InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: SMAD7

Summary

InnateDB Protein

IDBP-3197.6

Last Modified

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

Gene Symbol

SMAD7

Protein Name

SMAD family member 7

Synonyms

CRCS3; MADH7; MADH8;

Species

Homo sapiens

Ensembl Protein

ENSP00000262158

InnateDB Gene

IDBG-3195 (SMAD7)

Protein Structure

UniProt Annotation

Function

Antagonist of signaling by TGF-beta (transforming growth factor) type 1 receptor superfamily members; has been shown to inhibit TGF-beta (Transforming growth factor) and activin signaling by associating with their receptors thus preventing SMAD2 access. Functions as an adapter to recruit SMURF2 to the TGF-beta receptor complex. Also acts by recruiting the PPP1R15A- PP1 complex to TGFBR1, which promotes its dephosphorylation. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator (By similarity). {ECO:0000250}.

Subcellular Localization

Nucleus. Cytoplasm. Note=Interaction with NEDD4L or RNF111 or induces translocation from the nucleus to the cytoplasm. TGF-beta stimulates its translocation from the nucleus to the cytoplasm. PDPK1 inhibits its translocation from the nucleus to the cytoplasm in response to TGF-beta.

Disease Associations

Colorectal cancer 3 (CRCS3) [MIM:612229]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. {ECO:0000269PubMed:17934461}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Tissue Specificity

Ubiquitous with higher expression in the lung and vascular endothelium.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 161 experimentally validated interaction(s) in this database.
They are also associated with 26 interaction(s) predicted by orthology.

Experimentally validated
Total	161 [view]
Protein-Protein	144 [view]
Protein-DNA	9 [view]
Protein-RNA	0
DNA-DNA	8 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	26 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0005515	protein binding
GO:0005518	collagen binding
GO:0008013	beta-catenin binding
GO:0030617	transforming growth factor beta receptor, inhibitory cytoplasmic mediator activity
GO:0031625	ubiquitin protein ligase binding
GO:0034713	type I transforming growth factor beta receptor binding
GO:0044212	transcription regulatory region DNA binding
GO:0046872	metal ion binding
GO:0048185	activin binding
GO:0070411	I-SMAD binding

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0001657	ureteric bud development
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:0010467	gene expression
GO:0010719	negative regulation of epithelial to mesenchymal transition
GO:0010801	negative regulation of peptidyl-threonine phosphorylation
GO:0010944	negative regulation of transcription by competitive promoter binding
GO:0017015	regulation of transforming growth factor beta receptor signaling pathway
GO:0022409	positive regulation of cell-cell adhesion
GO:0030336	negative regulation of cell migration
GO:0030509	BMP signaling pathway
GO:0030512	negative regulation of transforming growth factor beta receptor signaling pathway
GO:0030514	negative regulation of BMP signaling pathway
GO:0031397	negative regulation of protein ubiquitination
GO:0031398	positive regulation of protein ubiquitination
GO:0032436	positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0032925	regulation of activin receptor signaling pathway
GO:0033137	negative regulation of peptidyl-serine phosphorylation
GO:0034333	adherens junction assembly
GO:0034616	response to laminar fluid shear stress
GO:0034629	cellular protein complex localization
GO:0035556	intracellular signal transduction
GO:0043433	negative regulation of sequence-specific DNA binding transcription factor activity
GO:0045087	innate immune response (InnateDB)
GO:0045892	negative regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0048844	artery morphogenesis
GO:0050821	protein stabilization
GO:0051444	negative regulation of ubiquitin-protein transferase activity
GO:0055010	ventricular cardiac muscle tissue morphogenesis
GO:0055117	regulation of cardiac muscle contraction
GO:0060373	regulation of ventricular cardiac muscle cell membrane depolarization
GO:0060389	pathway-restricted SMAD protein phosphorylation
GO:0060394	negative regulation of pathway-restricted SMAD protein phosphorylation
GO:0060412	ventricular septum morphogenesis
GO:0071560	cellular response to transforming growth factor beta stimulus

Cellular Component

GO:0005622	intracellular
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005667	transcription factor complex
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0005913	cell-cell adherens junction
GO:0016342	catenin complex
GO:0043234	protein complex