The SMAD2 gene and its putative association with human ageing

Cell Types

Lung cancer

Cell Lines

A549

Cancer Cell?

Yes

Method

Knockdown, Mutation

Type of senescence

Unclear

Senescence Effect

Inhibits

Primary Reference

Gao et al. (2019) Lung cancer deficient in the tumor suppressor GATA4 is sensitive to TGFBR1 inhibition. Nat Commun 10(1)1665 (PubMed)

HGNC symbol

SMAD2

Aliases

JV18-1; MADH2; MADR2

Common name

SMAD family member 2

Entrez Id

4087

Description

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 Ontology

Process:

GO:6355; regulation of transcription, DNA-templated
GO:45944; positive regulation of transcription by RNA polymerase II
GO:45893; positive regulation of transcription, DNA-templated
GO:7179; transforming growth factor beta receptor signaling pathway
GO:90101; negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway
GO:90287; regulation of cellular response to growth factor stimulus
GO:35556; intracellular signal transduction
GO:30154; cell differentiation
GO:9653; anatomical structure morphogenesis
GO:45165; cell fate commitment
GO:30509; BMP signaling pathway
GO:60395; SMAD protein signal transduction
GO:45892; negative regulation of transcription, DNA-templated
GO:30513; positive regulation of BMP signaling pathway
GO:62009; secondary palate development
GO:17015; regulation of transforming growth factor beta receptor signaling pathway
GO:10718; positive regulation of epithelial to mesenchymal transition
GO:9952; anterior/posterior pattern specification
GO:7352; zygotic specification of dorsal/ventral axis
GO:32924; activin receptor signaling pathway
GO:7369; gastrulation
GO:1707; mesoderm formation
GO:70723; response to cholesterol
GO:7183; SMAD protein complex assembly
GO:31053; primary miRNA processing
GO:38092; nodal signaling pathway
GO:7182; common-partner SMAD protein phosphorylation
GO:1657; ureteric bud development
GO:1701; in utero embryonic development
GO:1706; endoderm formation
GO:6468; protein phosphorylation
GO:7389; pattern specification process
GO:7492; endoderm development
GO:7507; heart development
GO:8285; negative regulation of cell population proliferation
GO:9749; response to glucose
GO:9791; post-embryonic development
GO:9880; embryonic pattern specification
GO:10628; positive regulation of gene expression
GO:10629; negative regulation of gene expression
GO:23019; signal transduction involved in regulation of gene expression
GO:30073; insulin secretion
GO:30324; lung development
GO:30325; adrenal gland development
GO:31016; pancreas development
GO:35265; organ growth
GO:42060; wound healing
GO:48340; paraxial mesoderm morphogenesis
GO:48589; developmental growth
GO:48617; embryonic foregut morphogenesis
GO:48701; embryonic cranial skeleton morphogenesis
GO:51098; regulation of binding
GO:60039; pericardium development
GO:1900224; positive regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry

Cellular component:

GO:5737; cytoplasm
GO:5634; nucleus
GO:5667; transcription regulator complex
GO:785; chromatin
GO:5654; nucleoplasm
GO:5829; cytosol
GO:32991; protein-containing complex
GO:71144; heteromeric SMAD protein complex
GO:32444; activin responsive factor complex
GO:71141; SMAD protein complex
GO:71142; homomeric SMAD protein complex
GO:16020; membrane
GO:16021; integral component of membrane

Function:

GO:5515; protein binding
GO:46872; metal ion binding
GO:3677; DNA binding
GO:981; DNA-binding transcription factor activity, RNA polymerase II-specific
GO:978; RNA polymerase II cis-regulatory region sequence-specific DNA binding
GO:140297; DNA-binding transcription factor binding
GO:1228; DNA-binding transcription activator activity, RNA polymerase II-specific
GO:19902; phosphatase binding
GO:3690; double-stranded DNA binding
GO:70412; R-SMAD binding
GO:3700; DNA-binding transcription factor activity
GO:48156; tau protein binding
GO:70410; co-SMAD binding
GO:31625; ubiquitin protein ligase binding
GO:34713; type I transforming growth factor beta receptor binding
GO:70411; I-SMAD binding
GO:987; cis-regulatory region sequence-specific DNA binding
GO:97718; disordered domain specific binding
GO:46332; SMAD binding
GO:61629; RNA polymerase II-specific DNA-binding transcription factor binding
GO:5160; transforming growth factor beta receptor binding
GO:3682; chromatin binding
GO:42802; identical protein binding

Hide GO terms

Caenorhabditis elegans

sma-2

Danio rerio

smad2

Drosophila melanogaster

Smox

Mus musculus

Smad2

Rattus norvegicus

Smad2

GenAge model organism genes