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SMAD2 (mothers against decapentaplegic homolog 2 (Drosophila))

Written2004-07Raphael Saffroy, Antoinette Lemoine, Brigitte Debuire
Service de Biochimie et Biologie moleculaire, Hopital Paul Brousse, Faculte de Medecine Paris Sud, 94 800 Villejuif, France

(Note : for Links provided by Atlas : click)

Identity

Alias (NCBI)MADH2
MADR2
JV18-1
JV18
HGNC (Hugo) SMAD2
HGNC Alias symbMADR2
JV18-1
HGNC Previous nameMADH2
HGNC Previous nameMAD, mothers against decapentaplegic homolog 2 (Drosophila)
 SMAD, mothers against DPP homolog 2 (Drosophila)
LocusID (NCBI) 4087
Atlas_Id 370
Location 18q21.1  [Link to chromosome band 18q21]
Location_base_pair Starts at 47808957 and ends at 47930659 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping SMAD2.png]
 
  Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
BCAP31 (Xq28)::SMAD2 (18q21.1)CTIF (18q21.1)::SMAD2 (18q21.1)SMAD2 (18q21.1)::C10orf90 (10q26.2)
SMAD2 (18q21.1)::CD226 (18q22.2)SMAD2 (18q21.1)::PGAM1 (10q24.1)SMAD2 (18q21.1)::PPP6R3 (11q13.2)
SMAD2 (18q21.1)::ZBTB7C (18q21.1)

DNA/RNA

Description The gene encompasses 90 kb of DNA; 12 exons.
Transcription 2285 nucleotides mRNA. Alternative splicing was described.

Protein

Description 467 amino acids; 52 kDa protein. A short 438 amino acids isoform was also described. Smad2 belongs to the Darfwin proteins family which are composed of two conserved amino- and carboxyl-terminal domains known as MH1 and MH2, respectively.
Expression High expression levels in skeletal muscle, heart and placenta.
Function Smad2 is an intracellular mediator of TGF-beta family and activin type 1 receptor. Smad2 mediate TGF-beta signaling to regulate cell growth and differentiation. Smad2 is released from cytoplasmic retention by TGF-beta receptor-mediated phosphorylation. The phosphorylated Smad2 then forms a heterodimeric complex with Smad4, and this complex translocates from cytoplasm into nucleus. By interacting with DNA-binding proteins, Smad complexes then positively or negatively regulate the transcription of target genes.
Homology With the other members of the Darfwin/Smad family.

Implicated in

Note
Disease Colorectal cancers
Oncogenesis Smad2 was proposed to be a tumor suppressor gene that may function to disrupt TGF-beta signaling. Inactivating mutations in Smad2 have been found in various cancer including colorectal carcinomas. The majority of tumor-derived mutations cluster in the carboxy-terminal MH2 domain, and some of these have been shown to disrupt TGF-beta signaling by blocking receptor-dependent phosphorylation or by preventing heterodimeric interactions between Smads. A mutation at position 133 in the amino-terminal MH1 domain has also been associated with colorectal carcinoma. Nevertheless, loss of Smad2 activation and/or expression was related to occur in less than 10% of colorectal cancers.
  

To be noted

Smad2 gene has also been found alterated in lung carcinomas, cervical carcinomas and hepatocellular carcinomas.

Bibliography

A novel mesoderm inducer, Madr2, functions in the activin signal transduction pathway.
Baker JC, Harland RM
Genes & development. 1996 ; 10 (15) : 1880-1889.
PMID 8756346
 
MADR2 maps to 18q21 and encodes a TGFbeta-regulated MAD-related protein that is functionally mutated in colorectal carcinoma.
Eppert K, Scherer SW, Ozcelik H, Pirone R, Hoodless P, Kim H, Tsui LC, Bapat B, Gallinger S, Andrulis IL, Thomsen GH, Wrana JL, Attisano L
Cell. 1996 ; 86 (4) : 543-552.
PMID 8752209
 
Identification and characterization of constitutively active Smad2 mutants: evaluation of formation of Smad complex and subcellular distribution.
Funaba M, Mathews LS
Molecular endocrinology (Baltimore, Md.). 2000 ; 14 (10) : 1583-1591.
PMID 11043574
 
MADR2 is a substrate of the TGFbeta receptor and its phosphorylation is required for nuclear accumulation and signaling.
Macías-Silva M, Abdollah S, Hoodless PA, Pirone R, Attisano L, Wrana JL
Cell. 1996 ; 87 (7) : 1215-1224.
PMID 8980228
 
Loss of expression, and mutations of Smad 2 and Smad 4 in human cervical cancer.
Maliekal TT, Antony ML, Nair A, Paulmurugan R, Karunagaran D
Oncogene. 2003 ; 22 (31) : 4889-4897.
PMID 12894231
 
Identification of Smad2, a human Mad-related protein in the transforming growth factor beta signaling pathway.
Nakao A, Röijer E, Imamura T, Souchelnytskyi S, Stenman G, Heldin CH, ten Dijke P
The Journal of biological chemistry. 1997 ; 272 (5) : 2896-2900.
PMID 9006934
 
Evidence that Smad2 is a tumor suppressor implicated in the control of cellular invasion.
Prunier C, Mazars A, Noë V, Bruyneel E, Mareel M, Gespach C, Atfi A
The Journal of biological chemistry. 1999 ; 274 (33) : 22919-22922.
PMID 10438456
 
Mad-related genes in the human.
Riggins GJ, Thiagalingam S, Rozenblum E, Weinstein CL, Kern SE, Hamilton SR, Willson JK, Markowitz SD, Kinzler KW, Vogelstein B
Nature genetics. 1996 ; 13 (3) : 347-349.
PMID 8673135
 
Mutation analysis of SMAD2, SMAD3, and SMAD4 genes in hereditary non-polyposis colorectal.
Roth S, Johansson M, Loukola A, Peltomäki P, Järvinen H, Mecklin JP, Aaltonen LA
Journal of medical genetics. 2000 ; 37 (4) : 298-300.
PMID 10819637
 
Somatic alterations of the SMAD-2 gene in human colorectal cancers.
Takagi Y, Koumura H, Futamura M, Aoki S, Ymaguchi K, Kida H, Tanemura H, Shimokawa K, Saji S
British journal of cancer. 1998 ; 78 (9) : 1152-1155.
PMID 9820171
 
Mutation analysis of the Smad2 gene in human colon cancers using genomic DNA and intron primers.
Takenoshita S, Tani M, Mogi A, Nagashima M, Nagamachi Y, Bennett WP, Hagiwara K, Harris CC, Yokota J
Carcinogenesis. 1998 ; 19 (5) : 803-807.
PMID 9635866
 
Somatic in vivo alterations of the JV18-1 gene at 18q21 in human lung cancers.
Uchida K, Nagatake M, Osada H, Yatabe Y, Kondo M, Mitsudomi T, Masuda A, Takahashi T, Takahashi T
Cancer research. 1996 ; 56 (24) : 5583-5585.
PMID 8971158
 
Smad2 signaling in extraembryonic tissues determines anterior-posterior polarity of the early mouse embryo.
Waldrip WR, Bikoff EK, Hoodless PA, Wrana JL, Robertson EJ
Cell. 1998 ; 92 (6) : 797-808.
PMID 9529255
 
Structural basis of Smad2 recognition by the Smad anchor for receptor activation.
Wu G, Chen YG, Ozdamar B, Gyuricza CA, Chong PA, Wrana JL, Massagué J, Shi Y
Science (New York, N.Y.). 2000 ; 287 (5450) : 92-97.
PMID 10615055
 
Crystal structure of a phosphorylated Smad2. Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-beta signaling.
Wu JW, Hu M, Chai J, Seoane J, Huse M, Li C, Rigotti DJ, Kyin S, Muir TW, Fairman R, Massagué J, Shi Y
Molecular cell. 2001 ; 8 (6) : 1277-1289.
PMID 11779503
 
Loss of Smad signaling in human colorectal cancer is associated with advanced disease and poor prognosis.
Xie W, Rimm DL, Lin Y, Shih WJ, Reiss M
Cancer journal (Sudbury, Mass.). 2003 ; 9 (4) : 302-312.
PMID 12967141
 
Mutations in the tumor suppressors Smad2 and Smad4 inactivate transforming growth factor beta signaling by targeting Smads to the ubiquitin-proteasome pathway.
Xu J, Attisano L
Proceedings of the National Academy of Sciences of the United States of America. 2000 ; 97 (9) : 4820-4825.
PMID 10781087
 
Smad2 nucleocytoplasmic shuttling by nucleoporins CAN/Nup214 and Nup153 feeds TGFbeta signaling complexes in the cytoplasm and nucleus.
Xu L, Kang Y, Cöl S, Massagué J
Molecular cell. 2002 ; 10 (2) : 271-282.
PMID 12191473
 
Smad2 and Smad4 gene mutations in hepatocellular carcinoma.
Yakicier MC, Irmak MB, Romano A, Kew M, Ozturk M
Oncogene. 1999 ; 18 (34) : 4879-4883.
PMID 10490821
 

Citation

This paper should be referenced as such :
Saffroy, R ; Lemoine, A ; Debuire, B
SMAD2 (mothers against decapentaplegic homolog 2 (Drosophila))
Atlas Genet Cytogenet Oncol Haematol. 2004;8(3):241-242.
Free journal version : [ pdf ]   [ DOI ]


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 2 ]
  del(18)(p11)
t(18;18)(q21;q21) SMAD2::ZBTB7C


External links

 

Nomenclature
HGNC (Hugo)SMAD2   6768
Cards
AtlasSMAD2ID370
Entrez_Gene (NCBI)SMAD2    SMAD family member 2
AliasesJV18; JV18-1; MADH2; MADR2; 
hMAD-2; hSMAD2
GeneCards (Weizmann)SMAD2
Ensembl hg19 (Hinxton)ENSG00000175387 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000175387 [Gene_View]  ENSG00000175387 [Sequence]  chr18:47808957-47930659 [Contig_View]  SMAD2 [Vega]
ICGC DataPortalENSG00000175387
TCGA cBioPortalSMAD2
AceView (NCBI)SMAD2
Genatlas (Paris)SMAD2
SOURCE (Princeton)SMAD2
Genetics Home Reference (NIH)SMAD2
Genomic and cartography
GoldenPath hg38 (UCSC)SMAD2  -     chr18:47808957-47930659 -  18q21.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)SMAD2  -     18q21.1   [Description]    (hg19-Feb_2009)
GoldenPathSMAD2 - 18q21.1 [CytoView hg19]  SMAD2 - 18q21.1 [CytoView hg38]
ImmunoBaseENSG00000175387
Genome Data Viewer NCBISMAD2 [Mapview hg19]  
OMIM601366   
Gene and transcription
Genbank (Entrez)AA081871 AA418737 AF027964 AI087928 AI453799
RefSeq transcript (Entrez)NM_001003652 NM_001135937 NM_005901
Consensus coding sequences : CCDS (NCBI)SMAD2
Gene ExpressionSMAD2 [ NCBI-GEO ]   SMAD2 [ EBI - ARRAY_EXPRESS ]   SMAD2 [ SEEK ]   SMAD2 [ MEM ]
Gene Expression Viewer (FireBrowse)SMAD2 [ Firebrowse - Broad ]
GenevisibleExpression of SMAD2 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)4087
GTEX Portal (Tissue expression)SMAD2
Human Protein AtlasENSG00000175387-SMAD2 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ15796   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ15796  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ15796
PhosPhoSitePlusQ15796
Domaine pattern : Prosite (Expaxy)MH1 (PS51075)    MH2 (PS51076)   
Domains : Interpro (EBI)Dwarfin    MAD_homology1_Dwarfin-type    MAD_homology_MH1    SMAD-like_dom_sf    SMAD_dom_Dwarfin-type    SMAD_FHA_dom_sf    SMAD_MH1_sf   
Domain families : Pfam (Sanger)MH1 (PF03165)    MH2 (PF03166)   
Domain families : Pfam (NCBI)pfam03165    pfam03166   
Domain families : Smart (EMBL)DWA (SM00523)  DWB (SM00524)  
Conserved Domain (NCBI)SMAD2
PDB (RSDB)1DEV    1KHX    1U7V    2LB3    5XOD    5ZOJ   
PDB Europe1DEV    1KHX    1U7V    2LB3    5XOD    5ZOJ   
PDB (PDBSum)1DEV    1KHX    1U7V    2LB3    5XOD    5ZOJ   
PDB (IMB)1DEV    1KHX    1U7V    2LB3    5XOD    5ZOJ   
Structural Biology KnowledgeBase1DEV    1KHX    1U7V    2LB3    5XOD    5ZOJ   
SCOP (Structural Classification of Proteins)1DEV    1KHX    1U7V    2LB3    5XOD    5ZOJ   
CATH (Classification of proteins structures)1DEV    1KHX    1U7V    2LB3    5XOD    5ZOJ   
SuperfamilyQ15796
AlphaFold pdb e-kbQ15796   
Human Protein Atlas [tissue]ENSG00000175387-SMAD2 [tissue]
HPRD03221
Protein Interaction databases
DIP (DOE-UCLA)Q15796
IntAct (EBI)Q15796
Complex Portal (EBI)Q15796 CPX-3208 SMAD2-SMAD4 complex
Q15796 CPX-3208 SMAD2-SMAD4 complex
Q15796 CPX-1 SMAD2-SMAD3-SMAD4 complex
Q15796 CPX-11 SMAD2 homotrimer
Q15796 CPX-11 SMAD2 homotrimer
Q15796 CPX-11 SMAD2 homotrimer
BioGRIDSMAD2
STRING (EMBL)SMAD2
ZODIACSMAD2
Ontologies - Pathways
QuickGOQ15796
Ontology : AmiGOnegative regulation of transcription by RNA polymerase II  chromatin  chromatin  RNA polymerase II cis-regulatory region sequence-specific DNA binding  RNA polymerase II cis-regulatory region sequence-specific DNA binding  DNA-binding transcription factor activity, RNA polymerase II-specific  DNA-binding transcription factor activity, RNA polymerase II-specific  cis-regulatory region sequence-specific DNA binding  DNA-binding transcription activator activity, RNA polymerase II-specific  DNA-binding transcription activator activity, RNA polymerase II-specific  ureteric bud development  in utero embryonic development  endoderm formation  mesoderm formation  DNA binding  chromatin binding  double-stranded DNA binding  DNA-binding transcription factor activity  DNA-binding transcription factor activity  transforming growth factor beta receptor binding  protein binding  nucleus  nucleoplasm  transcription regulator complex  cytoplasm  cytosol  regulation of transcription by RNA polymerase II  transforming growth factor beta receptor signaling pathway  transforming growth factor beta receptor signaling pathway  transforming growth factor beta receptor signaling pathway  transforming growth factor beta receptor signaling pathway  common-partner SMAD protein phosphorylation  SMAD protein complex assembly  zygotic specification of dorsal/ventral axis  gastrulation  transcription factor binding  negative regulation of cell population proliferation  anatomical structure morphogenesis  response to glucose  post-embryonic development  anterior/posterior pattern specification  positive regulation of gene expression  positive regulation of epithelial to mesenchymal transition  protein deubiquitination  regulation of transforming growth factor beta receptor signaling pathway  phosphatase binding  signal transduction involved in regulation of gene expression  insulin secretion  cell differentiation  lung development  adrenal gland development  BMP signaling pathway  negative regulation of transforming growth factor beta receptor signaling pathway  positive regulation of BMP signaling pathway  pancreas development  primary miRNA processing  ubiquitin protein ligase binding  activin responsive factor complex  activin receptor signaling pathway  protein-containing complex  type I transforming growth factor beta receptor binding  somatic stem cell population maintenance  organ growth  intracellular signal transduction  nodal signaling pathway  wound healing  identical protein binding  cell fate commitment  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription by RNA polymerase II  positive regulation of transcription by RNA polymerase II  positive regulation of transcription by RNA polymerase II  SMAD binding  metal ion binding  tau protein binding  paraxial mesoderm morphogenesis  embryonic foregut morphogenesis  embryonic cranial skeleton morphogenesis  regulation of binding  pericardium development  SMAD protein signal transduction  secondary palate development  co-SMAD binding  I-SMAD binding  I-SMAD binding  R-SMAD binding  response to cholesterol  SMAD protein complex  heteromeric SMAD protein complex  heteromeric SMAD protein complex  disordered domain specific binding  DNA-binding transcription factor binding  positive regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry  
Ontology : EGO-EBInegative regulation of transcription by RNA polymerase II  chromatin  chromatin  RNA polymerase II cis-regulatory region sequence-specific DNA binding  RNA polymerase II cis-regulatory region sequence-specific DNA binding  DNA-binding transcription factor activity, RNA polymerase II-specific  DNA-binding transcription factor activity, RNA polymerase II-specific  cis-regulatory region sequence-specific DNA binding  DNA-binding transcription activator activity, RNA polymerase II-specific  DNA-binding transcription activator activity, RNA polymerase II-specific  ureteric bud development  in utero embryonic development  endoderm formation  mesoderm formation  DNA binding  chromatin binding  double-stranded DNA binding  DNA-binding transcription factor activity  DNA-binding transcription factor activity  transforming growth factor beta receptor binding  protein binding  nucleus  nucleoplasm  transcription regulator complex  cytoplasm  cytosol  regulation of transcription by RNA polymerase II  transforming growth factor beta receptor signaling pathway  transforming growth factor beta receptor signaling pathway  transforming growth factor beta receptor signaling pathway  transforming growth factor beta receptor signaling pathway  common-partner SMAD protein phosphorylation  SMAD protein complex assembly  zygotic specification of dorsal/ventral axis  gastrulation  transcription factor binding  negative regulation of cell population proliferation  anatomical structure morphogenesis  response to glucose  post-embryonic development  anterior/posterior pattern specification  positive regulation of gene expression  positive regulation of epithelial to mesenchymal transition  protein deubiquitination  regulation of transforming growth factor beta receptor signaling pathway  phosphatase binding  signal transduction involved in regulation of gene expression  insulin secretion  cell differentiation  lung development  adrenal gland development  BMP signaling pathway  negative regulation of transforming growth factor beta receptor signaling pathway  positive regulation of BMP signaling pathway  pancreas development  primary miRNA processing  ubiquitin protein ligase binding  activin responsive factor complex  activin receptor signaling pathway  protein-containing complex  type I transforming growth factor beta receptor binding  somatic stem cell population maintenance  organ growth  intracellular signal transduction  nodal signaling pathway  wound healing  identical protein binding  cell fate commitment  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription by RNA polymerase II  positive regulation of transcription by RNA polymerase II  positive regulation of transcription by RNA polymerase II  SMAD binding  metal ion binding  tau protein binding  paraxial mesoderm morphogenesis  embryonic foregut morphogenesis  embryonic cranial skeleton morphogenesis  regulation of binding  pericardium development  SMAD protein signal transduction  secondary palate development  co-SMAD binding  I-SMAD binding  I-SMAD binding  R-SMAD binding  response to cholesterol  SMAD protein complex  heteromeric SMAD protein complex  heteromeric SMAD protein complex  disordered domain specific binding  DNA-binding transcription factor binding  positive regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry  
Pathways : BIOCARTATGF beta signaling pathway [Genes]   
Pathways : KEGGFoxO signaling pathway    Cell cycle    Endocytosis    TGF-beta signaling pathway    Hippo signaling pathway    Adherens junction    Chagas disease (American trypanosomiasis)    HTLV-I infection    Pathways in cancer    Proteoglycans in cancer    Colorectal cancer    Pancreatic cancer    Inflammatory bowel disease (IBD)   
REACTOMEQ15796 [protein]
REACTOME PathwaysR-HSA-9617828 [pathway]   
NDEx NetworkSMAD2
Atlas of Cancer Signalling NetworkSMAD2
Wikipedia pathwaysSMAD2
Orthology - Evolution
OrthoDB4087
GeneTree (enSembl)ENSG00000175387
Phylogenetic Trees/Animal Genes : TreeFamSMAD2
Homologs : HomoloGeneSMAD2
Homology/Alignments : Family Browser (UCSC)SMAD2
Gene fusions - Rearrangements
Fusion : MitelmanCTIF::SMAD2 [18q21.1/18q21.1]  
Fusion : MitelmanSMAD2::C10orf90 [18q21.1/10q26.2]  
Fusion : MitelmanSMAD2::CD226 [18q21.1/18q22.2]  
Fusion : MitelmanSMAD2::ZBTB7C [18q21.1/18q21.1]  
Fusion : QuiverSMAD2
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSMAD2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SMAD2
dbVarSMAD2
ClinVarSMAD2
MonarchSMAD2
1000_GenomesSMAD2 
Exome Variant ServerSMAD2
GNOMAD BrowserENSG00000175387
Varsome BrowserSMAD2
ACMGSMAD2 variants
VarityQ15796
Genomic Variants (DGV)SMAD2 [DGVbeta]
DECIPHERSMAD2 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisSMAD2 
Mutations
ICGC Data PortalSMAD2 
TCGA Data PortalSMAD2 
Broad Tumor PortalSMAD2
OASIS PortalSMAD2 [ Somatic mutations - Copy number]
Cancer Gene: CensusSMAD2 
Somatic Mutations in Cancer : COSMICSMAD2  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DSMAD2
Mutations and Diseases : HGMDSMAD2
intOGen PortalSMAD2
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
BioMutaSMAD2
DgiDB (Drug Gene Interaction Database)SMAD2
DoCM (Curated mutations)SMAD2
CIViC (Clinical Interpretations of Variants in Cancer)SMAD2
OncoKBSMAD2
NCG (London)SMAD2
Cancer3DSMAD2
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM601366   
Orphanet
DisGeNETSMAD2
MedgenSMAD2
Genetic Testing Registry SMAD2
NextProtQ15796 [Medical]
GENETestsSMAD2
Target ValidationSMAD2
Huge Navigator SMAD2 [HugePedia]
ClinGenSMAD2
Clinical trials, drugs, therapy
MyCancerGenomeSMAD2
Protein Interactions : CTDSMAD2
Pharm GKB GenePA134959722
PharosQ15796
Clinical trialSMAD2
Miscellaneous
canSAR (ICR)SMAD2
HarmonizomeSMAD2
DataMed IndexSMAD2
Other databasehttp://cancergenome.broadinstitute.org/index.php?tgene=SMAD2
Probes
Litterature
PubMed499 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
EVEXSMAD2
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Oct 8 21:28:16 CEST 2021

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