======= SMAD2 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: SMAD2
  * **<color #00a2e8>Official Name</color>**: SMAD family member 2
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=4087|4087]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q15796|Q15796]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=SMAD2&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20SMAD2|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/601366|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  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]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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:0000269|PubMed:16751101, ECO:0000269|PubMed:16862174, ECO:0000269|PubMed:17327236, ECO:0000269|PubMed:19289081, ECO:0000269|PubMed:9892009}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|MH1|
|MH2|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|heteromeric SMAD protein complex|
|positive regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry|
|activin responsive factor complex|
|zygotic specification of dorsal/ventral axis|
|transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity|
|regulation of nodal signaling pathway involved in determination of left/right asymmetry|
|positive regulation of mesoderm development|
|regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry|
|common-partner SMAD protein phosphorylation|
|SMAD protein complex assembly|
|SMAD protein complex|
|primary miRNA binding|
|positive regulation of activin receptor signaling pathway|
|regulation of nodal signaling pathway|
|embryonic foregut morphogenesis|
|primary miRNA processing|
|foregut morphogenesis|
|paraxial mesoderm morphogenesis|
|type I transforming growth factor beta receptor binding|
|dorsal/ventral axis specification|
|I-SMAD binding|
|nodal signaling pathway|
|co-SMAD binding|
|enhancer binding|
|regulation of mesoderm development|
|paraxial mesoderm development|
|signal transduction involved in regulation of gene expression|
|pericardium development|
|R-SMAD binding|
|secondary palate development|
|regulation of activin receptor signaling pathway|
|adrenal gland development|
|activin receptor signaling pathway|
|response to cholesterol|
|production of miRNAs involved in gene silencing by miRNA|
|response to sterol|
|positive regulation of BMP signaling pathway|
|activating transcription factor binding|
|production of small RNA involved in gene silencing by RNA|
|dsRNA processing|
|disordered domain specific binding|
|embryonic axis specification|
|insulin secretion|
|transforming growth factor beta receptor binding|
|tau protein binding|
|embryonic cranial skeleton morphogenesis|
|endoderm formation|
|gene silencing by miRNA|
|positive regulation of epithelial to mesenchymal transition|
|digestive tract morphogenesis|
|phosphatase binding|
|mesenchyme morphogenesis|
|SMAD binding|
|SMAD protein signal transduction|
|posttranscriptional gene silencing by RNA|
|peptide hormone secretion|
|posttranscriptional gene silencing|
|embryonic pattern specification|
|somatic stem cell population maintenance|
|cranial skeletal system development|
|mesoderm formation|
|mesoderm morphogenesis|
|hormone secretion|
|pancreas development|
|negative regulation of transforming growth factor beta receptor signaling pathway|
|endoderm development|
|negative regulation of cellular response to transforming growth factor beta stimulus|
|hormone transport|
|dorsal/ventral pattern formation|
|regulation of epithelial to mesenchymal transition|
|axis specification|
|ureteric bud development|
|mesonephric epithelium development|
|mesonephric tubule development|
|gene silencing by RNA|
|regulation of BMP signaling pathway|
|post-embryonic development|
|roof of mouth development|
|mesonephros development|
|embryonic skeletal system morphogenesis|
|organ growth|
|transforming growth factor beta receptor signaling pathway|
|double-stranded DNA binding|
|positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway|
|formation of primary germ layer|
|regulation of transforming growth factor beta receptor signaling pathway|
|regulation of cellular response to transforming growth factor beta stimulus|
|negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway|
|endocrine system development|
|mesoderm development|
|embryonic skeletal system development|
|kidney epithelium development|
|digestive tract development|
|stem cell population maintenance|
|maintenance of cell number|
|response to glucose|
|response to hexose|
|digestive system development|
|negative regulation of cellular response to growth factor stimulus|
|response to monosaccharide|
|gene silencing|
|cellular response to transforming growth factor beta stimulus|
|protein secretion|
|gastrulation|
|establishment of protein localization to extracellular region|
|response to transforming growth factor beta|
|protein localization to extracellular region|
|lung development|
|signal release|
|response to carbohydrate|
|respiratory tube development|
|peptide secretion|
|respiratory system development|
|transmembrane receptor protein serine/threonine kinase signaling pathway|
|transcription factor complex|
|anterior/posterior pattern specification|
|mesenchyme development|
|response to alcohol|
|regulation of transmembrane receptor protein serine/threonine kinase signaling pathway|
|regulation of gene expression, epigenetic|
|nuclear chromatin|
|skeletal system morphogenesis|
|cell fate commitment|
|kidney development|
|regulation of cellular response to growth factor stimulus|
|protein deubiquitination|
|renal system development|
|embryonic organ morphogenesis|
|ubiquitin protein ligase binding|
|protein modification by small protein removal|
|urogenital system development|
|regionalization|
|transcription factor binding|
|regulation of binding|
|in utero embryonic development|
|ncRNA processing|
|developmental growth|
|growth|
|chromatin binding|
|gland development|
|embryonic organ development|
|pattern specification process|
|DNA-binding transcription activator activity, RNA polymerase II-specific|
|ncRNA metabolic process|
|wound healing|
|protein heterodimerization activity|
|skeletal system development|
|cellular response to growth factor stimulus|
|RNA polymerase II proximal promoter sequence-specific DNA binding|
|posttranscriptional regulation of gene expression|
|heart development|
|response to growth factor|
|regulation of hormone levels|
|tissue morphogenesis|
|embryonic morphogenesis|
|response to wounding|
|protein-containing complex|
|chordate embryonic development|
|embryo development ending in birth or egg hatching|
|tube morphogenesis|
|DNA-binding transcription factor activity|
|negative regulation of cell population proliferation|
|enzyme linked receptor protein signaling pathway|
|cellular protein-containing complex assembly|
|tube development|
|response to lipid|
|negative regulation of transcription by RNA polymerase II|
|circulatory system development|
|RNA processing|
|protein homodimerization activity|
|anatomical structure formation involved in morphogenesis|
|response to organic cyclic compound|
|animal organ morphogenesis|
|positive regulation of cell differentiation|
|protein phosphorylation|
|embryo development|
|protein modification by small protein conjugation or removal|
|secretion by cell|
|export from cell|
|epithelium development|
|cell-cell signaling|
|secretion|
|negative regulation of transcription, DNA-templated|
|positive regulation of transcription by RNA polymerase II|
|cellular response to endogenous stimulus|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|negative regulation of signal transduction|
|proteolysis|
|phosphorylation|
|negative regulation of RNA metabolic process|
|negative regulation of cell communication|
|negative regulation of signaling|
|positive regulation of developmental process|
|negative regulation of cellular macromolecule biosynthetic process|
|negative regulation of nucleobase-containing compound metabolic process|
|DNA binding|
|negative regulation of macromolecule biosynthetic process|
|response to endogenous stimulus|
|protein transport|
|negative regulation of cellular biosynthetic process|
|peptide transport|
|positive regulation of transcription, DNA-templated|
|negative regulation of biosynthetic process|
|response to oxygen-containing compound|
|protein-containing complex assembly|
|DNA-binding transcription factor activity, RNA polymerase II-specific|
|amide transport|
|establishment of protein localization|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|positive regulation of signal transduction|
|RNA metabolic process|
|intracellular signal transduction|
|negative regulation of gene expression|
|positive regulation of RNA metabolic process|
|positive regulation of multicellular organismal process|
|tissue development|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|nitrogen compound transport|
|protein-containing complex subunit organization|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|gene expression|
|positive regulation of biosynthetic process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp282|Fluvastatin 2.2μM R06 exp282]]|-2.05|
|[[:results:exp487|Hinokiflavone 12μM R08 exp487]]|-1.92|
|[[:results:exp348|Cyclosporin-A 3μM R07 exp348]]|1.76|
|[[:results:exp504|MK2206 4μM R08 exp504]]|1.76|
|[[:results:exp239|PFI-2 4μM R05 exp239]]|1.83|
|[[:results:exp230|Epigallocatechin gallate 20μM R05 exp230]]|1.84|
|[[:results:exp416|Tubacin 1.6μM R07 exp416]]|1.9|
|[[:results:exp42|BI-6727 0.001μM R01 exp42]]|2.35|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:p:prim1|PRIM1]]|0.489|
|[[:human genes:h:hgc6.3|HGC6.3]]|0.445|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/25|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/15|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/14|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/7|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 17623
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 7.77 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='SMAD2 Expression in NALM6 Cells: 7.77'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>