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Aliases for SMAD2 Gene

Aliases for SMAD2 Gene

  • SMAD Family Member 2 2 3 4
  • MADH2 3 4 6
  • MAD Homolog 2 3 4
  • HSMAD2 3 4
  • JV18-1 3 4
  • HMAD-2 3 4
  • MADR2 3 4
  • MAD, Mothers Against Decapentaplegic Homolog 2 (Drosophila) 2
  • SMAD, Mothers Against DPP Homolog 2 (Drosophila) 2
  • Mothers Against Decapentaplegic Homolog 2 3
  • SMAD, Mothers Against DPP Homolog 2 3
  • Sma- And Mad-Related Protein 2 3
  • Mothers Against DPP Homolog 2 4
  • Mother Against DPP Homolog 2 3
  • Mad-Related Protein 2 4
  • SMAD 2 4
  • JV18, 6
  • Smad2 4
  • JV18 3

External Ids for SMAD2 Gene

Previous HGNC Symbols for SMAD2 Gene

  • MADH2

Previous GeneCards Identifiers for SMAD2 Gene

  • GC18M043620
  • GC18M043621
  • GC18M045357
  • GC18M042208

Summaries for SMAD2 Gene

Entrez Gene Summary for SMAD2 Gene

  • 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]

GeneCards Summary for SMAD2 Gene

SMAD2 (SMAD Family Member 2) is a Protein Coding gene. Diseases associated with SMAD2 include buschke-ollendorff syndrome and melorheostosis. Among its related pathways are Signaling by GPCR and Proteoglycans in cancer. GO annotations related to this gene include sequence-specific DNA binding transcription factor activity and transcription factor binding. An important paralog of this gene is SMAD1.

UniProtKB/Swiss-Prot for SMAD2 Gene

  • 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.

Gene Wiki entry for SMAD2 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SMAD2 Gene

Genomics for SMAD2 Gene

Regulatory Elements for SMAD2 Gene

Transcription factor binding sites by QIAGEN in the SMAD2 gene promoter:

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for SMAD2 Gene

Start:
47,808,957 bp from pter
End:
47,931,193 bp from pter
Size:
122,237 bases
Orientation:
Minus strand

Genomic View for SMAD2 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for SMAD2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SMAD2 Gene

Proteins for SMAD2 Gene

  • Protein details for SMAD2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q15796-SMAD2_HUMAN
    Recommended name:
    Mothers against decapentaplegic homolog 2
    Protein Accession:
    Q15796
    Secondary Accessions:

    Protein attributes for SMAD2 Gene

    Size:
    467 amino acids
    Molecular mass:
    52306 Da
    Quaternary structure:
    • Momomer; the absence of TGF-beta. Heterodimer; in the presence of TGF-beta. Forms a heterodimer with co-SMAD, SMAD4, in the nucleus to form the transactivation complex SMAD2/SMAD4. Interacts with AIP1, HGS, PML and WWP1 (By similarity). Interacts with NEDD4L in response to TGF-beta (By similarity). Found in a complex with SMAD3 and TRIM33 upon addition of TGF-beta. Interacts with ACVR1B, SMAD3 and TRIM33. Interacts (via the MH2 domain) with ZFYVE9; may form trimers with the SMAD4 co-SMAD. Interacts with FOXH1, homeobox protein TGIF, PEBP2-alpha subunit, CREB-binding protein (CBP), EP300, SKI and SNW1. Interacts with SNON; when phosphorylated at Ser-465/467. Interacts with SKOR1 and SKOR2. Interacts with PRDM16. Interacts (via MH2 domain) with LEMD3. Interacts with RBPMS. Interacts with WWP1. Interacts (dephosphorylated form, via the MH1 and MH2 domains) with RANBP3 (via its C-terminal R domain); the interaction results in the export of dephosphorylated SMAD3 out of the nucleus and termination of the TGF-beta signaling. Interacts with PDPK1 (via PH domain). Interacts with DAB2; the interactions are enhanced upon TGF-beta stimulation. Interacts with USP15. Interacts with PPP5C. Interacts with ZNF580. Interacts with LDLRAD4 (via the SMAD interaction motif). Interacts (via MH2 domain) with PMEPA1 (via the SMAD interaction motif).

    Three dimensional structures from OCA and Proteopedia for SMAD2 Gene

    Alternative splice isoforms for SMAD2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SMAD2 Gene

Proteomics data for SMAD2 Gene at MOPED

Post-translational modifications for SMAD2 Gene

  • Acetylated on Lys-19 by coactivators in response to TGF-beta signaling, which increases transcriptional activity. Isoform short: Acetylation increases DNA binding activity in vitro and enhances its association with target promoters in vivo. Acetylation in the nucleus by EP300 is enhanced by TGF-beta.
  • In response to TGF-beta, ubiquitinated by NEDD4L; which promotes its degradation (By similarity). Monoubiquitinated, leading to prevent DNA-binding. Deubiquitination by USP15 alleviates inhibition and promotes activation of TGF-beta target genes.
  • Phosphorylated on one or several of Thr-220, Ser-245, Ser-250, and Ser-255. In response to TGF-beta, phosphorylated on Ser-465/467 by TGF-beta and activin type 1 receptor kinases. TGF-beta-induced Ser-465/467 phosphorylation declines progressively in a SETD8-dependent manner. Able to interact with SMURF2 when phosphorylated on Ser-465/467, recruiting other proteins, such as SNON, for degradation. In response to decorin, the naturally occurring inhibitor of TGF-beta signaling, phosphorylated on Ser-240 by CaMK2. Phosphorylated by MAPK3 upon EGF stimulation; which increases transcriptional activity and stability, and is blocked by calmodulin. Phosphorylated by PDPK1.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for SMAD2 (Smad2)

No data available for DME Specific Peptides for SMAD2 Gene

Domains for SMAD2 Gene

Gene Families for SMAD2 Gene

HGNC:

Graphical View of Domain Structure for InterPro Entry

Q15796

UniProtKB/Swiss-Prot:

SMAD2_HUMAN :
  • Q15796
Domain:
  • Contains 1 MH1 (MAD homology 1) domain.
  • Contains 1 MH2 (MAD homology 2) domain.
Family:
  • Belongs to the dwarfin/SMAD family.
genes like me logo Genes that share domains with SMAD2: view

Function for SMAD2 Gene

Molecular function for SMAD2 Gene

UniProtKB/Swiss-Prot Function: 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.

Gene Ontology (GO) - Molecular Function for SMAD2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding IDA 9389648
GO:0001077 RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription IDA 9389648
GO:0003677 contributes_to DNA binding IDA 9389648
GO:0003682 chromatin binding IEA --
GO:0003690 double-stranded DNA binding ISS --
genes like me logo Genes that share ontologies with SMAD2: view
genes like me logo Genes that share phenotypes with SMAD2: view

Animal Models for SMAD2 Gene

MGI Knock Outs for SMAD2:

Animal Model Products

CRISPR Products

Targeting motifs for SMAD2 Gene
HOMER Transcription Factor Regulatory Elements motif SMAD2
  • Consensus sequence: CTGTCTGG Submotif: canonical Cell Type: ES GeoId: GSE29422

miRNA Products

In Situ Assay Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) and Transcription Factor Targeting for SMAD2 Gene

Localization for SMAD2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SMAD2 Gene

Cytoplasm. Nucleus. Note=Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4. On dephosphorylation by phosphatase PPM1A, released from the SMAD2/SMAD4 complex, and exported out of the nucleus by interaction with RANBP1.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for SMAD2 Gene COMPARTMENTS Subcellular localization image for SMAD2 gene
Compartment Confidence
nucleus 5
cytosol 4
extracellular 3
cytoskeleton 2
mitochondrion 2
plasma membrane 2
endoplasmic reticulum 1
endosome 1
peroxisome 1

Gene Ontology (GO) - Cellular Components for SMAD2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000790 nuclear chromatin IDA 21828274
GO:0005622 intracellular --
GO:0005634 nucleus IDA 12411310
GO:0005654 nucleoplasm TAS --
GO:0005667 transcription factor complex IDA 17438144
genes like me logo Genes that share ontologies with SMAD2: view

Pathways for SMAD2 Gene

genes like me logo Genes that share pathways with SMAD2: view

PCR Array Products

Gene Ontology (GO) - Biological Process for SMAD2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription from RNA polymerase II promoter TAS --
GO:0001657 ureteric bud development IEA --
GO:0001701 in utero embryonic development IEA --
GO:0001706 endoderm formation IEA --
GO:0001707 mesoderm formation ISS --
genes like me logo Genes that share ontologies with SMAD2: view

Compounds for SMAD2 Gene

(1) Drugbank Compounds for SMAD2 Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
Phosphonoserine
target

(33) Novoseek inferred chemical compound relationships for SMAD2 Gene

Compound -log(P) Hits PubMed IDs
tgf beta1 77.4 31
asiaticoside 59.2 6
threonine 58.9 4
sb 203580 56.3 7
pd 98,059 51.9 4
genes like me logo Genes that share compounds with SMAD2: view

Transcripts for SMAD2 Gene

Unigene Clusters for SMAD2 Gene

SMAD family member 2:
Representative Sequences:

CRISPR Products

miRNA Products

Primer Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for SMAD2 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2a · 2b · 2c · 2d ^ 3 ^ 4 ^ 5a · 5b ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10a · 10b · 10c ^ 11a · 11b · 11c ^ 12 ^ 13 ^ 14 ^
SP1: - - - - - - - - - - -
SP2: - - - - - - - -
SP3: - - - - - - - - - - - - -
SP4: - -
SP5: - -
SP6: - - - - - - - -
SP7: - - - -
SP8: - - - - - - - -
SP9: - - - - - - - -
SP10: - - - - -
SP11: - - - - - -
SP12:
SP13: -

ExUns: 15 ^ 16 ^ 17a · 17b
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:
SP13:

Relevant External Links for SMAD2 Gene

GeneLoc Exon Structure for
SMAD2
ECgene alternative splicing isoforms for
SMAD2

Expression for SMAD2 Gene

mRNA expression in normal human tissues for SMAD2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for SMAD2 Gene

SOURCE GeneReport for Unigene cluster for SMAD2 Gene Hs.12253

mRNA Expression by UniProt/SwissProt for SMAD2 Gene

Q15796-SMAD2_HUMAN
Tissue specificity: Expressed at high levels in skeletal muscle, endothelial cells, heart and placenta.
genes like me logo Genes that share expressions with SMAD2: view

In Situ Assay Products

No data available for mRNA differential expression in normal tissues for SMAD2 Gene

Orthologs for SMAD2 Gene

This gene was present in the common ancestor of animals.

Orthologs for SMAD2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SMAD2 35
  • 99.71 (n)
  • 100 (a)
SMAD2 36
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia SMAD2 35
  • 94.79 (n)
  • 99.79 (a)
SMAD2 36
  • 100 (a)
OneToOne
dog
(Canis familiaris)
Mammalia SMAD2 35
  • 93.65 (n)
  • 100 (a)
SMAD2 36
  • 100 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Smad2 35
  • 92.22 (n)
  • 99.57 (a)
Smad2 16
Smad2 36
  • 100 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia SMAD2 36
  • 100 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia SMAD2 36
  • 99 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Smad2 35
  • 91.36 (n)
  • 99.36 (a)
chicken
(Gallus gallus)
Aves -- 36
  • 99 (a)
OneToMany
MADH2 36
  • 99 (a)
OneToMany
SMAD2 35
  • 85.3 (n)
  • 99.36 (a)
lizard
(Anolis carolinensis)
Reptilia SMAD2 36
  • 74 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Xl.85 35
tropical clawed frog
(Silurana tropicalis)
Amphibia smad2 35
  • 83.3 (n)
  • 98.5 (a)
Str.11098 35
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.3591 35
zebrafish
(Danio rerio)
Actinopterygii madh2 35
smad2 35
  • 79.73 (n)
  • 95.29 (a)
smad2 36
  • 92 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta Smox 36
  • 62 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea sma-2 36
  • 50 (a)
OneToMany
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.560 35
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 51 (a)
ManyToMany
-- 36
  • 68 (a)
ManyToMany
Species with no ortholog for SMAD2:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for SMAD2 Gene

ENSEMBL:
Gene Tree for SMAD2 (if available)
TreeFam:
Gene Tree for SMAD2 (if available)

Paralogs for SMAD2 Gene

Paralogs for SMAD2 Gene

Selected SIMAP similar genes for SMAD2 Gene using alignment to 7 proteins:

genes like me logo Genes that share paralogs with SMAD2: view

Variants for SMAD2 Gene

Sequence variations from dbSNP and Humsavar for SMAD2 Gene

SNP ID Clin Chr 18 pos Sequence Context AA Info Type MAF
rs1981 -- 47,834,620(-) CCTTT(C/T)AGCAA utr-variant-3-prime
rs8671 -- 47,833,293(-) CAAAA(A/T)AAGTT utr-variant-3-prime
rs12241 -- 47,833,422(-) ATGTG(C/G/T)TTCCT utr-variant-3-prime
rs12385 -- 47,835,204(+) TGAGG(C/T)GTGAG utr-variant-3-prime
rs15003 -- 47,841,464(-) TTTTA(G/T)TTTGC utr-variant-3-prime

Structural Variations from Database of Genomic Variants (DGV) for SMAD2 Gene

Variant ID Type Subtype PubMed ID
nsv132205 CNV Loss 16902084
esv1323042 CNV Insertion 17803354
esv2627568 CNV Deletion 19546169
esv2717053 CNV Deletion 23290073
esv2667321 CNV Deletion 23128226
nsv909614 CNV Loss 21882294
nsv2288 CNV Insertion 18451855
nsv909615 CNV Loss 21882294

Relevant External Links for SMAD2 Gene

HapMap Linkage Disequilibrium report
SMAD2
Human Gene Mutation Database (HGMD)
SMAD2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SMAD2 Gene

Disorders for SMAD2 Gene

(4) University of Copenhagen DISEASES for SMAD2 Gene

(50) Novoseek inferred disease relationships for SMAD2 Gene

Disease -log(P) Hits PubMed IDs
pancreatic cancer 52.3 7
keloid 49.7 9
tumors 39.9 65
cancer 38.1 26
scars hypertrophic 37.3 6

Relevant External Links for SMAD2

Genetic Association Database (GAD)
SMAD2
Human Genome Epidemiology (HuGE) Navigator
SMAD2
genes like me logo Genes that share disorders with SMAD2: view

No data available for UniProtKB/Swiss-Prot for SMAD2 Gene

Publications for SMAD2 Gene

  1. MADR2 is a substrate of the TGFbeta receptor and its phosphorylation is required for nuclear accumulation and signaling. (PMID: 8980228) Macias-Silva M. … Wrana J.L. (Cell 1996) 3 4 23
  2. Characterization of the MADH2/Smad2 gene, a human Mad homolog responsible for the transforming growth factor-beta and activin signal transduction pathway. (PMID: 9503010) Takenoshita S. … Hagiwara K. (Genomics 1998) 3 4 23
  3. SARA, a FYVE domain protein that recruits Smad2 to the TGFbeta receptor. (PMID: 9865696) Tsukazaki T. … Wrana J.L. (Cell 1998) 3 4 23
  4. Alternatively spliced variant of Smad2 lacking exon 3. Comparison with wild-type Smad2 and Smad3. (PMID: 9873005) Yagi K. … Miyazono K. (J. Biol. Chem. 1999) 3 4 23
  5. Decorin suppresses transforming growth factor-beta-induced expression of plasminogen activator inhibitor-1 in human mesangial cells through a mechanism that involves Ca2+-dependent phosphorylation of Smad2 at serine-240. (PMID: 11879191) Abdel-Wahab N. … Chantry A. (Biochem. J. 2002) 3 4 23

Products for SMAD2 Gene

  • Addgene plasmids for SMAD2

Sources for SMAD2 Gene

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