SMAD2 (mothers against decapentaplegic homolog 2 (Drosophila))

2004-07-01   Raphael Saffroy  , Antoinette Lemoine  , Brigitte Debuire  

Service de Biochimie et Biologie moleculaire, Hopital Paul Brousse, Faculte de Medecine Paris Sud, 94 800 Villejuif, France

Identity

HGNC
SMAD2
LOCATION
18q21.1
IMAGE
Atlas Image
LEGEND
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
LOCUSID
4087
ALIAS
JV18,JV18-1,MADH2,MADR2,hMAD-2,hSMAD2
FUSION GENES
Show Gene Fusions

DNA/RNA

Description

The gene encompasses 90 kb of DNA; 12 exons.

Transcription

2285 nucleotides mRNA. Alternative splicing was described.

Proteins

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.

Article Bibliography

Pubmed IDLast YearTitleAuthors
87563461996A novel mesoderm inducer, Madr2, functions in the activin signal transduction pathway.Baker JC et al
87522091996MADR2 maps to 18q21 and encodes a TGFbeta-regulated MAD-related protein that is functionally mutated in colorectal carcinoma.Eppert K et al
110435742000Identification and characterization of constitutively active Smad2 mutants: evaluation of formation of Smad complex and subcellular distribution.Funaba M et al
89802281996MADR2 is a substrate of the TGFbeta receptor and its phosphorylation is required for nuclear accumulation and signaling.Macías-Silva M et al
128942312003Loss of expression, and mutations of Smad 2 and Smad 4 in human cervical cancer.Maliekal TT et al
90069341997Identification of Smad2, a human Mad-related protein in the transforming growth factor beta signaling pathway.Nakao A et al
104384561999Evidence that Smad2 is a tumor suppressor implicated in the control of cellular invasion.Prunier C et al
86731351996Mad-related genes in the human.Riggins GJ et al
108196372000Mutation analysis of SMAD2, SMAD3, and SMAD4 genes in hereditary non-polyposis colorectal.Roth S et al
98201711998Somatic alterations of the SMAD-2 gene in human colorectal cancers.Takagi Y et al
96358661998Mutation analysis of the Smad2 gene in human colon cancers using genomic DNA and intron primers.Takenoshita S et al
89711581996Somatic in vivo alterations of the JV18-1 gene at 18q21 in human lung cancers.Uchida K et al
95292551998Smad2 signaling in extraembryonic tissues determines anterior-posterior polarity of the early mouse embryo.Waldrip WR et al
106150552000Structural basis of Smad2 recognition by the Smad anchor for receptor activation.Wu G et al
117795032001Crystal structure of a phosphorylated Smad2. Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-beta signaling.Wu JW et al
129671412003Loss of Smad signaling in human colorectal cancer is associated with advanced disease and poor prognosis.Xie W et al
107810872000Mutations in the tumor suppressors Smad2 and Smad4 inactivate transforming growth factor beta signaling by targeting Smads to the ubiquitin-proteasome pathway.Xu J et al
121914732002Smad2 nucleocytoplasmic shuttling by nucleoporins CAN/Nup214 and Nup153 feeds TGFbeta signaling complexes in the cytoplasm and nucleus.Xu L et al
104908211999Smad2 and Smad4 gene mutations in hepatocellular carcinoma.Yakicier MC et al

Other Information

Locus ID:

NCBI: 4087
MIM: 601366
HGNC: 6768
Ensembl: ENSG00000175387

Variants:

dbSNP: 4087
ClinVar: 4087
TCGA: ENSG00000175387
COSMIC: SMAD2

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000175387ENST00000262160Q15796
ENSG00000175387ENST00000262160Q53XR6
ENSG00000175387ENST00000356825Q15796
ENSG00000175387ENST00000402690Q15796
ENSG00000175387ENST00000402690Q53XR6
ENSG00000175387ENST00000585978K7ESI8
ENSG00000175387ENST00000586040Q15796
ENSG00000175387ENST00000586514K7EJX0
ENSG00000175387ENST00000587269K7EJX0
ENSG00000175387ENST00000587421K7ERC7
ENSG00000175387ENST00000589877K7EL92
ENSG00000175387ENST00000591214B7Z5N5

Expression (GTEx)

0
1
2
3
4
5
6
7
8
9
10
Adipose - Subcutaneous
Adipose - Visceral
Adrenal Gland
Artery - Aorta
Artery - Tibial
Bladder
Brain - Amygdala
Brain - Anterior cingulate cortex
Brain - Caudate
Brain - Cerebellar Hemisphere
Brain - Cerebellum
Brain - Cortex
Brain - Frontal Cortex
Brain - Hippocampus
Brain - Hypothalamus
Brain - Nucleus accumbens
Brain - Putamen
Brain - Spinal cord
Brain - Substantia nigra
Breast - Mammary Tissue
Cells - Cultured fibroblasts
Cells - EBV - transformed lymphocytes
Cervix - Ectocervix
Cervix - Endocervix
Colon - Sigmoid
Colon - Transverse
Esophagus - Gastroesophageal Junction
Esophagus - Mucosa
Esophagus - Muscularis
Fallopian Tube
Heart - Atrial Appendage
Heart - Left Ventricle
Kidney - Cortex
Kidney - Medulla
Liver
Lung
Minor Salivary Gland
Muscle - Skeletal
Nerve - Tibial
Ovary
Pancreas
Pituitary
Prostate
Skin - Not Sun Exposed
Skin - Sun Exposed
Small Intestine - Terminal Ileum
Spleen
Stomach
Testis
Thyroid
Uterus
Vagina
Whole Blood

Pathways

PathwaySourceExternal ID
Cell cycleKEGGko04110
TGF-beta signaling pathwayKEGGko04350
Adherens junctionKEGGko04520
Colorectal cancerKEGGko05210
Pancreatic cancerKEGGko05212
Cell cycleKEGGhsa04110
TGF-beta signaling pathwayKEGGhsa04350
Adherens junctionKEGGhsa04520
Pathways in cancerKEGGhsa05200
Colorectal cancerKEGGhsa05210
Pancreatic cancerKEGGhsa05212
EndocytosisKEGGko04144
EndocytosisKEGGhsa04144
Chagas disease (American trypanosomiasis)KEGGko05142
Chagas disease (American trypanosomiasis)KEGGhsa05142
HTLV-I infectionKEGGko05166
HTLV-I infectionKEGGhsa05166
Hippo signaling pathwayKEGGhsa04390
Hippo signaling pathwayKEGGko04390
Proteoglycans in cancerKEGGhsa05205
Proteoglycans in cancerKEGGko05205
Inflammatory bowel disease (IBD)KEGGhsa05321
Inflammatory bowel disease (IBD)KEGGko05321
FoxO signaling pathwayKEGGhsa04068
Signaling pathways regulating pluripotency of stem cellsKEGGhsa04550
Signaling pathways regulating pluripotency of stem cellsKEGGko04550
TGF-beta signalingKEGGhsa_M00680
Activin signalingKEGGhsa_M00681
TGF-beta signalingKEGGM00680
Activin signalingKEGGM00681
Metabolism of proteinsREACTOMER-HSA-392499
Post-translational protein modificationREACTOMER-HSA-597592
DiseaseREACTOMER-HSA-1643685
Diseases of signal transductionREACTOMER-HSA-5663202
Signaling by TGF-beta Receptor Complex in CancerREACTOMER-HSA-3304351
Loss of Function of SMAD4 in CancerREACTOMER-HSA-3304347
SMAD4 MH2 Domain Mutants in CancerREACTOMER-HSA-3311021
Loss of Function of SMAD2/3 in CancerREACTOMER-HSA-3304349
SMAD2/3 Phosphorylation Motif Mutants in CancerREACTOMER-HSA-3304356
SMAD2/3 MH2 Domain Mutants in CancerREACTOMER-HSA-3315487
Loss of Function of TGFBR1 in CancerREACTOMER-HSA-3656534
TGFBR1 KD Mutants in CancerREACTOMER-HSA-3656532
Signal TransductionREACTOMER-HSA-162582
Signaling by TGF-beta Receptor ComplexREACTOMER-HSA-170834
TGF-beta receptor signaling activates SMADsREACTOMER-HSA-2173789
Downregulation of TGF-beta receptor signalingREACTOMER-HSA-2173788
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimerREACTOMER-HSA-2173793
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcriptionREACTOMER-HSA-2173796
Downregulation of SMAD2/3:SMAD4 transcriptional activityREACTOMER-HSA-2173795
Signaling by ActivinREACTOMER-HSA-1502540
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Developmental BiologyREACTOMER-HSA-1266738
Signaling by NODALREACTOMER-HSA-1181150
Transcriptional regulation of pluripotent stem cellsREACTOMER-HSA-452723
AGE-RAGE signaling pathway in diabetic complicationsKEGGko04933
AGE-RAGE signaling pathway in diabetic complicationsKEGGhsa04933
DeubiquitinationREACTOMER-HSA-5688426
Ub-specific processing proteasesREACTOMER-HSA-5689880
Th17 cell differentiationKEGGko04659
Th17 cell differentiationKEGGhsa04659
Apelin signaling pathwayKEGGhsa04371

Protein levels (Protein atlas)

Not detected
Low
Medium
High
cerebral cortex
cerebellum
hippocampus
caudate
thyroid gland
parathyroid gland
adrenal gland
nasopharynx
bronchus
lung
oral mucosa
salivary gland
esophagus
stomach 1
stomach 2
duodenum
small intestine
colon
rectum
liver
gallbladder
pancreas
kidney
urinary bladder
testis
epididymis
seminal vesicle
prostate
vagina
ovary
fallopian tube
endometrium 1
endometrium 2
cervix, uterine
placenta
breast
heart muscle
smooth muscle
skeletal muscle
soft tissue 1
soft tissue 2
adipose tissue
skin 1
skin 2
appendix
spleen
lymph node
tonsil
bone marrow

References

Pubmed IDYearTitleCitations
377390892024BRD9-SMAD2/3 Orchestrates Stemness and Tumorigenesis in Pancreatic Ductal Adenocarcinoma.3
377556642024Exosomes Derived from Human Adipose Mesenchymal Stem Cells Inhibits Fibrosis and Treats Oral Submucous Fibrosis via the miR-181a-5p/Smad2 Axis.3
383838422024MAP4K4 and WT1 mediate SOX6-induced cellular senescence by synergistically activating the ATF2-TGFβ2-Smad2/3 signaling pathway in cervical cancer.0
384112672024TMED3 stabilizes SMAD2 by counteracting NEDD4-mediated ubiquitination to promote ovarian cancer.0
384958102024DUSP22 Ameliorates Endothelial-to-Mesenchymal Transition in HUVECs through Smad2/3 and MAPK Signaling Pathways.0
387896302024Exosomes derived from adipose tissue-derived stem cells alleviated H(2)O(2)-induced oxidative stress and endothelial-to-mesenchymal transition in human umbilical vein endothelial cells by inhibition of the mir-486-3p/Sirt6/Smad signaling pathway.0
377390892024BRD9-SMAD2/3 Orchestrates Stemness and Tumorigenesis in Pancreatic Ductal Adenocarcinoma.3
377556642024Exosomes Derived from Human Adipose Mesenchymal Stem Cells Inhibits Fibrosis and Treats Oral Submucous Fibrosis via the miR-181a-5p/Smad2 Axis.3
383838422024MAP4K4 and WT1 mediate SOX6-induced cellular senescence by synergistically activating the ATF2-TGFβ2-Smad2/3 signaling pathway in cervical cancer.0
384112672024TMED3 stabilizes SMAD2 by counteracting NEDD4-mediated ubiquitination to promote ovarian cancer.0
384958102024DUSP22 Ameliorates Endothelial-to-Mesenchymal Transition in HUVECs through Smad2/3 and MAPK Signaling Pathways.0
387896302024Exosomes derived from adipose tissue-derived stem cells alleviated H(2)O(2)-induced oxidative stress and endothelial-to-mesenchymal transition in human umbilical vein endothelial cells by inhibition of the mir-486-3p/Sirt6/Smad signaling pathway.0
362264682023SMAD2/3 Phosphorylation Is Downregulated in T Cells in HIV-Infected Patients.0
363354712023APOBEC3B expression is promoted by lincNMR collaborating with TGF-β-Smad pathway.2
363459382023The TGF-β/Smad(2/3) signaling pathway is involved in Musashi2-induced invasion and metastasis of colorectal cancer.1

Citation

Raphael Saffroy ; Antoinette Lemoine ; Brigitte Debuire

SMAD2 (mothers against decapentaplegic homolog 2 (Drosophila))

Atlas Genet Cytogenet Oncol Haematol. 2004-07-01

Online version: http://atlasgeneticsoncology.org/gene/370/smad2-(mothers-against-decapentaplegic-homolog-2-(drosophila))