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O70436 (SMAD2_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mothers against decapentaplegic homolog 2

Short name=MAD homolog 2
Short name=Mothers against DPP homolog 2
Alternative name(s):
Mad-related protein 2
SMAD family member 2
Short name=SMAD 2
Short name=Smad2
Gene names
Name:Smad2
Synonyms:Madh2
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length467 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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 By similarity.

Subunit structure

Momomer; the absence of TGF-beta By similarity. Interacts with ZNF580 By similarity. Heterodimer; in the presence of TGF-beta. Forms a heterodimer with co-SMAD, SMAD4, in the nucleus to form the transactivation complex SMAD2/SMAD4 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 (via PY-motif) with SMURF2. Interacts with AIP1 and HGS. Interacts with NEDD4L in response to TGF-beta. 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 PML. Interacts with PDPK1 (via PH domain). Interacts with DAB2; the interactions are enhanced upon TGF-beta stimulation. Interacts with USP15. Interacts with PPP5C By similarity.

Subcellular location

Cytoplasm By similarity. Nucleus By similarity. 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 By similarity.

Post-translational modification

In response to TGF-beta, phosphorylated on the C-terminal SXS motif by TGF-beta and activin type 1 receptor kinases, phosphorylation declines progressively in a SETD8-dependent manner. Phosphorylation in this motif is required for interaction with a number of proteins including SMURF2, SNON and SMAD4 in response to TGF-beta. Dephosphorylated in this motif by PPM1A leading to disruption of the SMAD2/3-SMAD4 complex, nuclear export and termination of the TGF-beta signaling. 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 By similarity.

In response to TGF-beta, ubiquitinated by NEDD4L; which promotes its degradation. Monoubiquitinated, leading to prevent DNA-binding. Deubiquitination by USP15 alleviates inhibition and promotes activation of TGF-beta target genes By similarity.

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.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   LigandDNA-binding
Metal-binding
Zinc
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processSMAD protein complex assembly

Inferred from electronic annotation. Source: Ensembl

anterior/posterior pattern specification

Inferred from sequence or structural similarity. Source: UniProtKB

cell fate commitment

Inferred from sequence or structural similarity. Source: UniProtKB

common-partner SMAD protein phosphorylation

Inferred from electronic annotation. Source: Ensembl

developmental growth

Inferred from electronic annotation. Source: Ensembl

embryonic cranial skeleton morphogenesis

Inferred from electronic annotation. Source: Ensembl

embryonic foregut morphogenesis

Inferred from electronic annotation. Source: Ensembl

endoderm formation

Inferred from electronic annotation. Source: Ensembl

in utero embryonic development

Inferred from electronic annotation. Source: Ensembl

insulin secretion

Inferred from electronic annotation. Source: Ensembl

intracellular signal transduction

Inferred from sequence or structural similarity. Source: UniProtKB

lung development

Inferred from electronic annotation. Source: Ensembl

mesoderm formation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell proliferation

Inferred from mutant phenotype PubMed 15987742. Source: RGD

negative regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: Ensembl

nodal signaling pathway

Inferred from electronic annotation. Source: Ensembl

organ growth

Inferred from electronic annotation. Source: Ensembl

palate development

Inferred from electronic annotation. Source: Ensembl

pancreas development

Inferred from electronic annotation. Source: Ensembl

paraxial mesoderm morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

pericardium development

Inferred from electronic annotation. Source: Ensembl

positive regulation of BMP signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of epithelial to mesenchymal transition

Inferred from electronic annotation. Source: Ensembl

positive regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

post-embryonic development

Inferred from electronic annotation. Source: Ensembl

regulation of binding

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of transforming growth factor beta receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

response to cholesterol

Inferred from electronic annotation. Source: Ensembl

response to glucose

Inferred from electronic annotation. Source: Ensembl

signal transduction involved in regulation of gene expression

Inferred from mutant phenotype PubMed 22073128. Source: BHF-UCL

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

transforming growth factor beta receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

ureteric bud development

Inferred from electronic annotation. Source: Ensembl

zygotic specification of dorsal/ventral axis

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentSMAD protein complex

Inferred from electronic annotation. Source: Ensembl

activin responsive factor complex

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay PubMed 16570350. Source: RGD

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

protein complex

Inferred from direct assay PubMed 16959941. Source: RGD

transcription factor complex

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionchromatin binding

Inferred from electronic annotation. Source: Ensembl

double-stranded DNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: InterPro

transcription factor binding

Inferred from sequence or structural similarity. Source: UniProtKB

transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Akt1P471962EBI-7948047,EBI-7204362

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 467466Mothers against decapentaplegic homolog 2
PRO_0000090854

Regions

Domain10 – 176167MH1
Domain274 – 467194MH2
Motif221 – 2255PY-motif By similarity

Sites

Metal binding741Zinc By similarity
Metal binding1491Zinc By similarity
Metal binding1611Zinc By similarity
Metal binding1661Zinc By similarity

Amino acid modifications

Modified residue21N-acetylserine By similarity
Modified residue81Phosphothreonine By similarity
Modified residue191N6-acetyllysine By similarity
Modified residue2401Phosphoserine; by CAMK2 By similarity
Modified residue4581Phosphoserine By similarity
Modified residue4601Phosphoserine By similarity
Modified residue4641Phosphoserine By similarity
Modified residue4651Phosphoserine; by TGFBR1 By similarity
Modified residue4671Phosphoserine; by TGFBR1 By similarity

Sequences

Sequence LengthMass (Da)Tools
O70436 [UniParc].

Last modified August 1, 1998. Version 1.
Checksum: 3A775444411F6619

FASTA46752,239
        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 YAFSLKKDEV 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

References

« Hide 'large scale' references
[1]"Involvement of Smad proteins in the differentiation of pancreatic AR42J cells induced by activin A."
Zhang Y.-Q., Kanzaki M., Furukawa M., Shibata H., Ozeki M., Kojima I.
Diabetologia 42:719-727(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Sprague-Dawley.
Tissue: Brain.
[2]"cDNA cloning and chromosomal mapping of rat Smad2 and Smad4 and their expression in cultured rat articular chondrocytes."
Osaki M., Tsukazaki T., Ono N., Yonekura A., Hirota Y., Miyazaki Y., Shindo H., Sonta S., Yamashita S.
Endocr. J. 46:695-701(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Molecular cloning of rat Smad2 gene."
Miyakita A., Okuno S., Watanabe T.K., Oga K., Tsuji A., Hishigaki H., Kato S., Sano A., Suto T., Nakagawa K., Nakahara Y., Haraguchi N., Higashi K.
Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Testis.
[4]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB017912 mRNA. Translation: BAA33453.1.
AF056001 mRNA. Translation: AAC12780.1.
AB010147 mRNA. Translation: BAA81909.1.
BC127497 mRNA. Translation: AAI27498.1.
RefSeqNP_001264379.1. NM_001277450.1.
NP_062064.1. NM_019191.2.
UniGeneRn.2755.

3D structure databases

ProteinModelPortalO70436.
SMRO70436. Positions 7-172, 265-467.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid248011. 2 interactions.
IntActO70436. 1 interaction.
MINTMINT-2739674.

PTM databases

PhosphoSiteO70436.

Proteomic databases

PaxDbO70436.
PRIDEO70436.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000046847; ENSRNOP00000048329; ENSRNOG00000018140.
GeneID29357.
KEGGrno:29357.

Organism-specific databases

CTD4087.
RGD3031. Smad2.

Phylogenomic databases

eggNOGNOG320700.
GeneTreeENSGT00600000084186.
HOGENOMHOG000286018.
HOVERGENHBG053353.
InParanoidO70436.
KOK04500.
OMAMNQSMDT.
OrthoDBEOG7W1540.
PhylomeDBO70436.
TreeFamTF314923.

Gene expression databases

GenevestigatorO70436.

Family and domain databases

Gene3D2.60.200.10. 1 hit.
3.90.520.10. 1 hit.
InterProIPR013790. 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]
PANTHERPTHR13703. PTHR13703. 1 hit.
PfamPF03165. MH1. 1 hit.
PF03166. MH2. 1 hit.
[Graphical view]
SMARTSM00523. DWA. 1 hit.
SM00524. DWB. 1 hit.
[Graphical view]
SUPFAMSSF49879. SSF49879. 1 hit.
SSF56366. SSF56366. 2 hits.
PROSITEPS51075. MH1. 1 hit.
PS51076. MH2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio608870.
PROO70436.

Entry information

Entry nameSMAD2_RAT
AccessionPrimary (citable) accession number: O70436
Secondary accession number(s): A0JPM1
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: August 1, 1998
Last modified: April 16, 2014
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families