SMAD2 (mothers against decapentaplegic homolog 2 (Drosophila))

Identity

Other names	MADH2
	MADR2
	JV18-1
	JV18
HGNC	SMAD2
Location	18q21.1
Location_base_pair	Starts at 43613464 and ends at 43711510 bp from pter ( according to hg18-Mar_2006).

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

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.

External links

	Nomenclature
HGNC	SMAD2   6768
Entrez_Gene	SMAD2  4087  SMAD family member 2
	Cards
Atlas	SMAD2ID370
GeneCards	SMAD2
Ensembl	ENSG00000175387 [Gene_View]  SMAD2 [Vega]
Genatlas	SMAD2
	Genomic and cartography
GoldenPath	SMAD2  -  18q21.1   chr18:43613464-43711510 -  18q21   [Description]    (hg18-Mar_2006)
Ensembl	SMAD2 - 18q21 [CytoView]
NCBI	Mapview
OMIM	601366 Disease map [OMIM]
HomoloGene	SMAD2
	Gene and transcription
Genbank	AA081871 [ ENTREZ ]
Genbank	AA418737 [ ENTREZ ]
Genbank	AF027964 [ ENTREZ ]
Genbank	AI087928 [ ENTREZ ]
Genbank	AI765747 [ ENTREZ ]
RefSeq	NM_001003652 [ SRS ]    NM_001003652 [ ENTREZ ]
RefSeq	NM_005901 [ SRS ]    NM_005901 [ ENTREZ ]
RefSeq	AC_000061 [ SRS ]    AC_000061 [ ENTREZ ]
RefSeq	AC_000150 [ SRS ]    AC_000150 [ ENTREZ ]
RefSeq	NC_000018 [ SRS ]    NC_000018 [ ENTREZ ]
RefSeq	NT_010966 [ SRS ]    NT_010966 [ ENTREZ ]
RefSeq	NW_001838468 [ SRS ]    NW_001838468 [ ENTREZ ]
RefSeq	NW_927106 [ SRS ]    NW_927106 [ ENTREZ ]
CCDS	SMAD2 CCDS - NCBI
AceView	SMAD2 AceView - NCBI
Unigene	Hs.705764 [ SRS ]    Hs.705764 [ NCBI ]
Fast-db	4185 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	Q15796 [ SRS]    Q15796 [ EXPASY ]     Q15796 [ INTERPRO ]     Q15796 [ UNIPROT ] Q15796 [ VarSplice FASTA ]
Prosite	PS51075 MH1 [ SRS ]    PS51075 MH1 [ Expasy ]
Prosite	PS51076 MH2 [ SRS ]    PS51076 MH2 [ Expasy ]
Interpro	IPR013790 Dwarfin [ SRS ]    IPR013790 Dwarfin [ EBI ]
Interpro	IPR013019 MAD_MH1 [ SRS ]    IPR013019 MAD_MH1 [ EBI ]
Interpro	IPR003619 MH1_Dwarfin-type [ SRS ]    IPR003619 MH1_Dwarfin-type [ EBI ]
Interpro	IPR017855 SMAD_dom-like [ SRS ]    IPR017855 SMAD_dom-like [ EBI ]
Interpro	IPR001132 SMAD_dom_Dwarfin-type [ SRS ]    IPR001132 SMAD_dom_Dwarfin-type [ EBI ]
CluSTr	Q15796
Pfam	PF03165 MH1 [ SRS ]    PF03165 MH1 [ Sanger ]    pfam03165 [ NCBI-CDD ]
Pfam	PF03166 MH2 [ SRS ]    PF03166 MH2 [ Sanger ]    pfam03166 [ NCBI-CDD ]
Smart	SM00523 DWA [EMBL]
Smart	SM00524 DWB [EMBL]
Blocks	Q15796
PDB	1DEV [ SRS ]    1DEV [ PdbSum ],   1DEV [ IMB ]   1DEV [ RSDB ]
PDB	1KHX [ SRS ]    1KHX [ PdbSum ],   1KHX [ IMB ]   1KHX [ RSDB ]
PDB	1U7V [ SRS ]    1U7V [ PdbSum ],   1U7V [ IMB ]   1U7V [ RSDB ]
HPRD	03221
	Protein Interaction databases
DIP	Q15796
IntAct	Q15796
	Polymorphism : SNP, mutations, diseases
OMIM	601366    [ map ]
GENETests	601366
SNP	SMAD2 [dbSNP-NCBI]
SNP	NM_001003652 [SNP-NCI]
SNP	NM_005901 [SNP-NCI]
SNP	SMAD2 [GeneSNPs - Utah]  SMAD2] [HGBASE - SRS]
HAPMAP	SMAD2 [HAPMAP]
COSMIC	SMAD2 [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	SMAD2
Genetic Association	SMAD2
CDC HuGE	SMAD2
	General knowledge
Family Browser	SMAD2 [UCSC Family Browser]
SOURCE	NM_001003652
SOURCE	NM_005901
SMD	Hs.705764
SAGE	Hs.705764
GO	mesoderm formation [Amigo]  mesoderm formation
GO	double-stranded DNA binding [Amigo]  double-stranded DNA binding
GO	transcription factor activity [Amigo]  transcription factor activity
GO	intracellular [Amigo]  intracellular
GO	nucleus [Amigo]  nucleus
GO	nucleoplasm [Amigo]  nucleoplasm
GO	transcription factor complex [Amigo]  transcription factor complex
GO	cytoplasm [Amigo]  cytoplasm
GO	cytosol [Amigo]  cytosol
GO	transcription [Amigo]  transcription
GO	intracellular signaling cascade [Amigo]  intracellular signaling cascade
GO	transcription factor binding [Amigo]  transcription factor binding
GO	transcription factor binding [Amigo]  transcription factor binding
GO	anterior/posterior pattern formation [Amigo]  anterior/posterior pattern formation
GO	transcription activator activity [Amigo]  transcription activator activity
GO	regulation of transforming growth factor beta receptor signaling pathway [Amigo]  regulation of transforming growth factor beta receptor signaling pathway
GO	cell fate commitment [Amigo]  cell fate commitment
GO	negative regulation of transcription, DNA-dependent [Amigo]  negative regulation of transcription, DNA-dependent
GO	positive regulation of transcription from RNA polymerase II promoter [Amigo]  positive regulation of transcription from RNA polymerase II promoter
GO	paraxial mesoderm morphogenesis [Amigo]  paraxial mesoderm morphogenesis
GO	regulation of binding [Amigo]  regulation of binding
BIOCARTA	TGF beta signaling pathway    [Genes]
KEGG	Cell cycle
KEGG	Wnt signaling pathway
KEGG	TGF-beta signaling pathway
KEGG	Adherens junction
KEGG	Colorectal cancer
PubGene	SMAD2
TreeFam	SMAD2
CTD	4087 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	SMAD2 Related clones (RZPD - Berlin)
	PubMed
PubMed	173 Pubmed reference(s) in Entrez

Bibliography

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Mutation analysis of SMAD2, SMAD3, and SMAD4 genes in hereditary non-polyposis colorectal.

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Smad2 nucleocytoplasmic shuttling by nucleoporins CAN/Nup214 and Nup153 feeds TGFbeta signaling complexes in the cytoplasm and nucleus.

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Contributor(s)

Written	07-2004	Raphael Saffroy, Antoinette Lemoine, Brigitte Debuire

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. July 2004 . URL : http://AtlasGeneticsOncology.org/Genes/SMAD2ID370.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Thu Nov 27 13:29:30 2008