Human Gene SMAD3 (ENST00000327367.9) from GENCODE V39
  Description: Homo sapiens SMAD family member 3 (SMAD3), transcript variant 1, mRNA. (from RefSeq NM_005902)
RefSeq Summary (NM_005902): The SMAD family of proteins are a group of intracellular signal transducer proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. The SMAD3 protein functions in the transforming growth factor-beta signaling pathway, and transmits signals from the cell surface to the nucleus, regulating gene activity and cell proliferation. It also functions as a tumor suppressor. Mutations in this gene are associated with aneurysms-osteoarthritis syndrome and Loeys-Dietz Syndrome 3. [provided by RefSeq, Nov 2019].
Gencode Transcript: ENST00000327367.9
Gencode Gene: ENSG00000166949.17
Transcript (Including UTRs)
   Position: hg38 chr15:67,065,602-67,195,169 Size: 129,568 Total Exon Count: 9 Strand: +
Coding Region
   Position: hg38 chr15:67,066,155-67,190,536 Size: 124,382 Coding Exon Count: 9 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesGeneReviewsMethods
Data last updated at UCSC: 2022-01-17 08:30:34

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr15:67,065,602-67,195,169)mRNA (may differ from genome)Protein (425 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCHPRDLynxMGImyGene2neXtProt
OMIMPubMedReactomeUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: SMAD3_HUMAN
DESCRIPTION: RecName: Full=Mothers against decapentaplegic homolog 3; Short=MAD homolog 3; Short=Mad3; Short=Mothers against DPP homolog 3; Short=hMAD-3; AltName: Full=JV15-2; AltName: Full=SMAD family member 3; Short=SMAD 3; Short=Smad3; Short=hSMAD3;
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 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 (By similarity). Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.
SUBUNIT: 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 and WWP1. 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.
INTERACTION: P60709:ACTB; NbExp=3; IntAct=EBI-347161, EBI-353944; Q9H2X0:CHRD; NbExp=2; IntAct=EBI-347161, EBI-947551; P98082:DAB2; NbExp=3; IntAct=EBI-347161, EBI-1171238; Q9BZ29:DOCK9; NbExp=3; IntAct=EBI-347161, EBI-2695893; Q99836:MYD88; NbExp=3; IntAct=EBI-347161, EBI-447677; Q16822:PCK2; NbExp=2; IntAct=EBI-347161, EBI-2825219; Q9BZL4:PPP1R12C; NbExp=2; IntAct=EBI-347161, EBI-721802; P24158:PRTN3; NbExp=2; IntAct=EBI-347161, EBI-465028; Q96EP0:RNF31; NbExp=2; IntAct=EBI-347161, EBI-948111; Q9BYW2:SETD2; NbExp=2; IntAct=EBI-347161, EBI-945869; Q15796:SMAD2; NbExp=2; IntAct=EBI-347161, EBI-1040141; Q13485:SMAD4; NbExp=9; IntAct=EBI-347161, EBI-347263; Q13501:SQSTM1; NbExp=3; IntAct=EBI-347161, EBI-307104; Q12772:SREBF2; NbExp=3; IntAct=EBI-347161, EBI-465059; Q05066:SRY; NbExp=3; IntAct=EBI-347161, EBI-464987; Q9Y3Q8:TSC22D4; NbExp=2; IntAct=EBI-347161, EBI-739485; Q93009:USP7; NbExp=2; IntAct=EBI-347161, EBI-302474; O00308:WWP2; NbExp=4; IntAct=EBI-347161, EBI-743923; Q5D1E8:ZC3H12A; NbExp=2; IntAct=EBI-347161, EBI-747793;
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. 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.
DOMAIN: The MH1 domain is required for DNA binding. Also binds zinc ions which are necessary for the DNA binding.
DOMAIN: The MH2 domain is required for both homomeric and heteromeric interactions and for transcriptional regulation. Sufficient for nuclear import.
DOMAIN: The linker region is required for the TGFbeta-mediated transcriptional activity and acts synergistically with the MH2 domain.
PTM: 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 G(1)/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.
PTM: Acetylation in the nucleus by EP300 in the MH2 domain regulates positively its transcriptional activity and is enhanced by TGF-beta.
PTM: Ubiquitinated. Monoubiquitinated, leading to prevent DNA- binding. Deubiquitination by USP15 alleviates inhibition and promotes activation of TGF-beta target genes.
DISEASE: Defects in SMAD3 may be a cause of colorectal cancer (CRC) [MIM:114500].
DISEASE: Defects in SMAD3 are the cause of 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=SMAD3 mutations have been reported to be also associated with thoracic aortic aneurysms and dissection (TAAD) (PubMed:21778426). 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 (PubMed:21778426), they have been classified as LDS3 by the OMIM resource.
SIMILARITY: Belongs to the dwarfin/SMAD family.
SIMILARITY: Contains 1 MH1 (MAD homology 1) domain.
SIMILARITY: Contains 1 MH2 (MAD homology 2) domain.

-  MalaCards Disease Associations
  MalaCards Gene Search: SMAD3
Diseases sorted by gene-association score: loeys-dietz syndrome 3* (1580), smad3-related loeys-dietz syndrome* (500), thoracic aortic aneurysms and aortic dissections* (179), smad3-related thoracic aortic aneurysms and aortic dissections* (100), renal fibrosis (16), loeys-dietz syndrome (16), clear cell adenocarcinoma (15), keloids (15), peyronie's disease (12), aortic aneurysm (11), familial thoracic aortic aneurysm and dissection (11), colorectal cancer 5 (10), ureteral disease (10), localized scleroderma (9), hypertrophic scars (9), ovarian clear cell adenocarcinoma (9), aneurysm (9), bifid uvula (8), pulmonary fibrosis (7), colorectal cancer (7), nephrogenic systemic fibrosis (7), adenocarcinoma (6), penile disease (6), osteoarthritis (5), hepatocellular carcinoma (5), pancreatic cancer (5), urinary tract obstruction (4), aortic aneurysm, familial thoracic 1 (4), hypochondrogenesis (4), colitis (4), multiple endocrine neoplasia 1 (2), pulmonary fibrosis, idiopathic (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 21.56 RPKM in Thyroid
Total median expression: 538.88 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -312.70553-0.565 Picture PostScript Text
3' UTR -1487.104633-0.321 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR013790 - Dwarfin
IPR003619 - MAD_homology1_Dwarfin-type
IPR013019 - MAD_homology_MH1
IPR017855 - SMAD_dom-like
IPR001132 - SMAD_dom_Dwarfin-type
IPR008984 - SMAD_FHA_domain

Pfam Domains:
PF03165 - MH1 domain
PF03166 - MH2 domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1MHD - X-ray MuPIT 1MJS - X-ray MuPIT 1MK2 - X-ray MuPIT 1OZJ - X-ray MuPIT 1U7F - X-ray MuPIT 2LAJ - NMR MuPIT 2LB2 - NMR MuPIT


ModBase Predicted Comparative 3D Structure on P84022
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl   
Protein SequenceProtein SequenceProtein Sequence   
AlignmentAlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding
GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0000983 transcription factor activity, RNA polymerase II core promoter sequence-specific
GO:0000987 core promoter proximal region sequence-specific DNA binding
GO:0001102 RNA polymerase II activating transcription factor binding
GO:0003677 DNA binding
GO:0003682 chromatin binding
GO:0003690 double-stranded DNA binding
GO:0003700 transcription factor activity, sequence-specific DNA binding
GO:0005160 transforming growth factor beta receptor binding
GO:0005515 protein binding
GO:0005518 collagen binding
GO:0008013 beta-catenin binding
GO:0008134 transcription factor binding
GO:0008270 zinc ion binding
GO:0017151 DEAD/H-box RNA helicase binding
GO:0019899 enzyme binding
GO:0019901 protein kinase binding
GO:0019902 phosphatase binding
GO:0030618 transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity
GO:0031490 chromatin DNA binding
GO:0031625 ubiquitin protein ligase binding
GO:0031962 mineralocorticoid receptor binding
GO:0035259 glucocorticoid receptor binding
GO:0035326 enhancer binding
GO:0042802 identical protein binding
GO:0042803 protein homodimerization activity
GO:0043130 ubiquitin binding
GO:0043425 bHLH transcription factor binding
GO:0043565 sequence-specific DNA binding
GO:0044212 transcription regulatory region DNA binding
GO:0046332 SMAD binding
GO:0046872 metal ion binding
GO:0046982 protein heterodimerization activity
GO:0070410 co-SMAD binding
GO:0070412 R-SMAD binding
GO:0070878 primary miRNA binding
GO:0000989 transcription factor activity, transcription factor binding

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0001501 skeletal system development
GO:0001649 osteoblast differentiation
GO:0001657 ureteric bud development
GO:0001666 response to hypoxia
GO:0001701 in utero embryonic development
GO:0001707 mesoderm formation
GO:0001756 somitogenesis
GO:0001889 liver development
GO:0001947 heart looping
GO:0002076 osteoblast development
GO:0002520 immune system development
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006357 regulation of transcription from RNA polymerase II promoter
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0006955 immune response
GO:0007050 cell cycle arrest
GO:0007179 transforming growth factor beta receptor signaling pathway
GO:0007183 SMAD protein complex assembly
GO:0007369 gastrulation
GO:0007492 endoderm development
GO:0008285 negative regulation of cell proliferation
GO:0009880 embryonic pattern specification
GO:0010628 positive regulation of gene expression
GO:0010694 positive regulation of alkaline phosphatase activity
GO:0010718 positive regulation of epithelial to mesenchymal transition
GO:0016202 regulation of striated muscle tissue development
GO:0016579 protein deubiquitination
GO:0017015 regulation of transforming growth factor beta receptor signaling pathway
GO:0019049 evasion or tolerance of host defenses by virus
GO:0023019 signal transduction involved in regulation of gene expression
GO:0030308 negative regulation of cell growth
GO:0030325 adrenal gland development
GO:0030335 positive regulation of cell migration
GO:0030501 positive regulation of bone mineralization
GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway
GO:0030878 thyroid gland development
GO:0031053 primary miRNA processing
GO:0032332 positive regulation of chondrocyte differentiation
GO:0032731 positive regulation of interleukin-1 beta production
GO:0032909 regulation of transforming growth factor beta2 production
GO:0032916 positive regulation of transforming growth factor beta3 production
GO:0032924 activin receptor signaling pathway
GO:0033689 negative regulation of osteoblast proliferation
GO:0038092 nodal signaling pathway
GO:0042060 wound healing
GO:0042110 T cell activation
GO:0042177 negative regulation of protein catabolic process
GO:0042307 positive regulation of protein import into nucleus
GO:0043066 negative regulation of apoptotic process
GO:0045216 cell-cell junction organization
GO:0045429 positive regulation of nitric oxide biosynthetic process
GO:0045599 negative regulation of fat cell differentiation
GO:0045668 negative regulation of osteoblast differentiation
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045930 negative regulation of mitotic cell cycle
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0048340 paraxial mesoderm morphogenesis
GO:0048589 developmental growth
GO:0048617 embryonic foregut morphogenesis
GO:0048701 embryonic cranial skeleton morphogenesis
GO:0050678 regulation of epithelial cell proliferation
GO:0050728 negative regulation of inflammatory response
GO:0050776 regulation of immune response
GO:0050821 protein stabilization
GO:0050927 positive regulation of positive chemotaxis
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051098 regulation of binding
GO:0051481 negative regulation of cytosolic calcium ion concentration
GO:0051496 positive regulation of stress fiber assembly
GO:0051894 positive regulation of focal adhesion assembly
GO:0060039 pericardium development
GO:0060070 canonical Wnt signaling pathway
GO:0060290 transdifferentiation
GO:0060395 SMAD protein signal transduction
GO:0061045 negative regulation of wound healing
GO:0061767 negative regulation of lung blood pressure
GO:0070306 lens fiber cell differentiation
GO:0071345 cellular response to cytokine stimulus
GO:0071560 cellular response to transforming growth factor beta stimulus
GO:0090263 positive regulation of canonical Wnt signaling pathway
GO:0097191 extrinsic apoptotic signaling pathway
GO:0097296 activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
GO:1901203 positive regulation of extracellular matrix assembly
GO:1902895 positive regulation of pri-miRNA transcription from RNA polymerase II promoter
GO:1903243 negative regulation of cardiac muscle hypertrophy in response to stress

Cellular Component:
GO:0000790 nuclear chromatin
GO:0005622 intracellular
GO:0005634 nucleus
GO:0005637 nuclear inner membrane
GO:0005654 nucleoplasm
GO:0005667 transcription factor complex
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0032991 macromolecular complex
GO:0043235 receptor complex
GO:0071141 SMAD protein complex
GO:0071144 SMAD2-SMAD3 protein complex


-  Descriptions from all associated GenBank mRNAs
  AK290881 - Homo sapiens cDNA FLJ76792 complete cds, highly similar to Homo sapiens SMAD, mothers against DPP homolog 3 (Drosophila) (SMAD3), mRNA.
HW061230 - JP 2012529430-A/105: METHODS FOR TREATING CHRONIC KIDNEY DISEASE.
HW286095 - JP 2013143917-A/1: CURATIVE OR PREVENTIVE AGENT FOR FIBROSIS.
JB252038 - Sequence 105 from Patent EP2440214.
LP764937 - Sequence 105 from Patent EP3276004.
LX148400 - JP 2017079741-A/1: CURATIVE OR PREVENTIVE AGENT FOR FIBROSIS.
BC050743 - Homo sapiens SMAD family member 3, mRNA (cDNA clone MGC:60396 IMAGE:6094328), complete cds.
U68019 - Homo sapiens mad protein homolog (hMAD-3) mRNA, complete cds.
U76622 - Human mad homolog JV15-2 mRNA, complete cds.
AB464213 - Synthetic construct DNA, clone: pF1KB8191, Homo sapiens SMAD3 gene for SMAD family member 3, without stop codon, in Flexi system.
EU446487 - Synthetic construct Homo sapiens clone IMAGE:100069864; IMAGE:100011696; FLH258539.01L SMAD family member 3 (SMAD3) gene, encodes complete protein.
KJ897155 - Synthetic construct Homo sapiens clone ccsbBroadEn_06549 SMAD3 gene, encodes complete protein.
KR711077 - Synthetic construct Homo sapiens clone CCSBHm_00020082 SMAD3 (SMAD3) mRNA, encodes complete protein.
KR712265 - Synthetic construct Homo sapiens clone CCSBHm_00900229 SMAD3 (SMAD3) mRNA, encodes complete protein.
AB209616 - Homo sapiens mRNA for MAD, mothers against decapentaplegic homolog 3 variant protein.
JD396566 - Sequence 377590 from Patent EP1572962.
JD383492 - Sequence 364516 from Patent EP1572962.
JD452263 - Sequence 433287 from Patent EP1572962.
JD387343 - Sequence 368367 from Patent EP1572962.
JD456211 - Sequence 437235 from Patent EP1572962.
HW061231 - JP 2012529430-A/106: METHODS FOR TREATING CHRONIC KIDNEY DISEASE.
JB252039 - Sequence 106 from Patent EP2440214.
LP764938 - Sequence 106 from Patent EP3276004.
AK316017 - Homo sapiens cDNA, FLJ78916 complete cds, highly similar to Mothers against decapentaplegic homolog 3 (SMAD3).
AK298139 - Homo sapiens cDNA FLJ54532 complete cds, highly similar to Mothers against decapentaplegic homolog 3 (SMAD3).
HW061232 - JP 2012529430-A/107: METHODS FOR TREATING CHRONIC KIDNEY DISEASE.
JB252040 - Sequence 107 from Patent EP2440214.
LP764939 - Sequence 107 from Patent EP3276004.
EU016553 - Homo sapiens mutant mothers against decapentaplegic 3 (SMAD3) mRNA, partial sequence; alternatively spliced.
HW061233 - JP 2012529430-A/108: METHODS FOR TREATING CHRONIC KIDNEY DISEASE.
JB252041 - Sequence 108 from Patent EP2440214.
LP764940 - Sequence 108 from Patent EP3276004.
AK300614 - Homo sapiens cDNA FLJ59989 complete cds, highly similar to Mothers against decapentaplegic homolog 3 (SMAD3).
AK301348 - Homo sapiens cDNA FLJ56254 complete cds, highly similar to Mothers against decapentaplegic homolog 3 (SMAD3).
AK026690 - Homo sapiens cDNA: FLJ23037 fis, clone LNG02036, highly similar to HSU68019 Homo sapiens mad protein homolog (hMAD-3) mRNA.
EU016554 - Homo sapiens mutant mothers against decapentaplegic 3 (SMAD3) mRNA, partial sequence; alternatively spliced.
EU016552 - Homo sapiens mutant mothers against decapentaplegic 3 (SMAD3) mRNA, partial sequence; alternatively spliced.
CR749287 - Homo sapiens mRNA; cDNA DKFZp686J10186 (from clone DKFZp686J10186).
JD350828 - Sequence 331852 from Patent EP1572962.
JD475131 - Sequence 456155 from Patent EP1572962.
JD188508 - Sequence 169532 from Patent EP1572962.
JD557713 - Sequence 538737 from Patent EP1572962.
JD482782 - Sequence 463806 from Patent EP1572962.
JD153362 - Sequence 134386 from Patent EP1572962.
JD191218 - Sequence 172242 from Patent EP1572962.
JD390692 - Sequence 371716 from Patent EP1572962.
JD184078 - Sequence 165102 from Patent EP1572962.
JD067622 - Sequence 48646 from Patent EP1572962.
JD091786 - Sequence 72810 from Patent EP1572962.
JD439431 - Sequence 420455 from Patent EP1572962.
JD387163 - Sequence 368187 from Patent EP1572962.
JD322573 - Sequence 303597 from Patent EP1572962.
JD377118 - Sequence 358142 from Patent EP1572962.
HV347492 - JP 2011513238-A/19: MICRO-RNAS THAT MODULATE SMOOTH MUSCLE PROLIFERATION AND DIFFERENTIATION AND USES THEREOF.
DQ579122 - Homo sapiens piRNA piR-47234, complete sequence.
AL110265 - Homo sapiens mRNA; cDNA DKFZp586N0721 (from clone DKFZp586N0721).
JD343511 - Sequence 324535 from Patent EP1572962.
JD036755 - Sequence 17779 from Patent EP1572962.
JD546145 - Sequence 527169 from Patent EP1572962.
JD098131 - Sequence 79155 from Patent EP1572962.
JD067771 - Sequence 48795 from Patent EP1572962.
JD403791 - Sequence 384815 from Patent EP1572962.
JD555622 - Sequence 536646 from Patent EP1572962.
JD416084 - Sequence 397108 from Patent EP1572962.
JD061538 - Sequence 42562 from Patent EP1572962.
AK313812 - Homo sapiens cDNA, FLJ94430.
JD196988 - Sequence 178012 from Patent EP1572962.
JD387579 - Sequence 368603 from Patent EP1572962.
JD234604 - Sequence 215628 from Patent EP1572962.
AF151027 - Homo sapiens HSPC193 mRNA, complete cds.
BC000414 - Homo sapiens SMAD family member 3, mRNA (cDNA clone IMAGE:2961412).
BC007496 - Homo sapiens SMAD family member 3, mRNA (cDNA clone IMAGE:2961412).
KJ901561 - Synthetic construct Homo sapiens clone ccsbBroadEn_10955 SMAD3 gene, encodes complete protein.
CR457386 - Homo sapiens full open reading frame cDNA clone RZPDo834F0510D for gene DKFZP586N0721, DKFZP586N0721 protein; complete cds, incl. stopcodon.
JD513835 - Sequence 494859 from Patent EP1572962.
JD449244 - Sequence 430268 from Patent EP1572962.
JD352725 - Sequence 333749 from Patent EP1572962.
JD122805 - Sequence 103829 from Patent EP1572962.
JD089916 - Sequence 70940 from Patent EP1572962.
JD350519 - Sequence 331543 from Patent EP1572962.
JD284540 - Sequence 265564 from Patent EP1572962.
JD228736 - Sequence 209760 from Patent EP1572962.
JD104195 - Sequence 85219 from Patent EP1572962.
JD290532 - Sequence 271556 from Patent EP1572962.
JD154802 - Sequence 135826 from Patent EP1572962.
JD205715 - Sequence 186739 from Patent EP1572962.
JD325365 - Sequence 306389 from Patent EP1572962.
JD526534 - Sequence 507558 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04110 - Cell cycle
hsa04144 - Endocytosis
hsa04310 - Wnt signaling pathway
hsa04350 - TGF-beta signaling pathway
hsa04520 - Adherens junction
hsa05142 - Chagas disease
hsa05200 - Pathways in cancer
hsa05210 - Colorectal cancer
hsa05212 - Pancreatic cancer
hsa05220 - Chronic myeloid leukemia

BioCarta from NCI Cancer Genome Anatomy Project
h_g1Pathway - Cell Cycle: G1/S Check Point
h_nthiPathway - NFkB activation by Nontypeable Hemophilus influenzae
h_tgfbPathway - TGF beta signaling pathway
h_tob1Pathway - Role of Tob in T-cell activation

Reactome (by CSHL, EBI, and GO)

Protein P84022 (Reactome details) participates in the following event(s):

R-HSA-2187375 SMAD3 binds STUB1 (CHIP)
R-HSA-9008692 IL37(?-218) binds SMAD3
R-HSA-9009910 IL37(?-218) binds p-S423,S425-SMAD3
R-HSA-2187368 STUB1 (CHIP) ubiquitinates SMAD3
R-HSA-170835 An anchoring protein, ZFYVE9 (SARA), recruits SMAD2/3
R-HSA-1181355 Phosphorylation of R-SMAD2/3 by NODAL receptor
R-HSA-1549526 Phosphorylation of SMAD2/3 by Activin:Activin Receptor
R-HSA-2187358 PMEPA1 sequesters unphosphorylated SMAD2/3
R-HSA-2187395 Dephosphorylated SMAD2/3 translocates to the cytosol
R-HSA-2187401 MTMR4 dephosphorylates SMAD2/3
R-HSA-170847 Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4
R-HSA-2187355 PMEPA1 sequesters phosphorylated SMAD2/3
R-HSA-2187405 MTMR4 binds phosphorylated SMAD2/3
R-HSA-170850 Phosphorylated SMAD2/3 dissociates from TGFBR
R-HSA-8878143 RUNX3 binds SMAD3 and SMAD4
R-HSA-870449 TRIM33 monoubiquitinates SMAD4
R-HSA-209055 PPM1A dephosphorylates nuclear SMAD2/3
R-HSA-170868 Activated type I receptor phosphorylates SMAD2/3 directly
R-HSA-6781764 USP15 deubiquitinates SMAD1,SMAD2,SMAD3, SMAD7:SMURF,KEAP1
R-HSA-173488 The SMAD2/3:SMAD4 complex transfers to the nucleus
R-HSA-2031355 WWTR1 binds SMAD2/3:SMAD4 heterotrimer
R-HSA-8878178 The complex of RUNX3, SMAD3 and SMAD4 binds the CDKN1A gene promoter
R-HSA-8952226 RUNX3 binds the BCL2L11 (BIM) gene
R-HSA-173481 SKI/SKIL binds SMAD complex, suppressing TGF-beta signaling
R-HSA-870538 TRIM33 (Ectodermin) binds SMAD heterotrimer in the nucleus
R-HSA-1225919 Phospho R-SMAD(SMAD2/3):CO-SMAD(SMAD4):FOXH1 binds Activin Response Element
R-HSA-1535903 Phospho R-SMAD(SMAD2/3):CO-SMAD(SMAD4):FOXO3 binds FoxO3a-binding elements
R-HSA-2127257 SMAD2/3:SMAD4 heterotrimer forms a complex with RBL1, E2F4/5 and DP1/2
R-HSA-2176475 Phosphorylation of SMAD2 and SMAD3 linker regions by CDK8 or CDK9
R-HSA-2186607 TGIF recruits HDAC1 to SMAD2/3:SMAD4 heterotrimer
R-HSA-2186643 MEN1 binds SMAD2/3:SMAD4 heterotrimer
R-HSA-2187309 SMAD2/3:SMAD4 heterotrimer binds SP1
R-HSA-2187330 PARP1 binds SMAD2/3:SMAD4 heterotrimer
R-HSA-2187388 PPM1A protein phosphatase binds phosphorylated SMAD2/3
R-HSA-2186747 Ubiquitination of SKI/SKIL by RNF111/SMURF2
R-NUL-2186755 Ubiquitination of SKI/SKIL by Rnf111
R-HSA-2176491 NEDD4L binds phosphorylated linker region of SMAD2/3
R-HSA-2179274 SMURF2 binds SMAD3 phosphorylated in the linker region
R-HSA-2179276 SMURF2 monoubiquitinates SMAD3
R-HSA-2187325 PARP1 ADP-ribosylates SMAD3 and SMAD4
R-HSA-3713560 An anchoring protein, ZFYVE9 (SARA), recruits SMAD2/3 phosphorylation motif mutants
R-HSA-3702186 Phosphorylated SMAD2/3 MH2 domain mutants dissociate from TGFBR
R-HSA-3702153 An anchoring protein, ZFYVE9 (SARA), recruits SMAD2/3 MH2 domain mutants
R-HSA-2106579 WWTR1:SMAD translocates to the nucleus
R-NUL-2186736 Rnf111 binds SKI/SKIL in complex with SMAD2/3:SMAD4 upon TGF-beta stimulation
R-HSA-2186741 SMAD2/3 activation induces binding of RNF111/SMURF2 to SKI/SKIL
R-HSA-2176502 NEDD4L ubiquitinates SMAD2/3
R-HSA-3702184 Activated type I receptor phosphorylates SMAD2/3 MH2 domain mutants directly
R-HSA-2173788 Downregulation of TGF-beta receptor signaling
R-HSA-9008059 Interleukin-37 signaling
R-HSA-2173789 TGF-beta receptor signaling activates SMADs
R-HSA-1181150 Signaling by NODAL
R-HSA-1502540 Signaling by Activin
R-HSA-3656532 TGFBR1 KD Mutants in Cancer
R-HSA-2173795 Downregulation of SMAD2/3:SMAD4 transcriptional activity
R-HSA-446652 Interleukin-1 family signaling
R-HSA-2173796 SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
R-HSA-3311021 SMAD4 MH2 Domain Mutants in Cancer
R-HSA-8941855 RUNX3 regulates CDKN1A transcription
R-HSA-170834 Signaling by TGF-beta Receptor Complex
R-HSA-1266738 Developmental Biology
R-HSA-9006936 Signaling by TGF-beta family members
R-HSA-3656534 Loss of Function of TGFBR1 in Cancer
R-HSA-2173793 Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer
R-HSA-5689880 Ub-specific processing proteases
R-HSA-449147 Signaling by Interleukins
R-HSA-3304347 Loss of Function of SMAD4 in Cancer
R-HSA-8952158 RUNX3 regulates BCL2L11 (BIM) transcription
R-HSA-8878159 Transcriptional regulation by RUNX3
R-HSA-3304356 SMAD2/3 Phosphorylation Motif Mutants in Cancer
R-HSA-3315487 SMAD2/3 MH2 Domain Mutants in Cancer
R-HSA-162582 Signal Transduction
R-HSA-3304351 Signaling by TGF-beta Receptor Complex in Cancer
R-HSA-212436 Generic Transcription Pathway
R-HSA-5688426 Deubiquitination
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-3304349 Loss of Function of SMAD2/3 in Cancer
R-HSA-5663202 Diseases of signal transduction
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-597592 Post-translational protein modification
R-HSA-168256 Immune System
R-HSA-1643685 Disease
R-HSA-74160 Gene expression (Transcription)
R-HSA-392499 Metabolism of proteins

-  Other Names for This Gene
  Alternate Gene Symbols: A8K4B6, B7Z4Z5, B7Z9Q2, ENST00000327367.1, ENST00000327367.2, ENST00000327367.3, ENST00000327367.4, ENST00000327367.5, ENST00000327367.6, ENST00000327367.7, ENST00000327367.8, MADH3, NM_005902, O09064, O09144, O14510, O35273, P84022, Q92940, Q93002, Q9GKR4, SMAD3_HUMAN, uc002aqj.1, uc002aqj.2, uc002aqj.3, uc002aqj.4, uc002aqj.5
UCSC ID: ENST00000327367.9
RefSeq Accession: NM_005902
Protein: P84022 (aka SMAD3_HUMAN or SMA3_HUMAN)
CCDS: CCDS10222.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene SMAD3:
loeys-dietz (Loeys-Dietz Syndrome)
taa (Heritable Thoracic Aortic Disease Overview)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.