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O70436

- SMAD2_RAT

UniProt

O70436 - SMAD2_RAT

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Protein

Mothers against decapentaplegic homolog 2

Gene

Smad2

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi74 – 741ZincBy similarity
Metal bindingi149 – 1491ZincBy similarity
Metal bindingi161 – 1611ZincBy similarity
Metal bindingi166 – 1661ZincBy similarity

GO - Molecular functioni

  1. chromatin binding Source: Ensembl
  2. double-stranded DNA binding Source: UniProtKB
  3. metal ion binding Source: UniProtKB-KW
  4. sequence-specific DNA binding transcription factor activity Source: InterPro
  5. transcription factor binding Source: UniProtKB
  6. transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity Source: Ensembl

GO - Biological processi

  1. anterior/posterior pattern specification Source: UniProtKB
  2. cell fate commitment Source: UniProtKB
  3. common-partner SMAD protein phosphorylation Source: Ensembl
  4. developmental growth Source: Ensembl
  5. embryonic cranial skeleton morphogenesis Source: Ensembl
  6. embryonic foregut morphogenesis Source: Ensembl
  7. endoderm formation Source: Ensembl
  8. insulin secretion Source: Ensembl
  9. intracellular signal transduction Source: UniProtKB
  10. in utero embryonic development Source: Ensembl
  11. lung development Source: Ensembl
  12. mesoderm formation Source: UniProtKB
  13. negative regulation of cell proliferation Source: RGD
  14. negative regulation of transcription, DNA-templated Source: Ensembl
  15. nodal signaling pathway Source: Ensembl
  16. organ growth Source: Ensembl
  17. palate development Source: Ensembl
  18. pancreas development Source: Ensembl
  19. paraxial mesoderm morphogenesis Source: UniProtKB
  20. pericardium development Source: Ensembl
  21. positive regulation of BMP signaling pathway Source: Ensembl
  22. positive regulation of epithelial to mesenchymal transition Source: Ensembl
  23. positive regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry Source: Ensembl
  24. positive regulation of transcription, DNA-templated Source: UniProtKB
  25. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  26. post-embryonic development Source: Ensembl
  27. regulation of binding Source: UniProtKB
  28. regulation of transforming growth factor beta receptor signaling pathway Source: Ensembl
  29. response to cholesterol Source: Ensembl
  30. response to glucose Source: Ensembl
  31. signal transduction involved in regulation of gene expression Source: BHF-UCL
  32. SMAD protein complex assembly Source: Ensembl
  33. transcription, DNA-templated Source: UniProtKB-KW
  34. transforming growth factor beta receptor signaling pathway Source: UniProtKB
  35. ureteric bud development Source: Ensembl
  36. zygotic specification of dorsal/ventral axis Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_194628. Signaling by Activin.
REACT_194629. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
REACT_194639. Downregulation of SMAD2/3:SMAD4 transcriptional activity.
REACT_194641. Downregulation of TGF-beta receptor signaling.
REACT_194651. SMAD2/3 MH2 Domain Mutants in Cancer.
REACT_194653. SMAD4 MH2 Domain Mutants in Cancer.
REACT_194657. TGFBR1 KD Mutants in Cancer.
REACT_194664. Signaling by NODAL.
REACT_194677. TGF-beta receptor signaling activates SMADs.
REACT_194682. SMAD2/3 Phosphorylation Motif Mutants in Cancer.
REACT_228003. Transcriptional regulation of pluripotent stem cells.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Smad2
Synonyms:Madh2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 18

Organism-specific databases

RGDi3031. Smad2.

Subcellular locationi

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).By similarity

GO - Cellular componenti

  1. activin responsive factor complex Source: Ensembl
  2. cytoplasm Source: RGD
  3. nuclear chromatin Source: Ensembl
  4. nucleus Source: UniProtKB
  5. protein complex Source: RGD
  6. SMAD2-SMAD3 protein complex Source: Ensembl
  7. transcription factor complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 467466Mothers against decapentaplegic homolog 2PRO_0000090854Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineBy similarity
Modified residuei8 – 81PhosphothreonineBy similarity
Modified residuei19 – 191N6-acetyllysineBy similarity
Modified residuei240 – 2401Phosphoserine; by CAMK2PROSITE-ProRule annotation
Modified residuei458 – 4581PhosphoserinePROSITE-ProRule annotation
Modified residuei460 – 4601PhosphoserinePROSITE-ProRule annotation
Modified residuei464 – 4641PhosphoserinePROSITE-ProRule annotation
Modified residuei465 – 4651Phosphoserine; by TGFBR1PROSITE-ProRule annotation
Modified residuei467 – 4671Phosphoserine; by TGFBR1PROSITE-ProRule annotation

Post-translational modificationi

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).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).By similarity
Acetylated on Lys-19 by coactivators in response to TGF-beta signaling, which increases transcriptional activity.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiO70436.
PRIDEiO70436.

PTM databases

PhosphoSiteiO70436.

Expressioni

Gene expression databases

GenevestigatoriO70436.

Interactioni

Subunit structurei

Momomer; the absence of TGF-beta. Interacts with ZNF580. Heterodimer; in the presence of TGF-beta. Forms a heterodimer with co-SMAD, SMAD4, in the nucleus to form the transactivation complex SMAD2/SMAD4. Found in a complex with ACVR1B, SMAD3 and TRIM33 upon addition of TGF-beta. Interacts with 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 of 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. Interacts with LDLRAD4 (via the SMAD interaction motif). Interacts (via MH2 domain) with PMEPA1 (via the SMAD interaction motif) (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Akt1P471962EBI-7948047,EBI-7204362

Protein-protein interaction databases

BioGridi248011. 2 interactions.
IntActiO70436. 1 interaction.
MINTiMINT-2739674.

Structurei

3D structure databases

ProteinModelPortaliO70436.
SMRiO70436. Positions 7-172, 265-467.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini10 – 176167MH1PROSITE-ProRule annotationAdd
BLAST
Domaini274 – 467194MH2PROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi221 – 2255PY-motifBy similarity

Sequence similaritiesi

Belongs to the dwarfin/SMAD family.Curated
Contains 1 MH1 (MAD homology 1) domain.PROSITE-ProRule annotation
Contains 1 MH2 (MAD homology 2) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG320700.
GeneTreeiENSGT00760000119091.
HOGENOMiHOG000286018.
HOVERGENiHBG053353.
InParanoidiO70436.
KOiK04500.
OMAiMNQSMDT.
OrthoDBiEOG7W1540.
PhylomeDBiO70436.
TreeFamiTF314923.

Family and domain databases

Gene3Di2.60.200.10. 1 hit.
3.90.520.10. 1 hit.
InterProiIPR013790. 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]
PANTHERiPTHR13703. PTHR13703. 1 hit.
PfamiPF03165. MH1. 1 hit.
PF03166. MH2. 1 hit.
[Graphical view]
SMARTiSM00523. DWA. 1 hit.
SM00524. DWB. 1 hit.
[Graphical view]
SUPFAMiSSF49879. SSF49879. 1 hit.
SSF56366. SSF56366. 2 hits.
PROSITEiPS51075. MH1. 1 hit.
PS51076. MH2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O70436-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MSSILPFTPP VVKRLLGWKK SAGGSGGAGG GEQNGQEEKW CEKAVKSLVK
60 70 80 90 100
KLKKTGRLDE LEKAITTQNC NTKCVTIPST CSEIWGLSTA NTVDQWDTTG
110 120 130 140 150
LYSFSEQTRS LDGRLQVSHR KGLPHVIYCR LWRWPDLHSH HELKAIENCE
160 170 180 190 200
YAFSLKKDEV CVNPYHYQRV ETPVLPPVLV PRHTEILTEL PPLDDYTHSI
210 220 230 240 250
PENTNFPAGI EPQSNYIPET PPPGYISEDG ETSDQQLNQS MDTGSPAELS
260 270 280 290 300
PTTLSPVNHS LDLQPVTYSE PAFWCSIAYY ELNQRVGETF HASQPSLTVD
310 320 330 340 350
GFTDPSNSER FCLGLLSNVN RNATVEMTRR HIGRGVRLYY IGGEVFAECL
360 370 380 390 400
SDSAIFVQSP NCNQRYGWHP ATVCKIPPGC NLKIFNNQEF AALLAQSVNQ
410 420 430 440 450
GFEAVYQLTR MCTIRMSFVK GWGAEYRRQT VTSTPCWIEL HLNGPLQWLD
460
KVLTQMGSPS VRCSSMS
Length:467
Mass (Da):52,239
Last modified:August 1, 1998 - v1
Checksum:i3A775444411F6619
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB017912 mRNA. Translation: BAA33453.1.
AF056001 mRNA. Translation: AAC12780.1.
AB010147 mRNA. Translation: BAA81909.1.
BC127497 mRNA. Translation: AAI27498.1.
RefSeqiNP_001264379.1. NM_001277450.1.
NP_062064.1. NM_019191.2.
UniGeneiRn.2755.

Genome annotation databases

EnsembliENSRNOT00000046847; ENSRNOP00000048329; ENSRNOG00000018140.
GeneIDi29357.
KEGGirno:29357.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB017912 mRNA. Translation: BAA33453.1 .
AF056001 mRNA. Translation: AAC12780.1 .
AB010147 mRNA. Translation: BAA81909.1 .
BC127497 mRNA. Translation: AAI27498.1 .
RefSeqi NP_001264379.1. NM_001277450.1.
NP_062064.1. NM_019191.2.
UniGenei Rn.2755.

3D structure databases

ProteinModelPortali O70436.
SMRi O70436. Positions 7-172, 265-467.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 248011. 2 interactions.
IntActi O70436. 1 interaction.
MINTi MINT-2739674.

PTM databases

PhosphoSitei O70436.

Proteomic databases

PaxDbi O70436.
PRIDEi O70436.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000046847 ; ENSRNOP00000048329 ; ENSRNOG00000018140 .
GeneIDi 29357.
KEGGi rno:29357.

Organism-specific databases

CTDi 4087.
RGDi 3031. Smad2.

Phylogenomic databases

eggNOGi NOG320700.
GeneTreei ENSGT00760000119091.
HOGENOMi HOG000286018.
HOVERGENi HBG053353.
InParanoidi O70436.
KOi K04500.
OMAi MNQSMDT.
OrthoDBi EOG7W1540.
PhylomeDBi O70436.
TreeFami TF314923.

Enzyme and pathway databases

Reactomei REACT_194628. Signaling by Activin.
REACT_194629. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
REACT_194639. Downregulation of SMAD2/3:SMAD4 transcriptional activity.
REACT_194641. Downregulation of TGF-beta receptor signaling.
REACT_194651. SMAD2/3 MH2 Domain Mutants in Cancer.
REACT_194653. SMAD4 MH2 Domain Mutants in Cancer.
REACT_194657. TGFBR1 KD Mutants in Cancer.
REACT_194664. Signaling by NODAL.
REACT_194677. TGF-beta receptor signaling activates SMADs.
REACT_194682. SMAD2/3 Phosphorylation Motif Mutants in Cancer.
REACT_228003. Transcriptional regulation of pluripotent stem cells.

Miscellaneous databases

NextBioi 608870.
PROi O70436.

Gene expression databases

Genevestigatori O70436.

Family and domain databases

Gene3Di 2.60.200.10. 1 hit.
3.90.520.10. 1 hit.
InterProi 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 ]
PANTHERi PTHR13703. PTHR13703. 1 hit.
Pfami PF03165. MH1. 1 hit.
PF03166. MH2. 1 hit.
[Graphical view ]
SMARTi SM00523. DWA. 1 hit.
SM00524. DWB. 1 hit.
[Graphical view ]
SUPFAMi SSF49879. SSF49879. 1 hit.
SSF56366. SSF56366. 2 hits.
PROSITEi PS51075. MH1. 1 hit.
PS51076. MH2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiSMAD2_RAT
AccessioniPrimary (citable) accession number: O70436
Secondary accession number(s): A0JPM1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: August 1, 1998
Last modified: October 29, 2014
This is version 134 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3