Q62432 (SMAD2_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified April 16, 2014. Version 147. 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||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|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. Ref.7
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 SKOR1 and SKOR2. Interacts with PRDM16. Interacts (via MH2 domain) with LEMD3. Interacts with RBPMS. 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 By similarity. Interacts with NEDD4L in response to TGF-beta. Interacts with WWP1, AIP1 and HGS. 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. Ref.7 Ref.8 Ref.11 Ref.12 Ref.13 Ref.14
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. Ref.14
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. Ref.7 Ref.10
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.
|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:
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_0000090853|
|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|
|Alternative sequence||79 – 108||30||Missing in isoform Short.||VSP_021571|
|Sequence conflict||42||1||E → Q in AAB03612. Ref.1|
|Sequence conflict||42||1||E → Q in AAB62269. Ref.2|
|||"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
|||"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
Strain: A/J and BALB/c.
|||"Both SMAD2 and SMAD3 mediate activin-stimulated expression of the follicle-stimulating hormone beta subunit in mouse gonadotrope cells."|
Mol. Endocrinol. 18:606-623(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT).
|||"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
|||"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] (ISOFORM LONG).
|||"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] [Europe PMC] [Abstract]
Cited for: REVIEW.
|||"Cytoplasmic PML function in TGF-beta signalling."|
Lin H.K., Bergmann S., Pandolfi P.P.
Nature 431:205-211(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION, INTERACTION WITH PML AND ZFYVE9/SARA.
|||"Negative regulation of transforming growth factor-beta (TGF-beta) signaling by WW domain-containing protein 1 (WWP1)."|
Komuro A., Imamura T., Saitoh M., Yoshida Y., Yamori T., Miyazono K., Miyazawa K.
Oncogene 23:6914-6923(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH WWP1.
|||"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] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORM SHORT).
|||"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-465 AND SER-467.
|||"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AIP1.
|||"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HGS.
|||"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NEDD4L, UBIQUITINATION.
|||"Protein phosphatase 5 modulates SMAD3 function in the transforming growth factor-? pathway."|
Bruce D.L., Macartney T., Yong W., Shou W., Sapkota G.P.
Cell. Signal. 24:1999-2006(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PPP5C, SUBCELLULAR LOCATION.
|+||Additional computationally mapped references.|
|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.
|RefSeq||NP_001239410.1. NM_001252481.1. |
3D structure databases
|SMR||Q62432. Positions 7-172, 265-467. |
Protein-protein interaction databases
|BioGrid||201275. 35 interactions.|
|IntAct||Q62432. 4 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000025453; ENSMUSP00000025453; ENSMUSG00000024563. [Q62432-1]|
ENSMUST00000091831; ENSMUSP00000089439; ENSMUSG00000024563. [Q62432-2]
ENSMUST00000168423; ENSMUSP00000130115; ENSMUSG00000024563. [Q62432-1]
|UCSC||uc008fqn.2. mouse. [Q62432-1]|
uc008fqo.2. mouse. [Q62432-2]
|MGI||MGI:108051. 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: Q62432|
Secondary accession number(s): Q6GU18, Q6VP00, Q9D8P6
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|