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SMAD4

Engineered Antibody
This gene encodes a member of the Smad family of signal transduction proteins. Smad proteins are phosphorylated and activated by transmembrane serine-threonine receptor kinases in response to transforming growth factor (TGF)-beta signaling. The product of this gene forms homomeric complexes and heteromeric complexes with other activated Smad proteins, which then accumulate in the nucleus and regulate the transcription of target genes. This protein binds to DNA and recognizes an 8-bp palindromic sequence (GTCTAGAC) called the Smad-binding element (SBE). The protein acts as a tumor suppressor and inhibits epithelial cell proliferation. It may also have an inhibitory effect on tumors by reducing angiogenesis and increasng blood vessel hyperpermeability. The encoded protein is a crucial component of the bone morphogenetic protein signaling pathway. The Smad proteins are subject to complex regulation by post-translational modifications. Mutations or deletions in this gene have been shown to result in pancreatic cancer, juvenile polyposis syndrome, and hereditary hemorrhagic telangiectasia syndrome. [provided by RefSeq, Aug 2017]
SMAD4
Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Transcription factors

Predicted location

Intracellular

Single cell type specificity

Cell type enhanced (Granulosa cells)

Immune cell specificity

Low immune cell specificity

Cell line specificity

Low cell line specificity

Interaction

Monomer; in the absence of TGF-beta activation (PubMed:9670020). Heterotrimer; on TGF-beta activation (PubMed:15799969). Heterotrimer 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 (PubMed:15799969, PubMed:15350224). Found in a ternary complex composed of SMAD4, STK11/LKB1 and STK11IP. Found in a complex with SMAD1 and YY1 (By similarity). Identified in a complex that contains at least ZNF451, SMAD2, SMAD3 and SMAD4 (PubMed:24324267). Interacts with ATF2, COPS5, DACH1, MSG1, SKI, STK11/LKB1, STK11IP and TRIM33. Associates with ZNF423 or ZNF521 in response to BMP2 leading to activate transcription of BMP target genes. Interacts with USP9X. Interacts (via the MH1 and MH2 domains) with RBPMS. Interacts with WWTR1 (via coiled-coil domain). Interacts with CITED1 and CITED2. 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. Interacts (via MH2 domain) with ZNF451 (via N-terminal zinc-finger domains) (PubMed:24324267). Interacts with ZC3H3 (By similarity). Interacts weakly with ZNF8 (PubMed:12370310). Interacts with NUP93 and IPO7; translocates SMAD4 to the nucleus through the NPC upon BMP7 stimulation resulting in activation of SMAD4 signaling (PubMed:26878725). Interacts with CREB3L1, the interaction takes place upon TGFB1 induction and SMAD4 acts as CREB3L1 coactivator to induce the expression of genes involved in the assembly of collagen extracellular matrix (PubMed:25310401). Interacts with DLX1 (PubMed:14671321). Interacts with ZBTB7A; the interaction is direct and stimulated by TGFB1 (PubMed:25514493). Interacts with CREBBP; the recruitment of this transcriptional coactivator is negatively regulated by ZBTB7A (PubMed:25514493). Interacts with EP300; the interaction with this transcriptional coactivator is negatively regulated by ZBTB7A (PubMed:25514493). Interacts with HDAC1 (PubMed:25514493). Interacts (via MH2 domain) with ZMIZ1 (via SP-RING-type domain); in the TGF-beta signaling pathway increases the activity of the SMAD3/SMAD4 transcriptional complex (PubMed:16777850).

Molecular function

DNA-binding

More Types Infomation
Related Diseases
Colorectal Cancer Colorectal Cancer
Gastric Cancer Gastric Cancer
Pancreatic Cancer Pancreatic Cancer
AGE-RAGE Signaling Pathway in Diabetic Complications AGE-RAGE Signaling Pathway in Diabetic Complications
Related Signaling Pathways
JAK-STAT Signaling Pathway JAK-STAT Signaling Pathway
TGF-β Signaling Pathway TGF-β Signaling Pathway

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