SMAD2/MADH2; mothers against decapentaplegic homolog 2; mothers against DPP homolog 2; MAD homolog 2; Mad-related protein 2; hMAD-2; SMAD family member 2; SMAD 2; smad2; hSMAD2; JV18-1 (SMAD2, MADH2, MADR2)
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Function
- transcriptional modulator activated by TGF-beta receptor 1 & activin type 1 receptor kinase
- SMAD2 is a receptor-regulated SMAD (R-SMAD)
- phosphorylated SMAD2 binds to SMAD4 & enters the nucleus
- destruction of activated SMAD2 occurs in the nucleus & is mediated by E2 conjugating enzymes UbcH5b/c & Ubc3
- may act as a tumor suppressor in colorectal carcinoma
- phosphorylated on one or several of Thr-220, Ser-245, Ser-250, & Ser-255
- in response to TGF-beta, phosphorylated on Ser-465/467 by TGF-beta receptor 1 & activin type 1 receptor kinase
- able to interact with SMURF2 when phosphorylated on Ser-465/467, recruiting other proteins, such as SNON, for degradation
- phosphorylated on Ser-240 by CaMK2 in response to decorin, the naturally occurring inhibitor of TGF-beta signaling
- phosphorylated by MAPK3 upon EGF stimulation; which increases transcriptional activity & stability; phosphorylation is blocked by calmodulin
- in response to TGF-beta, ubiquitinated by NEDD4L; which promotes its degradation (putative)
- 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 & enhances its association with target promoters in vivo
- found in a complex with SMAD3 & TRIM33 upon addition of TGF-beta
- interacts with SMAD3 & TRIM33
- interacts with SARA (SMAD anchor for receptor activation); may form trimers with the SMAD4 co-SMAD
- interacts with FOXH1, homeobox protein TGIF, PEBP2-alpha subunit, CREB-binding protein (CBP), EP300 & SKI
- interacts with SNON; when phosphorylated at Ser-465/467
- interacts (via PY-motif) with SMURF2
- interacts with AIP1 & HGS
- interacts with NEDD4L in response to TGF-beta (putative)
- interacts with LBXCOR1 & CORL2. interacts with PRDM16
- interacts (via MH2 domain) with LEMD3
- interacts with RBPMS
- interacts with FAST1, FAST2
Structure
- belongs to the dwarfin/SMAD family
- contains 1 MH1 (MAD homology 1) domain
- contains 1 MH2 (MAD homology 2) domain
Compartment
- cytoplasm, nucleus
- cytoplasmic in the absence of ligand
- migrates to the nucleus when complexed with SMAD4
Alternative splicing
- named isoforms=2; long, short
Expression
- expressed at high levels in skeletal muscle, heart & placenta
Pathology
- defects in SMAD2 are found in sporadic cases of colorectal carcinoma
More general terms
Additional terms
Component of
References
- ↑ Derynck R et al Nomenclature: vertebrate mediators of TGFbeta family signals. Cell 87:173, 1996 PMID: https://www.ncbi.nlm.nih.gov/pubmed/8861901
- ↑ UniProt http://www.uniprot.org/uniprot/Q15796.html
- ↑ Izzi L & Attisano L Regulation of the TGFbeta signalling pathway by ubiquitin-mediated degradation. Oncogene 23:2071-8, 2004 PMID: https://www.ncbi.nlm.nih.gov/pubmed/15021894
- ↑ Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/SMAD2ID370.html