SMAD2
Summary: The protein encoded by this gene belongs to the SMAD, a family of proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein mediates the signal of the transforming growth factor (TGF)-beta, and thus regulates multiple cellular processes, such as cell proliferation, apoptosis, and differentiation. This protein is recruited to the TGF-beta receptors through its interaction with the SMAD anchor for receptor activation (SARA) protein. In response to TGF-beta signal, this protein is phosphorylated by the TGF-beta receptors. The phosphorylation induces the dissociation of this protein with SARA and the association with the family member SMAD4. The association with SMAD4 is important for the translocation of this protein into the nucleus, where it binds to target promoters and forms a transcription repressor complex with other cofactors. This protein can also be phosphorylated by activin type 1 receptor kinase, and mediates the signal from the activin. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2012].
| Name | OMIM ID | Ensembl ID | HGNC ID | PHARMGKB ID | Map Location |
|---|---|---|---|---|---|
| SMAD family member 2 | MIM:601366 | Ensembl:ENSG00000175387 | HGNC:HGNC:6768 | PA134959722 | 18q21.1 |
GO terms in SMAD2
| Term Type | Evidence Type | GO Term ID | GO Des. |
|---|---|---|---|
| CC | IDA | GO:0000790 | nuclear chromatin |
| CC | IDA | GO:0005634 | nucleus |
| CC | TAS | GO:0005654 | nucleoplasm |
| CC | IDA | GO:0005667 | transcription factor complex |
| CC | IDA | GO:0005737 | cytoplasm |
| CC | TAS | GO:0005829 | cytosol |
| CC | IDA | GO:0032444 | activin responsive factor complex |
| CC | IMP | GO:0032991 | protein-containing complex |
| CC | IDA | GO:0071141 | SMAD protein complex |
| CC | IDA | GO:0071144 | heteromeric SMAD protein complex |
| BP | TAS | GO:0000122 | negative regulation of transcription by RNA polymerase II |
| BP | IEA | GO:0001657 | ureteric bud development |
| BP | IEA | GO:0001701 | in utero embryonic development |
| BP | IEA | GO:0001706 | endoderm formation |
| BP | ISS | GO:0001707 | mesoderm formation |
| BP | IEA | GO:0006366 | transcription by RNA polymerase II |
| BP | IDA | GO:0007179 | transforming growth factor beta receptor signaling pathway |
| BP | IMP | GO:0007179 | transforming growth factor beta receptor signaling pathway |
| BP | TAS | GO:0007179 | transforming growth factor beta receptor signaling pathway |
| BP | IDA | GO:0007182 | common-partner SMAD protein phosphorylation |
| BP | IDA | GO:0007183 | SMAD protein complex assembly |
| BP | IMP | GO:0007352 | zygotic specification of dorsal/ventral axis |
| BP | TAS | GO:0007369 | gastrulation |
| BP | IEA | GO:0008285 | negative regulation of cell proliferation |
| BP | IEA | GO:0009749 | response to glucose |
| BP | IEA | GO:0009791 | post-embryonic development |
| BP | ISS | GO:0009952 | anterior/posterior pattern specification |
| BP | ISS | GO:0010718 | positive regulation of epithelial to mesenchymal transition |
| BP | TAS | GO:0016579 | protein deubiquitination |
| BP | IMP | GO:0017015 | regulation of transforming growth factor beta receptor signaling pathway |
| BP | IEA | GO:0023019 | signal transduction involved in regulation of gene expression |
| BP | IEA | GO:0030073 | insulin secretion |
| BP | IEA | GO:0030324 | lung development |
| BP | IEA | GO:0030325 | adrenal gland development |
| BP | TAS | GO:0030512 | negative regulation of transforming growth factor beta receptor signaling pathway |
| BP | IMP | GO:0030513 | positive regulation of BMP signaling pathway |
| BP | IEA | GO:0031016 | pancreas development |
| BP | TAS | GO:0031053 | primary miRNA processing |
| BP | IMP | GO:0032924 | activin receptor signaling pathway |
| BP | TAS | GO:0035019 | somatic stem cell population maintenance |
| BP | IEA | GO:0035265 | organ growth |
| BP | ISS | GO:0035556 | intracellular signal transduction |
| BP | IMP | GO:0038092 | nodal signaling pathway |
| BP | IEA | GO:0042060 | wound healing |
| BP | ISS | GO:0045165 | cell fate commitment |
| BP | IMP | GO:0045892 | negative regulation of transcription, DNA-templated |
| BP | IDA | GO:0045893 | positive regulation of transcription, DNA-templated |
| BP | IMP | GO:0045893 | positive regulation of transcription, DNA-templated |
| BP | ISS | GO:0045893 | positive regulation of transcription, DNA-templated |
| BP | IDA | GO:0045944 | positive regulation of transcription by RNA polymerase II |
| BP | ISS | GO:0045944 | positive regulation of transcription by RNA polymerase II |
| BP | TAS | GO:0045944 | positive regulation of transcription by RNA polymerase II |
| BP | ISS | GO:0048340 | paraxial mesoderm morphogenesis |
| BP | IEA | GO:0048617 | embryonic foregut morphogenesis |
| BP | IEA | GO:0048701 | embryonic cranial skeleton morphogenesis |
| BP | ISS | GO:0051098 | regulation of binding |
| BP | IEA | GO:0060039 | pericardium development |
| BP | IEA | GO:0060395 | SMAD protein signal transduction |
| BP | ISS | GO:0062009 | secondary palate development |
| BP | IDA | GO:0070723 | response to cholesterol |
| BP | IMP | GO:1900224 | positive regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry |
| MF | IDA | GO:0000978 | RNA polymerase II proximal promoter sequence-specific DNA binding |
| MF | ISA | GO:0000981 | RNA polymerase II transcription factor activity, sequence-specific DNA binding |
| MF | ISM | GO:0000981 | RNA polymerase II transcription factor activity, sequence-specific DNA binding |
| MF | NAS | GO:0000981 | RNA polymerase II transcription factor activity, sequence-specific DNA binding |
| MF | IDA | GO:0001077 | transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding |
| MF | ISS | GO:0001228 | transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific DNA binding |
| MF | IDA | GO:0003677 | DNA binding |
| MF | IEA | GO:0003682 | chromatin binding |
| MF | ISS | GO:0003690 | double-stranded DNA binding |
| MF | IDA | GO:0003700 | DNA-binding transcription factor activity |
| MF | IDA | GO:0003700 | DNA-binding transcription factor activity |
| MF | IPI | GO:0005160 | transforming growth factor beta receptor binding |
| MF | IPI | GO:0005515 | protein binding |
| MF | IPI | GO:0008134 | transcription factor binding |
| MF | IPI | GO:0019902 | phosphatase binding |
| MF | IDA | GO:0030618 | transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity |
| MF | IPI | GO:0031625 | ubiquitin protein ligase binding |
| MF | IPI | GO:0033613 | activating transcription factor binding |
| MF | IPI | GO:0034713 | type I transforming growth factor beta receptor binding |
| MF | IC | GO:0035326 | enhancer binding |
| MF | IEA | GO:0042803 | protein homodimerization activity |
| MF | IPI | GO:0046332 | SMAD binding |
| MF | IEA | GO:0046872 | metal ion binding |
| MF | IEA | GO:0046982 | protein heterodimerization activity |
| MF | ISS | GO:0048156 | tau protein binding |
| MF | IPI | GO:0070410 | co-SMAD binding |
| MF | IPI | GO:0070411 | I-SMAD binding |
| MF | IPI | GO:0070412 | R-SMAD binding |
| MF | IPI | GO:0070878 | primary miRNA binding |
| MF | IPI | GO:0097718 | disordered domain specific binding |
Gene expression in normal tissue: SMAD2
Gene-model tissue-cancer distribution: Bubble Plot
Gene-drug pathway distribution
Pathways in SMAD2
| Database | Pathway ID | Pathway Des. |
|---|---|---|
| biocarta | tgfbpathway | tgf beta signaling pathway |
| reactome | R-HSA-1181150 | Signaling by NODAL |
| reactome | R-HSA-1181150 | Signaling by NODAL |
| reactome | R-HSA-1266738 | Developmental Biology |
| reactome | R-HSA-1266738 | Developmental Biology |
| reactome | R-HSA-1502540 | Signaling by Activin |
| reactome | R-HSA-162582 | Signal Transduction |
| reactome | R-HSA-162582 | Signal Transduction |
| reactome | R-HSA-1643685 | Disease |
| reactome | R-HSA-170834 | Signaling by TGF-beta Receptor Complex |
| reactome | R-HSA-170834 | Signaling by TGF-beta Receptor Complex |
| reactome | R-HSA-212436 | Generic Transcription Pathway |
| reactome | R-HSA-212436 | Generic Transcription Pathway |
| reactome | R-HSA-2173788 | Downregulation of TGF-beta receptor signaling |
| reactome | R-HSA-2173789 | TGF-beta receptor signaling activates SMADs |
| reactome | R-HSA-2173793 | Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer |
| reactome | R-HSA-2173793 | Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer |
| reactome | R-HSA-2173795 | Downregulation of SMAD2/3:SMAD4 transcriptional activity |
| reactome | R-HSA-2173795 | Downregulation of SMAD2/3:SMAD4 transcriptional activity |
| reactome | R-HSA-2173796 | SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription |
| reactome | R-HSA-3304347 | Loss of Function of SMAD4 in Cancer |
| reactome | R-HSA-3304349 | Loss of Function of SMAD2/3 in Cancer |
| reactome | R-HSA-3304351 | Signaling by TGF-beta Receptor Complex in Cancer |
| reactome | R-HSA-3304356 | SMAD2/3 Phosphorylation Motif Mutants in Cancer |
| reactome | R-HSA-3311021 | SMAD4 MH2 Domain Mutants in Cancer |
| reactome | R-HSA-3315487 | SMAD2/3 MH2 Domain Mutants in Cancer |
| reactome | R-HSA-3656532 | TGFBR1 KD Mutants in Cancer |
| reactome | R-HSA-3656534 | Loss of Function of TGFBR1 in Cancer |
| reactome | R-HSA-392499 | Metabolism of proteins |
| reactome | R-HSA-452723 | Transcriptional regulation of pluripotent stem cells |
| reactome | R-HSA-5663202 | Diseases of signal transduction |
| reactome | R-HSA-5688426 | Deubiquitination |
| reactome | R-HSA-5689880 | Ub-specific processing proteases |
| reactome | R-HSA-597592 | Post-translational protein modification |
| reactome | R-HSA-73857 | RNA Polymerase II Transcription |
| reactome | R-HSA-73857 | RNA Polymerase II Transcription |
| reactome | R-HSA-74160 | Gene expression (Transcription) |
| reactome | R-HSA-74160 | Gene expression (Transcription) |
| reactome | R-HSA-9006936 | Signaling by TGF-beta family members |
| reactome | R-HSA-9006936 | Signaling by TGF-beta family members |
| wikipathways | WP2324 | AGE-RAGE pathway |
| wikipathways | WP2853 | Endoderm Differentiation |
| wikipathways | WP2857 | Mesodermal Commitment Pathway |
| wikipathways | WP2870 | Extracellular vesicle-mediated signaling in recipient cells |
| wikipathways | WP366 | TGF-beta Signaling Pathway |
| wikipathways | WP3668 | Hypothesized Pathways in Pathogenesis of Cardiovascular Disease |
| wikipathways | WP3674 | Tgif disruption of Shh signaling |
| wikipathways | WP3850 | Factors and pathways affecting insulin-like growth factor (IGF1)-Akt signaling |
| wikipathways | WP3859 | TGF-B Signaling in Thyroid Cells for Epithelial-Mesenchymal Transition |
| wikipathways | WP3874 | Canonical and Non-Canonical TGF-B signaling |
| wikipathways | WP3980 | Protein alkylation leading to liver fibrosis |
| wikipathways | WP4216 | Chromosomal and microsatellite instability in colorectal cancer |
| wikipathways | WP4239 | EMT transition in Colorectal Cancer |
| wikipathways | WP560 | TGF-beta Receptor Signaling |
| pid | glypican_1pathway | Glypican 1 network |
| pid | myc_represspathway | Validated targets of C-MYC transcriptional repression |
| pid | smad2_3nuclearpathway | Regulation of nuclear SMAD2/3 signaling |
| pid | smad2_3pathway | Regulation of cytoplasmic and nuclear SMAD2/3 signaling |
| pid | tgfbrpathway | TGF-beta receptor signaling |
| kegg | hsa04068 | FoxO signaling pathway - Homo sapiens (human) |
| kegg | hsa04110 | Cell cycle - Homo sapiens (human) |
| kegg | hsa04144 | Endocytosis - Homo sapiens (human) |
| kegg | hsa04218 | Cellular senescence - Homo sapiens (human) |
| kegg | hsa04350 | TGF-beta signaling pathway - Homo sapiens (human) |
| kegg | hsa04371 | Apelin signaling pathway - Homo sapiens (human) |
| kegg | hsa04390 | Hippo signaling pathway - Homo sapiens (human) |
| kegg | hsa04520 | Adherens junction - Homo sapiens (human) |
| kegg | hsa04550 | Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human) |
| kegg | hsa04659 | Th17 cell differentiation - Homo sapiens (human) |
| kegg | hsa04926 | Relaxin signaling pathway - Homo sapiens (human) |
| kegg | hsa04933 | AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human) |
| kegg | hsa05142 | Chagas disease (American trypanosomiasis) - Homo sapiens (human) |
| kegg | hsa05166 | HTLV-I infection - Homo sapiens (human) |
| kegg | hsa05200 | Pathways in cancer - Homo sapiens (human) |
| kegg | hsa05205 | Proteoglycans in cancer - Homo sapiens (human) |
| kegg | hsa05210 | Colorectal cancer - Homo sapiens (human) |
| kegg | hsa05212 | Pancreatic cancer - Homo sapiens (human) |
| kegg | hsa05225 | Hepatocellular carcinoma - Homo sapiens (human) |
| kegg | hsa05226 | Gastric cancer - Homo sapiens (human) |
| kegg | hsa05321 | Inflammatory bowel disease (IBD) - Homo sapiens (human) |
| netpath | Pathway_Alpha6Beta4Integrin | Alpha6Beta4Integrin |
| netpath | Pathway_EGFR1 | EGFR1 |
| netpath | Pathway_TGF_beta_Receptor | TGF_beta_Receptor |
Gene-Drug: Aster Plot
| Drug ID | Drug Name | Model Num. |
|---|---|---|
| iGMDRD781 | Sirolimus | 2 |
| iGMDRD670 | ML 210 | 3 |
| iGMDRD772 | BRD4770 | 2 |
| iGMDRD425 | ERASTIN | 2 |
| iGMDRD1008 | SR-II-138A | 2 |
| iGMDRD433 | Lexibulin | 3 |
| iGMDRD280 | CYTOCHALASIN B | 6 |
| iGMDRD639 | YK 4-279 | 3 |
| iGMDRD885 | Compound 110 | 3 |
| iGMDRD318 | PAC-1 | 1 |
| iGMDRD187 | BRD9876 | 3 |
| iGMDRD870 | BRD63610 | 3 |
| iGMDRD802 | 4-methylfasudil | 6 |
| iGMDRD138 | PX 12 | 2 |
| iGMDRD690 | PRIMA-1MET | 2 |
| iGMDRD60 | Quinoclamine | 2 |
| iGMDRD64 | Parbendazole | 1 |
| iGMDRD506 | Fedratinib | 3 |
| iGMDRD780 | PP-30 | 2 |
| iGMDRD332 | A-770041 | 1 |
| iGMDRD887 | Compound 23 citrate | 2 |
| iGMDRD248 | BRD4354 | 1 |
| iGMDRD84 | Lovastatin acid | 2 |
| iGMDRD307 | Manumycin A | 2 |
| iGMDRD132 | (-)-gallocatechin-3-O-gallate | 1 |
| iGMDRD211 | (1S,3R)-RSL3 | 2 |
| iGMDRD177 | Teniposide | 5 |
| iGMDRD123 | Isoevodiamine | 2 |
| iGMDRD57 | Chloropentafluorobenzene | 3 |
| iGMDRD231 | Importazole | 1 |
| iGMDRD5 | Tyrphostin AG 1478 | 3 |
| iGMDRD202 | Curcumin | 4 |
| iGMDRD158 | NSC141540 | 3 |
| iGMDRD137 | Indisulam | 3 |
| iGMDRD552 | AZD-1775 | 1 |
| iGMDRD147 | Prima-1 | 2 |
| iGMDRD329 | Merck60 | 4 |
| iGMDRD882 | CIL41 | 2 |
Gene in drug-gene network: Network Plot
Gene-drug targets distribution
Gene Structure: PDB
Models in SMAD2
CLASSFICATION
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