SubmitCancel

Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

P84022

- SMAD3_HUMAN

UniProt

P84022 - SMAD3_HUMAN

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein
Mothers against decapentaplegic homolog 3
Gene
SMAD3, MADH3
Organism
Homo sapiens (Human)
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 SMAD3/SMAD4 complex, activates transcription. Also can form a SMAD3/SMAD4/JUN/FOS complex at the AP-1/SMAD site to regulate TGF-beta-mediated transcription. Has an inhibitory effect on wound healing probably by modulating both growth and migration of primary keratinocytes and by altering the TGF-mediated chemotaxis of monocytes. This effect on wound healing appears to be hormone-sensitive. Regulator of chondrogenesis and osteogenesis and inhibits early healing of bone fractures. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.11 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei40 – 401Required for trimerization
Sitei41 – 411Required for interaction with DNA and JUN and for functional cooperation with JUN
Metal bindingi64 – 641Zinc
Metal bindingi109 – 1091Zinc
Metal bindingi121 – 1211Zinc
Metal bindingi126 – 1261Zinc

GO - Molecular functioni

  1. R-SMAD binding Source: BHF-UCL
  2. RNA polymerase II activating transcription factor binding Source: BHF-UCL
  3. bHLH transcription factor binding Source: BHF-UCL
  4. beta-catenin binding Source: BHF-UCL
  5. chromatin DNA binding Source: Ensembl
  6. co-SMAD binding Source: BHF-UCL
  7. core promoter proximal region sequence-specific DNA binding Source: UniProtKB
  8. double-stranded DNA binding Source: Ensembl
  9. enhancer binding Source: BHF-UCL
  10. phosphatase binding Source: UniProtKB
  11. protein binding Source: UniProtKB
  12. protein homodimerization activity Source: BHF-UCL
  13. protein kinase binding Source: UniProtKB
  14. sequence-specific DNA binding Source: BHF-UCL
  15. sequence-specific DNA binding transcription factor activity Source: UniProtKB
  16. transcription factor binding Source: BHF-UCL
  17. transcription regulatory region DNA binding Source: BHF-UCL
  18. transforming growth factor beta receptor binding Source: BHF-UCL
  19. transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity Source: BHF-UCL
  20. ubiquitin binding Source: UniProtKB
  21. ubiquitin protein ligase binding Source: BHF-UCL
  22. zinc ion binding Source: UniProtKB

GO - Biological processi

  1. SMAD protein complex assembly Source: BHF-UCL
  2. T cell activation Source: Ensembl
  3. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: BHF-UCL
  4. activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway Source: Ensembl
  5. activin receptor signaling pathway Source: BHF-UCL
  6. cell cycle arrest Source: BHF-UCL
  7. cell-cell junction organization Source: BHF-UCL
  8. developmental growth Source: Ensembl
  9. embryonic cranial skeleton morphogenesis Source: Ensembl
  10. embryonic foregut morphogenesis Source: Ensembl
  11. embryonic pattern specification Source: Ensembl
  12. endoderm development Source: Ensembl
  13. evasion or tolerance of host defenses by virus Source: BHF-UCL
  14. extrinsic apoptotic signaling pathway Source: BHF-UCL
  15. gene expression Source: Reactome
  16. heart looping Source: Ensembl
  17. immune response Source: BHF-UCL
  18. immune system development Source: Ensembl
  19. in utero embryonic development Source: Ensembl
  20. intracellular signal transduction Source: GOC
  21. lens fiber cell differentiation Source: Ensembl
  22. liver development Source: Ensembl
  23. mesoderm formation Source: Ensembl
  24. negative regulation of apoptotic process Source: Ensembl
  25. negative regulation of cell growth Source: BHF-UCL
  26. negative regulation of inflammatory response Source: Ensembl
  27. negative regulation of mitotic cell cycle Source: BHF-UCL
  28. negative regulation of osteoblast differentiation Source: Ensembl
  29. negative regulation of osteoblast proliferation Source: Ensembl
  30. negative regulation of protein catabolic process Source: BHF-UCL
  31. negative regulation of protein phosphorylation Source: BHF-UCL
  32. negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  33. negative regulation of transforming growth factor beta receptor signaling pathway Source: Reactome
  34. negative regulation of wound healing Source: Ensembl
  35. nodal signaling pathway Source: BHF-UCL
  36. osteoblast development Source: Ensembl
  37. paraxial mesoderm morphogenesis Source: Ensembl
  38. pericardium development Source: Ensembl
  39. positive regulation of alkaline phosphatase activity Source: Ensembl
  40. positive regulation of bone mineralization Source: Ensembl
  41. positive regulation of canonical Wnt signaling pathway Source: BHF-UCL
  42. positive regulation of catenin import into nucleus Source: BHF-UCL
  43. positive regulation of cell migration Source: Ensembl
  44. positive regulation of chondrocyte differentiation Source: Ensembl
  45. positive regulation of epithelial to mesenchymal transition Source: BHF-UCL
  46. positive regulation of focal adhesion assembly Source: Ensembl
  47. positive regulation of gene expression involved in extracellular matrix organization Source: BHF-UCL
  48. positive regulation of interleukin-1 beta production Source: Ensembl
  49. positive regulation of positive chemotaxis Source: Ensembl
  50. positive regulation of stress fiber assembly Source: Ensembl
  51. positive regulation of transcription factor import into nucleus Source: BHF-UCL
  52. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  53. positive regulation of transcription, DNA-templated Source: BHF-UCL
  54. positive regulation of transforming growth factor beta3 production Source: Ensembl
  55. primary miRNA processing Source: BHF-UCL
  56. protein stabilization Source: BHF-UCL
  57. regulation of binding Source: Ensembl
  58. regulation of epithelial cell proliferation Source: Ensembl
  59. regulation of immune response Source: Ensembl
  60. regulation of striated muscle tissue development Source: Ensembl
  61. regulation of transforming growth factor beta receptor signaling pathway Source: BHF-UCL
  62. regulation of transforming growth factor beta2 production Source: BHF-UCL
  63. response to hypoxia Source: BHF-UCL
  64. signal transduction involved in regulation of gene expression Source: Ensembl
  65. somitogenesis Source: Ensembl
  66. thyroid gland development Source: Ensembl
  67. transcription initiation from RNA polymerase II promoter Source: Reactome
  68. transcription, DNA-templated Source: Reactome
  69. transdifferentiation Source: Ensembl
  70. transforming growth factor beta receptor signaling pathway Source: UniProtKB
  71. transport Source: BHF-UCL
  72. ureteric bud development Source: Ensembl
  73. wound healing Source: BHF-UCL
Complete GO annotation...

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_111057. Signaling by NODAL.
REACT_120727. Downregulation of TGF-beta receptor signaling.
REACT_120734. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
REACT_120850. TGF-beta receptor signaling activates SMADs.
REACT_121111. Downregulation of SMAD2/3:SMAD4 transcriptional activity.
REACT_150238. Signaling by Activin.
REACT_169103. SMAD2/3 Phosphorylation Motif Mutants in Cancer.
REACT_169107. SMAD4 MH2 Domain Mutants in Cancer.
REACT_169165. SMAD2/3 MH2 Domain Mutants in Cancer.
REACT_169263. TGFBR1 KD Mutants in Cancer.
SignaLinkiP84022.

Names & Taxonomyi

Protein namesi
Recommended name:
Mothers against decapentaplegic homolog 3
Short name:
MAD homolog 3
Short name:
Mad3
Short name:
Mothers against DPP homolog 3
Short name:
hMAD-3
Alternative name(s):
JV15-2
SMAD family member 3
Short name:
SMAD 3
Short name:
Smad3
Short name:
hSMAD3
Gene namesi
Name:SMAD3
Synonyms:MADH3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 15

Organism-specific databases

HGNCiHGNC:6769. SMAD3.

Subcellular locationi

Cytoplasm. Nucleus
Note: Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4. Through the action of the phosphatase PPM1A, released from the SMAD2/SMAD4 complex, and exported out of the nucleus by interaction with RANBP1. Co-localizes with LEMD3 at the nucleus inner membrane. MAPK-mediated phosphorylation appears to have no effect on nuclear import. PDPK1 prevents its nuclear translocation in response to TGF-beta.8 Publications

GO - Cellular componenti

  1. SMAD protein complex Source: UniProtKB
  2. SMAD2-SMAD3 protein complex Source: BHF-UCL
  3. cytoplasm Source: UniProtKB
  4. cytosol Source: Reactome
  5. nuclear chromatin Source: BHF-UCL
  6. nuclear inner membrane Source: UniProtKB
  7. nucleoplasm Source: Reactome
  8. nucleus Source: UniProtKB
  9. plasma membrane Source: Ensembl
  10. receptor complex Source: BHF-UCL
  11. transcription factor complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
Note: The disease may be caused by mutations affecting the gene represented in this entry.
Loeys-Dietz syndrome 3 (LDS3) [MIM:613795]: An aortic aneurysm syndrome with widespread systemic involvement. The disorder is characterized by the triad of arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. Patients with LDS3 also manifest early-onset osteoarthritis. They lack craniosynostosis and mental retardation.
Note: The disease is caused by mutations affecting the gene represented in this entry. SMAD3 mutations have been reported to be also associated with thoracic aortic aneurysms and dissection (TAAD) (1 Publication). This phenotype is distinguised from LDS3 by having aneurysms restricted to thoracic aorta. As individuals carrying these mutations also exhibit aneurysms of other arteries, including abdominal aorta, iliac, and/or intracranial arteries (1 Publication), they have been classified as LDS3 by the OMIM resource.2 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti112 – 1121A → V in LDS3. 1 Publication
VAR_067051
Natural varianti239 – 2391E → K in LDS3. 1 Publication
VAR_067047
Natural varianti261 – 2611T → I in LDS3. 1 Publication
VAR_065578
Natural varianti279 – 2791R → K in LDS3. 1 Publication
VAR_067048
Natural varianti287 – 2871R → W in LDS3. 1 Publication
VAR_065579

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi8 – 81T → V: Reduced phosphorylation, increased transcriptional and antiproliferative activities. Further increase in transcriptional and antiproliferative activities; when associated with V-179 and A-213. 1 Publication
Mutagenesisi33 – 331K → R: Slightly decreased monoubiquitination. 1 Publication
Mutagenesisi40 – 401K → A: Little effect on interaction with DNA or JUN. Abolishes interaction with DNA and JUN; when associated with A-41; A-43 and A-44. 1 Publication
Mutagenesisi41 – 411K → A: Greatly reduced interaction with DNA and JUN. Abolishes interaction with DNA and JUN; when associated with A-40; A-44 and A-43. 1 Publication
Mutagenesisi43 – 431K → A: Little effect on interaction with DNA or JUN. Abolishes interaction with DNA and JUN; when associated with A-40; A-41 and A-44. 1 Publication
Mutagenesisi44 – 441K → A: Little effect on interaction with DNA or JUN. Abolishes interaction with JUN; when associated with A-40; A-41 and A-43. 1 Publication
Mutagenesisi53 – 531K → R: Slightly decreased monoubiquitination. 1 Publication
Mutagenesisi74 – 741R → D: Reduced interaction with JUN. Loss of transcriptional activity and cooperation with JUN. 1 Publication
Mutagenesisi81 – 811K → R: Decreased monoubiquitination. 1 Publication
Mutagenesisi179 – 1791T → V: Reduced phosphorylation, increased transcriptional and increased antiproliferative activities. Further increase in transcriptional and antiproliferative activities; when associated with V-8 and A-213. 3 Publications
Mutagenesisi204 – 2041S → A: Increased transcriptional activity. Further increased transcriptional activity; when associated with S-208. 3 Publications
Mutagenesisi208 – 2081S → A: Increased transcriptional activity. Further increased transcriptional activity; when associated with S-208. 3 Publications
Mutagenesisi213 – 2131S → A: Reduced phosphorylation. Increased transcriptional and antiproliferative activities. Further increase in transcriptional and antiproliferative activities; when associated with V-8 and V-179. 1 Publication
Mutagenesisi333 – 3331K → R: No effect on acetylation. Completely abolishes acetylation and 97% reduction in transcriptional activity; when associated with R-341; R-378 and R-409. 1 Publication
Mutagenesisi341 – 3411K → R: No effect on acetylation. Completely abolishes acetylation and 97% reduction in transcriptional activity; when associated with R-333; R-378 and R-409. 1 Publication
Mutagenesisi378 – 3781K → Q: Increased transcriptional activity. No further increase in transcriptional activity with EP300. 1 Publication
Mutagenesisi378 – 3781K → R: Greatly reduced acetylation and 85% reduction in transcriptional activity. Completely abolishes acetylation and 97% reduction in transcriptional activity; when associated with R-333; R-341 and R-409. 1 Publication
Mutagenesisi409 – 4091K → R: No effect on acetylation. Completely abolishes acetylation and 97% reduction in transcriptional activity; when associated with R-333; R-341 and R-378. 1 Publication
Mutagenesisi418 – 4181S → A: Increased constitutive activity. 1 Publication
Mutagenesisi418 – 4181S → D: Decreased activity. 1 Publication
Mutagenesisi422 – 4254SSVS → AAVA: Does not abolish protein nuclear export. Abolishes almost completely acetylation. 3 Publications
Mutagenesisi422 – 4254SSVS → EEVE: Forms heterotrimers. 3 Publications
Mutagenesisi422 – 4254SSVS → RRVR: Diminishes cargo protein export. 3 Publications

Keywords - Diseasei

Aortic aneurysm, Disease mutation

Organism-specific databases

MIMi114500. phenotype.
613795. phenotype.
Orphaneti284984. Aneurysm - osteoarthritis syndrome.
91387. Familial thoracic aortic aneurysm and aortic dissection.
PharmGKBiPA30526.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 425424Mothers against decapentaplegic homolog 3
PRO_0000090856Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserine2 Publications
Modified residuei8 – 81Phosphothreonine; by CDK2 and CDK41 Publication
Cross-linki33 – 33Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Inferred
Cross-linki81 – 81Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Inferred
Modified residuei179 – 1791Phosphothreonine; by CDK2, CDK4 and MAPK3 Publications
Modified residuei204 – 2041Phosphoserine; by GSK3 and MAPK3 Publications
Modified residuei208 – 2081Phosphoserine; by MAPK3 Publications
Modified residuei213 – 2131Phosphoserine; by CDK2 and CDK41 Publication
Modified residuei378 – 3781N6-acetyllysine1 Publication
Modified residuei416 – 4161Phosphoserine1 Publication
Modified residuei418 – 4181Phosphoserine; by CK11 Publication
Modified residuei422 – 4221Phosphoserine; by TGFBR1 By similarity
Modified residuei423 – 4231Phosphoserine; by TGFBR1 By similarity
Modified residuei425 – 4251Phosphoserine; by TGFBR1 By similarity

Post-translational modificationi

Phosphorylated on serine and threonine residues. Enhanced phosphorylation in the linker region on Thr-179, Ser-204 and Ser-208 on EGF and TGF-beta treatment. Ser-208 is the main site of MAPK-mediated phosphorylation. CDK-mediated phosphorylation occurs in a cell-cycle dependent manner and inhibits both the transcriptional activity and antiproliferative functions of SMAD3. This phosphorylation is inhibited by flavopiridol. Maximum phosphorylation at the G1/S junction. Also phosphorylated on serine residues in the C-terminal SXS motif by TGFBR1 and ACVR1. TGFBR1-mediated phosphorylation at these C-terminal sites is required for interaction with SMAD4, nuclear location and transactivational activity, and appears to be a prerequisite for the TGF-beta mediated phosphorylation in the linker region. Dephosphorylated in the C-terminal SXS motif by PPM1A. This dephosphorylation disrupts the interaction with SMAD4, promotes nuclear export and terminates TGF-beta-mediated signaling. Phosphorylation at Ser-418 by CSNK1G2/CK1 promotes ligand-dependent ubiquitination and subsequent proteasome degradation, thus inhibiting SMAD3-mediated TGF-beta responses. Phosphorylated by PDPK1.10 Publications
Acetylation in the nucleus by EP300 in the MH2 domain regulates positively its transcriptional activity and is enhanced by TGF-beta.1 Publication
Ubiquitinated. Monoubiquitinated, leading to prevent DNA-binding. Deubiquitination by USP15 alleviates inhibition and promotes activation of TGF-beta target genes.2 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP84022.
PaxDbiP84022.
PRIDEiP84022.

PTM databases

PhosphoSiteiP84022.

Expressioni

Gene expression databases

ArrayExpressiP84022.
BgeeiP84022.
CleanExiHS_SMAD3.
GenevestigatoriP84022.

Organism-specific databases

HPAiCAB008094.

Interactioni

Subunit structurei

Monomer; in the absence of TGF-beta. Homooligomer; in the presence of TGF-beta. Heterotrimer; forms a heterotrimer in the presence of TGF-beta consisting of two molecules of C-terminally phosphorylated SMAD2 or SMAD3 and one of SMAD4 to form the transcriptionally active SMAD2/SMAD3-SMAD4 complex. Interacts with TGFBR1. Part of a complex consisting of AIP1, ACVR2A, ACVR1B and SMAD3. Interacts with AIP1, TGFB1I1, TTRAP, FOXL2, PML, PRDM16, HGS, WWP1 and SNW1. Interacts (via MH2 domain) with CITED2 (via C-terminus) By similarity. Interacts with NEDD4L; the interaction requires TGF-beta stimulation By similarity. Interacts (via the MH2 domain) with ZFYVE9. Interacts with HDAC1, VDR, TGIF and TGIF2, RUNX3, CREBBP, SKOR1, SKOR2, SNON, ATF2, SMURF2 and TGFB1I1. Interacts with DACH1; the interaction inhibits the TGF-beta signaling. Forms a complex with SMAD2 and TRIM33 upon addition of TGF-beta. Found in a complex with SMAD3, RAN and XPO4. Interacts in the complex directly with XPO4. Interacts (via the MH2 domain) with LEMD3; the interaction represses SMAD3 transcriptional activity through preventing the formation of the heteromeric complex with SMAD4 and translocation to the nucleus. Interacts with RBPMS. Interacts (via MH2 domain) with MECOM. Interacts with WWTR1 (via its coiled-coil domain). Interacts (via the linker region) with EP300 (C-terminal); the interaction promotes SMAD3 acetylation and is enhanced by TGF-beta phosphorylation in the C-terminal of SMAD3. This interaction can be blocked by competitive binding of adenovirus oncoprotein E1A to the same C-terminal site on EP300, which then results in partially inhibited SMAD3/SMAD4 transcriptional activity. Interacts with SKI; the interaction represses SMAD3 transcriptional activity. Component of the multimeric complex SMAD3/SMAD4/JUN/FOS which forms at the AP1 promoter site; required for syngernistic transcriptional activity in response to TGF-beta. Interacts (via an N-terminal domain) with JUN (via its basic DNA binding and leucine zipper domains); this interaction is essential for DNA binding and cooperative transcriptional activity in response to TGF-beta. Interacts with PPM1A; the interaction dephosphorylates SMAD3 in the C-terminal SXS motif leading to disruption of the SMAD2/3-SMAD4 complex, nuclear export and termination of TGF-beta signaling. 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 MEN1. Interacts with IL1F7. Interaction with CSNK1G2. Interacts with PDPK1 (via PH domain). Interacts with DAB2; the interactions are enhanced upon TGF-beta stimulation. Interacts with USP15. Interacts with PPP5C; the interaction decreases SMAD3 phosphorylation and protein levels.35 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CHRDQ9H2X02EBI-347161,EBI-947551
DAB2P980823EBI-347161,EBI-1171238
DOCK9Q9BZ293EBI-347161,EBI-2695893
MTMR4Q9NYA44EBI-347161,EBI-1052346
MYD88Q998363EBI-347161,EBI-447677
PCK2Q168222EBI-347161,EBI-2825219
PPP1R12CQ9BZL42EBI-347161,EBI-721802
RNF31Q96EP02EBI-347161,EBI-948111
SETD2Q9BYW22EBI-347161,EBI-945869
SKIP127552EBI-347161,EBI-347281
SMAD2Q157962EBI-347161,EBI-1040141
SMAD4Q1348517EBI-347161,EBI-347263
SMURF2Q9HAU47EBI-347161,EBI-396727
SNW1Q135735EBI-347161,EBI-632715
SQSTM1Q135013EBI-347161,EBI-307104
TSC22D4Q9Y3Q82EBI-347161,EBI-739485
USP7Q930092EBI-347161,EBI-302474
WWP2O003084EBI-347161,EBI-743923
ZC3H12AQ5D1E82EBI-347161,EBI-747793
ZFYVE9O954052EBI-347161,EBI-296817

Protein-protein interaction databases

BioGridi110263. 317 interactions.
DIPiDIP-29720N.
IntActiP84022. 148 interactions.
MINTiMINT-193987.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi10 – 167
Helixi25 – 4420
Helixi48 – 5710
Beta strandi60 – 623
Beta strandi66 – 683
Beta strandi75 – 773
Beta strandi80 – 823
Helixi84 – 929
Helixi100 – 1023
Beta strandi103 – 1053
Helixi113 – 1153
Beta strandi118 – 1214
Helixi124 – 1263
Beta strandi127 – 1293
Beta strandi221 – 2255
Beta strandi231 – 2399
Beta strandi242 – 2509
Beta strandi252 – 2587
Beta strandi268 – 2703
Helixi271 – 2733
Helixi281 – 29010
Beta strandi294 – 2996
Beta strandi302 – 3076
Beta strandi309 – 3113
Beta strandi313 – 3164
Helixi318 – 3214
Helixi323 – 3253
Beta strandi332 – 3343
Beta strandi339 – 3435
Helixi345 – 35814
Helixi360 – 3645
Helixi365 – 3706
Beta strandi371 – 3777
Beta strandi384 – 3863
Helixi389 – 3913
Beta strandi392 – 4009
Helixi401 – 41313

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1MHDX-ray2.80A/B1-132[»]
1MJSX-ray1.91A229-425[»]
1MK2X-ray2.74A220-425[»]
1OZJX-ray2.40A/B1-144[»]
1U7FX-ray2.60A/C228-425[»]
2LAJNMR-B202-211[»]
2LB2NMR-B178-189[»]
ProteinModelPortaliP84022.
SMRiP84022. Positions 7-132, 228-425.

Miscellaneous databases

EvolutionaryTraceiP84022.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini10 – 136127MH1
Add
BLAST
Domaini232 – 425194MH2
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni137 – 23195Linker
Add
BLAST
Regioni271 – 32454Sufficient for interaction with XPO4
Add
BLAST

Domaini

The MH1 domain is required for DNA binding. Also binds zinc ions which are necessary for the DNA binding.1 Publication
The MH2 domain is required for both homomeric and heteromeric interactions and for transcriptional regulation. Sufficient for nuclear import.1 Publication
The linker region is required for the TGFbeta-mediated transcriptional activity and acts synergistically with the MH2 domain.1 Publication

Sequence similaritiesi

Belongs to the dwarfin/SMAD family.

Phylogenomic databases

eggNOGiNOG320700.
HOGENOMiHOG000286018.
HOVERGENiHBG053353.
InParanoidiP84022.
KOiK04500.
OMAiAVELCEY.
PhylomeDBiP84022.
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. 1 hit.
PROSITEiPS51075. MH1. 1 hit.
PS51076. MH2. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P84022-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MSSILPFTPP IVKRLLGWKK GEQNGQEEKW CEKAVKSLVK KLKKTGQLDE    50
LEKAITTQNV NTKCITIPRS LDGRLQVSHR KGLPHVIYCR LWRWPDLHSH 100
HELRAMELCE FAFNMKKDEV CVNPYHYQRV ETPVLPPVLV PRHTEIPAEF 150
PPLDDYSHSI PENTNFPAGI EPQSNIPETP PPGYLSEDGE TSDHQMNHSM 200
DAGSPNLSPN PMSPAHNNLD LQPVTYCEPA FWCSISYYEL NQRVGETFHA 250
SQPSMTVDGF TDPSNSERFC LGLLSNVNRN AAVELTRRHI GRGVRLYYIG 300
GEVFAECLSD SAIFVQSPNC NQRYGWHPAT VCKIPPGCNL KIFNNQEFAA 350
LLAQSVNQGF EAVYQLTRMC TIRMSFVKGW GAEYRRQTVT STPCWIELHL 400
NGPLQWLDKV LTQMGSPSIR CSSVS 425
Length:425
Mass (Da):48,081
Last modified:July 5, 2004 - v1
Checksum:i46DF5E8B371321AC
GO
Isoform 2 (identifier: P84022-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-68: MSSILPFTPP...NVNTKCITIP → MSCLHPRQTWKGAALVHRKAWWMG

Note: No experimental confirmation available.

Show »
Length:381
Mass (Da):43,237
Checksum:iD436B607B2677761
GO
Isoform 3 (identifier: P84022-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-105: Missing.

Show »
Length:320
Mass (Da):35,895
Checksum:iCB3D9B2D53AAC9E9
GO
Isoform 4 (identifier: P84022-4) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-195: Missing.

Note: No experimental confirmation available.

Show »
Length:230
Mass (Da):25,722
Checksum:iAFC64318B5EC08D1
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti112 – 1121A → V in LDS3. 1 Publication
VAR_067051
Natural varianti170 – 1701I → V.
Corresponds to variant rs35874463 [ dbSNP | Ensembl ].
VAR_052021
Natural varianti239 – 2391E → K in LDS3. 1 Publication
VAR_067047
Natural varianti261 – 2611T → I in LDS3. 1 Publication
VAR_065578
Natural varianti279 – 2791R → K in LDS3. 1 Publication
VAR_067048
Natural varianti287 – 2871R → W in LDS3. 1 Publication
VAR_065579
Natural varianti393 – 3931P → L in a colorectal cancer sample; somatic mutation. 1 Publication
VAR_036474

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 195195Missing in isoform 4.
VSP_045348Add
BLAST
Alternative sequencei1 – 105105Missing in isoform 3.
VSP_043793Add
BLAST
Alternative sequencei1 – 6868MSSIL…CITIP → MSCLHPRQTWKGAALVHRKA WWMG in isoform 2.
VSP_042900Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti178 – 1781E → EVGTWAAQAGL in BAA22032. 1 Publication
Sequence conflicti360 – 3601F → L in BAH13315. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U68019 mRNA. Translation: AAB80960.1.
U76622 mRNA. Translation: AAB18967.1.
AB004930 Genomic DNA. Translation: BAA22032.1.
AF025300
, AF025293, AF025294, AF025295, AF025296, AF025297, AF025298, AF025299 Genomic DNA. Translation: AAL68976.1.
AK290881 mRNA. Translation: BAF83570.1.
AK298139 mRNA. Translation: BAH12731.1.
AK300614 mRNA. Translation: BAH13315.1.
AK316017 mRNA. Translation: BAH14388.1.
AC012568 Genomic DNA. No translation available.
AC087482 Genomic DNA. No translation available.
CH471082 Genomic DNA. Translation: EAW77788.1.
BC050743 mRNA. Translation: AAH50743.1.
CCDSiCCDS10222.1. [P84022-1]
CCDS45288.1. [P84022-2]
CCDS53950.1. [P84022-3]
CCDS53951.1. [P84022-4]
PIRiS71798.
RefSeqiNP_001138574.1. NM_001145102.1. [P84022-3]
NP_001138575.1. NM_001145103.1. [P84022-2]
NP_001138576.1. NM_001145104.1. [P84022-4]
NP_005893.1. NM_005902.3. [P84022-1]
UniGeneiHs.727986.
Hs.742270.

Genome annotation databases

EnsembliENST00000327367; ENSP00000332973; ENSG00000166949. [P84022-1]
ENST00000439724; ENSP00000401133; ENSG00000166949. [P84022-2]
ENST00000537194; ENSP00000445348; ENSG00000166949. [P84022-4]
ENST00000540846; ENSP00000437757; ENSG00000166949. [P84022-3]
GeneIDi4088.
KEGGihsa:4088.
UCSCiuc002aqj.3. human. [P84022-1]
uc010ujs.2. human. [P84022-2]

Polymorphism databases

DMDMi51338669.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U68019 mRNA. Translation: AAB80960.1 .
U76622 mRNA. Translation: AAB18967.1 .
AB004930 Genomic DNA. Translation: BAA22032.1 .
AF025300
, AF025293 , AF025294 , AF025295 , AF025296 , AF025297 , AF025298 , AF025299 Genomic DNA. Translation: AAL68976.1 .
AK290881 mRNA. Translation: BAF83570.1 .
AK298139 mRNA. Translation: BAH12731.1 .
AK300614 mRNA. Translation: BAH13315.1 .
AK316017 mRNA. Translation: BAH14388.1 .
AC012568 Genomic DNA. No translation available.
AC087482 Genomic DNA. No translation available.
CH471082 Genomic DNA. Translation: EAW77788.1 .
BC050743 mRNA. Translation: AAH50743.1 .
CCDSi CCDS10222.1. [P84022-1 ]
CCDS45288.1. [P84022-2 ]
CCDS53950.1. [P84022-3 ]
CCDS53951.1. [P84022-4 ]
PIRi S71798.
RefSeqi NP_001138574.1. NM_001145102.1. [P84022-3 ]
NP_001138575.1. NM_001145103.1. [P84022-2 ]
NP_001138576.1. NM_001145104.1. [P84022-4 ]
NP_005893.1. NM_005902.3. [P84022-1 ]
UniGenei Hs.727986.
Hs.742270.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1MHD X-ray 2.80 A/B 1-132 [» ]
1MJS X-ray 1.91 A 229-425 [» ]
1MK2 X-ray 2.74 A 220-425 [» ]
1OZJ X-ray 2.40 A/B 1-144 [» ]
1U7F X-ray 2.60 A/C 228-425 [» ]
2LAJ NMR - B 202-211 [» ]
2LB2 NMR - B 178-189 [» ]
ProteinModelPortali P84022.
SMRi P84022. Positions 7-132, 228-425.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 110263. 317 interactions.
DIPi DIP-29720N.
IntActi P84022. 148 interactions.
MINTi MINT-193987.

Chemistry

BindingDBi P84022.
ChEMBLi CHEMBL1293258.

PTM databases

PhosphoSitei P84022.

Polymorphism databases

DMDMi 51338669.

Proteomic databases

MaxQBi P84022.
PaxDbi P84022.
PRIDEi P84022.

Protocols and materials databases

DNASUi 4088.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000327367 ; ENSP00000332973 ; ENSG00000166949 . [P84022-1 ]
ENST00000439724 ; ENSP00000401133 ; ENSG00000166949 . [P84022-2 ]
ENST00000537194 ; ENSP00000445348 ; ENSG00000166949 . [P84022-4 ]
ENST00000540846 ; ENSP00000437757 ; ENSG00000166949 . [P84022-3 ]
GeneIDi 4088.
KEGGi hsa:4088.
UCSCi uc002aqj.3. human. [P84022-1 ]
uc010ujs.2. human. [P84022-2 ]

Organism-specific databases

CTDi 4088.
GeneCardsi GC15P067358.
GeneReviewsi SMAD3.
HGNCi HGNC:6769. SMAD3.
HPAi CAB008094.
MIMi 114500. phenotype.
603109. gene.
613795. phenotype.
neXtProti NX_P84022.
Orphaneti 284984. Aneurysm - osteoarthritis syndrome.
91387. Familial thoracic aortic aneurysm and aortic dissection.
PharmGKBi PA30526.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG320700.
HOGENOMi HOG000286018.
HOVERGENi HBG053353.
InParanoidi P84022.
KOi K04500.
OMAi AVELCEY.
PhylomeDBi P84022.
TreeFami TF314923.

Enzyme and pathway databases

Reactomei REACT_111057. Signaling by NODAL.
REACT_120727. Downregulation of TGF-beta receptor signaling.
REACT_120734. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
REACT_120850. TGF-beta receptor signaling activates SMADs.
REACT_121111. Downregulation of SMAD2/3:SMAD4 transcriptional activity.
REACT_150238. Signaling by Activin.
REACT_169103. SMAD2/3 Phosphorylation Motif Mutants in Cancer.
REACT_169107. SMAD4 MH2 Domain Mutants in Cancer.
REACT_169165. SMAD2/3 MH2 Domain Mutants in Cancer.
REACT_169263. TGFBR1 KD Mutants in Cancer.
SignaLinki P84022.

Miscellaneous databases

ChiTaRSi SMAD3. human.
EvolutionaryTracei P84022.
GeneWikii Mothers_against_decapentaplegic_homolog_3.
GenomeRNAii 4088.
NextBioi 16026.
PROi P84022.
SOURCEi Search...

Gene expression databases

ArrayExpressi P84022.
Bgeei P84022.
CleanExi HS_SMAD3.
Genevestigatori P84022.

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. 1 hit.
PROSITEi PS51075. MH1. 1 hit.
PS51076. MH2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "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 1), PHOSPHORYLATION.
    Tissue: Placenta.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  3. "Genomic structure of the human Smad3 gene and its infrequent alterations in colorectal cancers."
    Arai T., Akiyama Y., Okabe S., Ando M., Endo M., Yuasa Y.
    Cancer Lett. 122:157-163(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Tissue: Colon carcinoma.
  4. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  5. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2; 3 AND 4).
    Tissue: Brain.
  6. "Analysis of the DNA sequence and duplication history of human chromosome 15."
    Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A.
    , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
    Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  8. "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 1).
    Tissue: Pancreas.
  9. Cited for: INTERACTION WITH TGFBR1.
  10. "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.
  11. "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.
  12. "TGF-beta-induced phosphorylation of Smad3 regulates its interaction with coactivator p300/CREB-binding protein."
    Shen X., Hu P.P., Liberati N.T., Datto M.B., Frederick J.P., Wang X.F.
    Mol. Biol. Cell 9:3309-3319(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION, INTERACTION WITH EP300.
  13. "The oncoprotein Evi-1 represses TGF-beta signalling by inhibiting Smad3."
    Kurokawa M., Mitani K., Irie K., Matsuyama T., Takahashi T., Chiba S., Yazaki Y., Matsumoto K., Hirai H.
    Nature 394:92-96(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MECOM.
  14. "Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced transcription."
    Zhang Y., Feng X.H., Derynck R.
    Nature 394:909-913(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION AS A COMPONENT OF THE SMAD3/SMAD4/JUN/FOS COMPLEX, INTERACTION WITH JUN AND FOS, DNA-BINDING, FUNCTION.
  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. "Structural and functional characterization of the transforming growth factor-beta -induced Smad3/c-Jun transcriptional cooperativity."
    Qing J., Zhang Y., Derynck R.
    J. Biol. Chem. 275:38802-38812(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH JUN IN THE SMAD3/SMAD4/JUN/FOS COMPLEX, DNA-BINDING, FUNCTION, MUTAGENESIS OF LYS-40; LYS-41; LYS-43; LYS-44 AND ARG-74.
  17. "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.
  18. "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.
  19. "TGIF2 interacts with histone deacetylase 1 and represses transcription."
    Melhuish T.A., Gallo C.M., Wotton D.
    J. Biol. Chem. 276:32109-32114(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TGIF2.
  20. "The L3 loop and C-terminal phosphorylation jointly define Smad protein trimerization."
    Chacko B.M., Qin B., Correia J.J., Lam S.S., de Caestecker M.P., Lin K.
    Nat. Struct. Biol. 8:248-253(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT, PHOSPHORYLATION, MUTAGENESIS OF 422-SER--SER-425.
  21. "Inactivation of menin, a Smad3-interacting protein, blocks transforming growth factor type beta signaling."
    Kaji H., Canaff L., Lebrun J.J., Goltzman D., Hendy G.N.
    Proc. Natl. Acad. Sci. U.S.A. 98:3837-3842(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MEN1.
  22. Cited for: INTERACTION WITH DACH1.
  23. "Cyclin-dependent kinases regulate the antiproliferative function of Smads."
    Matsuura I., Denissova N.G., Wang G., He D., Long J., Liu F.
    Nature 430:226-231(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-8; THR-179; SER-204; SER-208 AND SER-213, FUNCTION, MUTAGENESIS OF THR-8; THR-179; SER-204; SER-208 AND SER-213.
  24. "The Smad3 linker region contains a transcriptional activation domain."
    Wang G., Long J., Matsuura I., He D., Liu F.
    Biochem. J. 386:29-34(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: TRANSCRIPTIONAL ACTIVATION DOMAIN, FUNCTION, PHOSPHORYLATION, SUBUNIT, INTERACTION WITH EP300.
  25. "Identification and characterization of ERK MAP kinase phosphorylation sites in Smad3."
    Matsuura I., Wang G., He D., Liu F.
    Biochemistry 44:12546-12553(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-179; SER-204 AND SER-208, SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF THR-179; SER-204 AND SER-208.
  26. "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: SUBCELLULAR LOCATION, INTERACTION WITH LEMD3.
  27. "Novel function of androgen receptor-associated protein 55/Hic-5 as a negative regulator of Smad3 signaling."
    Wang H., Song K., Sponseller T.L., Danielpour D.
    J. Biol. Chem. 280:5154-5162(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TGFB1I1.
  28. "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.
  29. "Nuclear targeting of transforming growth factor-beta-activated Smad complexes."
    Chen H.B., Rud J.G., Lin K., Xu L.
    J. Biol. Chem. 280:21329-21336(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT, SUBCELLULAR LOCATION.
  30. "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.
  31. "Oligomerization of Evi-1 regulated by the PR domain contributes to recruitment of corepressor CtBP."
    Nitta E., Izutsu K., Yamaguchi Y., Imai Y., Ogawa S., Chiba S., Kurokawa M., Hirai H.
    Oncogene 24:6165-6173(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MECOM.
  32. Cited for: INTERACTION WITH PPM1A, DEPHOSPHORYLATION, FUNCTION, SUBCELLULAR LOCATION.
  33. "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 SMAD2 AND TRIM33, INTERACTION WITH SMAD2 AND TRIM33.
  34. "The mechanism of nuclear export of Smad3 involves exportin 4 and Ran."
    Kurisaki A., Kurisaki K., Kowanetz M., Sugino H., Yoneda Y., Heldin C.-H., Moustakas A.
    Mol. Cell. Biol. 26:1318-1332(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION IN A COMPLEX WITH RAN AND XPO4, INTERACTION WITH XPO4, MUTAGENESIS OF 422-SER--SER-425.
  35. "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.
  36. "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, SUBCELLULAR LOCATION, PHOSPHORYLATION BY PDPK1, INTERACTION WITH PDPK1.
  37. "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.
  38. "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 AT LYS-378, FUNCTION, MUTAGENESIS OF LYS-333; LYS-341; LYS-378; LYS-409 AND 422-SER--SER-425.
  39. "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.
  40. "Ligand-dependent ubiquitination of Smad3 is regulated by casein kinase 1 gamma 2, an inhibitor of TGF-beta signaling."
    Guo X., Waddell D.S., Wang W., Wang Z., Liberati N.T., Yong S., Liu X., Wang X.-F.
    Oncogene 27:7235-7247(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CSNK1G2, UBIQUITINATION, PHOSPHORYLATION AT SER-418 BY CSNK1G2/CK1, MUTAGENESIS OF SER-418.
  41. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-416, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  42. "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], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
  43. "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.
  44. Cited for: INTERACTION WITH PRDM16; SKI AND HDAC1.
  45. "Transforming growth factor-{beta}-inducible phosphorylation of Smad3."
    Wang G., Matsuura I., He D., Liu F.
    J. Biol. Chem. 284:9663-9673(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-179; SER-204 AND SER-208, SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF THR-179; SER-204 AND SER-208.
  46. Cited for: INTERACTION WITH IL1F7.
  47. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  48. Cited for: UBIQUITINATION, DEUBIQUITINATION BY USP15, DNA-BINDING, INTERACTION WITH USP15, UBIQUITINATION AT LYS-33 AND LYS-81, MUTAGENESIS OF LYS-33; LYS-53 AND LYS-81.
  49. "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.
  50. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  51. "Crystal structure of a Smad MH1 domain bound to DNA: insights on DNA binding in TGF-beta signaling."
    Shi Y., Wang Y.-F., Jayaraman L., Yang H., Massague J., Pavletich N.P.
    Cell 94:585-594(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-144.
  52. "Smad3 allostery links TGF-beta receptor kinase activation to transcriptional control."
    Qin B.Y., Lam S.S., Correia J.J., Lin K.
    Genes Dev. 16:1950-1963(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.74 ANGSTROMS) OF 220-425 IN COMPLEX WITH ZFYVE9.
  53. "Features of a Smad3 MH1-DNA complex. Roles of water and zinc in DNA binding."
    Chai J., Wu J.W., Yan N., Massague J., Pavletich N.P., Shi Y.
    J. Biol. Chem. 278:20327-20331(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1-144 IN COMPLEX WITH DNA, ZINC.
  54. "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 228-424 IN COMPLEX WITH SMAD4, SUBUNIT.
  55. Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-393.
  56. "Exome sequencing identifies SMAD3 mutations as a cause of familial thoracic aortic aneurysm and dissection with intracranial and other arterial aneurysms."
    Regalado E.S., Guo D.C., Villamizar C., Avidan N., Gilchrist D., McGillivray B., Clarke L., Bernier F., Santos-Cortez R.L., Leal S.M., Bertoli-Avella A.M., Shendure J., Rieder M.J., Nickerson D.A., Milewicz D.M.
    Circ. Res. 109:680-686(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS LDS3 VAL-112; LYS-239 AND LYS-279.
  57. Cited for: VARIANTS LDS3 ILE-261 AND TRP-287.

Entry informationi

Entry nameiSMAD3_HUMAN
AccessioniPrimary (citable) accession number: P84022
Secondary accession number(s): A8K4B6
, B7Z4Z5, B7Z6M9, B7Z9Q2, F5H383, O09064, O09144, O14510, O35273, Q92940, Q93002, Q9GKR4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 5, 2004
Last sequence update: July 5, 2004
Last modified: September 3, 2014
This is version 132 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi