growth factor beta2 production

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

signal transduction involved in regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

skeletal system development

Inferred from genetic interaction PubMed 15183723. Source: MGI

somitogenesis

Inferred from mutant phenotype PubMed 15183723. Source: MGI

thyroid gland development

Inferred from genetic interaction PubMed 15183723. Source: MGI

transcription from RNA polymerase II promoter

Traceable author statement PubMed 10823886. Source: ProtInc

transdifferentiation

Inferred from electronic annotation. Source: Ensembl

transforming growth factor beta receptor signaling pathway

Inferred from direct assay PubMed 16619037PubMed 21937600. Source: MGI

transport

Inferred from electronic annotation. Source: Ensembl

ureteric bud development

Inferred from expression pattern PubMed 14656760. Source: UniProtKB

   Cellular_componentSMAD protein complex

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasm

Inferred from direct assay PubMed 11160896. Source: UniProtKB

nuclear inner membrane

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay PubMed 11160896. Source: UniProtKB

plasma membrane

Inferred from direct assay PubMed 12543979. Source: MGI

receptor complex

Inferred from electronic annotation. Source: Ensembl

transcription factor complex

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionchromatin DNA binding

Inferred from direct assay PubMed 16224064. Source: BHF-UCL

chromatin binding

Inferred from direct assay PubMed 16619037. Source: MGI

collagen binding

Inferred from physical interaction PubMed 14559231. Source: MGI

core promoter proximal region sequence-specific DNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

double-stranded DNA binding

Inferred from direct assay PubMed 15282343. Source: MGI

protein binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 12943993. Source: MGI

transcription factor binding

Inferred from physical interaction PubMed 11937490. Source: UniProtKB

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

Inferred from electronic annotation. Source: Ensembl

zinc ion binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 425424Mothers against decapentaplegic homolog 3
PRO_0000090857

Regions

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

Sites

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

Amino acid modifications

Modified residue21N-acetylserine By similarity
Modified residue81Phosphothreonine; by CDK2 and CDK4 By similarity
Modified residue1791Phosphothreonine; by CDK2, CDK4 and MAPK By similarity
Modified residue2041Phosphoserine; by GSK3 and MAPK By similarity
Modified residue2081Phosphoserine; by MAPK By similarity
Modified residue2131Phosphoserine; by CDK2 and CDK4 By similarity
Modified residue3781N6-acetyllysine By similarity
Modified residue4161Phosphoserine By similarity
Modified residue4181Phosphoserine; by CK1 By similarity
Modified residue4221Phosphoserine; by TGFBR1 Ref.5
Modified residue4231Phosphoserine; by TGFBR1 Ref.5
Modified residue4251Phosphoserine; by TGFBR1 Ref.5
Cross-link33Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link81Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Experimental info

Sequence conflict261Q → E in BAC38789. Ref.3
Sequence conflict2691F → L in AAB81755. Ref.2
Sequence conflict4081D → V in BAC33398. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q8BUN5 [UniParc].

Last modified July 5, 2004. Version 2.
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 


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References

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[1]"Cloning and studies of the mouse cDNA encoding Smad3."
Kano K., Notani A., Nam S.-Y., Fujisawa M., Kurohmaru M., Hayashi Y.
J. Vet. Med. Sci. 61:213-219(1999) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_058049.3. NM_016769.4.
UniGeneMm.7320.

3D structure databases

ProteinModelPortalQ8BUN5.
SMRQ8BUN5. Positions 7-132, 228-425.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201276. 34 interactions.
DIPDIP-29717N.
IntActQ8BUN5. 12 interactions.
MINTMINT-262056.

Chemistry

BindingDBQ8BUN5.

PTM databases

PhosphoSiteQ8BUN5.

Proteomic databases

PaxDbQ8BUN5.
PRIDEQ8BUN5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000034973; ENSMUSP00000034973; ENSMUSG00000032402.
GeneID17127.
KEGGmmu:17127.
UCSCuc009qbi.1. mouse.

Organism-specific databases

CTD4088.
MGIMGI:1201674. Smad3.

Phylogenomic databases

eggNOGNOG320700.
GeneTreeENSGT00600000084186.
HOVERGENHBG053353.
InParanoidQ8BUN5.
KOK04500.
OMAAVELCEY.
OrthoDBEOG7W1540.
PhylomeDBQ8BUN5.
TreeFamTF314923.

Gene expression databases

ArrayExpressQ8BUN5.
BgeeQ8BUN5.
CleanExMM_SMAD3.
GenevestigatorQ8BUN5.

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

NextBio16026.
PROQ8BUN5.
SOURCESearch...

Entry information

Entry nameSMAD3_MOUSE
AccessionPrimary (citable) accession number: Q8BUN5
Secondary accession number(s): O09064 expand/collapse secondary AC list , O09144, O14510, O35273, Q8BX84, Q92940, Q93002, Q9GKR4
Entry history
Integrated into UniProtKB/Swiss-Prot: July 5, 2004
Last sequence update: July 5, 2004
Last modified: April 16, 2014
This is version 118 of the entry and version 2 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