Browse SMAD2

Summary
SymbolSMAD2
NameSMAD family member 2
Aliases MADR2; JV18-1; MADH2; MAD, mothers against decapentaplegic homolog 2 (Drosophila); SMAD, mothers against DPP ......
Chromosomal Location18q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm Nucleus Note=Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 (PubMed:9865696). On dephosphorylation by phosphatase PPM1A, released from the SMAD2/SMAD4 complex, and exported out of the nucleus by interaction with RANBP1 (PubMed:16751101, PubMed:19289081).
Domain PF03165 MH1 domain
PF03166 MH2 domain
Function

Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD2/SMAD4 complex, activates transcription. May act as a tumor suppressor in colorectal carcinoma. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.

> Gene Ontology
 
Biological Process GO:0000578 embryonic axis specification
GO:0001501 skeletal system development
GO:0001655 urogenital system development
GO:0001657 ureteric bud development
GO:0001701 in utero embryonic development
GO:0001704 formation of primary germ layer
GO:0001706 endoderm formation
GO:0001707 mesoderm formation
GO:0001822 kidney development
GO:0001823 mesonephros development
GO:0001837 epithelial to mesenchymal transition
GO:0002790 peptide secretion
GO:0003002 regionalization
GO:0003140 determination of left/right asymmetry in lateral mesoderm
GO:0006417 regulation of translation
GO:0007178 transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0007179 transforming growth factor beta receptor signaling pathway
GO:0007182 common-partner SMAD protein phosphorylation
GO:0007183 SMAD protein complex assembly
GO:0007352 zygotic specification of dorsal/ventral axis
GO:0007368 determination of left/right symmetry
GO:0007369 gastrulation
GO:0007389 pattern specification process
GO:0007440 foregut morphogenesis
GO:0007492 endoderm development
GO:0007498 mesoderm development
GO:0007507 heart development
GO:0009306 protein secretion
GO:0009743 response to carbohydrate
GO:0009746 response to hexose
GO:0009749 response to glucose
GO:0009791 post-embryonic development
GO:0009798 axis specification
GO:0009799 specification of symmetry
GO:0009855 determination of bilateral symmetry
GO:0009880 embryonic pattern specification
GO:0009914 hormone transport
GO:0009950 dorsal/ventral axis specification
GO:0009952 anterior/posterior pattern specification
GO:0009953 dorsal/ventral pattern formation
GO:0010608 posttranscriptional regulation of gene expression
GO:0010717 regulation of epithelial to mesenchymal transition
GO:0010718 positive regulation of epithelial to mesenchymal transition
GO:0010817 regulation of hormone levels
GO:0015833 peptide transport
GO:0016441 posttranscriptional gene silencing
GO:0016458 gene silencing
GO:0017015 regulation of transforming growth factor beta receptor signaling pathway
GO:0017148 negative regulation of translation
GO:0019827 stem cell population maintenance
GO:0023019 signal transduction involved in regulation of gene expression
GO:0023061 signal release
GO:0030072 peptide hormone secretion
GO:0030073 insulin secretion
GO:0030323 respiratory tube development
GO:0030324 lung development
GO:0030509 BMP signaling pathway
GO:0030510 regulation of BMP signaling pathway
GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway
GO:0030513 positive regulation of BMP signaling pathway
GO:0031016 pancreas development
GO:0031047 gene silencing by RNA
GO:0031050 dsRNA fragmentation
GO:0031053 primary miRNA processing
GO:0032924 activin receptor signaling pathway
GO:0032925 regulation of activin receptor signaling pathway
GO:0032927 positive regulation of activin receptor signaling pathway
GO:0034248 regulation of cellular amide metabolic process
GO:0034249 negative regulation of cellular amide metabolic process
GO:0034284 response to monosaccharide
GO:0034470 ncRNA processing
GO:0035019 somatic stem cell population maintenance
GO:0035194 posttranscriptional gene silencing by RNA
GO:0035195 gene silencing by miRNA
GO:0035196 production of miRNAs involved in gene silencing by miRNA
GO:0035239 tube morphogenesis
GO:0035265 organ growth
GO:0036314 response to sterol
GO:0038092 nodal signaling pathway
GO:0038107 nodal signaling pathway involved in determination of left/right asymmetry
GO:0040029 regulation of gene expression, epigenetic
GO:0042886 amide transport
GO:0043331 response to dsRNA
GO:0045165 cell fate commitment
GO:0046879 hormone secretion
GO:0048332 mesoderm morphogenesis
GO:0048339 paraxial mesoderm development
GO:0048340 paraxial mesoderm morphogenesis
GO:0048368 lateral mesoderm development
GO:0048546 digestive tract morphogenesis
GO:0048562 embryonic organ morphogenesis
GO:0048565 digestive tract development
GO:0048568 embryonic organ development
GO:0048617 embryonic foregut morphogenesis
GO:0048701 embryonic cranial skeleton morphogenesis
GO:0048704 embryonic skeletal system morphogenesis
GO:0048705 skeletal system morphogenesis
GO:0048706 embryonic skeletal system development
GO:0048762 mesenchymal cell differentiation
GO:0051098 regulation of binding
GO:0055123 digestive system development
GO:0060021 palate development
GO:0060039 pericardium development
GO:0060395 SMAD protein signal transduction
GO:0060485 mesenchyme development
GO:0060541 respiratory system development
GO:0070723 response to cholesterol
GO:0070918 production of small RNA involved in gene silencing by RNA
GO:0071359 cellular response to dsRNA
GO:0071407 cellular response to organic cyclic compound
GO:0071559 response to transforming growth factor beta
GO:0071560 cellular response to transforming growth factor beta stimulus
GO:0071772 response to BMP
GO:0071773 cellular response to BMP stimulus
GO:0072001 renal system development
GO:0072073 kidney epithelium development
GO:0072132 mesenchyme morphogenesis
GO:0072163 mesonephric epithelium development
GO:0072164 mesonephric tubule development
GO:0090092 regulation of transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0090100 positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0090101 negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0090287 regulation of cellular response to growth factor stimulus
GO:0090288 negative regulation of cellular response to growth factor stimulus
GO:0097305 response to alcohol
GO:0098727 maintenance of cell number
GO:1900094 regulation of transcription from RNA polymerase II promoter involved in determination of left/right symmetry
GO:1900107 regulation of nodal signaling pathway
GO:1900145 regulation of nodal signaling pathway involved in determination of left/right asymmetry
GO:1900164 nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry
GO:1900175 regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry
GO:1900224 positive regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry
GO:1903844 regulation of cellular response to transforming growth factor beta stimulus
GO:1903845 negative regulation of cellular response to transforming growth factor beta stimulus
GO:1904888 cranial skeletal system development
GO:2000380 regulation of mesoderm development
GO:2000382 positive regulation of mesoderm development
Molecular Function GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0000982 transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0000987 core promoter proximal region sequence-specific DNA binding
GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0001159 core promoter proximal region DNA binding
GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding
GO:0003682 chromatin binding
GO:0005057 receptor signaling protein activity
GO:0005072 transforming growth factor beta receptor, cytoplasmic mediator activity
GO:0005126 cytokine receptor binding
GO:0005160 transforming growth factor beta receptor binding
GO:0008134 transcription factor binding
GO:0019902 phosphatase binding
GO:0030618 transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity
GO:0031625 ubiquitin protein ligase binding
GO:0033613 activating transcription factor binding
GO:0034713 type I transforming growth factor beta receptor binding
GO:0035326 enhancer binding
GO:0044389 ubiquitin-like protein ligase binding
GO:0046332 SMAD binding
GO:0046982 protein heterodimerization activity
GO:0070410 co-SMAD binding
GO:0070411 I-SMAD binding
GO:0070412 R-SMAD binding
Cellular Component GO:0000785 chromatin
GO:0000790 nuclear chromatin
GO:0005667 transcription factor complex
GO:0032444 activin responsive factor complex
GO:0044454 nuclear chromosome part
GO:0044798 nuclear transcription factor complex
GO:0071141 SMAD protein complex
GO:0071144 SMAD2-SMAD3 protein complex
GO:0090575 RNA polymerase II transcription factor complex
> KEGG and Reactome Pathway
 
KEGG hsa04068 FoxO signaling pathway
hsa04110 Cell cycle
hsa04144 Endocytosis
hsa04350 TGF-beta signaling pathway
hsa04390 Hippo signaling pathway
hsa04520 Adherens junction
hsa04550 Signaling pathways regulating pluripotency of stem cells
Reactome R-HSA-5688426: Deubiquitination
R-HSA-1266738: Developmental Biology
R-HSA-1643685: Disease
R-HSA-5663202: Diseases of signal transduction
R-HSA-2173795: Downregulation of SMAD2/3
R-HSA-2173788: Downregulation of TGF-beta receptor signaling
R-HSA-74160: Gene Expression
R-HSA-212436: Generic Transcription Pathway
R-HSA-3304349: Loss of Function of SMAD2/3 in Cancer
R-HSA-3304347: Loss of Function of SMAD4 in Cancer
R-HSA-3656534: Loss of Function of TGFBR1 in Cancer
R-HSA-392499: Metabolism of proteins
R-HSA-597592: Post-translational protein modification
R-HSA-3315487: SMAD2/3 MH2 Domain Mutants in Cancer
R-HSA-3304356: SMAD2/3 Phosphorylation Motif Mutants in Cancer
R-HSA-2173796: SMAD2/SMAD3
R-HSA-3311021: SMAD4 MH2 Domain Mutants in Cancer
R-HSA-162582: Signal Transduction
R-HSA-1502540: Signaling by Activin
R-HSA-1181150: Signaling by NODAL
R-HSA-170834: Signaling by TGF-beta Receptor Complex
R-HSA-3304351: Signaling by TGF-beta Receptor Complex in Cancer
R-HSA-2173789: TGF-beta receptor signaling activates SMADs
R-HSA-3656532: TGFBR1 KD Mutants in Cancer
R-HSA-2173793: Transcriptional activity of SMAD2/SMAD3
R-HSA-452723: Transcriptional regulation of pluripotent stem cells
R-HSA-5689880: Ub-specific processing proteases
Summary
SymbolSMAD2
NameSMAD family member 2
Aliases MADR2; JV18-1; MADH2; MAD, mothers against decapentaplegic homolog 2 (Drosophila); SMAD, mothers against DPP ......
Chromosomal Location18q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between SMAD2 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between SMAD2 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
27364554Melanoma; Lung carcinomaPromote immunityHere we show that activin A triggers SMAD2 and ERK1/2 pathways in dendritic cells (DC) expressing type I and II activin receptors, and upregulates production of the TNFα family cytokines BAFF (TALL-1, TNFSF13B) and APRIL (TALL-2, TNFSF13A), which is blocked by SMAD2 and ERK1/2 inhibitors, respectively.
27364554Melanoma; Lung carcinomaPromote immunity (T cell function)Here we show that activin A triggers SMAD2 and ERK1/2 pathways in dendritic cells (DC) expressing type I and II activin receptors, and upregulates production of the TNFα family cytokines BAFF (TALL-1, TNFSF13B) and APRIL (TALL-2, TNFSF13A), which is blocked by SMAD2 and ERK1/2 inhibitors, respectively. BAFF and APRIL derived from activin A-treated DCs upregulate proliferation and survival of T cells expressing the corresponding receptors, BAFF-R and TACI.
27756784NeuroblastomaPromote immunityGalunisertib suppressed SMAD activation in neuroblastoma cells induced by exogenous TGFβ1 or by patient blood and bone marrow plasma, and suppressed SMAD2 phosphorylation in human neuroblastoma cells growing in NSG mice. In NK cells treated in vitro with exogenous TGFβ1, galunisertib suppressed SMAD2 phosphorylation. Galunisertib suppresses activation of SMAD2 in neuroblastomas and aNK cells, restores NK cytotoxic mechanisms, and increases the efficacy of dinutuximab with aNK cells against neuroblastoma tumors.
25238097ovarian carcinomaPromote immunityMechanistically, Foxp1 interacted with the transcription factors Smad2 and Smad3 in preactivated CD8(+) T cells in response to microenvironmental transforming growth factor-beta (TGF-beta), and was essential for its suppressive activity. Therefore, Smad2 and Smad3-mediated c-Myc repression requires Foxp1 expression in T cells. Furthermore, Foxp1 directly mediated TGF-beta-induced c-Jun transcriptional repression, which abrogated T cell activity.
Summary
SymbolSMAD2
NameSMAD family member 2
Aliases MADR2; JV18-1; MADH2; MAD, mothers against decapentaplegic homolog 2 (Drosophila); SMAD, mothers against DPP ......
Chromosomal Location18q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of SMAD2 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NS NA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen Total # shRNA with >= 4-fold: 1 Resistant to T-cell proliferation
24476824shRNAmelanomaB16Secondary screen Total # shRNA with >= 4-fold: 5 Resistant to T-cell proliferation
Summary
SymbolSMAD2
NameSMAD family member 2
Aliases MADR2; JV18-1; MADH2; MAD, mothers against decapentaplegic homolog 2 (Drosophila); SMAD, mothers against DPP ......
Chromosomal Location18q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of SMAD2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.1280.587
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.4210.784
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.0890.94
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.2220.385
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.290.891
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.1370.96
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.0050.99
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.090.96
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.1510.942
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.1410.927
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.8370.708
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.0840.127
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of SMAD2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.71.42.30.469
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 01407.1-7.11
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.703.70.314
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)211705.9-5.90.447
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131109.1-9.10.458
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolSMAD2
NameSMAD family member 2
Aliases MADR2; JV18-1; MADH2; MAD, mothers against decapentaplegic homolog 2 (Drosophila); SMAD, mothers against DPP ......
Chromosomal Location18q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of SMAD2. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolSMAD2
NameSMAD family member 2
Aliases MADR2; JV18-1; MADH2; MAD, mothers against decapentaplegic homolog 2 (Drosophila); SMAD, mothers against DPP ......
Chromosomal Location18q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of SMAD2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by SMAD2.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolSMAD2
NameSMAD family member 2
Aliases MADR2; JV18-1; MADH2; MAD, mothers against decapentaplegic homolog 2 (Drosophila); SMAD, mothers against DPP ......
Chromosomal Location18q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of SMAD2. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolSMAD2
NameSMAD family member 2
Aliases MADR2; JV18-1; MADH2; MAD, mothers against decapentaplegic homolog 2 (Drosophila); SMAD, mothers against DPP ......
Chromosomal Location18q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of SMAD2 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolSMAD2
NameSMAD family member 2
Aliases MADR2; JV18-1; MADH2; MAD, mothers against decapentaplegic homolog 2 (Drosophila); SMAD, mothers against DPP ......
Chromosomal Location18q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between SMAD2 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolSMAD2
NameSMAD family member 2
Aliases MADR2; JV18-1; MADH2; MAD, mothers against decapentaplegic homolog 2 (Drosophila); SMAD, mothers against DPP ......
Chromosomal Location18q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting SMAD2 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting SMAD2.
ID Name Drug Type Targets #Targets
DB04522DexfosfoserineSmall MoleculeCFTR, KCNC4, PDPK1, PIM1, PRKACA, PRKCQ, PYGL, PYGM, REG1A, RHO, S ......13