Mothers against decapentaplegic homolog 2

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Alternative products

Sequence annotation (Features)

Sequences

References

Cross-references

Entry information

Relevant documents

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Alternative products

Sequence annotation (Features)

Sequences

References

Cross-references

Entry information

Relevant documents

Molecule processing

Regions

Amino acid modifications

Natural variations

Experimental info

Molecule processing

Regions

Amino acid modifications

Natural variations

Experimental info

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Protein names

Recommended name:
    Mothers against decapentaplegic homolog 2
      Short name=Mothers against DPP homolog 2
      Short name=MAD homolog 2
Alternative name(s):
    Mad-related protein 2
      Short name=mMad2
    SMAD 2

Gene names

Name:	Smad2
Synonyms:	Madh2, Madr2

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

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Sequence length	467 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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Function	Transcriptional modulator activated by TGF-beta and activin type 1 receptor kinase. SMAD2 is a receptor-regulated SMAD (R-SMAD). Required for gastrulation.
Subunit structure	Found in a complex with SMAD3 and TRIM33 upon addition of TGF-beta. Interacts with SMAD3 and TRIM33. Interacts with SARA (SMAD anchor for receptor activation); may form trimers with the SMAD4 co-SMAD. Interacts with FOXH1, homeobox protein TGIF, PEBP2-alpha subunit, CREB-binding protein (CBP), EP300 and SKI. Interacts with SNON; when phosphorylated at Ser-465/467. Interacts (via PY-motif) with SMURF2. Interacts with LBXCOR1 and CORL2. Interacts with PRDM16. Interacts (via MH2 domain) with LEMD3. Interacts with RBPMS; the interaction is direct By similarity. Interacts with AIP1 and HGS. Interacts with NEDD4L in response to TGF-beta. Ref.9 Ref.10 Ref.11
Subcellular location	Cytoplasm. Nucleus. Note: Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with SMAD4.
Post-translational modification	In response to TGF-beta, phosphorylated on Ser-465/467 by TGF-beta and activin type 1 receptor kinases. 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 By similarity. Ref.8 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 By similarity. Ref.8 In response to TGF-beta, ubiquitinated by NEDD4L; which promotes its degradation. Acetylated on Lys-19 by coactivators in response to TGF-beta signaling, which increases transcriptional activity By similarity.
Sequence similarities	Belongs to the dwarfin/SMAD family. Contains 1 MH1 (MAD homology 1) domain. Contains 1 MH2 (MAD homology 2) domain.

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Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
PTM	Acetylation Phosphoprotein Ubl conjugation
Gene Ontology (GO)
Biological process	anterior/posterior pattern formation Inferred from mutant phenotype. Source: MGI cell fate commitment Inferred from mutant phenotype. Source: MGI developmental growth Inferred from genetic interaction. Source: MGI embryonic cranial skeleton morphogenesis Inferred from genetic interaction. Source: MGI embryonic foregut morphogenesis Inferred from genetic interaction. Source: MGI endoderm development Inferred from genetic interaction. Source: MGI heart development Inferred from genetic interaction. Source: MGI in utero embryonic development Inferred from mutant phenotype. Source: MGI insulin secretion Inferred from genetic interaction. Source: MGI intracellular signaling cascade Inferred from direct assay. Source: MGI lung development Inferred from genetic interaction. Source: MGI mesoderm formation Inferred from mutant phenotype. Source: MGI organ growth Inferred from genetic interaction. Source: MGI palate development Inferred from mutant phenotype. Source: UniProtKB pancreas development Inferred from genetic interaction. Source: MGI paraxial mesoderm morphogenesis Inferred from mutant phenotype. Source: MGI pericardium development Inferred from genetic interaction. Source: MGI positive regulation of epithelial to mesenchymal transition Inferred from mutant phenotype. Source: UniProtKB positive regulation of gene-specific transcription Inferred from mutant phenotype. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay. Source: MGI post-embryonic development Inferred from genetic interaction. Source: MGI protein amino acid phosphorylation Inferred from direct assay. Source: MGI regulation of binding Inferred from direct assay. Source: MGI response to glucose stimulus Inferred from genetic interaction. Source: MGI transcription Inferred from electronic annotation. Source: UniProtKB-KW transforming growth factor beta receptor signaling pathway Inferred from direct assay. Source: MGI ureteric bud development Inferred from expression pattern. Source: UniProtKB
Cellular component	cytoplasm Inferred from direct assay. Source: UniProtKB
Molecular function	chromatin binding Inferred from direct assay. Source: MGI double-stranded DNA binding Inferred from direct assay. Source: MGI transcription activator activity Inferred from direct assay. Source: MGI transcription factor activity Inferred from electronic annotation. Source: InterPro transcription factor binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

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Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Initiator methionine

1

Removed By similarity

Chain

2 – 467

466

Mothers against decapentaplegic homolog 2

PRO_0000090853

Domain

10 – 176

167

MH1

Domain

274 – 467

194

MH2

Motif

221 – 225

5

PY-motif By similarity

Modified residue

2

1

N-acetylserine By similarity

Modified residue

8

1

Phosphothreonine By similarity

Modified residue

19

1

N6-acetyllysine By similarity

Modified residue

240

1

Phosphoserine; by CAMK2 By similarity

Modified residue

458

1

Phosphoserine By similarity

Modified residue

465

1

Phosphoserine Ref.8

Modified residue

467

1

Phosphoserine Ref.8

Alternative sequence

79 – 108

30

Missing in isoform Short.

VSP_021571

Sequence conflict

42

1

E → Q Ref.1

Sequence conflict

42

1

E → Q Ref.2

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Sequence		Length	Mass (Da)
Isoform Long [UniParc]. Last modified November 14, 2006. Version 2. Checksum: 31A2A36D463DB3E9 Show »	FASTA	467	52,266
10 20 30 40 50 60 MSSILPFTPP VVKRLLGWKK SAGGSGGAGG GEQNGQEEKW CEKAVKSLVK KLKKTGRLDE 70 80 90 100 110 120 LEKAITTQNC NTKCVTIPST CSEIWGLSTA NTVDQWDTTG LYSFSEQTRS LDGRLQVSHR 130 140 150 160 170 180 KGLPHVIYCR LWRWPDLHSH HELKAIENCE YAFNLKKDEV CVNPYHYQRV ETPVLPPVLV 190 200 210 220 230 240 PRHTEILTEL PPLDDYTHSI PENTNFPAGI EPQSNYIPET PPPGYISEDG ETSDQQLNQS 250 260 270 280 290 300 MDTGSPAELS PTTLSPVNHS LDLQPVTYSE PAFWCSIAYY ELNQRVGETF HASQPSLTVD 310 320 330 340 350 360 GFTDPSNSER FCLGLLSNVN RNATVEMTRR HIGRGVRLYY IGGEVFAECL SDSAIFVQSP 370 380 390 400 410 420 NCNQRYGWHP ATVCKIPPGC NLKIFNNQEF AALLAQSVNQ GFEAVYQLTR MCTIRMSFVK 430 440 450 460 GWGAEYRRQT VTSTPCWIEL HLNGPLQWLD KVLTQMGSPS VRCSSMS « Hide
Isoform Short (Deltaexon3). Checksum: 0E2FF38B009D2F9E Show »	FASTA	437	48,956
10 20 30 40 50 60 MSSILPFTPP VVKRLLGWKK SAGGSGGAGG GEQNGQEEKW CEKAVKSLVK KLKKTGRLDE 70 80 90 100 110 120 LEKAITTQNC NTKCVTIPRS LDGRLQVSHR KGLPHVIYCR LWRWPDLHSH HELKAIENCE 130 140 150 160 170 180 YAFNLKKDEV CVNPYHYQRV ETPVLPPVLV PRHTEILTEL PPLDDYTHSI PENTNFPAGI 190 200 210 220 230 240 EPQSNYIPET PPPGYISEDG ETSDQQLNQS MDTGSPAELS PTTLSPVNHS LDLQPVTYSE 250 260 270 280 290 300 PAFWCSIAYY ELNQRVGETF HASQPSLTVD GFTDPSNSER FCLGLLSNVN RNATVEMTRR 310 320 330 340 350 360 HIGRGVRLYY IGGEVFAECL SDSAIFVQSP NCNQRYGWHP ATVCKIPPGC NLKIFNNQEF 370 380 390 400 410 420 AALLAQSVNQ GFEAVYQLTR MCTIRMSFVK GWGAEYRRQT VTSTPCWIEL HLNGPLQWLD 430 KVLTQMGSPS VRCSSMS « Hide

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	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel mesoderm inducer, Madr2, functions in the activin signal transduction pathway." Baker J.C., Harland R.M. Genes Dev. 10:1880-1889(1996) [PubMed: 8756346] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG). Strain: 129/Sv.
[2]	"Smad4 (homolog of human DPC4) and Smad2 (homolog of human JV18-1): candidates for murine lung tumor resistance and suppressor genes." Devereux T.R., Anna C.H., Patel A.C., White C.M., Festing M.F., You M. Carcinogenesis 18:1751-1755(1997) [PubMed: 9328171] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG). Strain: A/J and BALB/c.
[3]	"Both SMAD2 and SMAD3 mediate activin-stimulated expression of the follicle-stimulating hormone beta subunit in mouse gonadotrope cells." Bernard D.J. Mol. Endocrinol. 18:606-623(2004) [PubMed: 14701940] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT).
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). Strain: C57BL/6J. Tissue: Pancreas.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
[6]	"Functions of mammalian Smad genes as revealed by targeted gene disruption in mice." Weinstein M., Yang X., Deng C.-X. Cytokine Growth Factor Rev. 11:49-58(2000) [PubMed: 10708952] [Abstract] Cited for: REVIEW.
[7]	"Mice exclusively expressing the short isoform of Smad2 develop normally and are viable and fertile." Dunn N.R., Koonce C.H., Anderson D.C., Islam A., Bikoff E.K., Robertson E.J. Genes Dev. 19:152-163(2005) [PubMed: 15630024] [Abstract] Cited for: ALTERNATIVE SPLICING (ISOFORM SHORT).
[8]	"Transforming growth factor-beta 1 inhibits non-pathogenic Gram negative bacteria-induced NF-kappa B recruitment to the interleukin-6 gene promoter in intestinal epithelial cells through modulation of histone acetylation." Haller D., Holt L., Kim S.C., Schwabe R.F., Sartor R.B., Jobin C. J. Biol. Chem. 278:23851-23860(2003) [PubMed: 12672795] [Abstract] Cited for: PHOSPHORYLATION AT SER-465 AND SER-467.
[9]	"Identification and characterization of a PDZ protein that interacts with activin types II receptors." Shoji H., Tsuchida K., Kishi H., Yamakawa N., Matsuzaki T., Liu Z., Nakamura T., Sugino H. J. Biol. Chem. 275:5485-5492(2000) [PubMed: 10681527] [Abstract] Cited for: INTERACTION WITH AIP1.
[10]	"Hgs (Hrs), a FYVE domain protein, is involved in Smad signaling through cooperation with SARA." Miura S., Takeshita T., Asao H., Kimura Y., Murata K., Sasaki Y., Hanai J., Beppu H., Tsukazaki T., Wrana J.L., Miyazono K., Sugamura K. Mol. Cell. Biol. 20:9346-9355(2000) [PubMed: 11094085] [Abstract] Cited for: INTERACTION WITH HGS.
[11]	"NEDD4-2 (neural precursor cell expressed, developmentally down-regulated 4-2) negatively regulates TGF-beta (transforming growth factor-beta) signalling by inducing ubiquitin-mediated degradation of Smad2 and TGF-beta type I receptor." Kuratomi G., Komuro A., Goto K., Shinozaki M., Miyazawa K., Miyazono K., Imamura T. Biochem. J. 386:461-470(2005) [PubMed: 15496141] [Abstract] Cited for: INTERACTION WITH NEDD4L, UBIQUITINATION.
+	Additional computationally mapped references.

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Sequence databases
EMBL GenBank DDBJ	U60530 mRNA. Translation: AAB03612.1. AF005743 mRNA. Translation: AAB62269.1. AK007817 mRNA. Translation: BAB25282.1. AY334552 mRNA. Translation: AAR00933.1. BC021342 mRNA. Translation: AAH21342.1. BC089184 mRNA. Translation: AAH89184.1.
IPI	IPI00458087. IPI00556692.
RefSeq	NP_034884.2.
UniGene	Mm.391091
3D structure databases
SMR	Q62432. Positions 7-172, 265-467.
ModBase	Search...
Protein-protein interaction databases
STRING	Q62432.
PTM databases
PhosphoSite	Q62432.
Proteomic databases
PRIDE	Q62432.
Genome annotation databases
Ensembl	ENSMUST00000025453; ENSMUSP00000025453; ENSMUSG00000024563; Mus musculus. [Genome view] ENSMUST00000091831; ENSMUSP00000089439; ENSMUSG00000024563; Mus musculus. [Genome view]
GeneID	17126.
KEGG	mmu:17126.
UCSC	uc008fqn.1. mouse. uc008fqo.1. mouse.
Organism-specific databases
CTD	17126.
MGI	MGI:108051. Smad2.
Phylogenomic databases
eggNOG	roNOG12697.
HOGENOM	HBG443554.
HOVERGEN	Q62432.
InParanoid	Q62432.
OMA	WKKSASG.
OrthoDB	EOG9DRCZ7.
PhylomeDB	Q62432.
Gene expression databases
ArrayExpress	Q62432.
Bgee	Q62432.
CleanEx	MM_SMAD2.
Genevestigator	Q62432.
GermOnline	ENSMUSG00000024563. Mus musculus.
Family and domain databases
InterPro	IPR013790. Dwarfin. IPR003619. MAD_homology1_Dwarfin-type. IPR013019. MAD_homology_MH1. IPR017855. SMAD_dom-like. IPR001132. SMAD_dom_Dwarfin-type. IPR008984. SMAD_FHA_domain. [Graphical view]
Gene3D	G3DSA:3.90.520.10. MAD_MH1. 1 hit. G3DSA:2.60.200.10. MH2_Dwarfin-type. 1 hit.
PANTHER	PTHR13703. Dwarfin. 1 hit.
Pfam	PF03165. MH1. 1 hit. PF03166. MH2. 1 hit. [Graphical view]
SMART	SM00523. DWA. 1 hit. SM00524. DWB. 1 hit. [Graphical view]
PROSITE	PS51075. MH1. 1 hit. PS51076. MH2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	291308.
SOURCE	Search...

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Entry name

SMAD2_MOUSE

Accession

Primary (citable) accession number: Q62432
Secondary accession number(s): Q6GU18, Q6VP00, Q9D8P6

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	November 14, 2006
Last modified:	February 9, 2010
This is version 108 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: mRNA corresponding to the isoform Long is approximately 20-fold more abundant. Both forms are coexpressed throughout mouse development.

Isoform Long (identifier: Q62432-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Short (identifier: Q62432-2)

Also known as: Deltaexon3;

The sequence of this isoform differs from the canonical sequence as follows:
79-108: Missing.