Q8BUN5 (SMAD3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	Smad3
Synonyms:	Madh3

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	425 AA.
Sequence status	Complete.
Protein existence	Evidence 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 By similarity. 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 By similarity. Interacts with PDPK1 (via PH domain). Interacts with DAB2; the interactions are enhanced upon TGF-beta stimulation. Interacts with USP15 By similarity. Ref.7 Ref.8 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17
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
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 process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Ligand	Metal-binding Zinc
PTM	Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	SMAD protein complex assembly Inferred from electronic annotation. Source: Compara T cell activation Inferred from mutant phenotype PubMed 10064594. Source: UniProtKB activation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from electronic annotation. Source: Compara cell cycle arrest Inferred from electronic annotation. Source: Compara cell-cell junction organization Inferred from electronic annotation. Source: Compara 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: Compara heart looping Inferred from genetic interaction PubMed 15183723. Source: MGI immune response Inferred from electronic annotation. Source: Compara immune system development Inferred from genetic interaction PubMed 15183723. Source: MGI in utero embryonic development Inferred from genetic interaction PubMed 15183723. Source: MGI induction of apoptosis Inferred from electronic annotation. Source: Compara 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: Compara negative regulation of cell growth Inferred from electronic annotation. Source: Compara negative regulation of inflammatory response Inferred from mutant phenotype Ref.6. Source: UniProtKB negative regulation of mitotic cell cycle Inferred from electronic annotation. Source: Compara 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: Compara negative regulation of protein phosphorylation Inferred from electronic annotation. Source: Compara 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: Compara osteoblast development Inferred from genetic interaction PubMed 15150273. Source: MGI 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: Compara positive regulation of bone mineralization Inferred from electronic annotation. Source: Compara positive regulation of canonical Wnt receptor signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of catenin import into nucleus Inferred from electronic annotation. Source: Compara positive regulation of cell migration Inferred from electronic annotation. Source: Compara 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: Compara positive regulation of focal adhesion assembly Inferred from electronic annotation. Source: Compara positive regulation of gene expression involved in extracellular matrix organization Inferred from electronic annotation. Source: Compara positive regulation of interleukin-1 beta production Inferred from electronic annotation. Source: Compara positive regulation of positive chemotaxis Inferred from electronic annotation. Source: Compara positive regulation of stress fiber assembly Inferred from electronic annotation. Source: Compara positive regulation of transcription factor import into nucleus Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 12943993PubMed 15150273PubMed 16619037. Source: MGI positive regulation of transforming growth factor beta3 production Inferred from electronic annotation. Source: Compara protein stabilization Inferred from electronic annotation. Source: Compara 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: Compara release of cytochrome c from mitochondria Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from electronic annotation. Source: Compara 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: Compara transforming growth factor beta receptor signaling pathway Inferred from direct assay PubMed 16619037PubMed 21937600. Source: MGI transport Inferred from electronic annotation. Source: Compara ureteric bud development Inferred from expression pattern PubMed 14656760. Source: UniProtKB
Cellular_component	SMAD 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: Compara plasma membrane Inferred from direct assay PubMed 12543979. Source: MGI receptor complex Inferred from electronic annotation. Source: Compara transcription factor complex Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	chromatin DNA binding Inferred from direct assay PubMed 16224064. Source: BHF-UCL 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: Compara sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 12943993. Source: MGI transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity Inferred from electronic annotation. Source: Compara zinc ion binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Pou5f1	P20263	13	EBI-2337983,EBI-1606219

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 425	425	Mothers against decapentaplegic homolog 3		PRO_0000090857
Regions
	Domain	10 – 136	127	MH1
	Domain	232 – 425	194	MH2
	Region	137 – 231	95	Linker
	Region	271 – 324	54	Sufficient for interaction with XPO4 By similarity
Sites
	Metal binding	64	1	Zinc By similarity
	Metal binding	109	1	Zinc By similarity
	Metal binding	121	1	Zinc By similarity
	Metal binding	126	1	Zinc By similarity
	Site	40	1	Required for trimerization By similarity
	Site	41	1	Required for interaction with DNA and JUN and for functional cooperation with JUN By similarity
Amino acid modifications
	Modified residue	8	1	Phosphothreonine; by CDK2 and CDK4 By similarity
	Modified residue	179	1	Phosphothreonine; by CDK2, CDK4 and MAPK By similarity
	Modified residue	204	1	Phosphoserine; by GSK3 and MAPK By similarity
	Modified residue	208	1	Phosphoserine; by MAPK By similarity
	Modified residue	213	1	Phosphoserine; by CDK2 and CDK4 By similarity
	Modified residue	378	1	N6-acetyllysine By similarity
	Modified residue	416	1	Phosphoserine By similarity
	Modified residue	418	1	Phosphoserine; by CK1 By similarity
	Modified residue	422	1	Phosphoserine; by TGFBR1 Ref.5
	Modified residue	423	1	Phosphoserine; by TGFBR1 Ref.5
	Modified residue	425	1	Phosphoserine; by TGFBR1 Ref.5
	Cross-link	33		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
	Cross-link	81		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Experimental info
	Sequence conflict	26	1	Q → E in BAC38789. Ref.3
	Sequence conflict	269	1	F → L in AAB81755. Ref.2
	Sequence conflict	408	1	D → V in BAC33398. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q8BUN5 [UniParc]. Last modified July 5, 2004. Version 2. Checksum: 46DF5E8B371321AC	FASTA	425	48,081
	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

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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. , 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.
+	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.
IPI	IPI00314870.
RefSeq	NP_058049.3. NM_016769.4.
UniGene	Mm.7320.
3D structure databases
ProteinModelPortal	Q8BUN5.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29717N.
IntAct	Q8BUN5. 8 interactions.
MINT	MINT-262056.
PTM databases
PhosphoSite	Q8BUN5.
Proteomic databases
PaxDb	Q8BUN5.
PRIDE	Q8BUN5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000034973; ENSMUSP00000034973; ENSMUSG00000032402.
GeneID	17127.
KEGG	mmu:17127.
Organism-specific databases
CTD	4088.
MGI	MGI:1201674. Smad3.
Phylogenomic databases
eggNOG	NOG320700.
GeneTree	ENSGT00600000084186.
HOVERGEN	HBG053353.
InParanoid	Q8BUN5.
KO	K04500.
OMA	AVELCEY.
OrthoDB	EOG48PMK5.
Gene expression databases
ArrayExpress	Q8BUN5.
Bgee	Q8BUN5.
CleanEx	MM_SMAD3.
Genevestigator	Q8BUN5.
GermOnline	ENSMUSG00000032402. Mus musculus.
Family and domain databases
Gene3D	2.60.200.10. 1 hit. 3.90.520.10. 1 hit.
InterPro	IPR013790. Dwarfin. IPR003619. MAD_homology1_Dwarfin-type. IPR013019. MAD_homology_MH1. IPR017855. SMAD_dom-like. IPR001132. SMAD_dom_Dwarfin-type. IPR008984. SMAD_FHA_domain. [Graphical view]
PANTHER	PTHR13703. PTHR13703. 1 hit.
Pfam	PF03165. MH1. 1 hit. PF03166. MH2. 1 hit. [Graphical view]
SMART	SM00523. DWA. 1 hit. SM00524. DWB. 1 hit. [Graphical view]
SUPFAM	SSF56366. MAD_MH1. 1 hit. SSF49879. SMAD_FHA. 1 hit.
PROSITE	PS51075. MH1. 1 hit. PS51076. MH2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q8BUN5.
NextBio	16026.
SOURCE	Search...

Entry information

Entry name

SMAD3_MOUSE

Accession

Primary (citable) accession number: Q8BUN5
Secondary accession number(s): O09064 , 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:	May 1, 2013
This is version 110 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program