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Subunit: Interacts with CITED2 (By similarity). Monomer; in the absence of TGF-beta activation. Heterodimer; on TGF-beta activation. Composed of two molecules of a C-terminally phosphorylated R-SMAD molecule, SMAD2 or SMAD3, and one molecule of SMAD4 to form the transcriptional active SMAD2/SMAD3-SMAD4 complex. Found in a ternary complex composed of SMAD4, STK11/LKB1 and STK11IP. Interacts with ATF2, COPS5, DACH1, MSG1, SKI, STK11/LKB1, STK11IP and TRIM33. Interacts with ZNF423; the interaction takes place in response to BMP2 leading to activation of transcription of BMP target genes. Interacts with ZNF521; the interaction takes place in response to BMP2 leading to activation of transcription of BMP target genes. Interacts with USP9X. Interacts (via the MH1 and MH2 domains) with RBPMS. Interacts with WWTR1 (via coiled-coil domain). 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 with CITED1. Interacts with PDPK1 (via PH domain) (By similarity). Interacts with VPS39; this interaction affects heterodimer formation with SMAD3, but not with SMAD2, and leads to inhibition of SMAD3-dependent transcription activation. Interactions with VPS39 and SMAD2 may be mutually exclusive 6 PDB 3D structures from [IMAGE] and Proteopedia [IMAGE] for SMAD4: 1DD1 (3D) [IMAGE] 1G88 (3D) [IMAGE] 1MR1 (3D) [IMAGE] 1U7F (3D) [IMAGE] 1U7V (3D) [IMAGE] 1YGS (3D) [IMAGE]
Function: UniProtKB/Swiss-Prot Summary: SMAD4_HUMAN, Q13485 Function: Common SMAD (co-SMAD) is the coactivator and mediator of signal transduction by TGF-beta (transforming growth factor). Component of the heterotrimeric SMAD2/SMAD3-SMAD4 complex that forms in the nucleus and is required for the TGF-mediated signaling. Promotes binding of the SMAD2/SMAD4/FAST-1 complex to DNA and provides an activation function required for SMAD1 or SMAD2 to stimulate transcription. Component of the multimeric SMAD3/SMAD4/JUN/FOS complex which forms at the AP1 promoter site; required for syngernistic transcriptional activity in response to TGF-beta. May act as a tumor suppressor. 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 17): 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:0001076 RNA polymerase II transcription factor binding transcription factor activity IEA -- GO:0001085 RNA polymerase II transcription factor binding IEA -- GO:0003677 contributes to DNA binding IDA 9389648 [IMAGE] Find genes that share ontologies with SMAD4 About GenesLikeMe Phenotypes: 6 GenomeRNAi human phenotypes for SMAD4: Increased S DNA content, incre Increased mitotic index Increased sensitivity to pacli S arrest Synthetic lethal with gemcitab Upregulation of Wnt/beta-caten Selected MGI mutant phenotypes (inferred from 17 alleles[IMAGE]) (MGI details for Smad4) (see all 19): behavior/neurological cardiovascular system cellular digestive/alimentary embryogenesis endocrine/exocrine gland growth/size/body hematopoietic system homeostasis/metabolism immune system integument liver/biliary system mortality/aging muscle nervous system [IMAGE] Find genes that share phenotypes with SMAD4 About GenesLikeMe Animal Models: MGI mouse knock-outs for SMAD4: Smad4tm1.1Rob Smad4tm1.1Rdp Smad4tm2.1Rob Smad4tm2.2Cxd Smad4tm1Cxd Smad4tm1Mak Smad4tm2Cxd Smad4tm1Mmt [IMAGE] inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for SMAD4 [IMAGE] inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for SMAD4 [IMAGE] genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for SMAD4 [IMAGE] genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for SMAD4 Transcription Factor Targeting: [IMAGE] Targeting motifs: HOMER Transcription Factor Regulatory Elements motif viewer [IMAGE] Consensus sequence: VBSYGTCTGG miRNA Products: miRTarBase miRNAs that target SMAD4: hsa-mir-155-5p (MIRT020774), hsa-mir-19b-3p (MIRT031156), hsa-mir-182-5p (MIRT007306), hsa-mir-130a-3p (MIRT007144), hsa-mir-454-3p (MIRT007251), hsa-mir-301a-3p (MIRT007250), hsa-mir-483-3p (MIRT004118), hsa-mir-20a-5p (MIRT005631), hsa-mir-93-5p (MIRT028004), hsa-mir-224-5p (MIRT006527), hsa-mir-26a-5p (MIRT003803), hsa-mir-146a-5p (MIRT006209), hsa-mir-18a-5p (MIRT004736), hsa-mir-92a-3p (MIRT005632), hsa-mir-17-5p (MIRT005629), hsa-mir-186-5p (MIRT021160), hsa-mir-130b-3p (MIRT020189), hsa-mir-199a-5p (MIRT007013), hsa-mir-19a-3p (MIRT005630) [IMAGE] Block miRNA regulation of human, mouse, rat SMAD4 using miScript Target Protectors [IMAGE] Selected qRT-PCR Assays for microRNAs that regulate SMAD4 (see all 195): hsa-miR-411* hsa-miR-106a hsa-miR-146a hsa-miR-605 hsa-miR-519a hsa-miR-3921 hsa-miR-298 hsa-miR-130b [IMAGE] SwitchGear 3'UTR luciferase reporter plasmid: SMAD4 3' UTR sequence Inhib. RNA Products: [IMAGE] OriGene RNAi products in human, mouse, rat for SMAD4 [IMAGE] Predesigned siRNA for gene silencing in human, mouse, rat SMAD4 Gene Editing Products: [IMAGE] DNA2.0 Custom Protein Engineering Service for SMAD4 Clone Products: [IMAGE] OriGene clones in human, mouse for SMAD4 (see all 7) OriGene ORF clones in mouse, rat for SMAD4 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling [IMAGE] GenScript: all cDNA clones in your preferred vector: SMAD4 (NM_005359) [IMAGE] Sino Biological Human cDNA Clone for SMAD4 [IMAGE] DNA2.0 Custom Codon Optimized Gene Synthesis Service for SMAD4 [IMAGE] Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat SMAD4 [IMAGE] Addgene plasmids for SMAD4 [IMAGE] Cell Line Products: [IMAGE] GenScript Custom overexpressing Cell Line Services for SMAD4 [IMAGE] Browse ESI BIO Cell Lines and PureStem Progenitors for SMAD4 [IMAGE] In Situ Assay Products: [IMAGE] Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for SMAD4 Flow Cytometry Products: [IMAGE] eBioscience FlowRNA Probe Sets (VA1-12103) for SMAD4 [IMAGE]
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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