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Aliases for SMAD2 Gene

Aliases for SMAD2 Gene

  • SMAD Family Member 2 2 3 4 5
  • MAD Homolog 2 3 4
  • HSMAD2 3 4
  • JV18-1 3 4
  • HMAD-2 3 4
  • MADH2 3 4
  • MADR2 3 4
  • MAD, Mothers Against Decapentaplegic Homolog 2 (Drosophila) 2
  • SMAD, Mothers Against DPP Homolog 2 (Drosophila) 2
  • 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
  • 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 melorheostosis and hypertrophic scars. Among its related pathways are Gene Expression and Signaling by GPCR. GO annotations related to this gene include transcription factor activity, sequence-specific DNA binding 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

Promoters for SMAD2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around SMAD2 on UCSC Golden Path with GeneCards custom track

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

Genomic Location for SMAD2 Gene

Chromosome:
18
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

Genes around SMAD2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SMAD2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
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

    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). Interacts with ZFHX3. Interacts with ZNF451 (PubMed:24324267). Identified in a complex that contains at least ZNF451, SMAD2, SMAD3 and SMAD4 (PubMed:24324267).

    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 KMT5A-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

No data available for DME Specific Peptides for SMAD2 Gene

Domains & Families for SMAD2 Gene

Gene Families for SMAD2 Gene

Graphical View of Domain Structure for InterPro Entry

Q15796

UniProtKB/Swiss-Prot:

SMAD2_HUMAN :
  • Contains 1 MH1 (MAD homology 1) domain.
  • Belongs to the dwarfin/SMAD family.
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:0005515 protein binding IEA,IPI 9389648
GO:0030618 transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity IDA 9256479
GO:0033613 activating transcription factor binding IPI 11160896
GO:0046332 SMAD binding IPI 11160896
GO:0070410 co-SMAD binding IPI 9111321
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

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

In Situ Assay Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology and Transcription Factor Targets 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 (PubMed:9865696). On dephosphorylation by phosphatase PPM1A, released from the SMAD2/SMAD4 complex, and exported out of the nucleus by interaction with RANBP1 (PubMed:16751101, PubMed:19289081). {ECO:0000269 PubMed:16751101, ECO:0000269 PubMed:19289081, ECO:0000269 PubMed:9865696}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for SMAD2 Gene COMPARTMENTS Subcellular localization image for SMAD2 gene
Compartment Confidence
cytosol 5
nucleus 5
cytoskeleton 2
extracellular 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:0005667 transcription factor complex IEA,IDA 17438144
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with SMAD2: view

Pathways & Interactions for SMAD2 Gene

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

SIGNOR curated interactions for SMAD2 Gene

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:0001706 endoderm formation IEA --
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0006366 transcription from RNA polymerase II promoter IDA 9389648
genes like me logo Genes that share ontologies with SMAD2: view

Drugs & Compounds for SMAD2 Gene

(26) Drugs for SMAD2 Gene - From: Novoseek, DrugBank, and ApexBio

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Phosphonoserine Experimental Pharma Target 0
Pirfenidone Investigational Pharma TGF-β production inhibitor, Antifibrotic agent; regulates cytokine levels in vivo 42
LDN193189 Hydrochloride Pharma ALK inhibitor,potent and selective 0
LY364947 Pharma Selective inhibitor of TGF-betaRI 0
RepSox Pharma ALK5 inhibitor,potent and selective 0

(12) Additional Compounds for SMAD2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs

(4) ApexBio Compounds for SMAD2 Gene

Compound Action Cas Number
LDN193189 Hydrochloride ALK inhibitor,potent and selective 1062368-62-0
LY364947 396129-53-6
Pirfenidone TGF-β production inhibitor 53179-13-8
RepSox ALK5 inhibitor,potent and selective 446859-33-2
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:

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

Protein differential expression in normal tissues from HIPED for SMAD2 Gene

This gene is overexpressed in Breast (27.7) and Peripheral blood mononuclear cells (9.2).

Integrated Proteomics: protein expression in normal tissues and cell lines 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 expression patterns with SMAD2: view

Protein tissue co-expression partners for SMAD2 Gene

- Elite partner

Primer Products

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
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
chimpanzee
(Pan troglodytes)
Mammalia SMAD2 35
  • 99.71 (n)
  • 100 (a)
SMAD2 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Smad2 35
  • 91.36 (n)
  • 99.36 (a)
oppossum
(Monodelphis domestica)
Mammalia SMAD2 36
  • 100 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia SMAD2 36
  • 99 (a)
OneToOne
chicken
(Gallus gallus)
Aves SMAD2 35
  • 85.3 (n)
  • 99.36 (a)
-- 36
  • 99 (a)
OneToMany
MADH2 36
  • 99 (a)
OneToMany
lizard
(Anolis carolinensis)
Reptilia SMAD2 36
  • 74 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia smad2 35
  • 83.3 (n)
  • 98.5 (a)
Str.11098 35
African clawed frog
(Xenopus laevis)
Amphibia Xl.85 35
zebrafish
(Danio rerio)
Actinopterygii madh2 35
smad2 35
  • 79.73 (n)
  • 95.29 (a)
smad2 36
  • 92 (a)
OneToOne
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.3591 35
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

(6) 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
VAR_011375 A colorectal carcinoma sample
VAR_011377 A colorectal carcinoma sample
VAR_011378 A colorectal carcinoma sample
VAR_011379 A colorectal carcinoma sample
VAR_036473 A colorectal cancer sample

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

Variation tolerance for SMAD2 Gene

Residual Variation Intolerance Score: 14.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.15; 3.43% of all genes are more intolerant (likely to be disease-causing)

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

MalaCards: The human disease database

(15) MalaCards diseases for SMAD2 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
melorheostosis
hypertrophic scars
  • scars hypertrophic
buschke-ollendorff syndrome
  • osteopoikilosis
ureteral disease
  • ureteral diseases
penile disease
  • penile diseases
- elite association - COSMIC cancer census association via MalaCards
Search SMAD2 in MalaCards View complete list of genes associated with diseases

Relevant External Links for SMAD2

Genetic Association Database (GAD)
SMAD2
Human Genome Epidemiology (HuGE) Navigator
SMAD2
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
SMAD2
genes like me logo Genes that share disorders with SMAD2: view

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

Publications for SMAD2 Gene

  1. Mad-related genes in the human. (PMID: 8673135) Riggins G.J. … Vogelstein B.V. (Nat. Genet. 1996) 2 3 4 67
  2. Ski co-repressor complexes maintain the basal repressed state of the TGF-beta target gene, SMAD7, via HDAC3 and PRMT5. (PMID: 19032343) Tabata T. … Ishii S. (Genes Cells 2009) 3 23
  3. Angiotensin II activates connective tissue growth factor and induces extracellular matrix changes involving Smad/activation and p38 mitogen-activated protein kinase signalling pathways in human dermal fibroblasts. (PMID: 19397700) Zhang G.Y. … Gao W.Y. (Exp. Dermatol. 2009) 3 23
  4. Transforming growth factor-beta1 up-regulation of human alpha(1)(I) collagen is mediated by Sp1 and Smad2 transacting factors. (PMID: 19558215) Sysa P. … Mezey E. (DNA Cell Biol. 2009) 3 23
  5. Role of SARA (SMAD anchor for receptor activation) in maintenance of epithelial cell phenotype. (PMID: 19620243) Runyan C.E. … Schnaper H.W. (J. Biol. Chem. 2009) 3 23

Products for SMAD2 Gene

  • Addgene plasmids for SMAD2

Sources for SMAD2 Gene

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