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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)

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

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 = 467 aa MW = 52 kD MOTIF: acetylation site SITE: N-TERMINUS EFFECTOR-BOUND: acetyl Thr phosphorylation site {T8} MH1 domain {10-176} Thr phosphorylation site {T220} PY {221-225} Ser phosphorylation site {S240} Ser phosphorylation site {S245} Ser phosphorylation site {S250} Ser phosphorylation site {S255} MH2 domain {274-467} MOTIF: Ser phosphorylation site {S458} Ser phosphorylation site {S465} Ser phosphorylation site {S467}

Database Correlations

OMIM 601366 UniProt Q15796 PFAM correlations Entrez Gene 4087 Kegg hsa:4087

References

  1. Derynck R et al Nomenclature: vertebrate mediators of TGFbeta family signals. Cell 87:173, 1996 PMID: 8861901
  2. UniProt :accession Q15796
  3. Izzi L & Attisano L Regulation of the TGFbeta signalling pathway by ubiquitin-mediated degradation. Oncogene 23:2071-8, 2004 PMID: 15021894
  4. Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/SMAD2ID370.html

Component-of

molecular complex