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Subunit: Monomer; in the absence of TGF-beta. Homooligomer; in the presence of TGF-beta. Heterotrimer; forms a heterotrimer in the presence of TGF-beta consisting of two molecules of C-terminally phosphorylated SMAD2 or SMAD3 and one of SMAD4 to form the transcriptionally active SMAD2/SMAD3-SMAD4 complex. Interacts with TGFBR1. Part of a complex consisting of AIP1, ACVR2A, ACVR1B and SMAD3. Interacts with AIP1, TGFB1I1, TTRAP, FOXL2, PML, PRDM16, HGS, WWP1 and SNW1. Interacts (via MH2 domain) with CITED2 (via C-terminus) (By similarity). Interacts with NEDD4L; the interaction requires TGF-beta stimulation (By similarity). Interacts (via the MH2 domain) with ZFYVE9. Interacts with HDAC1, VDR, TGIF and TGIF2, RUNX3, CREBBP, SKOR1, SKOR2, SNON, ATF2, SMURF2 and TGFB1I1. Interacts with DACH1; the interaction inhibits the TGF-beta signaling. 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 MEN1. Interacts with IL1F7. 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 Selected PDB 3D structures from [IMAGE] and Proteopedia [IMAGE] for SMAD3 (see all 7): 1MHD (3D) [IMAGE] 1MJS (3D) [IMAGE] 1MK2 (3D) [IMAGE] 1OZJ (3D) [IMAGE] 1U7F (3D) [IMAGE] 2LAJ (3D) [IMAGE]
Function: UniProtKB/Swiss-Prot Summary: SMAD3_HUMAN, P84022 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 Gene Ontology (GO): Selected molecular function terms (see all 26): About this table GO ID Qualified GO term Evidence PubMed IDs GO:0000987 core promoter proximal region sequence-specific DNA binding IDA 18832382 GO:0000988 contributes to protein binding transcription factor activity IDA 18832382 GO:0001102 RNA polymerase II activating transcription factor binding IPI 17251190 GO:0003677 DNA binding -- -- GO:0003682 chromatin binding -- -- [IMAGE] Find genes that share ontologies with SMAD3 About GenesLikeMe Phenotypes: Selected MGI mutant phenotypes (inferred from 5 alleles[IMAGE]) (MGI details for Smad3) (see all 21): behavior/neurological cardiovascular system cellular craniofacial digestive/alimentary embryogenesis endocrine/exocrine gland growth/size/body hematopoietic system homeostasis/metabolism immune system integument limbs/digits/tail liver/biliary system mortality/aging [IMAGE] Find genes that share phenotypes with SMAD3 About GenesLikeMe Animal Models: MGI mouse knock-outs for SMAD3: Smad3tm1Xfw Smad3tm1Sche Smad3tm1Cxd [IMAGE] inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for SMAD3 [IMAGE] inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for SMAD3 [IMAGE] genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for SMAD3 [IMAGE] genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for SMAD3 Transcription Factor Targeting: [IMAGE] Targeting motifs: HOMER Transcription Factor Regulatory Elements motif viewer [IMAGE] Consensus sequence: TWGTCTGV miRNA Products: miRTarBase miRNAs that target SMAD3: hsa-mir-17-5p (MIRT050933), hsa-mir-155-5p (MIRT020918), hsa-mir-200a-3p (MIRT007291), hsa-mir-335-5p (MIRT018567), hsa-mir-18a-5p (MIRT007323), hsa-mir-193b-3p (MIRT041360) [IMAGE] Block miRNA regulation of human, mouse, rat SMAD3 using miScript Target Protectors [IMAGE] Selected qRT-PCR Assays for microRNAs that regulate SMAD3 (see all 73): hsa-miR-323-3p hsa-miR-579 hsa-miR-3194-5p hsa-miR-607 hsa-miR-15a hsa-miR-489 hsa-miR-556-3p hsa-miR-3148 [IMAGE] Browse SwitchGear 3'UTR luciferase reporter plasmids Inhib. RNA Products: [IMAGE] OriGene RNAi products in human, mouse, rat for SMAD3 [IMAGE] Predesigned siRNA for gene silencing in human, mouse, rat SMAD3 Gene Editing Products: [IMAGE] DNA2.0 Custom Protein Engineering Service for SMAD3 Clone Products: [IMAGE] OriGene clones in human, mouse for SMAD3 (see all 21) OriGene ORF clones in mouse, rat for SMAD3 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling [IMAGE] GenScript: all cDNA clones in your preferred vector (see all 4): SMAD3 (NM_001145103) [IMAGE] Sino Biological Human cDNA Clone for SMAD3 [IMAGE] DNA2.0 Custom Codon Optimized Gene Synthesis Service for SMAD3 [IMAGE] Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat SMAD3 [IMAGE] Addgene plasmids for SMAD3 [IMAGE] Cell Line Products: [IMAGE] GenScript Custom overexpressing Cell Line Services for SMAD3 [IMAGE] Browse ESI BIO Cell Lines and PureStem Progenitors for SMAD3 [IMAGE] In Situ Assay Products: [IMAGE] Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for SMAD3
Similarity: Belongs to the dwarfin/SMAD family Contains 1 MH1 (MAD homology 1) domain Contains 1 MH2 (MAD homology 2) domain [IMAGE]
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