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SMAD2 Gene

protein-coding GIFtS: 70
GCID: GC18M045357

SMAD Family Member 2

(Previous names: MAD, mothers against decapentaplegic homolog 2 (Drosophila),...)
(Previous symbol: MADH2)

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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
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Aliases
SMAD Family Member 2¹ ² ³		SMAD, Mothers Against DPP Homolog 2 (Drosophila)¹
MADH2¹ ² ³ ⁵		Mother Against DPP Homolog 2²
JV18-1² ³		Mothers Against Decapentaplegic Homolog 2²
MADR2² ³		Sma- And Mad-Related Protein 2²
hMAD-2² ³		SMAD, Mothers Against DPP Homolog 2²
hSMAD2² ³		Smad2³
MAD Homolog 2² ³		Mad-Related Protein 2³
JV18² ⁵		Mothers Against DPP Homolog 2³
MAD, Mothers Against Decapentaplegic Homolog 2 (Drosophila)¹		SMAD 2³

External Ids:	HGNC: 6768¹	Entrez Gene: 4087²	Ensembl: ENSG00000175387⁷	OMIM: 601366⁵	UniProtKB: Q15796³

Export aliases for SMAD2 gene to outside databases

Previous GC identifers: GC18M043620 GC18M043621 GC18M042208

(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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 osteopoikilosis. GO annotations related to this gene include transcription factor binding and sequence-specific DNA binding transcription factor activity. An important paralog of this gene is SMAD3.

UniProtKB/Swiss-Prot: SMAD2_HUMAN, Q15796

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 Wiki entry for SMAD2 (Mothers against decapentaplegic homolog 2) Gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:

NC_000018.10 NT_010966.15 NC_018929.2

Regulatory elements:

Regulatory transcription factor binding sites in the SMAD2 gene promoter:
CREB deltaCREB
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: SMAD2 promoter sequence

Search Chromatin IP Primers for SMAD2

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat SMAD2

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 18q21.1 Ensembl cytogenetic band: 18q21.1 HGNC cytogenetic band: 18q21

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

GeneLoc information about chromosome 18 GeneLoc Exon Structure

GeneLoc location for GC18M045357: view genomic region (about GC identifiers)

Start:	45,357,922 bp from pter	End:	45,457,515 bp from pter
Size:	99,594 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, ²neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: SMAD2_HUMAN, Q15796 (See protein sequence)

Recommended Name: Mothers against decapentaplegic homolog 2

Size: 467 amino acids; 52306 Da

Subunit: 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 ot 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

4 PDB 3D structures from and Proteopedia for SMAD2:

1DEV (3D)

1KHX (3D)

1U7V (3D)

2LB3 (3D)

Alternative splicing: 2 isoforms: Q15796-1 Q15796-2

Explore the universe of human proteins at neXtProt for SMAD2: NX_Q15796

Explore proteomics data for SMAD2 at MOPED

Post-translational modifications:

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 PDPK1¹

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 genes¹

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-beta¹

Modification sites at neXtProt

Modification sites at PhosphoSitePlus

See SMAD2 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins (3 alternative transcripts):

NP_001003652.1 NP_001129409.1 NP_005892.1

ENSEMBL proteins:

ENSP00000262160 ENSP00000384449 ENSP00000466193 ENSP00000467075 ENSP00000466254

ENSP00000465355 ENSP00000468202 ENSP00000465971 ENSP00000468732 ENSP00000349282

Reactome Protein details: Q15796

SMAD2 Human Recombinant Protein Products:

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	Browse Proteins at Cloud-Clone Corp.

SMAD2 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of SMAD2
	R&D Systems Antibodies for SMAD2
	Cell Signaling Technology (CST) Antibodies for SMAD2
	OriGene Antibodies for SMAD2 OriGene Custom Antibody Services for SMAD2
	Novus Biologicals SMAD2 Antibodies
	Abcam antibodies for SMAD2 (Q99717, Q15796, P84022)
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	ThermoFisher Antibody for SMAD2
	LSBio Antibodies in human, mouse, rat for SMAD2

SMAD2 Assay Products:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Assay Services for SMAD2
	R&D Systems ELISAs for SMAD2
	GenScript Custom Assay Services for SMAD2
	Cell Signaling Technology (CST) Sandwich ELISA Kits for SMAD2
	Browse Enzo Life Sciences for kits & assays
	Browse ELISAs at Cloud-Clone Corp. Browse CLIAs at Cloud-Clone Corp.

(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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HGNC Gene Families:

SMAD: SMADs

Selected InterPro protein domains (see all 6):

IPR013019 MAD_homology_MH1

IPR008984 SMAD_FHA_domain

IPR001132 SMAD_dom_Dwarfin-type

IPR017855 SMAD_dom-like

IPR013790 Dwarfin

Graphical View of Domain Structure for InterPro Entry Q15796

ProtoNet protein and cluster: Q15796

1 Blocks protein domain: IPB001132 Dwarfin protein

UniProtKB/Swiss-Prot: SMAD2_HUMAN, Q15796

Similarity: Belongs to the dwarfin/SMAD family

Similarity: Contains 1 MH1 (MAD homology 1) domain

Similarity: Contains 1 MH2 (MAD homology 2) domain

SMAD2 for domains About GeneDecksing

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

UniProtKB/Swiss-Prot Summary: SMAD2_HUMAN, Q15796

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): Selected molecular function terms (see all 17): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0003677	contributes to DNA binding	IDA	9389648
GO:0003682	chromatin binding	IEA	--
GO:0003690	double-stranded DNA binding	ISS	--
GO:0003700	contributes to sequence-specific DNA binding transcription factor activity	IDA	17438144
GO:0005160	transforming growth factor beta receptor binding	IPI	9311995

SMAD2 for ontologies About GeneDecksing

Phenotypes:
3 GenomeRNAi human phenotypes for SMAD2:

Increased gamma-H2AX phosphory

Increased mitotic index

Upregulation of Wnt/beta-caten

Selected MGI mutant phenotypes (inferred from 21 alleles) (MGI details for Smad2) (see all 22):

behavior/neurological	cardiovascular system	cellular	craniofacial	digestive/alimentary
embryogenesis	endocrine/exocrine gland	growth/size/body	hematopoietic system	homeostasis/metabolism
immune system	integument	liver/biliary system	mortality/aging	nervous system

SMAD2 for phenotypes           About GeneDecksing

Animal Models:
     MGI mouse knock-outs for SMAD2: Smad2^tm2.1Rob Smad2^tm1Cxd Smad2^tm1.2Epb Smad2^tm1Enl Smad2^tm3Rob Smad2^tm1.2Mwst
                                                     Smad2^tm1Kato Smad2^tm1.3Mwst Smad2^tm1Rob Smad2^tm1Rak Smad2^tm1.3Epb

inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for SMAD2

inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for SMAD2

genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for SMAD2

genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for SMAD2

Transcription Factor Targeting:

Targeting motifs: HOMER Transcription Factor Regulatory Elements motif viewer

Consensus sequence: CTGTCTGG

miRNA Products:		miRTarBase miRNAs that target SMAD2: hsa-mir-200a-3p (MIRT007290), hsa-mir-155-5p (MIRT005872), hsa-mir-200b-3p (MIRT007322), hsa-mir-484 (MIRT042141), hsa-mir-324-5p (MIRT043212), hsa-mir-652-3p (MIRT039468)

		Block miRNA regulation of human, mouse, rat SMAD2 using miScript Target Protectors
		Selected qRT-PCR Assays for microRNAs that regulate SMAD2 (see all 180):
		hsa-miR-128 hsa-miR-4305 hsa-miR-4275 hsa-miR-149 hsa-miR-1243 hsa-miR-200b hsa-miR-509-3-5p hsa-miR-520b

		Browse SwitchGear 3'UTR luciferase reporter plasmids

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for SMAD2
		Predesigned siRNA for gene silencing in human, mouse, rat SMAD2

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for SMAD2

Clone Products:		OriGene clones in human, mouse for SMAD2 (see all 16) OriGene ORF clones in mouse, rat for SMAD2 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 3): SMAD2 (NM_001135937)
		Sino Biological Human cDNA Clone for SMAD2
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for SMAD2
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat SMAD2

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for SMAD2
		Browse ESI BIO Cell Lines and PureStem Progenitors for SMAD2

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for SMAD2

(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot

SMAD2_HUMAN, Q15796: 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:

Compartment	Confidence
nucleus	5
cytosol	4
extracellular	3
cytoskeleton	2
mitochondrion	2
plasma membrane	2
endoplasmic reticulum	1
endosome	1
peroxisome	1

About this image

Gene Ontology (GO): Selected cellular component terms (see all 9): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005622	intracellular	--	--
GO:0005634	nucleus	IDA	12411310
GO:0005654	nucleoplasm	TAS	--
GO:0005667	transcription factor complex	IDA	17438144
GO:0005737	cytoplasm	IDA	12411310

SMAD2 for ontologies About GeneDecksing

(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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SuperPaths for SMAD2 About (see all 41)

See pathways by source

SuperPath

Selected contained pathways About (see all per SuperPath)

Loss of Function of SMAD2/3 in Cancer

Transcriptional activity of SMAD2/SMAD3-SMAD4 heterotrimer	0.72	TGFBR2 Kinase Domain Mutants in Cancer	0.60
SMAD2/SMAD3-SMAD4 heterotrimer regulates transcription	0.72	Signaling by TGF-beta Receptor Complex	0.60
Loss of Function of SMAD2/3 in Cancer	0.60	TGFBR1 KD Mutants in Cancer	0.60
TGFBR2 MSI Frameshift Mutants in Cancer	0.60	SMAD2/3 MH2 Domain Mutants in Cancer	0.60

TGF-beta receptor signaling activates SMADs

Downregulation of TGF-beta receptor signaling

0.82

TGF-beta receptor signaling activates SMADs

0.82

Gene Expression

Generic Transcription Pathway

0.40

Gene Expression

0.40

Signaling by NODAL

Signaling by NODAL

0.39

Signaling by Activin

0.39

Prostate Cancer

Prostate Cancer

0.32

Integrated Cancer pathway

0.32

Pathways by source See SuperPaths
Show all pathways

2 R&D Systems Pathways for SMAD2

	Th17 Differentiation
	TGF-beta Signaling Pathways

Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for SMAD2 (see all 10)

	Factors Promoting Cardiogenesis in Vertebrates
	Molecular Mechanisms of Cancer
	JAK-STAT Pathway
	TGF-Beta Pathway
	TOB in T-Cell Signaling

1 Cell Signaling Technology (CST) Pathway for SMAD2

TGF-beta/Smad Signaling

5 GeneGo (Thomson Reuters) Pathways for SMAD2

	Signal transduction Activin A signaling regulation
	Cell cycle Regulation of G1/S transition (part 1)
	Development Role of Activin A in cell differentiation and proliferation
	Cytokine production by Th17 cells in CF (Mouse model)
	Development TGF-beta receptor signaling

Selected BioSystems Pathways for SMAD2 (see all 13)

	TGF Beta Signaling Pathway
	EGFR1 Signaling Pathway
	Integrated Breast Cancer Pathway
	AGE/RAGE pathway
	TGF-beta Receptor Signaling Pathway

1 Sino Biological Pathway for SMAD2

TGF-beta Signaling Pathway

Selected Reactome Pathways for SMAD2 (see all 10)

	TGF-beta receptor signaling activates SMADs
	SMAD2/3 MH2 Domain Mutants in Cancer
	SMAD4 MH2 Domain Mutants in Cancer
	Signaling by Activin
	Downregulation of SMAD2/3:SMAD4 transcriptional activity

Selected Kegg Pathways (Kegg details for SMAD2) (see all 13):

	FoxO signaling pathway
	Cell cycle
	Endocytosis
	TGF-beta signaling pathway
	Hippo signaling pathway

SMAD2 for pathways About GeneDecksing

Pathway & Disease-focused RT² Profiler PCR Arrays including SMAD2 (see all 8):

Osteogenesis in human mouse rat

Fibrosis in human mouse rat

Stem Cell Transcription Factors in human mouse rat

TGFB/BMP Signaling Pathway in human mouse rat

Stem Cell Signaling in human mouse rat

Interactions:

GeneGlobe Interaction Network for SMAD2

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

Selected Interacting proteins for SMAD2 (Q15796^{1, 2, 3} ENSP00000262160⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 510)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
ENSG00000237724	P08107³, ENSP00000406359⁴	I2D: score=1 STRING: ENSP00000406359
ENSG00000212866	P08107³	I2D: score=1
ENSG00000215328	P08107³	I2D: score=1
ENSG00000224501	P08107³	I2D: score=1
ENSG00000231555	P08107³	I2D: score=1

About this table

Gene Ontology (GO): Selected biological process terms (see all 49): About this table

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	--

SMAD2 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse compounds at ApexBio

Browse Tocris compounds for SMAD2

1 DrugBank Compound for SMAD2 About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Phosphonoserine	--	--	target	--	10592235

Selected Novoseek inferred chemical compound relationships for SMAD2 gene (see all 33) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
tgf beta1	77.4	37	16949833 (4), 11424093 (2), 16253118 (2), 17469181 (2) (see all 24)
asiaticoside	59.2	6	15323444 (2), 18201262 (2), 16557473 (2)
threonine	58.9	4	15210694 (1), 17270292 (1), 11106403 (1), 15702493 (1)
sb 203580	56.3	7	17124250 (2), 18471442 (1), 18583311 (1), 19397700 (1) (see all 6)
pd 98,059	51.9	4	17124250 (2), 10652224 (1), 15372629 (1)
serine	51.8	15	15210694 (3), 15522964 (1), 17270292 (1), 11278410 (1) (see all 11)
sphingosylphosphorylcholine	32.9	12	17481939 (3), 17105765 (3)
tranilast	30.3	4	16528248 (3), 16284627 (1)
procollagen	23	1	17051103 (1)
leptomycin b	20.7	2	11074002 (1), 12547835 (1)

SMAD2 for compounds About GeneDecksing

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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REFSEQ mRNAs for SMAD2 gene (3 alternative transcripts):

NM_001003652.3 NM_001135937.2 NM_005901.5

Unigene Cluster for SMAD2:

SMAD family member 2

Hs.12253 [show with all ESTs]

Unigene Representative Sequence: NM_001003652

12 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000262160(uc002lcy.3) ENST00000402690(uc002lcz.3) ENST00000586040

ENST00000591214 ENST00000587353 ENST00000587269 ENST00000586514 ENST00000587421

ENST00000586487 ENST00000589877 ENST00000585978 ENST00000356825(uc010xdc.2 uc010xdd.1)

miRNA Products:		Block miRNA regulation of human, mouse, rat SMAD2 using miScript Target Protectors
		Selected qRT-PCR Assays for microRNAs that regulate SMAD2 (see all 180):
		hsa-miR-128 hsa-miR-4305 hsa-miR-4275 hsa-miR-149 hsa-miR-1243 hsa-miR-200b hsa-miR-509-3-5p hsa-miR-520b

		Browse SwitchGear 3'UTR luciferase reporter plasmids

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for SMAD2
		Predesigned siRNA for gene silencing in human, mouse, rat SMAD2

Clone Products:		OriGene clones in human, mouse for SMAD2 (see all 16) OriGene ORF clones in mouse, rat for SMAD2 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 3): SMAD2 (NM_001135937)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for SMAD2
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat SMAD2

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Additional mRNA sequence:

AF027964.1 AK126373.1 AK312963.1 AY134745.1 BC014840.1 BC025699.1 BT007422.1 U59911.1

U65019.1 U68018.1

16 DOTS entries:

DT.454498 DT.97809192 DT.100816065 DT.97822192 DT.95369913 DT.121097527 DT.100022688 DT.65284280

DT.100816060 DT.100800384 DT.101973205 DT.121097501 DT.121097530 DT.91996304 DT.95171474 DT.100816063

Selected AceView cDNA sequences (see all 247):

AA418737 BU172569 BX426272 CD517923 BM874660 NM_001003652 AW207900 AA836967

BQ639008 AW243896 BM454449 AA594363 AL555419 AA418792 AI360313 BI832799

AA877333 BX455722 AA406238 R82670 BM721481 BM823882 AA283890 BM479698

GeneLoc Exon Structure

Selected Alternative Splicing Database (ASD) splice patterns (SP) for SMAD2 (see all 13) About this scheme

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:																													-		-

ExUns:	15	^	16	^	17a	·	17b
SP1:
SP2:
SP3:
SP4:
SP5:

ECgene alternative splicing isoforms for SMAD2

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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SMAD2 expression in normal human tissues (normalized intensities) SMAD2 embryonic expression: see
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: ATCCAGTATC

About this image

SMAD2 expression in embryonic tissues and stem cells About this table

Data from LifeMap, the Embryonic Development and Stem Cells Database
selected tissues (see all 11) fully expand


Primitive Streak (Early Embryo) fully expand to see all 3 entries
Primitive Streak Cells Anterior Primitive Streak

Epiblast (Early Embryo) fully expand to see all 2 entries
Primitive Streak Cells Anterior Primitive Streak

Endoderm (Gastrulation Derivatives)
Endoderm Progenitor Cells Anterior Primitive Streak

Brain (Nervous System) fully expand to see all 2 entries
Midbrain tegmentum

Neural Tube (Nervous System)
Mesencephalic Roof Plate

SMAD2 Protein expression data from MOPED¹, PaxDb² and MaxQB³:

About this image

SMAD2 Protein Expression

SOURCE GeneReport for Unigene cluster: Hs.12253

UniProtKB/Swiss-Prot: SMAD2_HUMAN, Q15796

Tissue specificity: Expressed at high levels in skeletal muscle, endothelial cells, heart and placenta

Pathway & Disease-focused RT² Profiler PCR Arrays including SMAD2 (see all 8):

Osteogenesis in human mouse rat

Fibrosis in human mouse rat

Stem Cell Transcription Factors in human mouse rat

TGFB/BMP Signaling Pathway in human mouse rat

Stem Cell Signaling in human mouse rat

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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of animals.

Orthologs for SMAD2 gene from Selected species (see all 17) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Smad2^{1 , 5}	MAD homolog 2 (Drosophila)⁵ SMAD family member 2¹	92.22(n)¹ 99.57(a)¹		18 (51.42 cM)⁵ 17126¹ NM_010754.5¹ NP_034884.2¹ 76241580⁵
chicken (Gallus gallus)	Aves	SMAD2¹	SMAD family member 2	85.3(n) 99.36(a)		395247 NM_204561.1 NP_989892.1
lizard (Anolis carolinensis)	Reptilia	SMAD2⁶	SMAD family member 2	74(a)	1 ↔ 1	GL343467.1(315873-333517)
African clawed frog (Xenopus laevis)	Amphibia	Xl.85²	Xenopus laevis Mad2 mRNA, complete cds	84.96(n)		L77885.1
zebrafish (Danio rerio)	Actinopterygii	madh2²	MAD homolog 2 (Drosophila)	79.93(n)		30639 AF229022.1
fruit fly (Drosophila melanogaster)	Insecta	Smox⁶	Smad on X	62(a)	1 → many	X(8032424-8036301)
worm (Caenorhabditis elegans)	Secernentea	sma-2⁶	Protein SMA-2 (sma-2) mRNA, complete cds	50(a)	1 → many	III(8749771-8757069) WBGene00004856

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

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for SMAD2 gene

SMAD3² SMAD1² SMAD6² SMAD5² SMAD4² SMAD9² SMAD7²

6 SIMAP similar genes for SMAD2 using alignment to 7 protein entries: SMAD2_HUMAN (see all proteins):

SMAD3 DKFZp781O1323 MADH5 SMAD9 SMAD5 SMAD1

SMAD2 for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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SNP ID	Valid	Clinical significance	Chr 18 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
VAR_011377⁴		A colorectal carcinoma sample⁴	--	see VAR_011377	2	L R	mis⁴		0	--	--	--	--
VAR_036473⁴		A colorectal cancer sample⁴	--	see VAR_036473	2	D V	mis⁴		0	--	--	--	--
VAR_011378⁴		A colorectal carcinoma sample⁴	--	see VAR_011378	2	P H	mis⁴		0	--	--	--	--
VAR_011375⁴		A colorectal carcinoma sample⁴	--	see VAR_011375	2	R C	mis⁴		0	--	--	--	--
VAR_011379⁴		A colorectal carcinoma sample⁴	--	see VAR_011379	2	D E	mis⁴		0	--	--	--	--
rs200373587^1,2		--	42219695(+)	`GAAGA-/ACAAAAA`	3	--	int¹		0	--	--	--	--
rs17813908^1,2	C,F,H	--	42219696(+)	`AAGAAC/AAAAAA`	3	--	int¹		8		NA NS EA	498
rs57746325^1,2	C	--	42219696(+)	`AAGAA-/CAAAAA`	3	--	int¹		0	--	--	--	--
rs74172078^1,2	C	--	42225207(+)	`GTATG-/TATA /TATATATATAT`	3	--	int¹		1		NA	2
rs77914902^1,2	C	--	42262711(+)	`ATATGC/AAAAAA`	3	--	int¹		1		NA	2

HapMap Linkage Disequilibrium report for SMAD2 (45357922 - 45457515 bp)

Structural Variations
Database of Genomic Variants (DGV) 8 variations for SMAD2: About this table

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

Human Gene Mutation Database (HGMD): SMAD2

Site Specific Mutation Identification with PCR Assays

SeqTarget long-range PCR primers for resequencing SMAD2

DNA2.0 Custom Variant and Variant Library Synthesis for SMAD2

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 601366 OMIM disorders: --

Selected diseases for SMAD2 (see all 86): About MalaCards

buschke ollendorff syndrome osteopoikilosis nephrogenic systemic fibrosis melorheostosis

keloids clear cell adenocarcinoma ovarian clear cell adenocarcinoma hypertrophic scars

sertoli cell-only syndrome vernal keratoconjunctivitis ureteral obstruction thoracic aortic aneurysm

familial colorectal cancer tuberous sclerosis complex peutz-jeghers syndrome focal segmental glomerulosclerosis

keratoconjunctivitis hepatopulmonary syndrome tuberous sclerosis congenital heart defect

4 diseases from the University of Copenhagen DISEASES database for SMAD2:

Ureteral disease Pulmonary fibrosis Kidney disease Carcinoma

SMAD2 for disorders About GeneDecksing

Congresses - knowledge worth sharing:
The International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD) 9 - 13 March 2014

Selected Novoseek inferred disease relationships for SMAD2 gene (see all 50) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
pancreatic cancer	52.3	7	10505717 (5), 15249209 (1), 10781087 (1)
keloid	49.7	11	17051103 (4), 17144456 (2), 15453837 (1), 15978417 (1) (see all 5)
tumors	39.9	74	11391794 (4), 12894231 (3), 10781087 (3), 11438451 (3) (see all 45)
cancer	38.1	29	10505717 (2), 12237237 (2), 9006934 (2), 9264367 (1) (see all 23)
scars hypertrophic	37.3	7	11955370 (5), 18616749 (1)
colorectal cancer	34.8	22	15711891 (2), 9635866 (2), 12967141 (2), 9264367 (1) (see all 13)
pancreatic carcinoma	29.1	9	9892110 (2), 12140283 (1)
adenocarcinoma clear cell	26.4	2	16820918 (1)
gastric carcinoma	23.4	4	10073143 (2), 19351925 (1), 15067346 (1)
sclerosis systemic	21.6	1	20430497 (1)

Genetic Association Database (GAD): SMAD2
Human Genome Epidemiology (HuGE) Navigator: SMAD2 (20 documents)

Export disorders for SMAD2 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for SMAD2 gene, integrated from 10 sources (see all 800):
(articles sorted by number of sources associating them with SMAD2)

Utopia: connect your pdf to the dynamic
world of online information

Mad-related genes in the human. (PubMed id 8673135)^{1, 2, 3} Riggins G.J.... Vogelstein B.V. (Nat. Genet. 1996)
MADR2 maps to 18q21 and encodes a TGFbeta-regulated MAD-related protein that is functionally mutated in colorectal carcinoma. (PubMed id 8752209)^{1, 2, 3} Eppert K.... Attisano L. (Cell 1996)
Modulation of Smad2-mediated signaling by extracellular signal- regulated kinase. (PubMed id 12193595)^{1, 2, 9} Funaba M.... Mathews L.S. (J. Biol. Chem. 2002)
Potentiation of Smad-mediated transcriptional activation by the RNA- binding protein RBPMS. (PubMed id 17099224)^{1, 2, 9} Sun Y.... Ye Q. (Nucleic Acids Res. 2006)
Alternatively spliced variant of Smad2 lacking exon 3. Comparison with wild-type Smad2 and Smad3. (PubMed id 9873005)^{1, 2, 9} Yagi K.... Miyazono K. (J. Biol. Chem. 1999)
SARA, a FYVE domain protein that recruits Smad2 to the TGFbeta receptor. (PubMed id 9865696)^{1, 2, 9} Tsukazaki T.... Wrana J.L. (Cell 1998)
Characterization of the MADH2/Smad2 gene, a human Mad homolog responsible for the transforming growth factor-beta and activin signal transduction pathway. (PubMed id 9503010)^{1, 2, 9} Takenoshita S.... Hagiwara K. (Genomics 1998)
Dual role of the Smad4/DPC4 tumor suppressor in TGFbeta-inducible transcriptional complexes. (PubMed id 9389648)^{1, 2, 9} Liu F.... Massague J. (Genes Dev. 1997)
MADR2 is a substrate of the TGFbeta receptor and its phosphorylation is required for nuclear accumulation and signaling. (PubMed id 8980228)^{1, 2, 9} Macias-Silva M....Wrana J.L. (Cell 1996)
Nuclear export of Smad2 and Smad3 by RanBP3 facilitates termination of TGF-beta signaling. (PubMed id 19289081)^{1, 2, 9} Dai F.... Feng X.H. (Dev. Cell 2009)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 4087	HGNC: 6768	AceView: SMAD2	Ensembl:ENSG00000175387	euGenes: HUgn4087
ECgene: SMAD2	Kegg: 4087	H-InvDB: SMAD2

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for SMAD2	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for SMAD2	Genetics and Cytogenetics in Oncology and Haematology

Intellectual Property for SMAD2 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for SMAD2 gene:
Search GeneIP for patents involving SMAD2

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

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