Mothers against decapentaplegic homolog 2 (SMAD2)
The protein contains 467 amino acids for an estimated molecular weight of 52306 Da.
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. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Activin receptor signaling pathway
Adrenal gland development
Anatomical structure morphogenesis
Anterior/posterior pattern specification
BMP signaling pathway
Cell differentiation
Cell fate commitment
Common-partner SMAD protein phosphorylation
Developmental growth
Embryonic cranial skeleton morphogenesis
Embryonic foregut morphogenesis
Endoderm formation
Gastrulation
Gene expression
In utero embryonic development
Insulin secretion
Intracellular signal transduction
Lung development
Mesoderm formation
Negative regulation of cell population proliferation
Negative regulation of transcription by RNA polymerase II
Negative regulation of transcription, DNA-templated
Negative regulation of transforming growth factor beta receptor signaling pathway
Nodal signaling pathway
Organ growth
Pancreas development
Paraxial mesoderm morphogenesis
Pericardium development
Positive regulation of BMP signaling pathway
Positive regulation of epithelial to mesenchymal transition
Positive regulation of gene expression
Positive regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry
Positive regulation of transcription by RNA polymerase II
Positive regulation of transcription, DNA-templated
Post-embryonic development
Primary miRNA processing
Protein deubiquitination
Regulation of binding
Regulation of transforming growth factor beta receptor signaling pathway
Response to cholesterol
Response to glucose
Roof of mouth development
Secondary palate development
Signal transduction involved in regulation of gene expression
SMAD protein complex assembly
SMAD protein signal transduction
Somatic stem cell population maintenance
Transcription initiation from RNA polymerase II promoter
Transcription, DNA-templated
Transforming growth factor beta receptor signaling pathway
Ureteric bud development
Wound healing
Zygotic specification of dorsal/ventral axis
Cellular Component
Activin responsive factor complex
Chromatin
Cytoplasm
Cytosol
Heteromeric SMAD protein complex
Nuclear chromatin
Nucleoplasm
Nucleus
Protein complex
Protein-containing complex
SMAD protein complex
Transcription regulator complex
Molecular Function
Activating transcription factor binding
Chromatin binding
Cis-regulatory region binding
Cis-regulatory region sequence-specific DNA binding
Co-SMAD binding
Disordered domain specific binding
DNA-binding transcription activator activity, RNA polymerase II-specific
DNA-binding transcription factor activity
DNA-binding transcription factor activity, RNA polymerase II-specific
Double-stranded DNA binding
I-SMAD binding
Metal ion binding
Obsolete transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity
Phosphatase binding
Primary miRNA binding
Protein heterodimerization activity
Protein homodimerization activity
Proximal promoter DNA-binding transcription activator activity, RNA polymerase II-specific
R-SMAD binding
RNA polymerase II cis-regulatory region sequence-specific DNA binding
SMAD binding
Tau protein binding
Transcription factor binding
Transforming growth factor beta receptor binding
Type I transforming growth factor beta receptor binding
Ubiquitin protein ligase binding
The reference OMIM entry for this protein is 601366
Mothers against decapentaplegic, drosophila, homolog of, 2; smad2
Madh2
Sma- and mad-related protein 2 mad, drosophila, homolog of
Madr2
CLONING
Riggins et al. (1996) identified a homolog of the Drosophila 'mothers against decapentaplegic' (Mad) gene (also 'mothers against dpp'). The predicted 467-amino acid polypeptide, referred to by them as JV18-1, shows maximal homology to Mad genes at the amino and carboxy termini of the protein, with 62% identity to Mad over 373 amino acids. Drosophila Mad apparently acts downstream of the TGF-beta receptor (190181) to transduce signals from the members of the TGF-beta gene family (190180). The gene product shows 44% identity over 158 amino acids to another Mad homolog, DPC4 (SMAD4; 600993). Graff et al. (1996) described a family of Xenopus proteins homologous to the Drosophila Mad and C. elegans CEM genes. MAD and MAD-related proteins are important components of the serine/threonine kinase receptor signal transduction pathways. Eppert et al. (1996) cloned and characterized a member of this family, which they designated MADR2. The gene encodes a 467-amino acid protein that contains no common structural motifs known at that time. MADR2 shares high homology with MADR1 (601595) and significant homology with DPC4. They reported that MADR2 is rapidly phosphorylated by activation of the TGF-beta signaling pathway. By RT-PCR of human erythroleukemia cell mRNA using primers based on conserved regions between the Drosophila Mad and C. elegans Sma genes, Nakao et al. (1997) cloned a SMAD2 cDNA. Northern blot analysis of human tissues detected ubiquitously expressed 3.4- and 2.9-kb SMAD2 transcripts. The encoded protein has a molecular mass of 58 kD by SDS-PAGE. Baker and Harland (1996) identified the mouse Madr2 gene using a functional assay to clone mouse mesoderm inducers from Xenopus ectoderm. The mouse amino acid sequence is 46% identical to the human tumor suppressor DPC4. Madr2 was expressed widely in the mouse embryo (with the exception of heart and the tail bud) from embryonic days 6.5 to 10.5. Madr2 was found to be confined to the nucleus in the deep anterior cells of the second axis, whereas it was localized in the cytoplasm in the epidermal and more posterior cells. Because Madr2 localized to the nucleus in response to activin (see 147290) and because activin-like phenotypes were induced by overexpression of Madr2, Baker and Harland (1996) concluded that Madr2 is a signal transduction component that mediates the activity of activin.GENE FUNCTION
Macias-Silva et al. (1996) demonstrated that MADR2 and not the related protein DPC4 transiently interacts with the TGF-beta receptor and is directly phosphorylated by the complex on C-terminal serines. Interaction of MADR2 with receptors and phosphorylation requires activation of receptor I by receptor II and is mediated by the receptor I kinase. Mutation of the phosphorylation sites generated a dominant-negative MADR2 that blocks TGF-beta-dependent transcriptional responses, stably associates with receptors, and fails to accumulate in the nucleus in response to TGF-beta signaling. Thus, Macias-Silva et al. (1996) concluded that transient association and phosphorylation of MADR2 by the TGF-beta receptor is necessary for nuclear accumulation and initiation of signaling. SMAD proteins mediate TGF-beta signaling to regulate cell growth and differentiation. Stroschein et al. (1999) identified SnoN (165340) as a component of the SMAD pathway. They proposed a model of regulation of TGF-beta signaling by SnoN in which SnoN maintains the repressed state of TGF-beta target ge ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601366 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed