Human Gene SMAD2 (uc002lcz.4) Description and Page Index
Description: Homo sapiens SMAD family member 2 (SMAD2), transcript variant 2, mRNA. RefSeq Summary (NM_001003652): The protein encoded by this gene belongs to the SMAD, a family of proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein mediates the signal of the transforming growth factor (TGF)-beta, and thus regulates multiple cellular processes, such as cell proliferation, apoptosis, and differentiation. This protein is recruited to the TGF-beta receptors through its interaction with the SMAD anchor for receptor activation (SARA) protein. In response to TGF-beta signal, this protein is phosphorylated by the TGF-beta receptors. The phosphorylation induces the dissociation of this protein with SARA and the association with the family member SMAD4. The association with SMAD4 is important for the translocation of this protein into the nucleus, where it binds to target promoters and forms a transcription repressor complex with other cofactors. This protein can also be phosphorylated by activin type 1 receptor kinase, and mediates the signal from the activin. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2012]. Transcript (Including UTRs) Position: hg19 chr18:45,359,466-45,457,517 Size: 98,052 Total Exon Count: 11 Strand: - Coding Region Position: hg19 chr18:45,368,198-45,423,127 Size: 54,930 Coding Exon Count: 10
ID:SMAD2_HUMAN DESCRIPTION: RecName: Full=Mothers against decapentaplegic homolog 2; Short=MAD homolog 2; Short=Mothers against DPP homolog 2; AltName: Full=JV18-1; AltName: Full=Mad-related protein 2; Short=hMAD-2; AltName: Full=SMAD family member 2; Short=SMAD 2; Short=Smad2; Short=hSMAD2; 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 (By similarity). Interacts with NEDD4L in response to TGF-beta (By similarity). 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 C-terminal 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). Interacts with DAB2; the interactions are enhanced upon TGF-beta stimulation. Interacts with USP15. INTERACTION: P05060:CHGB; NbExp=2; IntAct=EBI-1040141, EBI-712619; P98082:DAB2; NbExp=4; IntAct=EBI-1040141, EBI-1171238; Q9BZ29:DOCK9; NbExp=3; IntAct=EBI-1040141, EBI-2695893; P07197:NEFM; NbExp=3; IntAct=EBI-1040141, EBI-1105035; P61586:RHOA; NbExp=2; IntAct=EBI-1040141, EBI-446668; P84022:SMAD3; NbExp=2; IntAct=EBI-1040141, EBI-347161; Q13485:SMAD4; NbExp=12; IntAct=EBI-1040141, EBI-347263; Q9H3D4:TP63; NbExp=3; IntAct=EBI-1040141, EBI-2337775; Q9UPN9:TRIM33; NbExp=6; IntAct=EBI-1040141, EBI-2214398; O00308:WWP2; NbExp=4; IntAct=EBI-1040141, EBI-743923; Q96KR1:ZFR; NbExp=2; IntAct=EBI-1040141, EBI-2513582; 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. PTM: 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-240 by CaMK2. Phosphorylated by MAPK3 upon EGF stimulation; which increases transcriptional activity and stability, and is blocked by calmodulin. Phosphorylated by PDPK1. PTM: In response to TGF-beta, ubiquitinated by NEDD4L; which promotes its degradation (By similarity). Monoubiquitinated, leading to prevent DNA-binding. Deubiquitination by USP15 alleviates inhibition and promotes activation of TGF-beta target genes. PTM: 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. SIMILARITY: Contains 1 MH1 (MAD homology 1) domain. SIMILARITY: Contains 1 MH2 (MAD homology 2) domain. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/SMAD2ID370.html";
Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): SMAD2 CDC HuGE Published Literature: SMAD2
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q15796
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.