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Rabbit Anti-phospho-Smad2 (Ser465)/FITC Conjugated antibody
background:
SMAD2 or Mothers against decapentaplegic homolog 2 is a polypeptide that, as its name describes, is a homolog of the Drosophila gene: "Mothers against decepentaplegic". It belongs to the SMAD family of proteins, which belong to the TGF-Beta superfamily of modulators. Like many other TGF-Beta family members SMAD2 is involved in cell signalling. SMAD2 modulates signals of activin and TGF-Beta's. It interacts with SMAD anchor for receptor activation (SARA). The binding of ligands causes the phosphorylation of the SMAD2 protein and the dissociation from SARA and the association with SMAD4. It is subsequently transferred to the nucleus where it forms complexes with other proteins and acts as a transcription factor. SMAD2 is a receptor regulated SMAD (R-SMAD) and is activated by bone morphogenetic protein type 1 receptor kinase. Smad2 (Mothers against decapentaplegic homolog 2; SMAD 2; Mothers against DPP homolog 2;)
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 SMAD2/SMAD4 complex, activates transcription. May act as a tumor suppressor in colorectal carcinoma. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.
Subunit:
Momomer; the absence of TGF-beta. Heterodimer; in the presence of TGF-beta. Forms a heterodimer with co-SMAD, SMAD4, in the nucleus to form the transactivation complex SMAD2/SMAD4. Interacts with AIP1, HGS, PML and WWP1. Interacts with NEDD4L in response to TGF-beta. Found in a complex with SMAD3 and TRIM33 upon addition of TGF-beta. Interacts with ACVR1B, SMAD3 and TRIM33. Interacts (via the MH2 domain) with ZFYVE9; may form trimers with the SMAD4 co-SMAD. Interacts with FOXH1, homeobox protein TGIF, PEBP2-alpha subunit, CREB-binding protein (CBP), EP300 and SKI. Interacts with SNON; when phosphorylated at Ser-465/467. Interacts with SKOR1 and SKOR2. Interacts with PRDM16. Interacts (via MH2 domain) with LEMD3. Interacts with RBPMS. Interacts with WWP1. Interacts (dephosphorylated form, via the MH1 and MH2 domains) with RANBP3 (via its SLCterminal R domain); the interaction results in the export of dephosphorylated SMAD3 out of the nucleus and termination ot the TGF-beta signaling. Interacts with PDPK1 (via PH domain).
Subcellular Location:
Cytoplasm. Nucleus. Note=Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4. On dephosphorylation by phosphatase PPM1A, released from the SMAD2/SMAD4 complex, and exported out of the nucleus by interaction with RANBP1.
Tissue Specificity:
Expressed at high levels in skeletal muscle, heart and placenta.
Post-translational modifications:
Phosphorylated on one or several of Thr-220, Ser-245, Ser-250, and Ser-255. In response to TGF-beta, phosphorylated on Ser-465/467 by TGF-beta and activin type 1 receptor kinases. Able to interact with SMURF2 when phosphorylated on Ser-465/467, recruiting other proteins, such as SNON, for degradation. In response to decorin, the naturally occurring inhibitor of TGF-beta signaling, phosphorylated on Ser-48 by CaMK2. Phosphorylated by MAPK3 upon EGF stimulation; which increases transcriptional activity and stability, and is blocked by calmodulin. Phosphorylated by PDPK1.
In response to TGF-beta, ubiquitinated by NEDD4L; which promotes its degradation.
Acetylated on Lys-19 by coactivators in response to TGF-beta signaling, which increases transcriptional activity. Isoform short: Acetylation increases DNA binding activity in vitro and enhances its association with target promoters in vivo. Acetylation in the nucleus by EP300 is enhanced by TGF-beta.
Similarity:
Belongs to the dwarfin/SMAD family.
Contains 1 MH1 (MAD homology 1) domain.
Contains 1 MH2 (MAD homology 2) domain.
Database links:
Entrez Gene: 4087 Human
Entrez Gene: 17126 Mouse
Entrez Gene: 29357 Rat
Omim: 601366 Human
SwissProt: Q15796 Human
SwissProt: Q62432 Mouse
SwissProt: O70436 Rat
Unigene: 12253 Human
Unigene: 705764 Human
Unigene: 391091 Mouse
Unigene: 2755 Rat
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
转录调节因子（Transcriptin Regulators）
Smads家族是最新发现的TGF-β信号转导途径中一个重要的新基因家族.是TGF-β特异的细胞内信号转导分子，SMAD2/3属于受体激活的SMADs.有学者认为：Smad2、Smad3在某些肿瘤中发生突变,有可能是一种肿瘤抑制基因。
Smad2/3蛋白与Smad1、Smad5有高度同源性。
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