InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: SMAD2

Summary

InnateDB Protein

IDBP-3131.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

SMAD2

Protein Name

SMAD family member 2

Synonyms

hMAD-2; hSMAD2; JV18; JV18-1; MADH2; MADR2;

Species

Homo sapiens

Ensembl Protein

ENSP00000349282

InnateDB Gene

IDBG-3127 (SMAD2)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:16751101, ECO:0000269PubMed:16862174, ECO:0000269PubMed:17327236, ECO:0000269PubMed:19289081, ECO:0000269PubMed:9892009}.

Subcellular Localization

Cytoplasm. Nucleus. Note=Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4. On dephosphorylation by phosphatase PPM1A, released from the SMAD2/SMAD4 complex, and exported out of the nucleus by interaction with RANBP1.

Disease Associations

Tissue Specificity

Expressed at high levels in skeletal muscle, endothelial cells, heart and placenta. {ECO:0000269PubMed:21599657}.

Comments

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: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: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: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: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:0030512	negative regulation of transforming growth factor beta receptor signaling pathway
GO:0030513	positive regulation of BMP signaling pathway
GO:0031053	primary miRNA processing
GO:0032924	activin receptor signaling pathway
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:0051098	regulation of binding
GO:0060021	palate 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:0071141	SMAD protein complex
GO:0071144	SMAD2-SMAD3 protein complex

Protein Structure and Domains

PDB ID

InterPro

IPR001132 SMAD domain, Dwarfin-type
IPR003619 MAD homology 1, Dwarfin-type
IPR008984 SMAD/FHA domain
IPR013019 MAD homology, MH1
IPR019471 Interferon regulatory factor-3

PFAM

PF03166
PF03165
PF10401

PRINTS

PIRSF

SMART

SM00524
SM00523

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q15796