SMAD3

Protein SMAD3 map

Identifiers
SMAD family member 3
HUGO:SMAD3 HGNC:6769 ENTREZ:4088 UNIPROT:P84022 GENECARDS:SMAD3 REACTOME:64620 KEGG:4088 ATLASONC:GC_SMAD3 WIKI:SMAD3
“MAD mothers against decapentaplegic homolog 3 (Drosophila)” MADH3 “SMAD mothers against DPP homolog 3 (Drosophila)”

Maps_Modules
 EMT  map  / EMT_REGULATORS  map
 Survival  map  / MAPK  map

References
TGF-β exerts its biological effects by binding to a cell surface receptor complex composed of type I (TbRI) and type II (TbRII) receptor serine/threonine kinases. Upon ligand binding TbRII phosphorylates and activates TbRI which subsequently phosphorylates the cytoplasmic Smad2 and Smad3 proteins. Phosphorylated Smad proteins form stable complexes with a common partner Smad4. The activated Smad2/4 and Smad3/4 complexes translocate into the nucleus where the Smad oligomers induce transcriptional activation (or inhibition) of specific target genes.
PMID:21614932

SMAD3@Cytoplasm

References
e_re221( EMT  map ):
PMID:9865696
SARA interacts directly with Smad2 and Smad3

SMAD3|​S423_pho|​S425_pho@Cytoplasm

References
e_re223( EMT  map ):
PMID:9865696
Phosphorylation of Smad2 induces dissociation from SARA
with concomitant formation of Smad2/ Smad4 complexes
and nuclear translocation.
e_re229( EMT  map ):
PMID:11792802
Following phosphorylation of R-Smads by TGFBR1, Smad oligomerization is thought to occur.
PMID:9670020
Smad2 and Smad3 form homo-oligomers upon phosphorylation by the constitutively active TGFBR1
This oligomerization does not require Smad4.
e_re1263( EMT  map ):
Phosphorylation of Smad2 induces dissociation from SARA with concomitant formation of Smad2/ Smad4 complexes and nuclear translocation.
e_re1276( EMT  map ):
PMID:10197981
PMID:12193595
PMID:16156666
Erk kinases phosphorylate Smad2 and Smad3 at specific sites in the region linking the DNA-binding domain and the transcriptional activation domain.
These sites are separate from the TGFB receptor phosphorylation sites that activate Smad nuclear translocation.
Feedback loop: TGFB activates Ras/Raf/Mek/Erk signaling (PMID:17673906) and Erk reduces TGFB/Smads transcriptional activity.
PMID:15241418
Feedback loop
CDK phosphorylation of Smad3 on Thr8/Thr179/Ser213 inhibits its transcriptional activity and antiproliferative function.
Because cancer cells often contain high levels of CDK activity, diminishing Smad3 activity by CDK phosphorylation may contribute to tumorigenesis and TGFB- resistance in
cancers.

SMAD3|​S423_pho|​S425_pho|​hm2|​active@Cytoplasm

Maps_Modules
 EMT  map  / EMT_REGULATORS  map
 EMT  map  / ECM  map

References
PMID:9670020
Smad2 and Smad3 form homo-oligomers upon phosphorylation by the constitutively active TGFBR1
This oligomerization does not require Smad4.
e_re229( EMT  map ):
PMID:11792802
Following phosphorylation of R-Smads by TGFBR1, Smad oligomerization is thought to occur.
e_re231( EMT  map ):
PMID:11224571
Phosphorylated Smad3 recruits Smad4 to form a heterotrimer
containing 2 Smad3 and 1 Smad4.

SMAD3|​T179_pho|​S204_pho|​S208_pho|​S213_pho|​S423_pho|​S425_pho@Cytoplasm

References
e_re1276( EMT  map ):
PMID:10197981
PMID:12193595
PMID:16156666
Erk kinases phosphorylate Smad2 and Smad3 at specific sites in the region linking the DNA-binding domain and the transcriptional activation domain.
These sites are separate from the TGFB receptor phosphorylation sites that activate Smad nuclear translocation.
Feedback loop: TGFB activates Ras/Raf/Mek/Erk signaling (PMID:17673906) and Erk reduces TGFB/Smads transcriptional activity.
PMID:15241418
Feedback loop
CDK phosphorylation of Smad3 on Thr8/Thr179/Ser213 inhibits its transcriptional activity and antiproliferative function.
Because cancer cells often contain high levels of CDK activity, diminishing Smad3 activity by CDK phosphorylation may contribute to tumorigenesis and TGFB- resistance in
cancers.


Modifications:
In compartment: Cytoplasm
  1. SMAD3@Cytoplasm map

  2. SMAD3|​S423_pho|​S425_pho@Cytoplasm map
  3. SMAD3|​S423_pho|​S425_pho|​hm2|​active@Cytoplasm map
  4. SMAD3|​T179_pho|​S204_pho|​S208_pho|​S213_pho|​S423_pho|​S425_pho@Cytoplasm map

Participates in complexes:
In compartment: Cytoplasm

  1. (SMAD3|​S423_pho|​S425_pho|​hm2:​SMAD4)|​active@Cytoplasm map

  2. SMAD2|​S467_pho|​S465_pho:​SMAD3|​S423_pho|​S425_pho@Cytoplasm map

In compartment: Early Endosome

  1. SARA*:​SMAD3@Early Endosome map

  2. SARA*:​SMAD3|​S423_pho|​S425_pho@Early Endosome map

In compartment: Nucleus

  1. (SMAD3|​S423_pho|​S425_pho|​hm2:​SMAD4)|​active@Nucleus map

  2. SMAD3|​S423_pho|​S425_pho|​hm2:​SMAD4:​SP1@Nucleus map
  3. (SMAD3|​S423_pho|​S425_pho|​hm2:​SMAD4:​SNAI1)|​active@Nucleus map
  4. (SMAD2|​S467_pho|​S464_pho|​S465_pho:​SMAD3|​S422_pho|​S423_pho|​S425_pho:​SMAD4:​SP1)|​active@Nucleus map
  5. (MIZ1*:​SMAD2|​S467_pho|​S464_pho|​S465_pho:​SMAD3|​S422_pho|​S423_pho|​S425_pho:​SMAD4:​SP1)|​active@Nucleus map

Participates in reactions:
As Reactant or Product:

  1. (SMAD3|​S423_pho|​S425_pho|​hm2:​SMAD4)|​active@Nucleus map + HMGA2@Nucleus map map HMGA2:​SMAD2_3*:​SMAD4@Nucleus map

  2. SMAD3|​S423_pho|​S425_pho@Cytoplasm map + SMAD2|​S467_pho|​S465_pho@Cytoplasm map map SMAD2|​S467_pho|​S465_pho:​SMAD3|​S423_pho|​S425_pho@Cytoplasm map
  3. SMAD2_3*@Cytoplasm map map SMAD3|​S423_pho|​S425_pho|​hm2|​active@Cytoplasm map
  4. SMAD2_3*@Cytoplasm map map SMAD2|​S467_pho|​S465_pho:​SMAD3|​S423_pho|​S425_pho@Cytoplasm map
  5. SMAD3|​S423_pho|​S425_pho@Cytoplasm map map SMAD3|​T179_pho|​S204_pho|​S208_pho|​S213_pho|​S423_pho|​S425_pho@Cytoplasm map
  6. rSMAD3@Nucleus map map SMAD3@Cytoplasm map
  7. SMAD3@Cytoplasm map + SARA*@Early Endosome map map SARA*:​SMAD3@Early Endosome map
  8. SARA*:​SMAD3@Early Endosome map + ATP@Cytoplasm map map SARA*:​SMAD3|​S423_pho|​S425_pho@Early Endosome map + ADP@Cytoplasm map
  9. SARA*:​SMAD3|​S423_pho|​S425_pho@Early Endosome map map SARA*@Early Endosome map + SMAD3|​S423_pho|​S425_pho@Cytoplasm map
  10. SMAD3|​S423_pho|​S425_pho@Cytoplasm map map SMAD3|​S423_pho|​S425_pho|​hm2|​active@Cytoplasm map
  11. SMAD4@Cytoplasm map + SMAD3|​S423_pho|​S425_pho|​hm2|​active@Cytoplasm map map (SMAD3|​S423_pho|​S425_pho|​hm2:​SMAD4)|​active@Cytoplasm map
  12. (SMAD3|​S423_pho|​S425_pho|​hm2:​SMAD4)|​active@Cytoplasm map map (SMAD3|​S423_pho|​S425_pho|​hm2:​SMAD4)|​active@Nucleus map
  13. SNAI1@Nucleus map + (SMAD3|​S423_pho|​S425_pho|​hm2:​SMAD4)|​active@Nucleus map map (SMAD3|​S423_pho|​S425_pho|​hm2:​SMAD4:​SNAI1)|​active@Nucleus map
  14. SMAD2_3*:​SMAD4@Nucleus map + SP1@Nucleus map map (SMAD2|​S467_pho|​S464_pho|​S465_pho:​SMAD3|​S422_pho|​S423_pho|​S425_pho:​SMAD4:​SP1)|​active@Nucleus map
  15. MIZ1*@Nucleus map + (SMAD2|​S467_pho|​S464_pho|​S465_pho:​SMAD3|​S422_pho|​S423_pho|​S425_pho:​SMAD4:​SP1)|​active@Nucleus map map (MIZ1*:​SMAD2|​S467_pho|​S464_pho|​S465_pho:​SMAD3|​S422_pho|​S423_pho|​S425_pho:​SMAD4:​SP1)|​active@Nucleus map
  16. (SMAD3|​S423_pho|​S425_pho|​hm2:​SMAD4)|​active@Nucleus map + SP1@Nucleus map map SMAD3|​S423_pho|​S425_pho|​hm2:​SMAD4:​SP1@Nucleus map
  17. SMAD3@Cytoplasm map + SMAD4@Cytoplasm map map s_s_mpk1_s1027

As Catalyser:

  1. gHEY1@Nucleus map map rHEY1@Nucleus map

  2. gCAR*@Nucleus map map rCAR*@Nucleus map
  3. gClaudin3*@Nucleus map map rClaudin3*@Nucleus map
  4. gp15INK4B*@Nucleus map map rp15INK4B*@Nucleus map
  5. gp21CIP1*@Nucleus map map rp21CIP1*@Nucleus map
  6. gE-Cadherin*@Nucleus map map rE-Cadherin*@Nucleus map
  7. gCOL1A2@Nucleus map map rCOL1A2@Nucleus map
  8. gOccludin*@Nucleus map map rOccludin*@Nucleus map
  9. gZEB1@Nucleus map map rZEB1@Nucleus map

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