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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)

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] a) bZIP transcription factors 1] c-jun 2] ATF2 3] CREB b) basic helix loop helix transcription factors - TFE3 c) runt domain transcription factors 1] AML1, AML2 2] CBFA1 d) nuclear receptors 1] vitamin D3 receptor - glucocorticoid receptor - androgen receptor - STAT3 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

Interactions

molecular events

Related

zinc finger FYVE domain-containing protein 9; mothers against decapentaplegic homolog-interacting protein; Madh-interacting protein; smad anchor for receptor activation; receptor activation anchor; hSARA; Novel serine protease; NSP (ZFYVE9, MADHIP, SARA, SMADIP)

General

phosphoprotein SMAD protein

Properties

SIZE: entity length = 425 aa MW = 48 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: Thr phosphorylation site {T8} MH1 domain {10-136} MH2 domain {232-425} MOTIF: domain {271-324} Ser phosphorylation site {S416} Ser phosphorylation site {S423} Ser phosphorylation site {S425}

References

  1. Derynck R et al Nomenclature: vertebrate mediators of TGFbeta family signals. Cell 87:173, 1996 PMID: 8861901
  2. Izzi L & Attisano L Regulation of the TGFbeta signalling pathway by ubiquitin-mediated degradation. Oncogene 23:2071-8, 2004 PMID: 15021894
  3. Derynck R et al. TGF-beta signaling in tumor suppression and cancer progression. Nature genetics 29:17-129, 2001 PMID: 11586292
  4. UniProt :accession Q92940

Component-of

molecular complex

Databases & Figures

OMIM correlations UniProt P84022 PFAM correlations Entrez Gene 4088 Kegg hsa:4088 TGF-beta/BMP signaling