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Q15796 (SMAD2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 167. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·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):
JV18-1
Mad-related protein 2
Short name=hMAD-2
SMAD family member 2
Short name=SMAD 2
Short name=Smad2
Short name=hSMAD2
Gene names
Name:SMAD2
Synonyms:MADH2, MADR2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

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. Ref.15 Ref.24 Ref.28 Ref.30 Ref.35

Subunit structure

Momomer; the absence of TGF-beta. Heterodimer; in the presence of TGF-beta. Forms a heterodimer with co-SMAD, SMAD4, in the nucleus to form the transactivation complex SMAD2/SMAD4. Interacts with AIP1, HGS, PML and WWP1 By similarity. Interacts with NEDD4L in response to TGF-beta 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 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 PDPK1 (via PH domain). Interacts with DAB2; the interactions are enhanced upon TGF-beta stimulation. Interacts with USP15. Interacts with PPP5C. Interacts with ZNF580. Ref.8 Ref.9 Ref.10 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.27 Ref.28 Ref.29 Ref.32 Ref.35 Ref.36 Ref.39 Ref.40 Ref.41 Ref.49 Ref.50

Subcellular location

Cytoplasm. Nucleus. 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. Ref.9 Ref.24 Ref.35 Ref.39 Ref.41

Tissue specificity

Expressed at high levels in skeletal muscle, endothelial cells, heart and placenta. Ref.39

Post-translational modification

Phosphorylated on one or several of Thr-220, Ser-245, Ser-250, and Ser-255. In response to TGF-beta, phosphorylated on Ser-465/467 by TGF-beta and activin type 1 receptor kinases. TGF-beta-induced Ser-465/467 phosphorylation declines progressively in a SETD8-dependent manner. 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. Phosphorylated by PDPK1. Ref.3 Ref.8 Ref.12 Ref.13 Ref.19 Ref.20 Ref.24 Ref.28 Ref.44

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

Acetylated on Lys-19 by coactivators in response to TGF-beta signaling, which increases transcriptional activity. Isoform short:Acetylation increases DNA binding activity in vitro and enhances its association with target promoters in vivo. Acetylation in the nucleus by EP300 is enhanced by TGF-beta. Ref.7 Ref.26 Ref.30

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
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandDNA-binding
Metal-binding
Zinc
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processSMAD protein complex assembly

Inferred from direct assay PubMed 9111321. Source: BHF-UCL

activin receptor signaling pathway

Inferred from mutant phenotype PubMed 15150278. Source: BHF-UCL

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 direct assay PubMed 16806156. Source: MGI

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

gastrulation

Traceable author statement PubMed 19018011. Source: BHF-UCL

gene expression

Traceable author statement. Source: Reactome

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 electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Traceable author statement. Source: Reactome

negative regulation of transcription, DNA-templated

Inferred from mutant phenotype PubMed 14555988. Source: BHF-UCL

negative regulation of transforming growth factor beta receptor signaling pathway

Traceable author statement. Source: Reactome

nodal signaling pathway

Inferred from mutant phenotype PubMed 15150278. Source: BHF-UCL

organ growth

Inferred from electronic annotation. Source: Ensembl

palate development

Inferred from sequence or structural similarity. Source: BHF-UCL

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 mutant phenotype PubMed 19366699. Source: BHF-UCL

positive regulation of epithelial to mesenchymal transition

Inferred from sequence or structural similarity. Source: BHF-UCL

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

Inferred from mutant phenotype PubMed 17239842. Source: BHF-UCL

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

primary miRNA processing

Traceable author statement PubMed 19018011. Source: BHF-UCL

regulation of binding

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of transforming growth factor beta receptor signaling pathway

Inferred from mutant phenotype PubMed 14555988. Source: BHF-UCL

response to cholesterol

Inferred from direct assay PubMed 17878231. Source: BHF-UCL

response to glucose

Inferred from electronic annotation. Source: Ensembl

signal transduction involved in regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

transcription initiation from RNA polymerase II promoter

Traceable author statement. Source: Reactome

transcription, DNA-templated

Traceable author statement. Source: Reactome

transforming growth factor beta receptor signaling pathway

Inferred from direct assay Ref.3Ref.4PubMed 9732876. Source: BHF-UCL

ureteric bud development

Inferred from electronic annotation. Source: Ensembl

zygotic specification of dorsal/ventral axis

Inferred from mutant phenotype PubMed 9436979. Source: BHF-UCL

   Cellular_componentSMAD protein complex

Inferred from direct assay PubMed 18832382. Source: UniProtKB

activin responsive factor complex

Inferred from direct assay Ref.4. Source: BHF-UCL

cytoplasm

Inferred from direct assay PubMed 12411310PubMed 9311995Ref.4. Source: BHF-UCL

cytosol

Traceable author statement. Source: Reactome

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.24Ref.39. Source: UniProtKB

transcription factor complex

Inferred from direct assay PubMed 17438144. Source: BHF-UCL

   Molecular_functionI-SMAD binding

Inferred from physical interaction PubMed 9256479. Source: BHF-UCL

R-SMAD binding

Inferred from physical interaction PubMed 9311995. Source: BHF-UCL

SMAD binding

Inferred from physical interaction PubMed 11160896. Source: UniProtKB

activating transcription factor binding

Inferred from physical interaction PubMed 11160896. Source: UniProtKB

chromatin binding

Inferred from electronic annotation. Source: Ensembl

co-SMAD binding

Inferred from physical interaction PubMed 9111321PubMed 9311995. Source: BHF-UCL

double-stranded DNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

phosphatase binding

Inferred from physical interaction Ref.24. Source: UniProtKB

sequence-specific DNA binding transcription factor activity

Inferred from direct assay Ref.4. Source: BHF-UCL

transcription factor binding

Inferred from physical interaction Ref.14. Source: UniProtKB

transforming growth factor beta receptor binding

Inferred from physical interaction PubMed 9311995. Source: BHF-UCL

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

Inferred from direct assay PubMed 9256479Ref.4. Source: BHF-UCL

type I transforming growth factor beta receptor binding

Inferred from physical interaction Ref.8. Source: BHF-UCL

ubiquitin protein ligase binding

Inferred from physical interaction PubMed 19122240. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Long (identifier: Q15796-1)

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: Q15796-2)

Also known as: Smad2Deltaexon3;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.7
Chain2 – 467466Mothers against decapentaplegic homolog 2
PRO_0000090852

Regions

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

Sites

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

Amino acid modifications

Modified residue21N-acetylserine Ref.7 Ref.34 Ref.37 Ref.42 Ref.43
Modified residue81Phosphothreonine; by MAPK3 Ref.20 Ref.31 Ref.37
Modified residue191N6-acetyllysine Ref.26
Modified residue2201Phosphothreonine Probable
Modified residue2401Phosphoserine; by CAMK2 Ref.19
Modified residue2451Phosphoserine Probable
Modified residue2501Phosphoserine Probable
Modified residue2551Phosphoserine Probable
Modified residue4581Phosphoserine Ref.33 Ref.37
Modified residue4601Phosphoserine Ref.37
Modified residue4641Phosphoserine
Modified residue4651Phosphoserine; by TGFBR1 Ref.12 Ref.13 Ref.44
Modified residue4671Phosphoserine; by TGFBR1 Ref.12 Ref.13 Ref.44

Natural variations

Alternative sequence79 – 10830Missing in isoform Short.
VSP_006178
Natural variant1331R → C in a colorectal carcinoma sample. Ref.3
VAR_011375
Natural variant3001D → V in a colorectal cancer sample; somatic mutation. Ref.51
VAR_036473
Natural variant344 – 35815Missing in a colorectal carcinoma sample.
VAR_011376
Natural variant4401L → R in a colorectal carcinoma sample. Ref.3
VAR_011377
Natural variant4451P → H in a colorectal carcinoma sample. Ref.3
VAR_011378
Natural variant4501D → E in a colorectal carcinoma sample. Ref.3
VAR_011379

Experimental info

Mutagenesis191K → R: Loss of acetylation. Ref.26
Mutagenesis201K → R: No effect on acetylation. Ref.26
Mutagenesis221 – 2255Missing: Loss of binding to SMURF2. Ref.18
Mutagenesis3811N → S: Loss of binding to SARA. Ref.49
Mutagenesis3981V → R: Increased binding to PPM1A. Ref.24
Mutagenesis4641S → A: Loss of phosphorylation by TGFBR1; when associated with A-465 and A-467. Ref.8
Mutagenesis465 – 4673SMS → AMA: Binds RANBP3. Ref.8 Ref.24 Ref.35
Mutagenesis465 – 4673SMS → DMD: Greatly reduced RANBP2 binding. Ref.8 Ref.24 Ref.35
Mutagenesis4651S → A: No change in binding to PPM1A. Loss of phosphorylation by TGFBR1; when associated with A-464 and A-467. Ref.8 Ref.24
Mutagenesis4651S → D: No change in binding to PPM1A. Ref.8 Ref.24
Mutagenesis4671S → A: No change in binding to PPM1A. Loss of phosphorylation by TGFBR1; when associated with A-464 and A-465. Ref.8 Ref.24
Mutagenesis4671S → D: No change in binding to PPM1A. Ref.8 Ref.24

Secondary structure

........................................... 467
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Long [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 95406DB5FC0AA4C9

FASTA46752,306
        10         20         30         40         50         60 
MSSILPFTPP VVKRLLGWKK SAGGSGGAGG GEQNGQEEKW CEKAVKSLVK KLKKTGRLDE 

        70         80         90        100        110        120 
LEKAITTQNC NTKCVTIPST CSEIWGLSTP NTIDQWDTTG 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 (Smad2Deltaexon3) [UniParc].

Checksum: 0E2FF38B009D2F9E
Show »

FASTA43748,956

References

« Hide 'large scale' references
[1]"Mad-related genes in the human."
Riggins G.J., Thiagalingam S., Rosenblum E., Weinstein C.L., Kern S.E., Hamilton S.R., Willson J.K.V., Markowitz S.D., Kinzler K.W., Vogelstein B.V.
Nat. Genet. 13:347-349(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), VARIANT 344-GLU--GLN-358 DEL.
[2]"Receptor-associated Mad homologues synergize as effectors of the TGF-beta response."
Zhang Y., Feng X.-H., Wu R.-Y., Derynck R.
Nature 383:168-172(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
Tissue: Placenta.
[3]"MADR2 maps to 18q21 and encodes a TGFbeta-regulated MAD-related protein that is functionally mutated in colorectal carcinoma."
Eppert K., Scherer S.W., Ozcelik H., Pirone R., Hoodless P., Kim H., Tsui L.-C., Bapat B., Gallinger S., Andrulis I.L., Thomsen G.H., Wrana J.L., Attisano L.
Cell 86:543-552(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), PHOSPHORYLATION BY TGFBR1, VARIANTS CYS-133; ARG-440; HIS-445 AND GLU-450.
Tissue: Kidney.
[4]"Dual role of the Smad4/DPC4 tumor suppressor in TGFbeta-inducible transcriptional complexes."
Liu F., Pouponnot C., Massague J.
Genes Dev. 11:3157-3167(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
[5]"Characterization of the MADH2/Smad2 gene, a human Mad homolog responsible for the transforming growth factor-beta and activin signal transduction pathway."
Takenoshita S., Mogi A., Nagashima M., Yang K., Yagi K., Hanyu A., Nagamachi Y., Miyazono K., Hagiwara K.
Genomics 48:1-11(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS LONG AND SHORT).
[6]"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).
Tissue: Kidney, Pancreas and Spleen.
[7]Bienvenut W.V., von Kriegsheim A., Kolch W.
Submitted (DEC-2008) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-14 AND 170-182, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Chronic myeloid leukemia cell.
[8]"MADR2 is a substrate of the TGFbeta receptor and its phosphorylation is required for nuclear accumulation and signaling."
Macias-Silva M., Abdollah S., Hoodless P.A., Pirone R., Attisano L., Wrana J.L.
Cell 87:1215-1224(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TGFBR1, PHOSPHORYLATION BY TGFBR1, MUTAGENESIS OF SER-464; SER-465 AND SER-467.
[9]"SARA, a FYVE domain protein that recruits Smad2 to the TGFbeta receptor."
Tsukazaki T., Chiang T.A., Davison A.F., Attisano L., Wrana J.L.
Cell 95:779-791(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ZFYVE9, SUBCELLULAR LOCATION.
[10]"Smad proteins exist as monomers in vivo and undergo homo- and hetero-oligomerization upon activation by serine/threonine kinase receptors."
Kawabata M., Inoue H., Hanyu A., Imamura T., Miyazono K.
EMBO J. 17:4056-4065(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[11]"Alternatively spliced variant of Smad2 lacking exon 3. Comparison with wild-type Smad2 and Smad3."
Yagi K., Goto D., Hamamoto T., Takenoshita S., Kato M., Miyazono K.
J. Biol. Chem. 274:703-709(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORMS LONG AND SHORT).
[12]"The TGF-beta family mediator Smad1 is phosphorylated directly and activated functionally by the BMP receptor kinase."
Kretzschmar M., Liu F., Hata A., Doody J., Massague J.
Genes Dev. 11:984-995(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-465 AND SER-467.
[13]"TbetaRI phosphorylation of Smad2 on Ser465 and Ser467 is required for Smad2-Smad4 complex formation and signaling."
Abdollah S., Macias-Silva M., Tsukazaki T., Hayashi H., Attisano L., Wrana J.L.
J. Biol. Chem. 272:27678-27685(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-465 AND SER-467 BY TGFBR1.
[14]"Characterization of human FAST-1, a TGF beta and activin signal transducer."
Zhou S., Zawel L., Lengauer C., Kinzler K.W., Vogelstein B.
Mol. Cell 2:121-127(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FOXH1.
Tissue: Colon adenocarcinoma.
[15]"Roles of pathway-specific and inhibitory Smads in activin receptor signaling."
Lebrun J.J., Takabe K., Chen Y., Vale W.
Mol. Endocrinol. 13:15-23(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ACVR1B, FUNCTION.
[16]"The adaptor molecule Disabled-2 links the transforming growth factor beta receptors to the Smad pathway."
Hocevar B.A., Smine A., Xu X.X., Howe P.H.
EMBO J. 20:2789-2801(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DAB2.
[17]"Ski-interacting protein interacts with Smad proteins to augment transforming growth factor-beta-dependent transcription."
Leong G.M., Subramaniam N., Figueroa J., Flanagan J.L., Hayman M.J., Eisman J.A., Kouzmenko A.P.
J. Biol. Chem. 276:18243-18248(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SNW1.
[18]"TGF-beta induces assembly of a Smad2-Smurf2 ubiquitin ligase complex that targets SnoN for degradation."
Bonni S., Wang H.R., Causing C.G., Kavsak P., Stroschein S.L., Luo K., Wrana J.L.
Nat. Cell Biol. 3:587-595(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SMURF2, MUTAGENESIS OF 221-PRO--TYR-225.
[19]"Decorin suppresses transforming growth factor-beta-induced expression of plasminogen activator inhibitor-1 in human mesangial cells through a mechanism that involves Ca2+-dependent phosphorylation of Smad2 at serine-240."
Abdel-Wahab N., Wicks S.J., Mason R.M., Chantry A.
Biochem. J. 362:643-649(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-240.
[20]"Modulation of Smad2-mediated signaling by extracellular signal-regulated kinase."
Funaba M., Zimmerman C.M., Mathews L.S.
J. Biol. Chem. 277:41361-41368(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-8; THR-220; SER-245; SER-250 AND SER-255.
[21]"MAN1, an integral protein of the inner nuclear membrane, binds Smad2 and Smad3 and antagonizes transforming growth factor-beta signaling."
Lin F., Morrison J.M., Wu W., Worman H.J.
Hum. Mol. Genet. 14:437-445(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LEMD3.
[22]"The integral inner nuclear membrane protein MAN1 physically interacts with the R-Smad proteins to repress signaling by the transforming growth factor-{beta} superfamily of cytokines."
Pan D., Estevez-Salmeron L.D., Stroschein S.L., Zhu X., He J., Zhou S., Luo K.
J. Biol. Chem. 280:15992-16001(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LEMD3.
[23]"Cloning and functional characterization of a new Ski homolog, Fussel-18, specifically expressed in neuronal tissues."
Arndt S., Poser I., Schubert T., Moser M., Bosserhoff A.-K.
Lab. Invest. 85:1330-1341(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SKOR2.
[24]"PPM1A functions as a Smad phosphatase to terminate TGFbeta signaling."
Lin X., Duan X., Liang Y.Y., Su Y., Wrighton K.H., Long J., Hu M., Davis C.M., Wang J., Brunicardi F.C., Shi Y., Chen Y.G., Meng A., Feng X.H.
Cell 125:915-928(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PPM1A, DEPHOSPHORYLATION, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF VAL-398; SER-465 AND SER-467.
[25]"Hematopoiesis controlled by distinct TIF1gamma and Smad4 branches of the TGFbeta pathway."
He W., Dorn D.C., Erdjument-Bromage H., Tempst P., Moore M.A., Massague J.
Cell 125:929-941(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH SMAD3 AND TRIM33, INTERACTION WITH TRIM33.
[26]"The DNA binding activities of Smad2 and Smad3 are regulated by coactivator-mediated acetylation."
Simonsson M., Kanduri M., Gronroos E., Heldin C.H., Ericsson J.
J. Biol. Chem. 281:39870-39880(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION AT LYS-19, MUTAGENESIS OF LYS-19 AND LYS-20.
[27]"Potentiation of Smad-mediated transcriptional activation by the RNA-binding protein RBPMS."
Sun Y., Ding L., Zhang H., Han J., Yang X., Yan J., Zhu Y., Li J., Song H., Ye Q.
Nucleic Acids Res. 34:6314-6326(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RBPMS.
[28]"3-Phosphoinositide-dependent PDK1 negatively regulates transforming growth factor-beta-induced signaling in a kinase-dependent manner through physical interaction with Smad proteins."
Seong H.A., Jung H., Kim K.T., Ha H.
J. Biol. Chem. 282:12272-12289(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION BY PDPK1, INTERACTION WITH PDPK1.
[29]"Fussel-15, a novel Ski/Sno homolog protein, antagonizes BMP signaling."
Arndt S., Poser I., Moser M., Bosserhoff A.-K.
Mol. Cell. Neurosci. 34:603-611(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SKOR1.
[30]"Smad3 is acetylated by p300/CBP to regulate its transactivation activity."
Inoue Y., Itoh Y., Abe K., Okamoto T., Daitoku H., Fukamizu A., Onozaki K., Hayashi H.
Oncogene 26:500-508(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION, FUNCTION.
[31]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-8, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[32]"TAZ controls Smad nucleocytoplasmic shuttling and regulates human embryonic stem-cell self-renewal."
Varelas X., Sakuma R., Samavarchi-Tehrani P., Peerani R., Rao B.M., Dembowy J., Yaffe M.B., Zandstra P.W., Wrana J.L.
Nat. Cell Biol. 10:837-848(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH WWTR1.
[33]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[34]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[35]"Nuclear export of Smad2 and Smad3 by RanBP3 facilitates termination of TGF-beta signaling."
Dai F., Lin X., Chang C., Feng X.H.
Dev. Cell 16:345-357(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RANBP3, SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF 465-SER--SER-467.
[36]"SKI and MEL1 cooperate to inhibit transforming growth factor-beta signal in gastric cancer cells."
Takahata M., Inoue Y., Tsuda H., Imoto I., Koinuma D., Hayashi M., Ichikura T., Yamori T., Nagasaki K., Yoshida M., Matsuoka M., Morishita K., Yuki K., Hanyu A., Miyazawa K., Inazawa J., Miyazono K., Imamura T.
J. Biol. Chem. 284:3334-3344(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PRDM16.
[37]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-8; SER-458 AND SER-460, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[38]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[39]"ZNF580, a novel C2H2 zinc-finger transcription factor, interacts with the TGF-beta signal molecule Smad2."
Luo Y., Hu W., Xu R., Hou B., Zhang L., Zhang W.
Cell Biol. Int. 35:1153-1157(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ZNF580, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[40]"USP15 is a deubiquitylating enzyme for receptor-activated SMADs."
Inui M., Manfrin A., Mamidi A., Martello G., Morsut L., Soligo S., Enzo E., Moro S., Polo S., Dupont S., Cordenonsi M., Piccolo S.
Nat. Cell Biol. 13:1368-1375(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, DEUBIQUITINATION BY USP15, DNA-BINDING, INTERACTION WITH USP15.
[41]"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.
[42]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[43]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[44]"CRL1-FBXO11 promotes Cdt2 ubiquitylation and degradation and regulates Pr-Set7/Set8-mediated cellular migration."
Abbas T., Mueller A.C., Shibata E., Keaton M., Rossi M., Dutta A.
Mol. Cell 49:1147-1158(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-465 AND SER-467.
[45]"TGF-beta signal transduction."
Massague J.
Annu. Rev. Biochem. 67:753-791(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[46]"Remarkable versatility of Smad proteins in the nucleus of transforming growth factor-beta activated cells."
Verschueren K., Huylebroeck D.
Cytokine Growth Factor Rev. 10:187-199(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[47]"The Smad pathway."
Wrana J.L., Attisano L.
Cytokine Growth Factor Rev. 11:5-13(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[48]"TGF-beta signaling by Smad proteins."
Miyazono K.
Cytokine Growth Factor Rev. 11:15-22(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[49]"Structural basis of Smad2 recognition by the Smad anchor for receptor activation."
Wu G., Chen Y.-G., Ozdamar B., Gyuricza C.A., Chong P.A., Wrana J.L., Massague J., Shi Y.
Science 287:92-97(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 261-456 IN COMPLEX WITH ZFYVE9, INTERACTION WITH SARA, MUTAGENESIS OF ASN-381.
[50]"Structural basis of heteromeric smad protein assembly in TGF-beta signaling."
Chacko B.M., Qin B.Y., Tiwari A., Shi G., Lam S., Hayward L.J., De Caestecker M., Lin K.
Mol. Cell 15:813-823(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 270-466 IN COMPLEX WITH SMAD4, SUBUNIT.
[51]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] VAL-300.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U59911 mRNA. Translation: AAC50789.1.
U68018 mRNA. Translation: AAB17087.1.
U65019 mRNA. Translation: AAB17054.1.
AF027964 mRNA. Translation: AAC51918.1.
U78733 expand/collapse EMBL AC list , U78727, U78728, U78729, U78730, U78731, U78732 Genomic DNA. Translation: AAC39657.1.
BC014840 mRNA. Translation: AAH14840.1.
BC025699 mRNA. Translation: AAH25699.1.
PIRS71797.
RefSeqNP_001003652.1. NM_001003652.3.
NP_005892.1. NM_005901.5.
XP_005258316.1. XM_005258259.1.
UniGeneHs.12253.
Hs.705764.
Hs.741342.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1DEVX-ray2.20A/C261-456[»]
1KHXX-ray1.80A241-467[»]
1U7VX-ray2.70A/C270-466[»]
2LB3NMR-B217-224[»]
ProteinModelPortalQ15796.
SMRQ15796. Positions 7-172, 265-467.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110262. 256 interactions.
DIPDIP-29716N.
IntActQ15796. 207 interactions.
MINTMINT-5006109.
STRING9606.ENSP00000262160.

PTM databases

PhosphoSiteQ15796.

Polymorphism databases

DMDM13633914.

Proteomic databases

PaxDbQ15796.
PRIDEQ15796.

Protocols and materials databases

DNASU4087.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262160; ENSP00000262160; ENSG00000175387. [Q15796-1]
ENST00000356825; ENSP00000349282; ENSG00000175387. [Q15796-2]
ENST00000402690; ENSP00000384449; ENSG00000175387. [Q15796-1]
ENST00000586040; ENSP00000466193; ENSG00000175387. [Q15796-2]
GeneID4087.
KEGGhsa:4087.
UCSCuc002lcy.4. human. [Q15796-1]
uc010xdc.3. human. [Q15796-2]

Organism-specific databases

CTD4087.
GeneCardsGC18M045357.
HGNCHGNC:6768. SMAD2.
HPACAB025507.
MIM601366. gene.
neXtProtNX_Q15796.
PharmGKBPA134959722.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG320700.
HOGENOMHOG000286018.
HOVERGENHBG053353.
InParanoidQ15796.
KOK04500.
OMAMNQSMDT.
OrthoDBEOG7W1540.
PhylomeDBQ15796.
TreeFamTF314923.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_71. Gene Expression.
SignaLinkQ15796.

Gene expression databases

ArrayExpressQ15796.
BgeeQ15796.
CleanExHS_SMAD2.
GenevestigatorQ15796.

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

ChiTaRSSMAD2. human.
EvolutionaryTraceQ15796.
GeneWikiMothers_against_decapentaplegic_homolog_2.
GenomeRNAi4087.
NextBio16020.
PROQ15796.
SOURCESearch...

Entry information

Entry nameSMAD2_HUMAN
AccessionPrimary (citable) accession number: Q15796
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 167 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM