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SMAD3

The protein encoded by this gene belongs to the SMAD, a family of proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein functions as a transcriptional modulator activated by transforming growth factor-beta and is thought to play a role in the regulation of carcinogenesis.
Full Name
SMAD Family Member 3
Alternative Names
SMAD Family Member 3; Mothers Against DPP Homolog 3; MAD Homolog 3; JV15-2; HMAD-3; HSMAD3; MADH3; MAD3; MAD, Mothers Against Decapentaplegic Homolog 3 (Drosophila); SMAD, Mothers Against DPP Homolog 3 (Drosophila); MAD, Mothers Against Decapentaplegic Homolog 3; Mothers Against Decapentaplegic Homolog 3;
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.
Biological Process
Activation of cysteine-type endopeptidase activity involved in apoptotic processManual Assertion Based On ExperimentIMP:BHF-UCL
Activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathwayIEA:Ensembl
Activin receptor signaling pathwayManual Assertion Based On ExperimentIMP:BHF-UCL
Adrenal gland developmentIEA:Ensembl
Anatomical structure morphogenesisManual Assertion Based On ExperimentIBA:GO_Central
BMP signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Cell differentiationManual Assertion Based On ExperimentIBA:GO_Central
Cell-cell junction organizationManual Assertion Based On ExperimentIMP:BHF-UCL
Cellular response to transforming growth factor beta stimulusManual Assertion Based On ExperimentIDA:CAFA
Cellular response to virusIEA:Ensembl
Developmental growthIEA:Ensembl
Embryonic cranial skeleton morphogenesisIEA:Ensembl
Embryonic foregut morphogenesisIEA:Ensembl
Embryonic pattern specificationIEA:Ensembl
Endoderm developmentIEA:Ensembl
Extrinsic apoptotic signaling pathwayManual Assertion Based On ExperimentIMP:BHF-UCL
Heart loopingIEA:Ensembl
Immune responseManual Assertion Based On ExperimentIMP:BHF-UCL
Immune system developmentIEA:Ensembl
In utero embryonic developmentIEA:Ensembl
JNK cascadeIEA:Ensembl
Lens fiber cell differentiationIEA:Ensembl
Liver developmentIEA:Ensembl
Mesoderm formationIEA:Ensembl
Negative regulation of apoptotic processIEA:Ensembl
Negative regulation of cardiac muscle hypertrophy in response to stressIEA:Ensembl
Negative regulation of cell growthManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of cell population proliferationManual Assertion Based On ExperimentIMP:BHF-UCL
Negative regulation of cytosolic calcium ion concentrationManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of fat cell differentiationManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of inflammatory responseIEA:Ensembl
Negative regulation of lung blood pressureIEA:Ensembl
Negative regulation of osteoblast differentiationIEA:Ensembl
Negative regulation of osteoblast proliferationIEA:Ensembl
Negative regulation of protein catabolic processIEA:Ensembl
Negative regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:ARUK-UCL
Negative regulation of wound healingIEA:Ensembl
Nodal signaling pathwayManual Assertion Based On ExperimentIMP:BHF-UCL
Osteoblast developmentIEA:Ensembl
Paraxial mesoderm morphogenesisIEA:Ensembl
Pericardium developmentIEA:Ensembl
Positive regulation of alkaline phosphatase activityIEA:Ensembl
Positive regulation of bone mineralizationIEA:Ensembl
Positive regulation of canonical Wnt signaling pathwayIEA:Ensembl
Positive regulation of cell migrationIEA:Ensembl
Positive regulation of chondrocyte differentiationIEA:Ensembl
Positive regulation of DNA-binding transcription factor activity1 PublicationNAS:BHF-UCL
Positive regulation of epithelial to mesenchymal transitionManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of extracellular matrix assemblyManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of focal adhesion assemblyIEA:Ensembl
Positive regulation of gene expressionManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of interleukin-1 beta productionIEA:Ensembl
Positive regulation of miRNA transcriptionManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of nitric oxide biosynthetic processManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of positive chemotaxisIEA:Ensembl
Positive regulation of protein import into nucleus1 PublicationNAS:BHF-UCL
Positive regulation of stress fiber assemblyIEA:Ensembl
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of transforming growth factor beta3 productionIEA:Ensembl
Primary miRNA processingManual Assertion Based On ExperimentTAS:BHF-UCL
Protein stabilizationIEA:Ensembl
Regulation of bindingIEA:Ensembl
Regulation of epithelial cell proliferationIEA:Ensembl
Regulation of immune responseIEA:Ensembl
Regulation of miRNA transcription1 PublicationIC:ARUK-UCL
Regulation of striated muscle tissue developmentIEA:Ensembl
Regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:NTNU_SB
Regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:ComplexPortal
Regulation of transforming growth factor beta receptor signaling pathwayManual Assertion Based On ExperimentIMP:BHF-UCL
Regulation of transforming growth factor beta2 productionManual Assertion Based On ExperimentIMP:BHF-UCL
Response to hypoxiaManual Assertion Based On ExperimentIMP:BHF-UCL
Signal transduction involved in regulation of gene expressionIEA:Ensembl
SMAD protein complex assemblyManual Assertion Based On ExperimentIDA:BHF-UCL
SMAD protein signal transductionManual Assertion Based On ExperimentIBA:GO_Central
SomitogenesisIEA:Ensembl
T cell activationIEA:Ensembl
Thyroid gland developmentIEA:Ensembl
TransdifferentiationIEA:Ensembl
Transforming growth factor beta receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Ureteric bud developmentIEA:Ensembl
Wound healingManual Assertion Based On ExperimentTAS:BHF-UCL
Cellular Location
Cytoplasm
Nucleus
Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 (PubMed:15799969, PubMed:21145499).
Through the action of the phosphatase PPM1A, released from the SMAD2/SMAD4 complex, and exported out of the nucleus by interaction with RANBP1 (PubMed:16751101, PubMed:19289081).
Co-localizes with LEMD3 at the nucleus inner membrane (PubMed:15601644).
MAPK-mediated phosphorylation appears to have no effect on nuclear import (PubMed:19218245).
PDPK1 prevents its nuclear translocation in response to TGF-beta (PubMed:17327236).
Localized mainly to the nucleus in the early stages of embryo development with expression becoming evident in the cytoplasm of the inner cell mass at the blastocyst stage (By similarity).
Involvement in disease
Colorectal cancer (CRC):
A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
Loeys-Dietz syndrome 3 (LDS3):
An aortic aneurysm syndrome with widespread systemic involvement. The disorder is characterized by the triad of arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. Patients with LDS3 also manifest early-onset osteoarthritis. They lack craniosynostosis and mental retardation.
PTM
Phosphorylated on serine and threonine residues. Enhanced phosphorylation in the linker region on Thr-179, Ser-204 and Ser-208 on EGF and TGF-beta treatment. Ser-208 is the main site of MAPK-mediated phosphorylation. CDK-mediated phosphorylation occurs in a cell-cycle dependent manner and inhibits both the transcriptional activity and antiproliferative functions of SMAD3. This phosphorylation is inhibited by flavopiridol. Maximum phosphorylation at the G1/S junction. Also phosphorylated on serine residues in the C-terminal SXS motif by TGFBR1 and ACVR1. TGFBR1-mediated phosphorylation at these C-terminal sites is required for interaction with SMAD4, nuclear location and transactivational activity, and appears to be a prerequisite for the TGF-beta mediated phosphorylation in the linker region. Dephosphorylated in the C-terminal SXS motif by PPM1A. This dephosphorylation disrupts the interaction with SMAD4, promotes nuclear export and terminates TGF-beta-mediated signaling. Phosphorylation at Ser-418 by CSNK1G2/CK1 promotes ligand-dependent ubiquitination and subsequent proteasome degradation, thus inhibiting SMAD3-mediated TGF-beta responses. Phosphorylated by PDPK1.
Acetylation in the nucleus by EP300 in the MH2 domain regulates positively its transcriptional activity and is enhanced by TGF-beta.
Poly-ADP-ribosylated by PARP1 and PARP2. ADP-ribosylation negatively regulates SMAD3 transcriptional responses during the course of TGF-beta signaling.
Ubiquitinated. Monoubiquitinated, leading to prevent DNA-binding (PubMed:21947082).
Deubiquitination by USP15 alleviates inhibition and promotes activation of TGF-beta target genes (PubMed:21947082).
Ubiquitinated by RNF111, leading to its degradation: only SMAD3 proteins that are 'in use' are targeted by RNF111, RNF111 playing a key role in activating SMAD3 and regulating its turnover (By similarity).
Undergoes STUB1-mediated ubiquitination and degradation (PubMed:24613385).

Anti-SMAD3 antibodies

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Target: SMAD3
Host: Mouse
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat
Clone: EC236
Application*: P
Target: SMAD3
Host: Mouse
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat
Clone: CB346A
Application*: ELISA, IHC
Target: SMAD3
Host: Mouse
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat
Clone: CB362
Application*: WB, IHC
Target: SMAD3
Host: Mouse
Antibody Isotype: IgG
Specificity: Human
Clone: 7F3
Application*: WB, E
Target: SMAD3
Host: Mouse
Antibody Isotype: IgG2a, κ
Specificity: Human
Clone: 4G12
Application*: WB, E
Target: SMAD3
Host: Mouse
Antibody Isotype: IgG2a, κ
Specificity: Human, Mouse
Clone: 4F9
Application*: WB, E
Target: SMAD3
Host: Mouse
Antibody Isotype: IgG2b, κ
Specificity: Human
Clone: 4D5
Application*: WB, E
Target: SMAD3
Host: Mouse
Antibody Isotype: IgG2a, κ
Specificity: Human
Clone: 4D4
Application*: WB, E
Target: SMAD3
Host: Mouse
Antibody Isotype: IgG2a, κ
Specificity: Human
Clone: 2G4
Application*: WB, E
Target: SMAD3
Host: Mouse
Antibody Isotype: IgG2b, κ
Specificity: Human, Mouse, Rat
Clone: 2F1
Application*: WB, E
Target: SMAD3
Host: Mouse
Antibody Isotype: IgG2b, κ
Specificity: Human, Rat
Clone: 2C12
Application*: WB, E
Target: SMAD3
Host: Mouse
Antibody Isotype: IgG2a, κ
Specificity: Human
Clone: 1D6
Application*: IF, E
Target: SMAD3
Host: Mouse
Antibody Isotype: IgG1, κ
Specificity: Human, Rat
Clone: 1C11
Application*: WB, E
Target: SMAD3
Host: Mouse
Antibody Isotype: IgG2a, κ
Specificity: Human
Clone: 1B7
Application*: WB, E
Target: SMAD3
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human, Mouse
Application*: WB, P, IF/IC
Target: SMAD3
Host: Mouse
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat
Clone: 1D9
Application*: P
Target: SMAD3
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat, Monkey, Frog, Zebrafish, Cattle
Clone: C25A9
Application*: WB, IP, CI
Target: SMAD3
Host: Rabbit
Antibody Isotype: IgG
Specificity: Cattle, Human, Mouse, Rat, Frog, Zebrafish
Clone: CBXS-6143
Application*: CI, F, IC, IF, IP, WB
Target: SMAD3
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human, Rat
Clone: CBXS-3522
Application*: IC, IH, IP, WB
Target: SMAD3
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat
Clone: CBXS-3409
Application*: E, F, IF, IP, WB
Target: SMAD3
Host: Mouse
Antibody Isotype: IgG1, κ
Specificity: Human
Clone: CBXS-3395
Application*: E, IH, WB
Target: SMAD3
Host: Mouse
Specificity: Human
Clone: CBXS-3238
Application*: E, IF
Target: SMAD3
Host: Mouse
Specificity: Human
Clone: CBXS-3235
Application*: E, IF, WB
Target: SMAD3
Host: Mouse
Specificity: Human
Clone: CBXS-3197
Application*: E, WB
Target: SMAD3
Host: Mouse
Specificity: Human
Clone: CBXS-2947
Application*: E, IF, WB
Target: SMAD3
Host: Mouse
Specificity: Human
Clone: CBXS-2903
Application*: E, WB
Target: SMAD3
Host: Mouse
Specificity: Human
Clone: CBXS-2744
Application*: E, IF, WB
Target: SMAD3
Host: Mouse
Specificity: Human
Clone: CBXS-2712
Application*: E, IF, WB
Target: SMAD3
Host: Mouse
Specificity: Human
Clone: CBXS-2700
Application*: E, WB
Target: SMAD3
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human, Mouse
Clone: CBXS-2448
Application*: E, WB
Target: SMAD3
Host: Rabbit
Antibody Isotype: IgG
Specificity: Mouse, Human, Fruit fly
Clone: CBXS-1231
Application*: WB, E, P, C, IF
Target: SMAD3
Host: Rabbit
Antibody Isotype: IgG
Specificity: Mouse, Rat, Human
Clone: CBXS-1214
Application*: WB, P, F, IF, SE
Target: SMAD3
Host: Mouse
Antibody Isotype: IgG2a, κ
Specificity: Human
Clone: CBXS-0520
Application*: IF, E, WB
Target: SMAD3
Host: Mouse
Antibody Isotype: IgG1, κ
Specificity: Human, Mouse, Rat
Clone: AF9F7
Application*: WB, E, IP, P
Target: SMAD3
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human, Mouse
Clone: 5G11
Application*: E, IC, IF, IH, WB
Target: SMAD3
Host: Mouse
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat
Clone: CBXS-5228
Application*: P
Target: SMAD3
Host: Mouse
Antibody Isotype: IgG2a, κ
Specificity: Human
Clone: CBXS-4432
Application*: E, P, WB
Target: SMAD3
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat, Monkey, Frog, Zebrafish, Cattle
Clone: CBXS-6002
Application*: WB, IP, IF, F, CI
Target: SMAD3
Host: Mouse
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat
Clone: CBXS-5923
Application*: WB, P
Target: SMAD3
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human, Mouse, Rat
Clone: CBXS-5902
Application*: WB, P, IF, IP
Target: SMAD3
Host: Rat
Antibody Isotype: IgG1
Specificity: Human
Clone: CBXS-1809
Application*: IS
Target: SMAD3
Host: Mouse
Specificity: Human
Clone: CBWJS-025
Application*: WB, IC, P, IH-F, E
Target: SMAD3
Host: Mouse
Antibody Isotype: IgG2b
Specificity: Human
Clone: 1C12
Application*: IP, M, WB
More Infomation
For Research Use Only. Not For Clinical Use.
(P): Predicted
* Abbreviations
IFImmunofluorescence
IHImmunohistochemistry
IPImmunoprecipitation
WBWestern Blot
EELISA
MMicroarray
CIChromatin Immunoprecipitation
FFlow Cytometry
FNFunction Assay
IDImmunodiffusion
RRadioimmunoassay
TCTissue Culture
GSGel Supershift
NNeutralization
BBlocking
AActivation
IInhibition
DDepletion
ESELISpot
DBDot Blot
MCMass Cytometry/CyTOF
CTCytotoxicity
SStimulation
AGAgonist
APApoptosis
IMImmunomicroscopy
BABioassay
CSCostimulation
EMElectron Microscopy
IEImmunoelectrophoresis
PAPeptide Array
ICImmunocytochemistry
PEPeptide ELISA
MDMeDIP
SHIn situ hybridization
IAEnzyme Immunoassay
SEsandwich ELISA
PLProximity Ligation Assay
ECELISA(Cap)
EDELISA(Det)
BIBioimaging
IOImmunoassay
LFLateral Flow Immunoassay
LALuminex Assay
CImmunohistochemistry-Frozen Sections
PImmunohistologyp-Paraffin Sections
ISIntracellular Staining for Flow Cytometry
MSElectrophoretic Mobility Shift Assay
RIRNA Binding Protein Immunoprecipitation (RIP)
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