O70436 (SMAD2_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified April 16, 2014. Version 130. History...
Names and origin
|Protein names||Recommended name:|
Mothers against decapentaplegic homolog 2
Short name=MAD homolog 2
Short name=Mothers against DPP homolog 2
Mad-related protein 2
SMAD family member 2
Short name=SMAD 2
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||467 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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.
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.
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.
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.
Belongs to the dwarfin/SMAD family.
Contains 1 MH1 (MAD homology 1) domain.
Contains 1 MH2 (MAD homology 2) domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Initiator methionine||1||1||Removed By similarity|
|Chain||2 – 467||466||Mothers against decapentaplegic homolog 2||PRO_0000090854|
|Domain||10 – 176||167||MH1|
|Domain||274 – 467||194||MH2|
|Motif||221 – 225||5||PY-motif By similarity|
|Metal binding||74||1||Zinc By similarity|
|Metal binding||149||1||Zinc By similarity|
|Metal binding||161||1||Zinc By similarity|
|Metal binding||166||1||Zinc By similarity|
Amino acid modifications
|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||460||1||Phosphoserine By similarity|
|Modified residue||464||1||Phosphoserine By similarity|
|Modified residue||465||1||Phosphoserine; by TGFBR1 By similarity|
|Modified residue||467||1||Phosphoserine; by TGFBR1 By similarity|
|||"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].
|||"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].
|||"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].
|||"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].
|+||Additional computationally mapped references.|
|AB017912 mRNA. Translation: BAA33453.1.|
AF056001 mRNA. Translation: AAC12780.1.
AB010147 mRNA. Translation: BAA81909.1.
BC127497 mRNA. Translation: AAI27498.1.
|RefSeq||NP_001264379.1. NM_001277450.1. |
3D structure databases
|SMR||O70436. Positions 7-172, 265-467. |
Protein-protein interaction databases
|BioGrid||248011. 2 interactions.|
|IntAct||O70436. 1 interaction.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSRNOT00000046847; ENSRNOP00000048329; ENSRNOG00000018140. |
|RGD||3031. Smad2. |
Gene expression databases
Family and domain databases
|Gene3D||184.108.40.206. 1 hit. |
3.90.520.10. 1 hit.
|InterPro||IPR013790. Dwarfin. |
|PANTHER||PTHR13703. PTHR13703. 1 hit. |
|Pfam||PF03165. MH1. 1 hit. |
PF03166. MH2. 1 hit.
|SMART||SM00523. DWA. 1 hit. |
SM00524. DWB. 1 hit.
|SUPFAM||SSF49879. SSF49879. 1 hit. |
SSF56366. SSF56366. 2 hits.
|PROSITE||PS51075. MH1. 1 hit. |
PS51076. MH2. 1 hit.
|Accession||Primary (citable) accession number: O70436|
Secondary accession number(s): A0JPM1
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families