Homo sapiens Gene: SMAD2
Summary
InnateDB Gene IDBG-3127.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol SMAD2
Gene Name SMAD family member 2
Synonyms hMAD-2; hSMAD2; JV18; JV18-1; MADH2; MADR2;
Species Homo sapiens
Ensembl Gene ENSG00000175387
Encoded Proteins
SMAD family member 2
SMAD family member 2
SMAD family member 2
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
Entrez Gene
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]
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]
Gene Information
Type Protein coding
Genomic Location Chromosome 18:47808957-47931146
Strand Reverse strand
Band q21.1
Transcripts
ENST00000262160 ENSP00000262160
ENST00000356825 ENSP00000349282
ENST00000402690 ENSP00000384449
ENST00000585978 ENSP00000468732
ENST00000587353
ENST00000587269 ENSP00000466254
ENST00000591214 ENSP00000467075
ENST00000587421 ENSP00000468202
ENST00000586514 ENSP00000465355
ENST00000586040 ENSP00000466193
ENST00000589877 ENSP00000465971
ENST00000586487
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 432 experimentally validated interaction(s) in this database.
They are also associated with 31 interaction(s) predicted by orthology.
Experimentally validated
Total 432 [view]
Protein-Protein 419 [view]
Protein-DNA 4 [view]
Protein-RNA 1 [view]
DNA-DNA 6 [view]
RNA-RNA 2 [view]
DNA-RNA 0
Predicted by orthology
Total 31 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0003677 DNA binding
GO:0003682 chromatin binding
GO:0003690 double-stranded DNA binding
GO:0003700 sequence-specific DNA binding transcription factor activity
GO:0005160 transforming growth factor beta receptor binding
GO:0005515 protein 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:0046332 SMAD binding
GO:0046872 metal ion binding
GO:0070410 co-SMAD binding
GO:0070411 I-SMAD binding
GO:0070412 R-SMAD binding
Biological Process
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0001657 ureteric bud development
GO:0001701 in utero embryonic development
GO:0001706 endoderm formation
GO:0001707 mesoderm formation
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006367 transcription initiation from RNA polymerase II promoter
GO:0006468 protein phosphorylation
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:0007369 gastrulation
GO:0007389 pattern specification process
GO:0007492 endoderm development
GO:0007507 heart development
GO:0008285 negative regulation of cell proliferation
GO:0009749 response to glucose
GO:0009791 post-embryonic development
GO:0009880 embryonic pattern specification
GO:0009952 anterior/posterior pattern specification
GO:0010467 gene expression
GO:0010718 positive regulation of epithelial to mesenchymal transition
GO:0017015 regulation of transforming growth factor beta receptor signaling pathway
GO:0023019 signal transduction involved in regulation of gene expression
GO:0030073 insulin secretion
GO:0030324 lung development
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:0031053 primary miRNA processing
GO:0032924 activin receptor signaling pathway
GO:0035265 organ growth
GO:0035556 intracellular signal transduction
GO:0038092 nodal signaling pathway
GO:0045165 cell fate commitment
GO:0045892 negative regulation of transcription, DNA-templated
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0048340 paraxial mesoderm morphogenesis
GO:0048589 developmental growth
GO:0048617 embryonic foregut morphogenesis
GO:0048701 embryonic cranial skeleton morphogenesis
GO:0051098 regulation of binding
GO:0060021 palate development
GO:0060039 pericardium development
GO:0070723 response to cholesterol
GO:1900224 positive regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry
Cellular Component
GO:0000790 nuclear chromatin
GO:0005622 intracellular
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005667 transcription factor complex
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0032444 activin responsive factor complex
GO:0043234 protein complex
GO:0071141 SMAD protein complex
GO:0071144 SMAD2-SMAD3 protein complex
Orthologs
Species
Mus musculus
Bos taurus
Gene ID
Gene Order
Method
Confidence
Comments
SSD Ortholog
Ortholog supports species divergence
Not yet available
SSD Ortholog
Ortholog supports species divergence
Pathways
NETPATH
Alpha6Beta4Integrin pathway
EGFR1 pathway
TGF_beta_Receptor pathway
TNFalpha pathway
REACTOME
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription pathway
SMAD4 MH2 Domain Mutants in Cancer pathway
Developmental Biology pathway
Loss of Function of SMAD4 in Cancer pathway
Loss of Function of SMAD2/3 in Cancer pathway
Signaling by TGF-beta Receptor Complex in Cancer pathway
TGFBR2 MSI Frameshift Mutants in Cancer pathway
Signal Transduction pathway
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer pathway
SMAD2/3 MH2 Domain Mutants in Cancer pathway
Loss of Function of TGFBR2 in Cancer pathway
Generic Transcription Pathway pathway
SMAD2/3 Phosphorylation Motif Mutants in Cancer pathway
Downregulation of TGF-beta receptor signaling pathway
TGFBR1 KD Mutants in Cancer pathway
Loss of Function of TGFBR1 in Cancer pathway
TGFBR1 LBD Mutants in Cancer pathway
Signaling by NODAL pathway
TGFBR2 Kinase Domain Mutants in Cancer pathway
TGF-beta receptor signaling activates SMADs pathway
Signaling by Activin pathway
Gene Expression pathway
Disease pathway
Signaling by TGF-beta Receptor Complex pathway
Downregulation of SMAD2/3:SMAD4 transcriptional activity pathway
KEGG
Cell cycle pathway
Endocytosis pathway
TGF-beta signaling pathway pathway
Adherens junction pathway
Chagas disease (American trypanosomiasis) pathway
Pathways in cancer pathway
Colorectal cancer pathway
Pancreatic cancer pathway
INOH
TGF-beta signaling pathway
BMP2 signaling pathway
PID BIOCARTA
Tgf beta signaling pathway [Biocarta view]
PID NCI
Glypican 1 network
Regulation of nuclear SMAD2/3 signaling
TGF-beta receptor signaling
Regulation of cytoplasmic and nuclear SMAD2/3 signaling
Cross-References
SwissProt Q15796
TrEMBL
UniProt Splice Variant
Entrez Gene 4087
UniGene Hs.12253 Hs.617511 Hs.625113 Hs.629015 Hs.702196 Hs.705764 Hs.741342
RefSeq NM_001135937 NM_001003652 NM_005901 XM_006722451
HUGO HGNC:6768
OMIM 601366
CCDS CCDS11934
HPRD 03221
IMGT
EMBL AF027964 BC014840 BC025699 U59911 U65019 U68018 U78727 U78728 U78729 U78730 U78731 U78732 U78733
GenPept AAB17054 AAB17087 AAC39657 AAC50789 AAC51918 AAH14840 AAH25699
RNA Seq Atlas 4087