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ALTERED TRANSFORMING GROWTH FACTOR-BETA SMAD DEPENDENT SIGNALING PATHWAY (PW:0000614)

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Description

Transforming growth factor-beta superfamily mediated pathways are central regulators of proliferation and survival, migration and differentiation, angiogenesis, embryonic development and wound healing. The transforming growth factor-beta (Tgf-b) Smad-dependent pathway is one of the best characterized modules of the Tgf-b superfamily signaling. Deregulation of Tgf-b Smad-dependent signaling renders the otherwise tumor-suppressive and growth-inhibitory pathway, a pro-growth and pro-tumorige

Pathway Diagram:

Ariadne Genomics Inc. Tgf-beta target genes Transcription factors/co-activators colorectal cancer pathway Colorectal Neoplasms Pancreatic Neoplasms Prostatic Neoplasms Smad7 Smurf2 Tgf-beta target genes ---> Colorectal Neoplasms Smad3 Smad2 Smad7 ---| Tgfbr1 Fkbp1a Zfyve9 Dcn A2m Tgfbr3 Smad3 ---- Zfyve9 Fkbp1a ---| Tgfbr1 A2m ---| Tgfb1 Smad7 ---| Tgfbr1 Smad2 ---- Zfyve9 Tgfbr1 ---- Zfyve9 Tgfb1 ---- Tgfbr3 Dcn ---| Tgfb1 Tgf-beta target genes ---> Smad7 Smurf1 Smad4 Tgf-beta target genes ---> colorectal cancer pathway Tgf-beta target genes ---> Pancreatic Neoplasms Translocated Smad ---> Tgf-beta target genes Tgfbr2 Tgfb1 ---- Tgfbr2 Tgfb1 Tgfbr1 Tgfb1 ---- Tgfbr1 Tgf-beta target genes ---> Prostatic Neoplasms Translocated Smad
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Genes in Pathway:


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altered transforming growth factor-beta Smad dependent signaling pathway term browser
Symbol Object Name Evidence Notes Source PubMed Reference(s) RGD Reference(s) Position
G Smad2 SMAD family member 2 ISO RGD PMID:17613544 PMID:18662538 RGD:2306282, RGD:2308865 NCBI chr18:69,849,884...69,918,926
Ensembl chr18:69,850,377...69,912,323
JBrowse link
G Smad3 SMAD family member 3 ISO RGD PMID:17613544 PMID:18772397 RGD:2306282, RGD:5490966 NCBI chr 8:64,126,829...64,236,960
Ensembl chr 8:64,110,039...64,236,960
JBrowse link
G Smad4 SMAD family member 4 ISO RGD PMID:17613544 PMID:18662538 PMID:18772397 PMID:19506583 RGD:2306282, RGD:2308865, RGD:5490966, RGD:5490965 NCBI chr18:67,243,742...67,274,438
Ensembl chr18:67,243,742...67,274,438
JBrowse link
G Smad7 SMAD family member 7 ISO RGD PMID:18662538 RGD:2308865 NCBI chr18:68,988,429...69,016,774
Ensembl chr18:68,988,429...69,016,765
JBrowse link
G Tgfb1 transforming growth factor, beta 1 ISO RGD PMID:18313409 PMID:17613544 RGD:2299005, RGD:2306282 NCBI chr 1:81,196,532...81,212,848
Ensembl chr 1:81,196,532...81,212,847
JBrowse link
G Tgfbr1 transforming growth factor, beta receptor 1 ISO RGD PMID:18313409 PMID:17613544 RGD:2299005, RGD:2306282 NCBI chr 5:61,653,773...61,710,777
Ensembl chr 5:61,653,233...61,710,777
JBrowse link
G Tgfbr2 transforming growth factor, beta receptor 2 ISO RGD PMID:18313409 PMID:17613544 PMID:18662538 PMID:18772397 PMID:19506583 RGD:2299005, RGD:2306282, RGD:2308865, RGD:5490966, RGD:5490965 NCBI chr 8:115,794,537...115,883,615
Ensembl chr 8:115,794,537...115,883,228
JBrowse link

Additional Elements in Pathway:

(includes Gene Groups, Small Molecules, Other Pathways..etc.)
Object TypePathway ObjectPathway Object Description
Pathwaycolorectal cancer pathwayColorectal cancer are malignant tumors of the colon and rectum
Gene Grouptranscription factors/co-activatorstranscription factors/co-activators associated with Smad2/3-4
Gene GroupTgf-beta target genestransforming growth factor, beta target genes

Pathway Gene Annotations

Disease Annotations Associated with Genes in the altered transforming growth factor-beta Smad dependent signaling pathway
Disease TermsGene Symbols
Acro-OsteolysisSmad4
acromicric dysplasiaSmad2 , Tgfb1
actinic keratosisTgfb1
acute kidney failureTgfb1 , Tgfbr1
Acute Lung InjuryTgfb1
adenocarcinomaTgfb1
alcoholic liver cirrhosisSmad3 , Tgfb1
allergic conjunctivitisTgfb1
allergic diseaseTgfb1
allergic rhinitisTgfb1
AnetodermaTgfb1
AneurysmSmad3
Animal Disease ModelsTgfbr1
anogenital venereal wartTgfb1
aortic aneurysmSmad3 , Tgfbr1 , Tgfbr2
aortic diseaseSmad3 , Smad4 , Tgfbr1
aortic dissectionSmad3
aortic valve disease 2Smad3
aortic valve insufficiencyTgfb1
aphthous stomatitisTgfb1
aplastic anemiaTgfb1
ARTERIAL DISSECTIONSmad3
arteriosclerosisTgfb1 , Tgfbr2
asthmaTgfb1
atopic dermatitisTgfb1
atrial fibrillationSmad7 , Tgfb1
autoimmune hepatitisTgfb1
autoimmune thrombocytopenic purpuraTgfb1
bacterial pneumoniaTgfb1
Behcet's diseaseTgfb1
berylliosisTgfb1
biliary atresiaTgfb1
Bloom syndromeSmad3
bone diseaseTgfbr2
Bone FracturesTgfbr2
Bone NeoplasmsTgfbr2
brachydactylySmad4
brain diseaseTgfb1
brain ischemiaTgfb1
Brain NeoplasmsTgfbr2
breast cancerSmad4 , Tgfb1
breast carcinomaSmad2
Breast NeoplasmsSmad4
CachexiaTgfb1
calcinosisTgfb1
Camurati-Engelmann diseaseTgfb1
carcinomaTgfb1 , Tgfbr2
carcinosarcomaTgfb1
Cardiac FibrosisTgfb1
CardiomegalyTgfb1
carotid artery diseaseTgfb1
Carotid Artery InjuriesTgfb1 , Tgfbr1 , Tgfbr2
Carpenter Syndrome 2Tgfb1
cervical cancerSmad2 , Smad4
cervical squamous cell carcinomaSmad3
Charlevoix-Saguenay spastic ataxiaTgfbr1
Chemical and Drug Induced Liver InjuryTgfb1 , Tgfbr1
chlamydiaTgfb1
cholangiocarcinomaSmad4 , Tgfb1 , Tgfbr2
chorioamnionitisTgfb1
Chronic Experimental PancreatitisTgfb1
Chronic HepatitisSmad2 , Tgfb1
Chronic Hepatitis BTgfb1
Chronic Hepatitis CSmad4
chronic myeloid leukemiaSmad4 , Tgfb1
chronic obstructive pulmonary diseaseSmad4 , Tgfb1
CicatrixSmad4
cleft palateTgfb1
cleft soft palateTgfbr2
Cocaine-Related DisordersSmad3
cognitive disorderSmad4
colon adenocarcinomaTgfb1
colon cancerSmad2 , Smad4 , Tgfb1 , Tgfbr2
colon carcinomaSmad4 , Tgfb1
Colonic NeoplasmsTgfbr2
colorectal adenomaSmad4
colorectal cancerSmad3 , Smad4 , Smad7 , Tgfb1 , Tgfbr1 , Tgfbr2
colorectal carcinomaSmad4
Colorectal NeoplasmsSmad3 , Smad4 , Smad7 , Tgfb1 , Tgfbr1
congenital disorder of glycosylation IiTgfbr1
congenital disorder of glycosylation type IITgfbr1
CONGENITAL HEART DEFECTS, MULTIPLE TYPES, 8, WITH OR WITHOUT HETEROTAXYSmad2
congenital hypoplastic anemiaTgfb1
congenital myasthenic syndrome 14Tgfbr1
connective tissue diseaseSmad3 , Tgfbr1 , Tgfbr2
Copper-Overload CirrhosisSmad2 , Tgfb1
coronary artery diseaseSmad3 , Tgfb1
Craniofacial AbnormalitiesSmad2 , Smad3 , Smad4 , Tgfbr2
craniosynostosisTgfb1 , Tgfbr1
Craniosynostosis Syndrome, Autosomal RecessiveTgfbr1
Crohn's diseaseSmad3
Cronkhite-Canada syndromeSmad4
cystic fibrosisTgfb1
DeafnessSmad4
degenerative disc diseaseTgfb1
diabetes mellitusTgfb1
Diabetic NephropathiesTgfb1 , Tgfbr2
diabetic neuropathyTgfb1
diabetic retinopathyTgfbr2
Diamond-Blackfan anemiaTgfb1
Diaphragmatic HerniaTgfb1
diffuse sclerodermaTgfbr1
DiGeorge syndromeTgfbr2
Dilatation, PathologicTgfb1
Disproportionate Tall StatureTgfbr1
Dissecting AneurysmSmad3 , Tgfbr1 , Tgfbr2
dry eye syndromeTgfb1
Duchenne muscular dystrophyTgfb1
duodenal ulcerTgfb1
Ehlers-Danlos syndromeSmad3 , Tgfb1 , Tgfbr1 , Tgfbr2
Ehlers-Danlos syndrome classic type 1Tgfbr1
end stage renal diseaseTgfb1
endometrial cancerSmad2 , Smad3 , Smad7
endometrial carcinomaSmad4
endomyocardial fibrosisTgfb1
eosinophilic esophagitisTgfb1
epilepsyTgfb1
esophageal cancerTgfbr2
esophageal carcinomaSmad4
Esophageal NeoplasmsTgfbr2
esophagus adenocarcinomaSmad4
esophagus squamous cell carcinomaTgfbr2
essential thrombocythemiaTgfb1
Experimental ArthritisTgfb1 , Tgfbr2
Experimental Autoimmune EncephalomyelitisTgfb1
Experimental ColitisSmad4
Experimental Diabetes MellitusTgfb1
Experimental Liver CirrhosisSmad2 , Smad3 , Smad4 , Tgfb1 , Tgfbr1 , Tgfbr2
Experimental Liver NeoplasmsTgfb1
Experimental Mammary NeoplasmsTgfb1 , Tgfbr1 , Tgfbr2
extrahepatic cholestasisTgfb1
Eye AbnormalitiesTgfbr2
factor VIII deficiencyTgfb1
familial hyperlipidemiaTgfb1
Familial Thoracic Aortic Aneurysm 1Smad3 , Tgfbr2
Familial Thoracic Aortic Aneurysm 6Smad3 , Tgfbr1
FatigueTgfbr2
female reproductive system diseaseSmad2
Ferguson-Smith tumorTgfbr1
FibrosisTgfb1
focal segmental glomerulosclerosisTgfb1
gallbladder cancerSmad4
Gallbladder NeoplasmsTgfb1
GallstonesSmad4
gastric adenocarcinomaSmad4
gastrointestinal stromal tumorTgfbr2
gastrointestinal system cancerSmad4
genetic diseaseSmad2 , Tgfb1 , Tgfbr2
goutTgfb1
Graves' diseaseTgfb1
Growth Mental Deficiency Syndrome of MyhreSmad4
head and neck squamous cell carcinomaSmad4
heart diseaseTgfb1
Heart InjuriesTgfb1
hemorrhagic diseaseSmad4
Hemorrhagic ShockTgfb1
hepatic encephalopathyTgfb1
Hepatic InsufficiencyTgfb1
hepatoblastomaTgfbr2
hepatocellular carcinomaSmad2 , Smad4 , Smad7 , Tgfb1 , Tgfbr2
HepatomegalyTgfb1
hereditary breast ovarian cancer syndromeSmad4 , Smad7
hereditary hemorrhagic telangiectasiaSmad4
Hereditary Hemorrhagic Telangiectasia, Type 1Smad4 , Tgfb1
Hereditary Neoplastic SyndromesSmad4
hereditary nonpolyposis colorectal cancer type 6Tgfbr2
Heterotopic OssificationSmad4
Human Viral HepatitisSmad4
HyperalgesiaTgfbr1
HyperoxiaTgfb1
HyperplasiaTgfb1 , Tgfbr2
hypertensionTgfb1
hypertrophic cardiomyopathyTgfb1
hyperuricemiaTgfb1
Hypoglossal Nerve InjuriesSmad2 , Smad3 , Smad4 , Smad7
idiopathic pulmonary fibrosisSmad2
IgA glomerulonephritisTgfb1
impotenceTgfb1
Infant, Newborn, DiseasesTgfb1
InflammationTgfb1
inflammatory bowel diseaseTgfb1
INFLAMMATORY BOWEL DISEASE, IMMUNODEFICIENCY, AND ENCEPHALOPATHYTgfb1
inguinal herniaTgfbr2
insulinomaTgfb1
intellectual disabilitySmad2 , Smad4 , Smad7 , Tgfbr1
interstitial lung diseaseTgfb1
intrahepatic cholangiocarcinomaSmad4
invasive ductal carcinomaSmad4
Joubert syndrome 1Tgfb1
juvenile polyposis syndromeSmad4
juvenile polyposis-hereditary hemorrhagic telangiectasia syndromeSmad4
juvenile rheumatoid arthritisSmad3
kidney diseaseTgfb1 , Tgfbr1 , Tgfbr2
Kidney Reperfusion InjuryTgfb1
leiomyomaSmad3 , Tgfbr1
liver cirrhosisSmad3 , Smad7 , Tgfb1 , Tgfbr1
Liver MetastasisSmad4
localized sclerodermaTgfb1
Loeys-Dietz syndromeSmad3 , Tgfbr1 , Tgfbr2
Loeys-Dietz syndrome 1Tgfbr1 , Tgfbr2
Loeys-Dietz syndrome 2Tgfbr2
Loeys-Dietz syndrome 3Smad3
Loeys-Dietz syndrome 6Smad2
Loeys-Dietz Syndrome, Type 1bTgfbr2
lung adenocarcinomaSmad4
lung cancerSmad3 , Smad4
lung diseaseTgfb1
Lung NeoplasmsTgfb1 , Tgfbr2
lung non-small cell carcinomaSmad3
Lymphatic MetastasisSmad4
Lymphomatoid PapulosisTgfb1
Lynch syndromeSmad2 , Smad3 , Smad4 , Tgfbr1 , Tgfbr2
maple syrup urine diseaseTgfb1
Marfan syndromeTgfbr1 , Tgfbr2
Marfan Syndrome Type 2Tgfbr2
Marfanoid Hypermobility SyndromeTgfbr1 , Tgfbr2
Meckel Syndrome 10Tgfb1
membranoproliferative glomerulonephritisTgfbr2
metabolic dysfunction-associated steatohepatitisSmad4
metabolic dysfunction-associated steatotic liver diseaseTgfb1
Metabolic SyndromeTgfb1
Microcephaly, Epilepsy, and Diabetes SyndromeSmad2
Microphthalmia, Cataracts, and Iris AbnormalitiesSmad4
Microsatellite InstabilityTgfbr2
middle cerebral artery infarctionTgfb1
migraineTgfbr2
mismatch repair cancer syndromeTgfbr2
multiple acyl-CoA dehydrogenase deficiencyTgfbr2
multiple myelomaTgfb1
muscular diseaseSmad4 , Tgfb1
myelofibrosisTgfb1
myocardial infarctionSmad2 , Smad3 , Smad4 , Tgfb1 , Tgfbr1 , Tgfbr2
Myocardial Reperfusion InjurySmad3 , Smad4 , Tgfb1
myoepitheliomaTgfbr1
Nasal PolypsTgfb1
Neoplasm InvasivenessTgfb1
Neoplasm MetastasisSmad4 , Tgfb1 , Tgfbr1 , Tgfbr2
Neoplastic Cell TransformationTgfb1
nephritisSmad7
nephroblastomaSmad4
nephrolithiasisTgfb1
nephronophthisisTgfbr1
nephrosclerosisTgfb1
nephrotic syndromeTgfb1
nephrotoxicityTgfb1
NeuralgiaTgfb1
neuronal ceroid lipofuscinosisSmad3
obesityTgfb1
occupational asthmaTgfb1
Occupational DiseasesTgfb1
Odontogenic CystsSmad4
oral submucous fibrosisTgfb1
osteoarthritisSmad3 , Tgfb1 , Tgfbr1
Osteoarthritis, HipSmad3
osteochondrodysplasiaTgfb1 , Tgfbr1
osteogenesis imperfectaSmad4
osteoporosisTgfb1
ovarian cancerSmad2 , Smad4
ovarian carcinomaSmad2
Ovarian NeoplasmsSmad7
pancreatic adenocarcinomaSmad4 , Smad7
pancreatic cancerSmad2 , Smad3 , Smad4 , Smad7 , Tgfb1 , Tgfbr2
pancreatic carcinomaSmad4
pancreatic ductal adenocarcinomaSmad2 , Tgfb1 , Tgfbr1
pancreatic ductal carcinomaSmad4 , Tgfb1 , Tgfbr2
papillomaTgfb1
Paraquat LungSmad7 , Tgfb1
Parasitic Liver DiseasesSmad4
Peritoneal FibrosisTgfb1
Peyronie's diseaseTgfb1
pleural diseaseTgfb1
pneumoniaTgfb1
Posterior Leukoencephalopathy SyndromeTgfb1
Postmenopausal OsteoporosisTgfb1
pre-malignant neoplasmSmad3 , Smad4
primary biliary cholangitisTgfb1
primary pulmonary hypertension 1Smad4
Progressive Diaphyseal Dysplasia 1Tgfb1
prostate adenocarcinomaSmad4
prostate cancerSmad3 , Tgfb1 , Tgfbr2
prostate carcinoma in situSmad4
Prostatic NeoplasmsSmad4 , Tgfb1 , Tgfbr2
prostatitisSmad4
proteinuriaTgfb1
psoriasisTgfb1
Pulmonary Arterial HypertensionSmad4 , Tgfbr1
pulmonary emphysemaTgfb1
pulmonary fibrosisSmad4 , Smad7 , Tgfb1 , Tgfbr2
pulmonary hypertensionSmad4 , Smad7 , Tgfb1 , Tgfbr1 , Tgfbr2
pulmonary sarcoidosisTgfb1
Radiation InjuriesTgfbr2
Radiation PneumonitisTgfb1
renal cell carcinomaSmad2 , Smad4 , Tgfb1
Reperfusion InjuryTgfbr2
rhinitisTgfb1
Right Ventricular HypertrophyTgfb1
sarcoidosisTgfb1
scimitar syndromeSmad2
seminomaSmad4
SepsisTgfb1
severe acute respiratory syndromeTgfb1
sickle cell anemiaTgfb1
Sjogren's syndromeTgfb1
Skin NeoplasmsTgfb1 , Tgfbr1
Spinal Cord InjuriesTgfb1
Spontaneous AbortionsTgfb1 , Tgfbr1
Spontaneous Neoplasm RegressionTgfb1
squamous cell carcinomaTgfb1
stomach cancerSmad4
Stomach NeoplasmsSmad4
StrokeTgfb1
systemic sclerodermaTgfbr1
thoracic aortic aneurysmSmad2 , Smad3 , Smad4 , Tgfbr1 , Tgfbr2
thrombocytopeniaTgfb1
tracheal stenosisTgfb1
transitional cell carcinomaSmad4
traumatic brain injuryTgfb1
Tubulointerstitial FibrosisSmad3 , Tgfb1
type 1 diabetes mellitusTgfb1
type 2 diabetes mellitusSmad4 , Tgfb1 , Tgfbr2
uremiaTgfb1 , Tgfbr1
ureteral obstructionSmad3 , Tgfb1
urethral obstructionTgfb1
urinary bladder cancerSmad2 , Smad4 , Tgfbr1
urticariaTgfb1
Uterine Cervical NeoplasmsSmad4
Uterine NeoplasmsSmad3
uveitisTgfb1
vascular dementiaSmad4
vasculogenic impotenceTgfbr2
Ventricular RemodelingSmad2 , Smad3 , Tgfb1
Vici syndromeSmad2
vitiligoTgfb1
Wallerian DegenerationTgfb1
Wolff-Parkinson-White syndromeTgfbr2
Wounds and InjuriesTgfb1
Pathway Annotations Associated with Genes in the altered transforming growth factor-beta Smad dependent signaling pathway
Pathway TermsGene Symbols
activin signaling pathwaySmad2 , Smad3
altered transforming growth factor-beta Smad dependent signaling pathwaySmad2 , Smad3 , Smad4 , Smad7 , Tgfb1 , Tgfbr1 , Tgfbr2
Bone morphogenetic proteins signaling pathwaySmad4 , Smad7
cell cycle pathway, mitoticSmad2 , Smad3 , Smad4 , Tgfb1
ceramide signaling pathwaySmad2 , Smad3 , Smad4 , Tgfb1 , Tgfbr1 , Tgfbr2
Chagas disease pathwaySmad2 , Smad3 , Tgfb1 , Tgfbr1 , Tgfbr2
chronic myeloid leukemia pathwaySmad3 , Smad4 , Tgfb1 , Tgfbr1 , Tgfbr2
colorectal cancer pathwaySmad2 , Smad3 , Smad4 , Smad7 , Tgfb1 , Tgfbr1 , Tgfbr2
cytokine mediated signaling pathwayTgfb1 , Tgfbr1 , Tgfbr2
dilated cardiomyopathy pathwayTgfb1
endocytosis pathwaySmad2 , Smad3 , Smad7 , Tgfb1 , Tgfbr1 , Tgfbr2
Entamoebiasis pathwayTgfb1
glypican signaling pathwaySmad2 , Tgfb1 , Tgfbr1 , Tgfbr2
hypertrophic cardiomyopathy pathwayTgfb1
hypoxia inducible factor pathwaySmad3 , Smad4
interleukin-27 signaling pathwayTgfb1
Leishmaniasis pathwayTgfb1
malaria pathwayTgfb1
mitogen activated protein kinase signaling pathwayTgfb1 , Tgfbr1 , Tgfbr2
pancreatic cancer pathwaySmad2 , Smad3 , Smad4 , Tgfb1 , Tgfbr1 , Tgfbr2
renal cell carcinoma pathwayTgfb1
rheumatoid arthritis pathwayTgfb1
syndecan signaling pathwayTgfb1
toxoplasmosis pathwayTgfb1
transforming growth factor-beta Smad dependent signaling pathwaySmad2 , Smad3 , Smad4 , Smad7 , Tgfb1 , Tgfbr1 , Tgfbr2
transforming growth factor-beta superfamily mediated signaling pathwaySmad2 , Smad3 , Smad4 , Smad7 , Tgfb1 , Tgfbr1 , Tgfbr2
tuberculosis pathwayTgfb1
type II interferon signaling pathwaySmad7
Wnt signaling pathwaySmad2 , Smad3 , Smad4
Phenotype Annotations Associated with Genes in the altered transforming growth factor-beta Smad dependent signaling pathway
Phenotype TermsGene Symbols
liver fibrosisSmad3

References Associated with the altered transforming growth factor-beta Smad dependent signaling pathway:

Ontology Path Diagram:

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Import into Pathway Studio: