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General Information



Gene_Symbol Gene_ID Gene_Name Chromosome Alias
SMAD3 4088 SMAD family member 3  15LDS3; LDS1C; MADH3; JV15-2; HSPC193; HsT17436 







  • Evidence
  • Gene
  • mRNA
  • CDS
  • Protein
  • PTM
  • Enzyme
  • PPi
  • Pathway
  • Structural
  • Domain
  • Ontology
  • SNP
  • Drug
  • External Links



Evidence Information


Pubmed ID Year Sample Information Techniques Mechanism Fold Change Remark
22278155   2012Cell line : -

Source : Tzaneio General Hospital, Pireaus, Greece.

Sample Type : CRC tumor and normal tissue

No. of Sample : 195 unrelated CRC specimens

Stage : TNM Stage I-IV

ImmunohistochemistryDown-regulation-TGF-B, TGF-BR2, Smad4, pSmad2/3, and E-cadherin emerge as valuable independent biomarkers of prognosis in CRC patients.

TGF-B, TGF-BR1, TGF-BR2, Smad4, pSmad2/3, and E-cadherin are closely related to TNM stage of CRC.

16828225   2007Cell line : SNU 61, SNU 407, SNU 769A, SNU 769B, SNU 1047, SNU 81, SNU 175 and A202V, SNU 1040, and SNU 769A.

Source : KCLB (the Korean Cell Line Bank) (Seoul, Korea).

Sample Type : -

No. of Sample : -

Stage : -

-Mutation-A missense mutation (R373H) in Smad3 gene was found in SNU-769A. This mutation was found to result in the inhibition of translocation of Smad3 protein to the nucleus and a reduction in the activity of Smad3 during TGF-beta-induced transcriptional activation.

23139211   2012Cell line : 36 CRC cell lines

Source : -

Sample Type : CRC tumor and normal tissue

No. of Sample : 744 primary CRCs

Stage : -

SNP microarrayMutation-744 primary CRCs and 36 CRC cell lines were sequenced for SMAD4, SMAD2, and SMAD3 and analyzed for allelic loss by single-nucleotide polymorphism (SNP) microarray analysis.

In silico analyses suggested the majority of the mutations were pathogenic, with most missense changes predicted to reduce protein stability or hinder SMAD complex formation.

15665291   2005Cell line : -

Source : Department of Surgical Pathology at Kansai Medical University Hospital.

Sample Type : CRC tumor and normal tissue

No. of Sample : -

Stage : -

RT-PCR, Immunohistochemistry, Immunoprecipitation and Immunoblotting, In vitro Kinase AssayPhosphorylation-Acceleration of Smad2 and Smad3 phosphorylation via c-Jun NH(2)-terminal kinase during human colorectal carcinogenesis.

16528675   2006Cell line : -

Source : -

Sample Type : -

No. of Sample : -

Stage : -

-Phosphorylation-TGF-beta signaling involves phosphorylation of Smad3 at serine residues 208 and 213 in the linker region and serine residues 423 and 425 in the C-terminal region.

17093904   2006Cell line : -

Source : -

Sample Type : -

No. of Sample : -

Stage : -

-Phosphorylation-During sporadic human colorectal carcinogenesis, TGF-beta signaling confers a selective advantage upon tumor cells by shifting from epithelial Tbeta RI/pSmad3C pathway to mesenchymal JNK/pSmad3L pathway.

Specific inhibition of the JNK/pSmad3L pathway will become a therapy for human colorectal cancer that restores the lost tumor-suppressive function observed in normal colorectal epithelial cells.

19531654   2009Cell line : ACBRI 519, COLO 320

Source : Applied Cell Biology Research Institute and Health Science Research Resources Bank, respectively.

Sample Type : -

No. of Sample : -

Stage : -

Immunoprecipitation and immunoblotting, Nuclear/cytosolic extracts and in vitro kinase assay, ImmunoPhosphorylation-Phosphorylation at linker and c- terminal.

The linker phosphorylation of Smad2 and Smad3 may represent a target for intervention in human metastatic cancer.

19541409   2010Cell line : HCT 116

Source : -

Sample Type : -

No. of Sample : -

Stage : -

-Phosphorylation--

21071512   2010Cell line : SW 620, SW 480, and HT 29

Source : Department of Pathology, Southern Hospital (Guangzhou, China).

Sample Type : -

No. of Sample : 168 Samples included 30 cases of normal colorectal mucosa, 93 cases of CRC tissues, 45 cases of metastatic lymph nodes, and 10 cases of metastatic livers

Stage : TNM Stage I-IV

Immunohistochemistry, Real timeRT- PCR assays, Western blotting, In vitro invasion assayPhosphorylation-A novel EMT and tumor promoting function for FMNL2, which is involved in TGF-B-induced EMT and colorectal carcinoma cell invasion via Smad3 effectors, or in collaboration with MAPK/MEK pathway.


Gene Details



Chromosome: 15; NC_000015.9 (67358195..67487533)

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Gene Type protein coding
Gene Family SMADs
Description The protein encoded by this gene belongs to the SMAD, a family of proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein functions as a transcriptional modulator activated by transforming growth factor-beta and is thought to play a role in the regulation of carcinogenesis. [provided by RefSeq, Apr 2009]  
Chromosome 15
Location 15q22.33
Start 67065627  
End 67195195  
Strand -  
Gene Sequence

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Length 129569  
OMIM ID 603109   
HGNC ID HGNC:6769   
Unigene ID Hs.727986   
Ensembl ID ENSG00000166949   
PharmGKB ID -   

mRNA Information


mRNA ID XM_011521559.1
Exon join(1..734,99269..99462,101153..101227,104928..104978, 115615..115827,119101..119238,121739..121883, 124787..129569)  
mRNA Sequence

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Length 6256  



CDS Information


   
Location join(529..734,99269..99462,99627..99758,101153..101227, 104928..104978,115615..115827,119101..119238, 121739..121883,124787..124910)
CDS Sequence

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CCDS ID CCDS10222.1



Protein Information


      
Protein IDNP_005893.1
Protein NameSMAD family member 3
Molecular Wt. (Da)47950
Protein Sequence

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Length 425  
Uniprot IDP24941
Ensembl Protein ID ENSP00000266970  



Post-translational Modification Information (Source : HPRD)


Residue Type site
SPhosphorylation208
SPhosphorylation213
SPhosphorylation422
SPhosphorylation423
SPhosphorylation425
SPhosphorylation208
SPhosphorylation204
TPhosphorylation179
SPhosphorylation213
TPhosphorylation8
TPhosphorylation8
TPhosphorylation179
TPhosphorylation179
SPhosphorylation213
SPhosphorylation213
SPhosphorylation204
SPhosphorylation204
SPhosphorylation208
SPhosphorylation208
SPhosphorylation416
SAcetylation2
KAcetylation378

Enzyme Information


No matching records could be found.

PPi Information


(Click to view network : Source STRING)      View   

                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
Interactant Gene ID (Source: HPRD) Gene Symbol HPRD ID Ref Seq ID Technique References
60ACTB32NP_001092.1in vitro15527767   
288ANK32715NP_066267.2yeast 2-hybrid15231748   
367AR2437NP_000035.2in vitro;in vivo11280774   
675BRCA22554NP_000050.2in vitro;in vivo12165866   
818CAMK2G3672NP_751911.1in vivo11027280   
860RUNX22566NP_001019801.3in vitro;in vivo10962029   
864RUNX32565AAH13362.1in vitro;in vivo15138260   
996CDC27304NP_001107563.1in vivo11691834   
1051CEBPB1801NP_005185.2in vitro12524424   
1386ATF2443NP_001871.2in vitro;in vivo;yeast 2-hybrid10085140   
1443CSH26688NP_066271.1yeast 2-hybrid15231748   
1499CTNNB1286NP_001895.1in vitro12000714   
1583CYP11A1326NP_000772.2yeast 2-hybrid15231748   
1601DAB23139NP_001334.2in vitro;in vivo11387212   
1655DDX51615NP_004387.1in vitro;in vivo;yeast 2-hybrid15464984   
1874E2F42806NP_001941.2in vivo12150994   
2034EPAS16787NP_001421.2yeast 2-hybrid15231748   
2122MECOM1310NP_001098547.3in vitro;in vivo9665135   
2308FOXO1645NP_002006.2in vitro;in vivo15084259   
2309FOXO34061NP_001446.1in vitro;in vivo15084259   
2316FLNA2060NP_001104026.1yeast 2-hybrid15231748   
2737GLI31313P10071in vitro9843199   
2908NR3C1679NP_001019265.1in vitro;in vivo1   290   233   810   518   520   
3096HIVEP11925NP_002105.2yeast 2-hybrid15231748   
3172HNF4A2612CAA89989.1in vitro;in vivo10995777   
3308HSPA49025NP_002145.3in vivo12963786   
3725JUN1302NP_002219.1in vitro;in vivo9732876   
3726JUNB1303NP_002220.1in vitro;in vivo10903323   
3837KPNB14114NP_002256.2in vitro10846168   
4087SMAD23221NP_005892.1in vivo9311995   
4089SMAD42995NP_005350.1in vitro;in vivo;yeast 2-hybrid9   311   995   109   957   770   000   000   000   000   000   
4093SMAD94484BAA21128.1yeast 2-hybrid15231748   
4149MAX1113NP_002373.3in vitro12551947   
4194MDM44082NP_002384.2in vitro;in vivo12483531   
4221MEN1564NP_000235.2in vitro11274402   
4303FOXO42070NP_005929.2in vitro;in vivo15084259   
4609MYC1818NP_002458.2in vitro;in vivo;yeast 2-hybrid11804592   
4654MYOD11166NP_002469.2in vitro;in vivo11711431   
4851NOTCH11827NP_060087.3in vitro;in vivo14638857   
5069PAPPA1448NP_002572.2yeast 2-hybrid15231748   
5097PCDH14692NP_115796.2yeast 2-hybrid15231748   
5324PLAG14321NP_002646.2yeast 2-hybrid15231748   
5325PLAGL116010NP_006709.2yeast 2-hybrid15231748   
5599MAPK83100NP_620637.1in vitro;in vivo10601313   
5657PRTN31512NP_002768.3in vitro15527767   
5717PSMD115119NP_002806.2yeast 2-hybrid15231748   
5933RBL1312NP_002886.2in vitro;in vivo12150994   
6175RPLP01610NP_444505.1yeast 2-hybrid15231748   
6497SKI1271NP_003027.1in vivo12857746   
6498SKIL1319NP_005405.2in vivo;yeast 2-hybrid1   053   106   215   231   740   
6625SNRNP701617NP_003080.2yeast 2-hybrid15231748   
6711SPTBN11683NP_003119.2in vitro;in vivo12543979   
6721SREBF22726NP_004590.2in vitro15527767   
6935ZEB11798NP_110378.3in vitro;in vivo12743038   
7030TFE32439NP_006512.2in vitro105   572   851   255   194   000   000   000   
7046TGFBR11822NP_004603.1in vivo9311995   
7048TGFBR21823NP_001020018.1in vitro8774881   
7052TGM21825NP_004604.2yeast 2-hybrid15231748   
7170TPM31840NP_689476.2in vitro15527767   
7431VIM1899NP_003371.2in vitro15527767   
7465WEE11907NP_003381.1in vivo15761153   
7554ZNF81919NP_066575.2in vitro;in vivo;yeast 2-hybrid12370310   
7704ZBTB1611762NP_005997.2yeast 2-hybrid15231748   
7750ZMYM23745NP_003444.1in vitro;yeast 2-hybrid14651998   
7849PAX81335NP_003457.1in vitro;in vivo14623893   
8313AXIN24935NP_004646.3in vivo11438668   
8454CUL14389NP_003583.2in vivo11359933   
8850KAT2B6780NP_003875.3in vitro;in vivo11058129   
8878SQSTM13319NP_003891.1in vivo15761153   
8888MCM3AP4483NP_003897.2yeast 2-hybrid15231748   
8945BTRC4596NP_378663.1in vivo11359933   
9146HGS5085NP_004703.1in vitro;in vivo11094085   
9972NUP1534899NP_005115.2in vitro12917407   
9978RBX16794NP_055063.1in vitro;in vivo;yeast 2-hybrid11359933   
10048RANBP94835NP_005484.2yeast 2-hybrid15231748   
10148EBI312051NP_005746.2yeast 2-hybrid15231748   
10401PIAS39068NP_006090.2in vivo14691252   
10428CFDP116282NP_006315.1yeast 2-hybrid15231748   
10610ST6GALNAC210231NP_006447.2yeast 2-hybrid15231748   
10664CTCF5005NP_006556.1in vitro12099698   
10691GMEB116059NP_006573.2yeast 2-hybrid15231748   
11018TMED15653NP_006849.1yeast 2-hybrid15231748   
11108PRDM410425NP_036538.3yeast 2-hybrid15231748   
22823MTF214342NP_031384.1yeast 2-hybrid15231748   
22938SNW14340NP_036377.1in vitro;yeast 2-hybrid11278756   
23054NCOA65599NP_054790.2yeast 2-hybrid15231748   
23462HEY14260NP_001035798.1yeast 2-hybrid15231748   
51176LEF11075NP_057353.1in vitro;in vivo10890911   
55146ZDHHC415719NP_060576.1in vitro15527767   
55769ZNF831935NP_060770.3yeast 2-hybrid15231748   
56288PARD35994NP_062565.2in vitro;yeast 2-hybrid12650946   
57154SMURF16902NP_065162.1in vivo15761153   
64115C10orf5415160AAH20568.1yeast 2-hybrid15231748   
79595SAP13018015NP_078821.2yeast 2-hybrid15231748   
79673ZNF3297779NP_078896.3yeast 2-hybrid15231748   
79987SVEP112942NP_699197.3yeast 2-hybrid15231748   


Pathway Information


                                                                                                      
Pathway Name Pathway ID
Adherens junction hsa04520
AGE-RAGE signaling pathway in diabetic complications hsa04933
Cell cycle hsa04110
Chagas disease (American trypanosomiasis) hsa05142
Chronic myeloid leukemia hsa05220
Colorectal cancer hsa05210
Endocytosis hsa04144
FoxO signaling pathway hsa04068
Hepatitis B hsa05161
Hippo signaling pathway hsa04390
HTLV-I infection hsa05166
Inflammatory bowel disease (IBD) hsa05321
Pancreatic cancer hsa05212
Pathways in cancer hsa05200
Signaling pathways regulating pluripotency of stem cells hsa04550
TGF-beta signaling pathway hsa04350
Wnt signaling pathway hsa04310


Structure Information


PDB ID1MHD
Resolution2.8
MethodX-RAY DIFFRACTION
Chains A,B,C  
Molecule DNA,SMAD3  
Model View



Domain Information




ID Location Description
cd10985224-414  MH2_SMAD_2_3
cl00056224-414  MH2 superfamily
cd104918-132  MH1_SMAD_2_3
cl000558-132  MH1 superfamily
cd10495232-412  MH2_R-SMAD
cd10497226-425  MH2_SMAD_1_5_9
pfam03166230-403  MH2
smart00524231-401  DWB
cd00050232-401  MH2
cd1048810-132  MH1_R-SMAD
cd0004910-132  MH1
cd10498229-411  MH2_SMAD_4
cd104907-132  MH1_SMAD_1_5_9
smart0052326-134  DWA
pfam0316545-131  MH1
cd1049247-130  MH1_SMAD_4
cd10496232-401  MH2_I-SMAD
cd10499228-401  MH2_SMAD_6
cd10500228-401  MH2_SMAD_7
cd1048962-130  MH1_SMAD_6_7
cd1049346-134  MH1_SMAD_6
cd1049447-133  MH1_SMAD_7


Ontology Information


   
HPRD ID298
Molecular ClassTranscription regulatory protein
Molecular FunctionKinase regulator activity (GO:0019207)
Biological ProcessRegulation of cell cycle (GO:0000074)  



SNP Information


View SNP Geneview Report   

Drug Information


No matching records could be found.

External Links


                                 
ArrayExpressGO
ICGCGO
Cancer3DGO
COSMICGO
NCGGO
TSGeneGO
Tumor Gene Family of DatabasesGO
CCDBGO
G2SBCGO
Osteosarcoma DatabaseGO
RCDBGO