SMAD2

Protein SMAD2 map

Identifiers
SMAD family member 2
HUGO:SMAD2 HGNC:6768 ENTREZ:4087 UNIPROT:Q15796 GENECARDS:SMAD2 REACTOME:405890 KEGG:4087 ATLASONC:SMAD2ID370 WIKI:SMAD2
“MAD mothers against decapentaplegic homolog 2 (Drosophila)” MADH2 “SMAD mothers against DPP homolog 2 (Drosophila)”

Maps_Modules
 EMT  map  / EMT_REGULATORS  map
 Survival  map  / MAPK  map
 Survival  map  / WNT_CANONICAL  map

References
PMID:9670020
Smad2 and Smad3 form homo-oligomers upon phosphorylation by the constitutively active TGFBR1
This oligomerization does not require Smad4.
PMID:11074002
Upon TGFB signaling, complex formation between Smad4 and activated Smad2 or -3 leads to nuclear accumulation of Smad4 through inhibition of its nuclear export.
After prolonged TGFB signaling Smad2 becomes dephosphorylated and Smad2 and Smad4 accumulate back in the cytoplasm
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

SMAD2@Cytoplasm

References
e_re216( EMT  map ):
PMID:9865696
SARA interacts directly with Smad2 and Smad3
PMID:11792802
SARA is a cytoplasmic protein that specifically interacts withe no-activated Smad2 and the receptor complex
SARA thus forms the bridge between the receptor and Smad2 and assisting in the specific phosphorylation of Smad2 by the TGFBR1
The stable interaction of SARA with non-phosphorylated Smad2 also inhibits nuclear import of Smad2
PMID:10934479
The nuclear import function of Smad2 is masked by SARA and unmasked by TGFB- dependent phosphorylation

SMAD2|​S467_pho|​S465_pho@Cytoplasm

References
e_re218( EMT  map ):
PMID:9865696
Phosphorylation of Smad2 induces dissociation from SARA
with concomitant formation of Smad2/ Smad4 complexes
and nuclear translocation.
e_re230( 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_re1277( 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.

SMAD2|​S467_pho|​S465_pho|​hm2|​active@Cytoplasm

References
e_re230( 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.

SMAD2|​S467_pho|​S465_pho|​T8_pho@Cytoplasm

References
e_re1277( 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.

SMAD2|​pho@Nucleus

Maps_Modules
 Survival  map  / WNT_CANONICAL  map

References
s_wca2_re48:( Survival  map ) part of canonical TGF pathway
s_wca2_re47:( Survival  map ) PMID:19104148


Modifications:
In compartment: Cytoplasm
  1. SMAD2@Cytoplasm map

  2. SMAD2|​S467_pho|​S465_pho@Cytoplasm map
  3. SMAD2|​S467_pho|​S465_pho|​T8_pho@Cytoplasm map
  4. SMAD2|​S467_pho|​S465_pho|​hm2|​active@Cytoplasm map

In compartment: Nucleus

  1. SMAD2|​pho@Nucleus map

Participates in complexes:
In compartment: Cytoplasm

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

In compartment: Early Endosome

  1. SARA*:​SMAD2@Early Endosome map

  2. SARA*:​SMAD2|​S467_pho|​S465_pho@Early Endosome map

In compartment: Nucleus

  1. SMAD2|​pho:​_beta_-Catenin*|​Y654_pho@Nucleus map

  2. (SMAD2|​S467_pho|​S464_pho|​S465_pho:​SMAD3|​S422_pho|​S423_pho|​S425_pho:​SMAD4:​SP1)|​active@Nucleus map
  3. (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@Cytoplasm map + SMAD2|​S467_pho|​S465_pho@Cytoplasm map map SMAD2|​S467_pho|​S465_pho:​SMAD3|​S423_pho|​S425_pho@Cytoplasm map

  2. SMAD2_3*@Cytoplasm map map SMAD2|​S467_pho|​S465_pho:​SMAD3|​S423_pho|​S425_pho@Cytoplasm map
  3. SMAD2_3*@Cytoplasm map map SMAD2|​S467_pho|​S465_pho|​hm2|​active@Cytoplasm map
  4. SMAD2|​S467_pho|​S465_pho@Cytoplasm map map SMAD2|​S467_pho|​S465_pho|​T8_pho@Cytoplasm map
  5. rSMAD2@Nucleus map map SMAD2@Cytoplasm map
  6. SMAD2@Cytoplasm map + SARA*@Early Endosome map map SARA*:​SMAD2@Early Endosome map
  7. SARA*:​SMAD2@Early Endosome map + ATP@Cytoplasm map map SARA*:​SMAD2|​S467_pho|​S465_pho@Early Endosome map + ADP@Cytoplasm map
  8. SARA*:​SMAD2|​S467_pho|​S465_pho@Early Endosome map map SMAD2|​S467_pho|​S465_pho@Cytoplasm map + SARA*@Early Endosome map
  9. SMAD2|​S467_pho|​S465_pho@Cytoplasm map map SMAD2|​S467_pho|​S465_pho|​hm2|​active@Cytoplasm map
  10. 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
  11. 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
  12. SMAD2@Cytoplasm map + SMAD4@Cytoplasm map map s_s_mpk1_s1028
  13. SMAD2|​pho:​_beta_-Catenin*|​Y654_pho@Nucleus map map TCF_LEF transcriptional_br_regulation@Nucleus map
  14. SMAD2|​pho:​_beta_-Catenin*|​Y654_pho@Nucleus map map EMT@Nucleus map
  15. _beta_-Catenin*|​Y654_pho@Nucleus map + SMAD2|​pho@Nucleus map map SMAD2|​pho:​_beta_-Catenin*|​Y654_pho@Nucleus map
  16. TGFB1:​TGFBR*@Cytoplasm map map SMAD2|​pho@Nucleus map

As Catalyser:

  1. gp15INK4B*@Nucleus map map rp15INK4B*@Nucleus map

  2. gp21CIP1*@Nucleus map map rp21CIP1*@Nucleus map

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