SMAD2 (SMAD family member 2)

Gene

• Entrez ID: 4087
• Gene name: SMAD family member 2
• Gene symbol: SMAD2
• Synonyms: JV18, JV18-1, MADH2, MADR2, hMAD-2, hSMAD2
• Chromosome: 18
• Chromosome location: 18q21.1
• Summary: 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]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs797044882	C>G	Pathogenic	Missense variant, genic downstream transcript variant, coding sequence variant
rs1064793873	C>A	Pathogenic	5 prime UTR variant, stop gained, coding sequence variant
rs1131691755	A>T	Pathogenic	Genic upstream transcript variant, 5 prime UTR variant, stop gained, coding sequence variant
rs1555658568	C>T	Likely-pathogenic	Genic upstream transcript variant, stop gained, coding sequence variant, 5 prime UTR variant
rs1598802389	->GG	Pathogenic	Coding sequence variant, 5 prime UTR variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT005872	hsa-miR-155-5p	Luciferase reporter assay, qRT-PCR, Western blot, Reporter assay;Western blot	21036908
MIRT005872	hsa-miR-155-5p	Reporter assay;Other	20584899
MIRT005872	hsa-miR-155-5p	qRT-PCR, Western blot, Luciferase reporter assay	22426647
MIRT005872	hsa-miR-155-5p	HITS-CLIP	22473208
MIRT007290	hsa-miR-200a-3p	Luciferase reporter assay	22020340
MIRT007322	hsa-miR-200b-3p	Luciferase reporter assay	23492772
MIRT039468	hsa-miR-652-3p	CLASH	23622248
MIRT042141	hsa-miR-484	CLASH	23622248
MIRT042141	hsa-miR-484	GFP reporter assay, Western blot	28286418
MIRT043212	hsa-miR-324-5p	CLASH	23622248
MIRT053419	hsa-miR-624-3p	Microarray	23807165
MIRT053419	hsa-miR-624-3p	Microarray	22942087
MIRT053560	hsa-miR-148a-3p	Luciferase reporter assay, qRT-PCR, Western blot	23873106
MIRT053560	hsa-miR-148a-3p	Flow, Immunofluorescence, Luciferase reporter assay, qRT-PCR, Western blot	26983401
MIRT053560	hsa-miR-148a-3p	Luciferase reporter assay, qRT-PCR, Western blot	26106521
MIRT053560	hsa-miR-148a-3p	Immunohistochemistry, Luciferase reporter assay, qRT-PCR, Western blot	25980823
MIRT053687	hsa-miR-181a-5p	Microarray	22942087
MIRT053699	hsa-miR-188-5p	Microarray	22942087
MIRT054664	hsa-let-7g-5p	Luciferase reporter assay, qRT-PCR, Western blot	24291274
MIRT054772	hsa-miR-146a-5p	qRT-PCR, Western blot	24892945
MIRT387526	hsa-miR-18a-5p	Microarray, Luciferase reporter assay	24664294
MIRT387526	hsa-miR-18a-5p	Luciferase reporter assay	27641158
MIRT387527	hsa-miR-18b-5p	Luciferase reporter assay, qRT-PCR, Western blot	23916701
MIRT495410	hsa-miR-192-3p	PAR-CLIP	23708386
MIRT495411	hsa-miR-6501-5p	PAR-CLIP	23708386
MIRT495412	hsa-miR-3613-3p	PAR-CLIP	23708386
MIRT495412	hsa-miR-3613-3p	HITS-CLIP	23824327
MIRT495414	hsa-miR-495-5p	PAR-CLIP	23708386
MIRT612462	hsa-miR-6891-3p	HITS-CLIP	23824327
MIRT612463	hsa-miR-6072	HITS-CLIP	23824327
MIRT612464	hsa-miR-1228-3p	HITS-CLIP	23824327
MIRT612465	hsa-miR-8485	HITS-CLIP	23824327
MIRT612466	hsa-miR-329-3p	HITS-CLIP	23824327
MIRT612467	hsa-miR-362-3p	HITS-CLIP	23824327
MIRT628988	hsa-miR-503-5p	HITS-CLIP	23824327
MIRT666206	hsa-miR-642a-5p	HITS-CLIP	23824327
MIRT666207	hsa-miR-196a-3p	HITS-CLIP	23824327
MIRT666208	hsa-miR-4469	HITS-CLIP	23824327
MIRT666209	hsa-miR-372-5p	HITS-CLIP	23824327
MIRT666210	hsa-miR-371a-5p	HITS-CLIP	23824327
MIRT666211	hsa-miR-2276-5p	HITS-CLIP	23824327
MIRT666212	hsa-miR-6892-3p	HITS-CLIP	23824327
MIRT699167	hsa-miR-106a-3p	HITS-CLIP	23313552
MIRT699168	hsa-miR-937-5p	HITS-CLIP	23313552
MIRT699169	hsa-miR-505-3p	HITS-CLIP	23313552
MIRT699170	hsa-miR-5702	HITS-CLIP	23313552
MIRT699171	hsa-miR-203a-3p	HITS-CLIP	23313552
MIRT699172	hsa-miR-1324	HITS-CLIP	23313552
MIRT699173	hsa-miR-5680	HITS-CLIP	23313552
MIRT699174	hsa-miR-548g-3p	HITS-CLIP	23313552
MIRT699175	hsa-miR-548av-3p	HITS-CLIP	23313552
MIRT724464	hsa-miR-374a-3p	HITS-CLIP	19536157
MIRT724465	hsa-miR-5089-3p	HITS-CLIP	19536157
MIRT724466	hsa-miR-361-5p	HITS-CLIP	19536157
MIRT724467	hsa-miR-6744-3p	HITS-CLIP	19536157
MIRT724468	hsa-miR-4757-5p	HITS-CLIP	19536157
MIRT724469	hsa-miR-4502	HITS-CLIP	19536157
MIRT724470	hsa-miR-2115-3p	HITS-CLIP	19536157
MIRT726493	hsa-miR-27a-3p	HITS-CLIP	22473208
MIRT726493	hsa-miR-27a-3p	Luciferase reporter assay, qRT-PCR, Western blot	28370334
MIRT726494	hsa-miR-27b-3p	HITS-CLIP	22473208
MIRT726494	hsa-miR-27b-3p	Luciferase reporter assay, Western blot	28095798
MIRT731256	hsa-miR-323a-3p	Immunoprecipitaion, Luciferase reporter assay, Western blot	26908446
MIRT731256	hsa-miR-323a-3p	qRT-PCR	27059796
MIRT731928	hsa-miR-128-3p	Luciferase reporter assay	27087048
MIRT732219	hsa-miR-425-5p	Luciferase reporter assay, qRT-PCR, Western blot	26674378
MIRT732557	hsa-miR-486-5p	Luciferase reporter assay, qRT-PCR, Western blot	26370615
MIRT732612	hsa-miR-206	Luciferase reporter assay	27014911
MIRT733758	hsa-miR-503-3p	Luciferase reporter assay, qRT-PCR, Western blot	28161325
MIRT733877	hsa-miR-15b-5p	Western blot	27499071
MIRT734288	hsa-miR-205-5p	Luciferase reporter assay, qRT-PCR, Western blot	27574009
MIRT735098	hsa-miR-125a-5p	Luciferase reporter assay	27388239
MIRT735099	hsa-miR-145-5p	Luciferase reporter assay	27388239
MIRT735157	hsa-miR-212-3p	GFP reporter assay, qRT-PCR, Western blot	25988335
MIRT735158	hsa-miR-132-3p	GFP reporter assay, qRT-PCR, Western blot	25988335
MIRT760967	hsa-let-7a-3p	PAR-CLIP	27292025
MIRT760980	hsa-let-7b-3p	PAR-CLIP	27292025
MIRT761025	hsa-let-7f-1-3p	PAR-CLIP	27292025
MIRT761027	hsa-let-7f-2-3p	PAR-CLIP	27292025
MIRT761205	hsa-miR-1185-1-3p	PAR-CLIP	27292025
MIRT761207	hsa-miR-1185-2-3p	PAR-CLIP	27292025
MIRT761744	hsa-miR-1266-3p	PAR-CLIP	27292025
MIRT761761	hsa-miR-1267	PAR-CLIP	27292025
MIRT764400	hsa-miR-300	PAR-CLIP	27292025
MIRT767547	hsa-miR-381-3p	PAR-CLIP	27292025
MIRT770827	hsa-miR-4666a-3p	PAR-CLIP	27292025
MIRT772346	hsa-miR-4789-5p	PAR-CLIP	27292025
MIRT781534	hsa-miR-7152-5p	PAR-CLIP	27292025
MIRT782981	hsa-miR-944	PAR-CLIP	27292025
MIRT783007	hsa-miR-98-3p	PAR-CLIP	27292025

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	TAS
GO:0000785	Component	Chromatin	IDA	21828274
GO:0000785	Component	Chromatin	ISA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA	21873635
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA	9389648, 31582430
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA	21873635
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0000987	Function	Cis-regulatory region sequence-specific DNA binding	IC	21828274
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IDA	9389648, 31582430
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	ISS	24964035
GO:0001657	Process	Ureteric bud development	IEA
GO:0001701	Process	In utero embryonic development	IEA
GO:0001706	Process	Endoderm formation	IEA
GO:0001707	Process	Mesoderm formation	ISS
GO:0003677	Function	DNA binding	IDA	9389648
GO:0003682	Function	Chromatin binding	IEA
GO:0003690	Function	Double-stranded DNA binding	ISS
GO:0003700	Function	DNA-binding transcription factor activity	IDA	9389648
GO:0003700	Function	DNA-binding transcription factor activity	IDA	17438144
GO:0005160	Function	Transforming growth factor beta receptor binding	IPI	9311995
GO:0005515	Function	Protein binding	IPI	9389648, 9702198, 9865696, 9892009, 10615055, 11278756, 11387212, 12764135, 15107821, 15231748, 15350224, 15647271, 16200078, 16751101, 17099224, 17292623, 18268325, 18511908, 18568018, 18729074, 18832382, 18923419, 19032343, 19049980, 19122240, 19135894, 19289081, 19345189, 2006138
GO:0005634	Component	Nucleus	IDA	8980228, 9311995, 9389648, 12411310, 16751101, 21145499, 21599657, 25893292
GO:0005654	Component	Nucleoplasm	TAS
GO:0005667	Component	Transcription regulator complex	IDA	17438144
GO:0005737	Component	Cytoplasm	IDA	9311995, 9389648, 12411310, 21145499
GO:0005829	Component	Cytosol	TAS
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA	21873635
GO:0007179	Process	Transforming growth factor beta receptor signaling pathway	IBA	21873635
GO:0007179	Process	Transforming growth factor beta receptor signaling pathway	IDA	8752209, 9389648, 9732876, 18548003
GO:0007179	Process	Transforming growth factor beta receptor signaling pathway	IMP	8980228
GO:0007179	Process	Transforming growth factor beta receptor signaling pathway	TAS
GO:0007182	Process	Common-partner SMAD protein phosphorylation	IDA	16806156
GO:0007183	Process	SMAD protein complex assembly	IDA	9111321
GO:0007352	Process	Zygotic specification of dorsal/ventral axis	IMP	9436979
GO:0007369	Process	Gastrulation	TAS	19018011
GO:0008134	Function	Transcription factor binding	IPI	9702198
GO:0008285	Process	Negative regulation of cell population proliferation	IEA
GO:0009653	Process	Anatomical structure morphogenesis	IBA	21873635
GO:0009749	Process	Response to glucose	IEA
GO:0009791	Process	Post-embryonic development	IEA
GO:0009952	Process	Anterior/posterior pattern specification	ISS
GO:0010718	Process	Positive regulation of epithelial to mesenchymal transition	ISS
GO:0016579	Process	Protein deubiquitination	TAS
GO:0017015	Process	Regulation of transforming growth factor beta receptor signaling pathway	IMP	14555988
GO:0019902	Function	Phosphatase binding	IPI	16751101
GO:0023019	Process	Signal transduction involved in regulation of gene expression	IEA
GO:0030073	Process	Insulin secretion	IEA
GO:0030154	Process	Cell differentiation	IBA	21873635
GO:0030324	Process	Lung development	IEA
GO:0030325	Process	Adrenal gland development	IEA
GO:0030509	Process	BMP signaling pathway	IBA	21873635
GO:0030512	Process	Negative regulation of transforming growth factor beta receptor signaling pathway	TAS
GO:0030513	Process	Positive regulation of BMP signaling pathway	IMP	19366699
GO:0031016	Process	Pancreas development	IEA
GO:0031053	Process	Primary miRNA processing	TAS	19018011
GO:0031625	Function	Ubiquitin protein ligase binding	IPI	19122240
GO:0032444	Component	Activin responsive factor complex	IDA	9389648
GO:0032924	Process	Activin receptor signaling pathway	IMP	15150278
GO:0032991	Component	Protein-containing complex	IMP	15231848
GO:0033613	Function	Activating transcription factor binding	IPI	11160896
GO:0034713	Function	Type I transforming growth factor beta receptor binding	IPI	8980228
GO:0035019	Process	Somatic stem cell population maintenance	TAS
GO:0035265	Process	Organ growth	IEA
GO:0035556	Process	Intracellular signal transduction	ISS
GO:0038092	Process	Nodal signaling pathway	IMP	15150278
GO:0042060	Process	Wound healing	IEA
GO:0045165	Process	Cell fate commitment	ISS
GO:0045892	Process	Negative regulation of transcription, DNA-templated	IMP	14555988
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IDA	9311995, 9389648, 9732876
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IMP	14555988
GO:0045893	Process	Positive regulation of transcription, DNA-templated	ISS
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	9389648
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	ISS
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	TAS
GO:0046332	Function	SMAD binding	IPI	11160896
GO:0046872	Function	Metal ion binding	IEA
GO:0048156	Function	Tau protein binding	ISS	24964035
GO:0048340	Process	Paraxial mesoderm morphogenesis	ISS
GO:0048617	Process	Embryonic foregut morphogenesis	IEA
GO:0048701	Process	Embryonic cranial skeleton morphogenesis	IEA
GO:0051098	Process	Regulation of binding	ISS
GO:0060039	Process	Pericardium development	IEA
GO:0060395	Process	SMAD protein signal transduction	IBA	21873635
GO:0062009	Process	Secondary palate development	ISS
GO:0070410	Function	Co-SMAD binding	IPI	9111321, 9311995
GO:0070411	Function	I-SMAD binding	IBA	21873635
GO:0070411	Function	I-SMAD binding	IPI	9256479
GO:0070412	Function	R-SMAD binding	IPI	9311995
GO:0070723	Process	Response to cholesterol	IDA	17878231
GO:0071141	Component	SMAD protein complex	IDA	18832382
GO:0071144	Component	Heteromeric SMAD protein complex	IBA	21873635
GO:0071144	Component	Heteromeric SMAD protein complex	IDA	21828274
GO:0097718	Function	Disordered domain specific binding	IPI	15231848
GO:1900224	Process	Positive regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry	IMP	17239842

Other IDs

• MIM: 601366
• HGNC: 6768
• e!Ensembl: ENSG00000175387

Protein

• UniProt ID: Q15796
• Protein name: Mothers against decapentaplegic homolog 2 (MAD homolog 2) (Mothers against DPP homolog 2) (JV18-1) (Mad-related protein 2) (hMAD-2) (SMAD family member 2) (SMAD 2) (Smad2) (hSMAD2)
• Protein 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.
• PDB: 1DEV, 1KHX, 1U7V, 2LB3, 5XOD, 5ZOJ, 6M64, 7CO1
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF03165	MH1	41 → 171	MH1 domain	Domain
  PF03166	MH2	272 → 443	MH2 domain	Family

• Sequence:

  MSSILPFTPPVVKRLLGWKKSAGGSGGAGGGEQNGQEEKWCEKAVKSLVKKLKKTGRLDE
  LEKAITTQNCNTKCVTIPSTCSEIWGLSTPNTIDQWDTTGLYSFSEQTRSLDGRLQVSHR
  KGLPHVIYCRLWRWPDLHSHHELKAIENCEYAFNLKKDEVCVNPYHYQRVETPVLPPVLV
  PRHTEILTELPPLDDYTHSIPENTNFPAGIEPQSNYIPETPPPGYISEDGETSDQQLNQS
  MDTGSPAELSPTTLSPVNHSLDLQPVTYSEPAFWCSIAYYELNQRVGETFHASQPSLTVD
  GFTDPSNSERFCLGLLSNVNRNATVEMTRRHIGRGVRLYYIGGEVFAECLSDSAIFVQSP
  NCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLAQSVNQGFEAVYQLTRMCTIRMSFVK
  GWGAEYRRQTVTSTPCWIELHLNGPLQWLDKVLTQMGSPSVRCSSMS

• Sequence length: 467