SMAD3

  • Official Full Name

    SMAD family member 3

  • Overview

    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. [provided by RefSeq, Apr 2009]
  • Synonyms

    SMAD3; SMAD family member 3; LDS3; LDS1C; MADH3; JV15-2; HSPC193; HsT17436; mothers against decapentaplegic homolog 3; mad3; hMAD-3; hSMAD3; MAD homolog 3; mad homolog JV15-2; mad protein homolog; mothers against DPP homolog 3; SMA- and MAD-related protein 3; SMAD, mothers against DPP homolog 3; MAD, mothers against decapentaplegic homolog 3;

  • Recombinant Proteins
  • Protein Pre-coupled Magnetic Beads
  • Cell & Tissue Lysates
  • Chicken
  • Human
  • Human/Mouse/Rat
  • Mouse
  • Rat
  • Rhesus Macaque
  • E.coli
  • HEK293
  • HEK293T
  • Human
  • Insect Cell
  • Insect Cells
  • Mammalian Cell
  • Mammalian cells
  • Flag
  • GST
  • His
  • His (Fc)
  • Avi
  • His|MBP
  • SUMO
  • Myc
  • DDK
  • Myc|DDK
  • N/A
  • N
Species Cat.# Product name Source (Host) Tag Protein Length Price
Human SMAD3-1094H Recombinant Human SMAD Family Member 3, GST-tagged E.coli GST
Human SMAD3-4599H Recombinant SMAD Family Member 3, His-tagged Human His
Human SMAD3-327H Recombinant Human SMAD3 protein, His/MBP-tagged E.coli His/MBP 241-425 aa
Human SMAD3-6915H Recombinant Human SMAD Family Member 3, His-tagged E.coli His 1-425aa
Human SMAD3-31191TH Recombinant Human SMAD3 E.coli N/A
Human SMAD3-31190TH Recombinant Human SMAD3, His-tagged E.coli His
Human SMAD3-295H Recombinant Human SMAD3 protein, GST-tagged E.coli GST
Human SMAD3-326H Recombinant Human SMAD3 protein, His/MBP-tagged E.coli His/MBP 16-221 aa
Human SMAD3-4788H Recombinant Human SMAD3 Protein, Myc/DDK-tagged, C13 and N15-labeled HEK293T Myc/DDK
Human SMAD3-304H Recombinant Human SMAD3 Protein, His-tagged E.coli His Phe231~Ser425
Human SMAD3-1918H Recombinant Human SMAD3 Protein, MYC/DDK-tagged HEK293 Myc/DDK
Human SMAD3-227HFL Active Recombinant Full Length Human SMAD3 Protein, C-Flag-tagged Mammalian cells Flag
Human SMAD3-2256H Recombinant Human SMAD3 protein, His-tagged Insect Cell His 1-425aa
Human SMAD3-2041H-B Recombinant Human SMAD3 Protein Pre-coupled Magnetic Beads HEK293
Human SMAD3-3506H Recombinant Human SMAD3 protein, His-SUMO-tagged E.coli His-SUMO 1-425aa
Human SMAD3-5867H Recombinant Human SMAD3 Protein (Asp220-Ser425), N-His tagged E.coli N-His Asp220-Ser425
Human SMAD3-1973HF Active Recombinant Full Length Human SMAD3 Protein, GST-tagged E.coli GST 1-425(end)
Human SMAD3-2041H Recombinant Human SMAD3 Protein, His (Fc)-Avi-tagged HEK293 His (Fc)-Avi
Mouse SMAD3-532M Recombinant Mouse Smad3, His-GST tagged Insect Cell GST
Mouse SMAD3-001MCL Recombinant Mouse SMAD3 cell lysate Insect Cell N/A
Mouse Smad3-5951M Recombinant Mouse Smad3 Protein, Myc/DDK-tagged HEK293T Myc/DDK
Mouse Smad3-305M Recombinant Mouse Smad3 Protein, His-tagged E.coli His Phe231~Ser425
Rat SMAD3-5608R Recombinant Rat SMAD3 Protein Mammalian Cell His
Rat SMAD3-5267R Recombinant Rat SMAD3 Protein, His (Fc)-Avi-tagged HEK293 His (Fc)-Avi
Rat SMAD3-5267R-B Recombinant Rat SMAD3 Protein Pre-coupled Magnetic Beads HEK293
Human/Mouse/Rat Smad3-0256H Recombinant Human/Mouse/Rat Smad3 protein, His&GST-tagged Insect Cells His/GST Met1-Ser425
Rhesus Macaque SMAD3-4331R Recombinant Rhesus monkey SMAD3 Protein, His-tagged Mammalian Cell His
Rhesus Macaque SMAD3-4147R Recombinant Rhesus Macaque SMAD3 Protein, His (Fc)-Avi-tagged HEK293 His (Fc)-Avi
Rhesus Macaque SMAD3-4147R-B Recombinant Rhesus Macaque SMAD3 Protein Pre-coupled Magnetic Beads HEK293
Chicken SMAD3-6045C Recombinant Chicken SMAD3 Mammalian Cell His
  • Background
  • Quality Guarantee
  • Case Study
  • Involved Pathway
  • Protein Function
  • Interacting Protein
  • Other Resource
  • SMAD3 Related Signal Pathway
SMAD3-9.jpg

Fig1. Signal transduction through STAT3 and Smad2/3. (Yuka Itoh, 2018)

What is SMAD3 protein?

SMAD3 (SMAD family member 3) gene is a protein coding gene which situated on the long arm of chromosome 15 at locus 15q22. 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. The SMAD3 protein is consisted of 425 amino acids and its molecular mass is approximately 48.1 kDa.

What is the function of SMAD3 protein?

SMAD3 is a direct mediator of transcriptional activation by the TGF receptor. The activity of SMAD3 is regulated by the TGF receptors, and SMAD3 is phosphorylated and associated with the ligand-bound receptor complex. TGF stimulation leads to phosphorylation and activation of SMAD3, which form a complex with SMAD4 that accumulate in the nucleus and regulate transcription of target genes such as CDK inhibitor. SMAD3 containing a C-terminal truncation acts as a dominant-negative inhibitor of the normal TGF response. SMAD3 is a major physiologic substrate of the G1 cyclin-dependent kinases CDK4 and CDK2.

SMAD3 Related Signaling Pathway

SMAD3 protein is a key transcription factor in transforming the growth factor-β (TGF-β) superfamily signaling pathway. In the TGF-β signaling pathway, when TGF-β ligand binds to its receptor, SMAD3 is activated and forms a complex with SMAD2 or SMAD4, which then moves into the nucleus to regulate the expression of target genes. In addition to the TGF-β signaling pathway, SMAD3 is also involved in signaling other members of the TGF-β superfamily, such as bone morphogenetic proteins (BMP), activins, and statins.

SMAD3 Related Diseases

Abnormal activation of SMAD3 is associated with the occurrence of many diseases, including cancer, cardiovascular disease and pulmonary fibrosis. In cancer, overactivation of SMAD3 can promote the growth and metastasis of tumor cells. In cardiovascular disease, abnormal activation of SMAD3 may lead to cardiac hypertrophy and heart valve disease. In pulmonary fibrosis, overactivation of SMAD3 can promote the occurrence of pulmonary interstitial fibrosis.

SMAD3-10.jpg

Fig2. Smad3 triggers the cell death pathways in acute kidney injury. (Wenjing Wu, 2022)

Bioapplications of SMAD3

At present, research on small molecule inhibitors or activators of SMAD3 is ongoing, with a view to developing novel drugs or therapies to treat related diseases. In addition, SMAD3 is also used as a biomarker to diagnose certain types of cancer or other diseases.

Case study 1: Chen Yang, 2021

Macroautophagy/autophagy dysregulation has been noted in diabetic nephropathy; however, the regulatory mechanisms controlling this process remain unclear. In this study, the researchers showed that SMAD3 (SMAD family member 3), the key effector of TGFB (transforming growth factor beta)-SMAD signaling, induces lysosome depletion via the inhibition of TFEB-dependent lysosome biogenesis. The pharmacological inhibition or genetic deletion of SMAD3 restored lysosome biogenesis activity by alleviating the suppression of TFEB, thereby protecting lysosomes from depletion and improving autophagic flux in renal tubular epithelial cells in diabetic nephropathy. Mechanistically, they found that SMAD3 directly binds to the 3'-UTR of TFEB and inhibits its transcription. Silencing TFEB suppressed lysosome biogenesis and resulted in a loss of the protective effects of SMAD3 inactivation on lysosome depletion under diabetic conditions. In conclusion, SMAD3 promotes lysosome depletion via the inhibition of TFEB-dependent lysosome biogenesis; this may be an important mechanism underlying autophagy dysregulation in the progression of diabetic nephropathy.

SMAD3-3.jpg

Fig1. Western blot analysis of phospho-SMAD3, LC3, and SQSTM1 expression in AGE-BSA or Co-BSA-treated HK-2 cells.

SMAD3-4.jpg
Fig2. Western blot analysis of phospho-SMAD3 expression in HK-2 cells.

Case study 2: Heeseog Kang, 2020

Melorheostosis is a rare sclerosing dysostosis characterized by asymmetric exuberant bone formation. Recently, the researchers reported that somatic mosaicism for MAP2K1-activating mutations causes radiographical "dripping candle wax" melorheostosis. They now report somatic SMAD3 mutations in bone lesions of four unrelated patients with endosteal pattern melorheostosis. In vitro, the SMAD3 mutations stimulated the TGF-β pathway in osteoblasts, enhanced nuclear translocation and target gene expression, and inhibited proliferation. Osteoblast differentiation and mineralization were stimulated by the SMAD3 mutation, consistent with higher mineralization in affected than in unaffected bone, but differing from MAP2K1 mutation-positive melorheostosis. Conversely, osteoblast differentiation and mineralization were inhibited when osteogenesis of affected osteoblasts was driven in the presence of BMP2. Transcriptome profiling displayed that TGF-β pathway activation and ossification-related processes were significantly influenced by the SMAD3 mutation. Co-expression clustering illuminated melorheostosis pathophysiology, including alterations in ECM organization, cell growth, and interferon signaling. These data reveal antagonism of TGF-β/SMAD3 activation by BMP signaling in SMAD3 mutation-positive endosteal melorheostosis, which may guide future therapies.

SMAD3-5.jpg

Fig3. SMAD3 phosphorylation upon TGF-β stimulation with or without TGFβRI inhibitor (SB431542) pretreatment was assessed by Western blotting (Melo-11, SMAD3 p.S264Y).

SMAD3-6.jpg
Fig4. Effect of the mutant SMAD3 with low VAF on TGF-β signaling activation. SMAD3 phosphorylation in affected cells of melorheostotic bone in response to TGF-β stimulation was comparable to that in unaffected cells.
SMAD3-7.jpg

Fig1. Smad3 signaling and crosstalk pathways in renal fibrosis. (Wenjing Wu, 2022)

SMAD3-8.jpg

Fig2. Smad3 signaling and crosstalk pathways in renal inflammation. (Wenjing Wu, 2022)

SMAD3 involved in several pathways and played different roles in them. We selected most pathways SMAD3 participated on our site, such as FoxO signaling pathway, Cell cycle, Endocytosis, which may be useful for your reference. Also, other proteins which involved in the same pathway with SMAD3 were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

Pathway Name Pathway Related Protein
FoxO signaling pathwayMAPK1;IRS1;FOXG1;INS2;NLK2;PIK3R3A;PRKAG3B;MAPK8A;BCL6A
Cell cycleGADD45A;TSGA14;CENPQ;TGFB1;CDC45;LIN52;CENPC1;STAG2;CSNK2A1
EndocytosisRHOAD;EHD3;CAPZA2;ASAP2B;VTA1;RAB4A;EPN3;ERBB3A;VPS24
Wnt signaling pathwayWNT4;DVL3A;TLE3A;WNT4A;PPP3CCA;PPP3R1B;FRAT2;PPP3CC;SOX17
TGF-beta signaling pathwayTGIF1;TFDP1A;ROCK2B;THBS1;BMP7B;ID1;SP1;INHBAB;PITX2
Hippo signaling pathwayLEF1;AJUBA;WTIP;BBC3;CTGF;BMP7;YAP1;FZD1;PARD6B
Adherens junctionSMAD3;CTNND1;PTBP3;MET;PARD3;CSNK2A2A;CSNK2A1;WASL;INSR
Signaling pathways regulating pluripotency of stem cellsSMAD9;WNT9A;SMAD5;WNT5B;FGFR3;NODAL;NEUROG1;PIK3CD;PIK3CG
Chagas disease (American trypanosomiasis)CD247;C1QC;IRAK1;Ccl12;IL1B;PIK3R1;GNAI1;CCL2;PIK3R5
Hepatitis BBIRC5;IFIH1;IL6;Ifna15;NFATC1;IFNA8;OSTN;RAF1;TGFB3
HTLV-I infectionCREM;APC;ITGB2;PIK3CG;TP53INP1;ANAPC4;PIK3CB;ITGB2L;WNT4
Pathways in cancerGNG2;ARNT;ITGA6;RALB;BAD;DAPK3;GNG4;APC2;FZD6
Colorectal cancerKRAS;DCC;GSK3B;MSH2;PIK3CA;TCF7;BCL2;SMAD3;BRAF
Pancreatic cancerMAPK3;BCL2L1;RAC3;PIK3R3;RAD51;VEGFA;CDC42;MAP2K1;ARAF
Chronic myeloid leukemiaRAF1;CBLB;TGFB2;TP53;MAP2K2;MECOM;SHC1;TGFB1;AKT1
Inflammatory bowel disease (IBD)RORC;IL13;TBX21;HLA-DOB;IL21;STAT3;HLA-DPB1;Il23a; Il12b;TLR5

SMAD3 has several biochemical functions, for example, R-SMAD binding, RNA polymerase II activating transcription factor binding, RNA polymerase II core promoter proximal region sequence-specific DNA binding. Some of the functions are cooperated with other proteins, some of the functions could acted by SMAD3 itself. We selected most functions SMAD3 had, and list some proteins which have the same functions with SMAD3. You can find most of the proteins on our site.

Function Related Protein
R-SMAD bindingCTNNB1;MEN1;PMEPA1;ZC3H3;RANBP3;ANKRD1;TRIM33;MYOCD;FOXH1
RNA polymerase II activating transcription factor bindingNCOR1;LDB1;TBX20;HEY2;BEX1;PITX2;CREB1;NFE2L2;DUSP26
RNA polymerase II core promoter proximal region sequence-specific DNA bindingRBPJA;NKX6-2;MYF5;EN1;ELF1;SMAD6;PYDC3;GLI3;NOBOX
bHLH transcription factor bindingTCF3A;USF1;RUNX2;SP1;BHLHE40;MAP3K10;SMAD3;TCF3B;ISL1
beta-catenin bindingCDH24;SALL1;TBL1X;TBL1XR1;ASH2L;DACT2;ESR1;VCL;CBY1
chromatin DNA bindingHDAC3;HIST1H1D;PRDM14;HIST1H1E;HIST1H1C;RXRA;NOTCH1;WBP2;HIST1H1A
co-SMAD bindingTRIM33;USP9X;TGIF1;CITED1;SMAD1;GATA4;FOXH1;SMAD2;SMAD3
collagen bindingSERPINH2;ITGA3;SERPINH1A;ITGA1;Itga10&Itgb1;CD44;TLL1;FN1;ABI3BP
core promoter proximal region sequence-specific DNA bindingSMAD4;GATA3;DMRT2A;ZFP516;DMRTC1B;DMRT3A;DMRT2;DMRTC1C2;SP3A
enhancer bindingRAI1;AHR;LEF1;MESP1;TCF3;FOXH1;SMAD3;ARNT;SMAD2
identical protein bindingPRPF3;ALCAMA;ORAI1;MLL1;CRYBB2;EED;APP;SORD;DRD2
phosphatase bindingMAPK3;MAST2;SH3GL1;DLG3;CRY1;CNST;PPP1R21;SYTL2;SH2D4A
protein bindingHOOK2;TRMT61B;CNIH4;TINAGL1;GGN;ERCC5;CCDC55;DAAM1;CAV2
protein heterodimerization activityYWHAH;ZHX2;ROPN1B;TGFB3;H3F3C;MCL1B;P2RY1;UGT1A6;BMP6
protein homodimerization activityTIGIT;PSPH;XBP1;MAP3K11;EEA1;GRPEL2;BCL2L10;PON3;DMRT2B
protein kinase bindingTCF7L2;PLK1;PPP1R12C;PRC1;CALM2;RICTOR;MAPK4;MSH2;CDK5RAP3
sequence-specific DNA bindingDLX5A;EVE1;NR5A2;DMBX1;CAMTA1;SMAD3;FOXN1;WHSC1;ATF4
transcription factor activity, RNA polymerase II core promoter sequence-specificHEY1;SMAD3;MEF2C;MAX;TFAP2B;PAX7;HEYL;NKX3;HEY2
contributes_to transcription factor activity, protein bindingSMAD3;SMAD4
transcription factor activity, sequence-specific DNA bindingHOXC8;ELF2A;ZFP2;ZNF518A;PCGF2;GLI3;MYCLA;ZNF461;FOXG1A
contributes_to transcription factor activity, sequence-specific DNA bindingRXRA;SOX1A;SMAD2;NFE2L2A;SMAD3;MAFGA;FOXH1;SOX19A;TAF12
transcription factor bindingGTF2A1;Ar;POU5F1;JUNBB;KCTD1;TRIB1;PAX6;TRIM11;HHEX
transcription regulatory region DNA bindingZFP513;KLF15;SMARCA2;BCL11AA;YAP1;NKX3-1;BCL11AB;KLF11;ARID5B
transforming growth factor beta receptor bindingLEFTY1;INHBC;TGFBRAP1;LRG1;GDF5;NDR2;USP15;MSTNB;GDF6B
transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activitySMAD2;SMAD3;SMAD9;SMAD1
ubiquitin bindingOTUB1B;RNF168;NBR1;MARK4;OTUB1;KCNS1;FAM125A;SHRPRBCK1R;UBR5
ubiquitin protein ligase bindingHIF1A;FZD5;BCL2;DBT;CLU;DIO2;GLMN;LC3;BAG5
zinc ion bindingEHMT2;BTR22;TRIM12A;LHX1;RNF148;KCMF1;PRDM2;ABLIM3;LHX3

SMAD3 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with SMAD3 here. Most of them are supplied by our site. Hope this information will be useful for your research of SMAD3.

SMAD4; SKI

Gene Family

TGF

Research Area

Related articles

Smithrithee, R; Niyonsaba, F; et al. Human beta-defensin-3 increases the expression of interleukin-37 through CCR6 in human keratinocytes. JOURNAL OF DERMATOLOGICAL SCIENCE 77:46-53(2015).
McMillin, M; Galindo, C; et al. Gli1 activation and protection against hepatic encephalopathy is suppressed by circulating transforming growth factor beta 1 in mice. JOURNAL OF HEPATOLOGY 61:1260-1266(2014).
  • Q&As
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Q&As (6)

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What is the method used to determine the expression level and activity of SMAD3 protein? 12/05/2022

The expression level of SMAD3 protein can be detected by immunohistochemistry, western blotting, real-time PCR and other techniques. At the same time, the activity of SMAD3 protein can be assessed by detecting the phosphorylation level and the amount of SMAD3 protein within the nucleus.

How are the interactions between SMAD3 protein and other proteins regulated? 05/25/2022

interaction between SMAD3 protein and other proteins is regulated by a variety of factors, including phosphorylation, methylation, acetylation and other modifications, and interactions with other proteins. These factors can affect the interaction between SMAD3 protein and other proteins, and then affect the regulation process of TGF-β signal transduction pathway.

How is SMAD3 protein involved in the TGF-β signaling pathway? 04/28/2022

In the TGF-β signaling pathway, SMAD3 protein is activated by TGF-β to form complexes with other SMAD proteins, and then enters the nucleus to regulate the expression of specific genes, thereby affecting the growth, differentiation, apoptosis and immune response of cells.

How is the expression level of SMAD3 protein regulated? 03/05/2022

expression level of SMAD3 protein is regulated by a variety of factors, including gene transcription, translation, modification, and degradation. These factors can affect the expression level of SMAD3 protein, which in turn affects the growth, differentiation and apoptosis of cells.

What is the main function of SMAD3 protein? 01/25/2022

The main function of SMAD3 protein is to transmit signals in the TGF-β signal transduction pathway and regulate cell growth, differentiation, apoptosis and immune response.

What is SMAD3 protein? 07/22/2020

SMAD3 protein is a protein that plays a key role in intracellular signal transduction and belongs to the SMAD family. It is an effector molecule in the transforming growth factor-β (TGF-β) signaling pathway.

Customer Reviews (3)

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Reviews
05/14/2021

    High expression level, good stability, suitable for high precision experiments.

    03/08/2021

      Compared with other brands I have used, this brand is more stable and reliable.

      01/29/2021

        Strong antibacterial activity, not easy to be contaminated.

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