SMAD4 Protein, Human (His)

SMAD4 is a class of common mediator SMAD (Co-SMAD), which belongs to the dwarfin/SMAD family. It conducts cell signals through the SMAD4/TGF-β pathway and plays an important role in promoting bone development and tissue homeostasis. SMAD4 induces chondrogenesis of human bone marrow mesenchymal stem cells, and specifically targets stem cells to participate in self-renewal of hematopoietic stem cells. SMAD4 can also protect cell apoptosis and inhibit epithelial cell proliferation, showing antitumor effects^[1][2]. SMAD4 Protein, Human (His) has the 552 a.a. sequence (M1-D552), produced in E.coli with C-terminal 6*His-tag.

SMAD4 belongs to the dwarfin/SMAD family. SMAD is a group of proteins that carry extracellular signals directly to the nucleus. Mammalian SMAD can be divided into three categories: receptor-regulated SMAD (R-SMAD), common-mediated SMAD (Co-SMAD), and inhibitory SMAD (I-SMAD). (1) R-SMAD included SMAD1, SMAD2, SMAD3, SMAD5 and SMAD8/9, among which Smad2/3 mediated signal transduction of TGF-β subfamily members. SMAD1/5/8 mediates signaling from members of the bone morphogenetic proteins (BMP) subfamily. (2) Co-SMAD includes SMAD4, which is the central mediator of TGF-β and BMP signaling pathways. (3) I-SMAD, including SMAD6 and SMAD7, inhibits receptor-mediated phosphorylation of R-SMAD, thereby preventing the formation of complexes with Co SMAD. SMAD4 plays an important role in cellular signaling of bone development (from chondrocyte precursors to mature osteocytes) and tissue homeostasis. Specifically, TGF-β signals upstream to activate SMAD4 and R-SMAD (i.e. SMAD2/3) to interact and form oligomer complexes that regulate the expression of target genes. However, SMAD3/4 mainly induced chondrogenesis of human bone marrow mesenchymal stem cells. Abnormal expression of SMAD4 can inhibit cartilage production in animal models, and even lead to uncontrolled cell growth and tumor induction. SMAD4 also specifically targets stem cells and may be involved in self-renewal of hematopoietic stem cells. At the same time, SMAD4 regulates the cell polarity of chondrocytes, affecting the shape, size, migration and orientation of chondrocytes. It also promotes cell migration, adhesion and cytoskeletal tissue generation in different cells through the SMAD4/TGF-β pathway. The SMAD4/TGF-β pathway is also extensively regulated by classical pathways such as MAPK, PI3K/AKT, and WNT/β-catenin to form complex networks. SMAD4 also regulates apoptosis, leading to follicular atresia by inhibiting granulosa cell apoptosis. In colorectal cancer cells, TGF-β induces Smad4-dependent epithelial-mesenchymal transformation, which leads to apoptosis. The protective effect of SMAD4 on apoptosis is also the key to the differentiation and proliferation of chondrocytes. In addition, apoptosis is crucial for differentiation and bone homeostasis, that is, osteoblast apoptosis promotes osteoclast generation and bone resorption, which is an important process of bone homeostasis. SMAD4 also controls gene regulatory networks in early limb buds, and chondrocyte specific Smad4-KO mice exhibit dwarfism and impaired growth plate tissue. SMAD4 protein also inhibited epithelial cell proliferation and decreased angiogenesis and increased vascular permeability, showing antitumor effects^[1][2].

SMAD4 knockout inhibits TGFβ/ activin/lymph node receptor signaling and restricts the rapid differentiation of human embryonic stem cells (hESCs)^[3].

Human

E. coli

C-6*His

Q13485 (M1-D552)

4089  [NCBI]

Full Length

MDNMSITNTPTSNDACLSIVHSLMCHRQGGESETFAKRAIESLVKKLKEKKDELDSLITAITTNGAHPSKCVTIQRTLDGRLQVAGRKGFPHVIYARLWRWPDLHKNELKHVKYCQYAFDLKCDSVCVNPYHYERVVSPGIDLSGLTLQSNAPSSMMVKDEYVHDFEGQPSLSTEGHSIQTIQHPPSNRASTETYSTPALLAPSESNATSTANFPNIPVASTSQPASILGGSHSEGLLQIASGPQPGQQQNGFTGQPATYHHNSTTTWTGSRTAPYTPNLPHHQNGHLQHHPPMPPHPGHYWPVHNELAFQPPISNHPAPEYWCSIAYFEMDVQVGETFKVPSSCPIVTVDGYVDPSGGDRFCLGQLSNVHRTEAIERARLHIGKGVQLECKGEGDVWVRCLSDHAVFVQSYYLDREAGRAPGDAVHKIYPSAYIKVFDLRQCHRQMQQQAATAQAAAAAQAAAVAGNIPGPGSVGGIAPAISLSAAAGIGVDDLRRLCILRMSFVKGWGPDYPRQSIKETPCWIEIHLHRALQLLDEVLHTMPIADPQPLD

Approximately 62 kDa, based on SDS-PAGE under reducing conditions.

≥ 80%, as determined by reducing SDS-PAGE.

<1 EU/μg, determined by LAL method.

• [1]. Pakravan K, et al. SMAD4 contributes to chondrocyte and osteocyte development. J Cell Mol Med. 2022 Jan;26(1):1-15.  [Content Brief]

  [2]. Zhao M, et al. The role of TGF-β/SMAD4 signaling in cancer. Int J Biol Sci. 2018 Jan 12;14(2):111-123.  [Content Brief]

  [3]. Avery S, et al. The role of SMAD4 in human embryonic stem cell self-renewal and stem cell fate. Stem Cells. 2010 May;28(5):863-73.  [Content Brief]