SMAD3/MADH3; mothers against decapentaplegic homolog 3; mothers against DPP homolog 3; MAD homolog 3; Mad3; hMAD-3; SMAD family member 3; SMAD 3; smad3; hSMAD3; JV15-2 (SMAD3, MADH3)
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Function
- transcriptional modulator activated by TGF-beta receptor 1 & activin type 1 receptor kinase
- SMAD3 is a receptor-regulated SMAD (R-SMAD) (putative)
- phosphorylated on Ser by TGF-beta receptor 1 & activin type 1 receptor kinases
- phosphorylated SMAD3 binds to SMAD4 & enters the nucleus
- SMAD3 has intrinsic DNA binding capability[3]
- interacts with HGS
- interacts with NEDD4L in response to TGF-beta
- interacts with TTRAP (putative)
- interacts with SARA (SMAD anchor for receptor activation); form trimers with another SMAD3 & the co-SMAD SMAD4
- interacts with HDAC1, JUN/FOS, vitamin D receptor, homeobox protein TGIF & TGIF2, PEBP2-alpha C subunit, CREB-binding protein (CBP), p300, SKI, SNON, ATF2, SMURF2, AIP1, DACH1 & TGFB1I1
- part of a complex consisting of AIP1, ACVR2A, ACVR1B & SMAD3
- found in a complex with SMAD2 & TRIM33 upon addition of TGF-beta
- interacts with SMAD2 & TRIM33
- found in a complex with SMAD3, Ran & XPO4
- interacts with XPO4
- interacts with LBXCOR1 & CORL2
- interacts with PRDM16
- interacts (via MH2 domain) with LEMD3; interaction with LEMD3 blocks the formation of heteromeric complex with SMAD4 & translocation to the nucleus
- interacts with RBPMS
- interacts with FOXL2 (putative)
- interacts (via MH2 domain) with MECOM
- SCF/Roc1 E3 ligase complex triggers ubiquitination of phosphorylated SMAD3
- transcription factors interacting with SMAD3[3]
Structure
- the MH2 domain is sufficient for nuclear export
- belongs to the dwarfin/SMAD family
- contains 1 MH1 (MAD homology 1) domain
- contains 1 MH2 (MAD homology 2) domain
Compartment
- cytoplasm, nucleus
- cytoplasm in the absence of ligand
- migration to the nucleus when complexed with SMAD4
- colocalizes with LEMD3 at the inner nuclear membrane
Pathology
- defects in SMAD3 may be a cause of colorectal cancer
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
- ↑ 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
- ↑ 3.0 3.1 3.2 Derynck R et al. TGF-beta signaling in tumor suppression and cancer progression. Nature genetics 29:17-129, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11586292
- ↑ UniProt http://www.uniprot.org/uniprot/Q92940.html