Smad4 (SMAD family member 4) - Rat Genome Database

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Gene: Smad4 (SMAD family member 4) Rattus norvegicus
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Symbol: Smad4
Name: SMAD family member 4
RGD ID: 3033
Description: Enables DNA binding activity; SMAD binding activity; and filamin binding activity. Involved in several processes, including ERK1 and ERK2 cascade; cardiac muscle hypertrophy in response to stress; and positive regulation of cardiac muscle cell apoptotic process. Part of protein-containing complex. Used to study pulmonary fibrosis. Biomarker of several diseases, including artery disease (multiple); gastrointestinal system cancer (multiple); lung disease (multiple); prostatitis; and type 2 diabetes mellitus. Human ortholog(s) of this gene implicated in several diseases, including female reproductive organ cancer (multiple); hereditary hemorrhagic telangiectasia; juvenile polyposis syndrome; juvenile polyposis-hereditary hemorrhagic telangiectasia syndrome; and seminoma. Orthologous to human SMAD4 (SMAD family member 4); PARTICIPATES IN transforming growth factor-beta Smad dependent signaling pathway; altered transforming growth factor-beta Smad dependent signaling pathway; Bone morphogenetic proteins signaling pathway; INTERACTS WITH 1,2-dimethylhydrazine; 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile; 2,2,2-tetramine.
Type: protein-coding
RefSeq Status: VALIDATED
Previously known as: MAD (mothers against decapentaplegic Drosophila) homolog 4; MAD (mothers against decapentaplegic, Drosophila) homolog 4; MAD homolog 4; MAD homolog 4 (Drosophila); Madh4; mothers against decapentaplegic homolog 4; mothers against DPP homolog 4; SMAD 4
RGD Orthologs
Human
Mouse
Chinchilla
Bonobo
Dog
Squirrel
Pig
Green Monkey
Naked Mole-Rat
Black Rat
Alliance Orthologs
More Info more info ...
Latest Assembly: GRCr8 - GRCr8 Assembly
Position:
Rat AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
GRCr81869,518,988 - 69,549,684 (-)NCBIGRCr8GRCr8GRCr8
GRCr8 Ensembl1869,518,988 - 69,549,684 (-)EnsemblGRCr8
mRatBN7.21867,243,742 - 67,274,438 (-)NCBImRatBN7.2mRatBN7.2
mRatBN7.2 Ensembl1867,243,742 - 67,274,438 (-)EnsemblmRatBN7.2
UTH_Rnor_SHR_Utx1869,351,818 - 69,382,528 (-)NCBIUTH_Rnor_SHR_UtxUTH_Rnor_SHR_Utx
UTH_Rnor_SHRSP_BbbUtx_1.01870,026,538 - 70,057,217 (-)NCBIUTH_Rnor_SHRSP_BbbUtx_1.0UTH_Rnor_SHRSP_BbbUtx_1.0
UTH_Rnor_WKY_Bbb_1.01867,891,801 - 67,922,479 (-)NCBIUTH_Rnor_WKY_Bbb_1.0UTH_Rnor_WKY_Bbb_1.0
Rnor_6.01869,626,682 - 69,657,373 (-)NCBIRnor_6.0Rnor_6.0rn6Rnor6.0
Rnor_6.0 Ensembl1869,627,757 - 69,671,199 (-)Ensemblrn6Rnor6.0
Rnor_5.01868,773,326 - 68,802,354 (-)NCBIRnor_5.0Rnor_5.0rn5
RGSC_v3.41870,432,705 - 70,461,541 (-)NCBIRGSC_v3.4RGSC_v3.4rn4
Celera1865,246,042 - 65,276,480 (-)NCBICelera
RGSC_v3.11870,504,785 - 70,534,814 (-)NCBI
Cytogenetic Map18q12.2NCBI
JBrowse:




Disease Annotations     Click to see Annotation Detail View
Acro-Osteolysis  (ISO)
aortic disease  (ISO)
brachydactyly  (ISO)
breast cancer  (ISO)
Breast Neoplasms  (ISO)
cervical cancer  (ISO)
cholangiocarcinoma  (ISO)
Chronic Hepatitis C  (ISO)
chronic myeloid leukemia  (ISO)
chronic obstructive pulmonary disease  (IEP)
Cicatrix  (IMP)
cognitive disorder  (ISO)
colon cancer  (IEP,ISO)
colon carcinoma  (ISO)
colorectal adenoma  (ISO)
colorectal cancer  (ISO)
colorectal carcinoma  (ISO)
Colorectal Neoplasms  (ISO)
Craniofacial Abnormalities  (ISO)
Cronkhite-Canada syndrome  (ISO)
Deafness  (ISO)
Desbuquois dysplasia  (ISO)
endometrial carcinoma  (ISO)
esophageal carcinoma  (ISO)
esophagus adenocarcinoma  (ISO)
Experimental Colitis  (ISO)
Experimental Liver Cirrhosis  (IEP,ISO)
Familial Pancreatic Carcinoma  (ISO)
gallbladder cancer  (ISO)
Gallstones  (ISO)
gastrointestinal system cancer  (ISO)
Growth Mental Deficiency Syndrome of Myhre  (ISO)
head and neck squamous cell carcinoma  (ISO)
hemorrhagic disease  (ISO)
hepatocellular carcinoma  (IEP,ISO)
hereditary breast ovarian cancer syndrome  (ISO)
hereditary hemorrhagic telangiectasia  (ISO)
Hereditary Hemorrhagic Telangiectasia, Type 1  (ISO)
Hereditary Neoplastic Syndromes  (ISO)
Heterotopic Ossification  (IMP)
Human Viral Hepatitis  (ISO)
Hypoglossal Nerve Injuries  (IEP)
intellectual disability  (ISO)
intrahepatic cholangiocarcinoma  (ISO)
invasive ductal carcinoma  (ISO)
juvenile polyposis syndrome  (ISO,ISS)
juvenile polyposis-hereditary hemorrhagic telangiectasia syndrome  (ISO)
Liver Metastasis  (ISO)
lung adenocarcinoma  (ISO)
lung cancer  (ISO)
Lymphatic Metastasis  (ISO)
Lynch syndrome  (ISO)
Marfan syndrome  (ISO)
metabolic dysfunction-associated steatohepatitis  (ISO)
Microphthalmia, Cataracts, and Iris Abnormalities  (ISO)
muscular disease  (ISO)
myocardial infarction  (IEP)
Myocardial Reperfusion Injury  (IEP)
Neoplasm Metastasis  (ISO)
nephroblastoma  (ISO)
Odontogenic Cysts  (ISO)
osteogenesis imperfecta  (ISS)
ovarian cancer  (ISO)
pancreatic cancer  (ISO)
pancreatic carcinoma  (ISO)
pancreatic ductal carcinoma  (ISO)
Parasitic Liver Diseases  (ISO)
pre-malignant neoplasm  (IEP)
primary pulmonary hypertension 1  (ISO)
prostate carcinoma in situ  (ISO)
Prostatic Neoplasms  (ISO)
prostatitis  (IEP)
Pulmonary Arterial Hypertension  (ISO)
pulmonary fibrosis  (IDA,IEP)
pulmonary hypertension  (IEP)
renal cell carcinoma  (ISO)
seminoma  (ISO)
stomach cancer  (ISO)
Stomach Neoplasms  (ISO)
thoracic aortic aneurysm  (ISO)
transitional cell carcinoma  (ISO)
type 2 diabetes mellitus  (IEP)
urinary bladder cancer  (ISO)
Uterine Cervical Neoplasms  (ISO)
vascular dementia  (ISO)

Gene-Chemical Interaction Annotations     Click to see Annotation Detail View
(-)-demecolcine  (ISO)
(-)-epigallocatechin 3-gallate  (ISO)
(1->4)-beta-D-glucan  (ISO)
(R,R,R)-alpha-tocopherol  (ISO)
1,2-dimethylhydrazine  (EXP,ISO)
1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile  (EXP)
17alpha-ethynylestradiol  (ISO)
17beta-estradiol  (ISO)
17beta-hydroxy-5alpha-androstan-3-one  (ISO)
2,2,2-tetramine  (EXP)
2,3',4,4',5-Pentachlorobiphenyl  (ISO)
2,3,7,8-tetrachlorodibenzodioxine  (EXP,ISO)
2,4-dinitrotoluene  (EXP)
2-acetamidofluorene  (EXP)
2-methoxyethanol  (EXP)
3H-1,2-dithiole-3-thione  (EXP)
4,4'-sulfonyldiphenol  (ISO)
5-fluorouracil  (ISO)
6-propyl-2-thiouracil  (EXP)
acetaldehyde  (ISO)
aflatoxin B1  (ISO)
aldehydo-D-glucose  (EXP,ISO)
all-trans-retinoic acid  (ISO)
amlodipine  (ISO)
ammonium chloride  (EXP)
Aroclor 1254  (ISO)
arsane  (ISO)
arsenic atom  (ISO)
arsenous acid  (ISO)
bellidifolin  (EXP,ISO)
benzo[a]pyrene diol epoxide I  (ISO)
bis(2-ethylhexyl) phthalate  (ISO)
bisphenol A  (EXP,ISO)
bisphenol AF  (ISO)
bisphenol F  (ISO)
cadmium atom  (EXP,ISO)
cadmium dichloride  (ISO)
Candesartan cilexetil  (EXP)
carbamazepine  (ISO)
carbon nanotube  (ISO)
CGP 52608  (ISO)
chlordecone  (ISO)
chlorpyrifos  (ISO)
chromium atom  (EXP)
citalopram  (EXP)
copper atom  (ISO)
copper(0)  (ISO)
copper(II) sulfate  (ISO)
curcumin  (EXP,ISO)
cyclosporin A  (ISO)
D-glucose  (EXP,ISO)
DDE  (ISO)
deguelin  (ISO)
dexamethasone  (ISO)
dextran sulfate  (ISO)
diarsenic trioxide  (ISO)
dibenziodolium  (EXP)
Dibutyl phosphate  (ISO)
diclofenac  (ISO)
dimethyl sulfoxide  (ISO)
dorsomorphin  (ISO)
doxazosin  (ISO)
doxorubicin  (EXP,ISO)
enzyme inhibitor  (ISO)
escitalopram  (EXP)
ethanol  (ISO)
Evodiamine  (EXP,ISO)
farrerol  (EXP)
fenofibrate  (ISO)
folic acid  (ISO)
galangin  (ISO)
gallic acid  (ISO)
gentamycin  (EXP)
glucose  (EXP,ISO)
glycerol 2-phosphate  (ISO)
glycyrrhizinic acid  (ISO)
glyphosate  (ISO)
hexadecanoic acid  (ISO)
icariin  (ISO)
Isoangustone A  (ISO)
ivermectin  (ISO)
L-ascorbic acid  (ISO)
leptomycin B  (ISO)
lipopolysaccharide  (ISO)
manganese atom  (ISO)
manganese(0)  (ISO)
manganese(II) chloride  (ISO)
Methylazoxymethanol acetate  (EXP)
methylisothiazolinone  (ISO)
methylmercury chloride  (ISO)
monosodium L-glutamate  (EXP)
N-ethyl-N-nitrosourea  (ISO)
N-methyl-4-phenylpyridinium  (ISO)
N-methyl-N-nitrosourea  (ISO)
N-nitrosodiethylamine  (EXP,ISO)
nitrates  (ISO)
nitric oxide  (EXP)
nitrofen  (ISO)
osthole  (ISO)
ouabain  (ISO)
paracetamol  (ISO)
patulin  (EXP)
pentacarbonyliron  (ISO)
perfluorooctane-1-sulfonic acid  (ISO)
phenylmercury acetate  (ISO)
phosphane  (EXP)
picoxystrobin  (ISO)
platycodin D  (ISO)
progesterone  (ISO)
quercetin  (ISO)
resveratrol  (EXP,ISO)
rolipram  (ISO)
rotenone  (EXP)
rutin  (EXP)
SB 431542  (ISO)
sodium arsenite  (EXP,ISO)
streptozocin  (EXP,ISO)
tamibarotene  (ISO)
testosterone enanthate  (ISO)
tetrachloromethane  (EXP)
theobromine  (EXP)
titanium dioxide  (ISO)
trichostatin A  (ISO)
triphenyl phosphate  (ISO)
triptonide  (ISO)
troglitazone  (ISO)
valproic acid  (ISO)
vanadyl sulfate  (ISO)
vincristine  (ISO)
vorinostat  (ISO)

Gene Ontology Annotations     Click to see Annotation Detail View

Biological Process
adrenal gland development  (IEP)
anatomical structure morphogenesis  (IBA)
anterior/posterior pattern specification  (ISO)
atrioventricular canal development  (IEA,ISO)
atrioventricular valve formation  (IEA,ISO)
axon guidance  (ISO)
BMP signaling pathway  (IBA,IEA,ISO)
brainstem development  (ISO)
branching involved in ureteric bud morphogenesis  (ISO)
cardiac muscle hypertrophy in response to stress  (IMP)
cardiac septum development  (IEA,ISO)
cell differentiation  (IBA)
cell population proliferation  (ISO)
cellular response to glucose stimulus  (IDA)
cellular response to transforming growth factor beta stimulus  (IEA,ISO)
developmental growth  (ISO)
DNA-templated transcription  (IEA,ISO)
embryonic digit morphogenesis  (IEA,ISO)
endocardial cell differentiation  (IEA,ISO)
endoderm development  (ISO)
endothelial cell activation  (IEA,ISO)
epithelial cell migration  (IEA,ISO)
epithelial to mesenchymal transition  (IEA,ISO)
epithelial to mesenchymal transition involved in endocardial cushion formation  (IEA,ISO)
ERK1 and ERK2 cascade  (IMP)
extrinsic apoptotic signaling pathway  (IEA,ISO)
female gonad development  (ISO)
female gonad morphogenesis  (ISO)
formation of anatomical boundary  (ISO)
gastrulation  (ISO)
gastrulation with mouth forming second  (ISO)
in utero embryonic development  (ISO)
interleukin-6-mediated signaling pathway  (IEA,ISO)
intracellular iron ion homeostasis  (IEA,ISO)
intracellular signal transduction  (IEA,ISO)
kidney development  (ISO)
left ventricular cardiac muscle tissue morphogenesis  (IEA,ISO)
male gonad development  (ISO)
mesoderm development  (ISO)
metanephric mesenchyme morphogenesis  (IEA,ISO)
negative regulation of canonical Wnt signaling pathway  (ISO)
negative regulation of cardiac muscle hypertrophy  (IEA,ISO)
negative regulation of cardiac myofibril assembly  (IEA,ISO)
negative regulation of cell growth  (IEA,ISO)
negative regulation of cell population proliferation  (ISO)
negative regulation of DNA-templated transcription  (IEA,ISO)
negative regulation of ERK1 and ERK2 cascade  (IEA,ISO)
negative regulation of protein catabolic process  (IMP)
negative regulation of transcription by RNA polymerase II  (IEA,ISO)
nephrogenic mesenchyme morphogenesis  (IEA,ISO)
neural crest cell differentiation  (ISO)
neuron fate commitment  (ISO)
neuron fate specification  (IEA,ISO)
osteoblast differentiation  (IMP)
outflow tract septum morphogenesis  (IEA,ISO)
ovarian follicle development  (IEA,IEP,ISO)
positive regulation of cardiac muscle cell apoptotic process  (IMP)
positive regulation of cell proliferation involved in heart valve morphogenesis  (IEA,ISO)
positive regulation of DNA-templated transcription  (IEA,ISO)
positive regulation of epithelial to mesenchymal transition  (IEA,ISO)
positive regulation of extracellular matrix assembly  (IEA,ISO)
positive regulation of follicle-stimulating hormone secretion  (ISO)
positive regulation of gene expression  (IEA,ISO)
positive regulation of luteinizing hormone secretion  (ISO)
positive regulation of miRNA transcription  (IEA,ISO)
positive regulation of SMAD protein signal transduction  (IEA,ISO)
positive regulation of transcription by RNA polymerase II  (IEA,ISO)
positive regulation of transforming growth factor beta receptor signaling pathway  (IEA,ISO)
regulation of cell population proliferation  (ISO)
regulation of DNA-templated transcription  (IEA)
regulation of hair follicle development  (ISO)
regulation of macromolecule metabolic process  (IEA)
regulation of primary metabolic process  (IEA)
regulation of transcription by RNA polymerase II  (IBA,ISO)
regulation of transforming growth factor beta2 production  (IEA,ISO)
response to hypoxia  (IEA,ISO)
response to transforming growth factor beta  (IEA,ISO)
sebaceous gland development  (ISO)
secondary palate development  (IEA,ISO)
seminiferous tubule development  (ISO)
single fertilization  (ISO)
SMAD protein signal transduction  (IBA,IEA,ISO)
somite rostral/caudal axis specification  (ISO)
spermatogenesis  (ISO)
tissue morphogenesis  (ISO)
transforming growth factor beta receptor signaling pathway  (IBA,IEA,ISO)
uterus development  (ISO)
ventricular septum morphogenesis  (IEA,ISO)

Cellular Component

References

References - curated
# Reference Title Reference Citation
1. Insulin-like growth factor-binding protein-5-induced laminin gamma1 transcription requires filamin A. Abrass CK and Hansen KM, J Biol Chem. 2010 Apr 23;285(17):12925-34. doi: 10.1074/jbc.M109.061754. Epub 2010 Feb 18.
2. Molecular mechanisms of TGF beta receptor-triggered signaling cascades rapidly induced by the calcineurin inhibitors cyclosporin A and FK506. Akool el-S, etal., J Immunol. 2008 Aug 15;181(4):2831-45.
3. SMAD4 mutation segregating in a family with juvenile polyposis, aortopathy, and mitral valve dysfunction. Andrabi S, etal., Am J Med Genet A. 2011 May;155A(5):1165-9. doi: 10.1002/ajmg.a.33968. Epub 2011 Apr 4.
4. Genotype-defined cancer risk in juvenile polyposis syndrome. Aytac E, etal., Br J Surg. 2015 Jan;102(1):114-8. doi: 10.1002/bjs.9693. Epub 2014 Nov 12.
5. Smad4 loss in mice causes spontaneous head and neck cancer with increased genomic instability and inflammation. Bornstein S, etal., J Clin Invest. 2009 Nov;119(11):3408-19. doi: 10.1172/JCI38854. Epub 2009 Oct 19.
6. A novel SMAD4 gene mutation in seminoma germ cell tumors. Bouras M, etal., Cancer Res. 2000 Feb 15;60(4):922-8.
7. Transforming growth factor-beta pathway in human renal cell carcinoma and surrounding normal-appearing renal parenchyma. Cardillo MR, etal., Anal Quant Cytol Histol. 2001 Apr;23(2):109-17.
8. [Effect of Budesonide on Smad4, PDGF-A and PAI-1 in a rat model of pulmonary fibrosis]. Chen JP, etal., Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2012 May;28(5):478-80.
9. Hepatocyte growth factor antagonizes the profibrotic action of TGF-beta1 in mesangial cells by stabilizing Smad transcriptional corepressor TGIF. Dai C and Liu Y, J Am Soc Nephrol. 2004 Jun;15(6):1402-12.
10. Emodin protects rat liver from CCl(4)-induced fibrogenesis via inhibition of hepatic stellate cells activation. Dong MX, etal., World J Gastroenterol. 2009 Oct 14;15(38):4753-62.
11. [Effect of schisandrin B on lung mRNA expression of transforming growth factor-beta1 signal transduction molecule in rat lungs exposed to silica]. Fan LH, etal., Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2011 Apr;29(4):255-9.
12. Zhonghua zhong liu za zhi [Chinese journal of oncology] Fan Z, etal., Zhonghua Zhong Liu Za Zhi. 2001 Mar;23(2):135-7.
13. Overlapping spectra of SMAD4 mutations in juvenile polyposis (JP) and JP-HHT syndrome. Gallione C, etal., Am J Med Genet A. 2010 Feb;152A(2):333-9. doi: 10.1002/ajmg.a.33206.
14. SMAD4 mutations found in unselected HHT patients. Gallione CJ, etal., J Med Genet. 2006 Oct;43(10):793-7. Epub 2006 Apr 13.
15. A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4). Gallione CJ, etal., Lancet. 2004 Mar 13;363(9412):852-9.
16. Disruption of Smad4 in odontoblasts causes multiple keratocystic odontogenic tumors and tooth malformation in mice. Gao Y, etal., Mol Cell Biol. 2009 Nov;29(21):5941-51. doi: 10.1128/MCB.00706-09. Epub 2009 Aug 24.
17. Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Gaudet P, etal., Brief Bioinform. 2011 Sep;12(5):449-62. doi: 10.1093/bib/bbr042. Epub 2011 Aug 27.
18. Rat ISS GO annotations from GOA human gene data--August 2006 GOA data from the GO Consortium
19. Interaction between angiotensin II and Smad proteins in fibroblasts in failing heart and in vitro. Hao J, etal., Am J Physiol Heart Circ Physiol. 2000 Dec;279(6):H3020-30.
20. Tumor suppression effects of bilberry extracts and enzymatically modified isoquercitrin in early preneoplastic liver cell lesions induced by piperonyl butoxide promotion in a two-stage rat hepatocarcinogenesis model. Hara S, etal., Exp Toxicol Pathol. 2014 Aug;66(5-6):225-34. doi: 10.1016/j.etp.2014.02.002. Epub 2014 Mar 26.
21. Prevalence of thoracic aortopathy in patients with juvenile Polyposis Syndrome-Hereditary Hemorrhagic Telangiectasia due to SMAD4. Heald B, etal., Am J Med Genet A. 2015 Aug;167A(8):1758-62. doi: 10.1002/ajmg.a.37093. Epub 2015 Apr 30.
22. Loss of BMP2, Smad8, and Smad4 expression in prostate cancer progression. Horvath LG, etal., Prostate. 2004 May 15;59(3):234-42.
23. Common deletion of SMAD4 in juvenile polyposis is a mutational hotspot. Howe JR, etal., Am J Hum Genet. 2002 May;70(5):1357-62. Epub 2002 Mar 27.
24. Mutations in the SMAD4/DPC4 gene in juvenile polyposis. Howe JR, etal., Science. 1998 May 15;280(5366):1086-8.
25. [Changes in TGF-beta1/Smads signaling pathway in rats with chemical hepatocarcinogenesis]. Hua YP, etal., Nan Fang Yi Ke Da Xue Xue Bao. 2008 Oct;28(10):1848-52.
26. Effect of wound type on Smad 2 and 4 translocation. Hutcheon AE, etal., Invest Ophthalmol Vis Sci. 2005 Jul;46(7):2362-8.
27. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Jones S, etal., Science. 2008 Sep 26;321(5897):1801-6. Epub 2008 Sep 4.
28. SMAD4 germinal mosaicism in a family with juvenile polyposis and hypertrophic osteoarthropathy. Lamireau T, etal., J Pediatr Gastroenterol Nutr. 2005 Jul;41(1):117-20.
29. Mutations at a single codon in Mad homology 2 domain of SMAD4 cause Myhre syndrome. Le Goff C, etal., Nat Genet. 2011 Dec 11;44(1):85-8. doi: 10.1038/ng.1016.
30. Expression of DPC4/Smad4 gene in stone-containing intrahepatic bile duct. Lee KT, etal., J Surg Oncol. 2006 Sep 15;94(4):338-43. doi: 10.1002/jso.20517.
31. Expression of Smad2 and Smad4, transforming growth factor-beta signal transducers in rat endometrium during the estrous cycle, pre-, and peri-implantation. Lin HY, etal., Anim Reprod Sci 2004 Feb;80(3-4):303-16.
32. Activation of TGF-beta-Smad signaling pathway following polyamine depletion in intestinal epithelial cells. Liu L, etal., Am J Physiol Gastrointest Liver Physiol 2003 Nov;285(5):G1056-67. Epub 2003 Jul 10.
33. cAMP inhibits transforming growth factor-beta-stimulated collagen synthesis via inhibition of extracellular signal-regulated kinase 1/2 and Smad signaling in cardiac fibroblasts. Liu X, etal., Mol Pharmacol. 2006 Dec;70(6):1992-2003. Epub 2006 Sep 7.
34. Inactivation of Smad4 leads to impaired ocular development and cataract formation. Liu Y, etal., Biochem Biophys Res Commun. 2010 Oct 1;400(4):476-82. doi: 10.1016/j.bbrc.2010.08.065. Epub 2010 Aug 22.
35. Expression and location of Smad2, 4 mRNAs during and after liver fibrogenesis of rats. Liu Y, etal., World J Gastroenterol. 2006 Mar 14;12(10):1577-82.
36. Loss of Smad4 expression predicts liver metastasis in human colorectal cancer. Losi L, etal., Oncol Rep. 2007 May;17(5):1095-9.
37. Effects of platycodins on liver complications of type 2 diabetes. Luan H, etal., Mol Med Rep. 2014 Sep;10(3):1597-603. doi: 10.3892/mmr.2014.2363. Epub 2014 Jul 4.
38. Downregulation of secretory leukocyte proteinase inhibitor in chronic obstructive lung disease: the role of TGF-beta/Smads signaling pathways. Luo BL, etal., Arch Med Res. 2008 May;39(4):388-96. doi: 10.1016/j.arcmed.2008.02.002.
39. Loss of expression, and mutations of Smad 2 and Smad 4 in human cervical cancer. Maliekal TT, etal., Oncogene. 2003 Jul 31;22(31):4889-97.
40. TGFbeta in Cancer. Massagué J, Cell. 2008 Jul 25;134(2):215-30. doi: 10.1016/j.cell.2008.07.001.
41. Rat ISS GO annotations from MGI mouse gene data--August 2006 MGD data from the GO Consortium
42. Expression of Smad4 during rat ovarian development. Miao ZL, etal., Di Yi Jun Yi Da Xue Xue Bao. 2005 Feb;25(2):127-31.
43. KAI1, CAR, and Smad4 expression in the progression of colorectal tumor. Mikami T, etal., J Gastroenterol. 2001 Jul;36(7):465-9. doi: 10.1007/s005350170069.
44. Higher frequency of Smad4 gene mutation in human colorectal cancer with distant metastasis. Miyaki M, etal., Oncogene. 1999 May 20;18(20):3098-103. doi: 10.1038/sj.onc.1202642.
45. SMAD4 gene mutation predicts poor prognosis in patients undergoing resection for colorectal liver metastases. Mizuno T, etal., Eur J Surg Oncol. 2018 May;44(5):684-692. doi: 10.1016/j.ejso.2018.02.247. Epub 2018 Mar 7.
46. Dysregulated bone morphogenetic protein signaling in monocrotaline-induced pulmonary arterial hypertension. Morty RE, etal., Arterioscler Thromb Vasc Biol. 2007 May;27(5):1072-8. Epub 2007 Mar 8.
47. Significance of pSmad2/3 and Smad4 in hepatitis C virus-related liver fibrosis and hepatocellular carcinoma. Moussa MM, etal., APMIS. 2018 Jun;126(6):477-485. doi: 10.1111/apm.12844.
48. Electronic Transfer of LocusLink and RefSeq Data NCBI rat LocusLink and RefSeq merged data July 26, 2002
49. Altered expression of Smad family members in injured motor neurons of rat. Okuyama N, etal., Brain Res. 2007 Feb 9;1132(1):36-41. Epub 2006 Dec 12.
50. OMIM Disease Annotation Pipeline OMIM Disease Annotation Pipeline
51. Expression and localization of the transforming growth factor-beta type I receptor and Smads in preneoplastic lesions during chemical hepatocarcinogenesis in rats. Park do Y, etal., J Korean Med Sci 2003 Aug;18(4):510-9.
52. TGF-beta signaling is disrupted in endometrioid-type endometrial carcinomas. Piestrzeniewicz-Ulanska D, etal., Gynecol Oncol. 2004 Oct;95(1):173-80.
53. KEGG Annotation Import Pipeline Pipeline to import KEGG annotations from KEGG into RGD
54. PID Annotation Import Pipeline Pipeline to import Pathway Interaction Database annotations from NCI into RGD
55. Deletion of Smad4 reduces hepatic inflammation and fibrogenesis during nonalcoholic steatohepatitis progression. Qin G, etal., J Dig Dis. 2018 May;19(5):301-313. doi: 10.1111/1751-2980.12599. Epub 2018 Jun 6.
56. Smad signaling in the rat model of monocrotaline pulmonary hypertension. Ramos MF, etal., Toxicol Pathol. 2008 Feb;36(2):311-20. doi: 10.1177/0192623307311402. Epub 2008 Mar 26.
57. GOA pipeline RGD automated data pipeline
58. ClinVar Automated Import and Annotation Pipeline RGD automated import pipeline for ClinVar variants, variant-to-disease annotations and gene-to-disease annotations
59. Data Import for Chemical-Gene Interactions RGD automated import pipeline for gene-chemical interactions
60. Age-dependent expression of Pten and Smad4 genes in the urogenital system of Wistar rats. Rocha BR, etal., Acta Cir Bras. 2014;29 Suppl 1:34-8.
61. Mutation analysis of SMAD2, SMAD3, and SMAD4 genes in hereditary non-polyposis colorectal. Roth S, etal., J Med Genet. 2000 Apr;37(4):298-300.
62. SMAD proteins are involved in apoptosis induction in ventricular cardiomyocytes. Schneiders D, etal., Cardiovasc Res. 2005 Jul 1;67(1):87-96. Epub 2005 Mar 23.
63. BMP type I receptor ALK2 is required for angiotensin II-induced cardiac hypertrophy. Shahid M, etal., Am J Physiol Heart Circ Physiol. 2016 Apr 15;310(8):H984-94. doi: 10.1152/ajpheart.00879.2015. Epub 2016 Feb 12.
64. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Shi Y and Massague J, Cell. 2003 Jun 13;113(6):685-700.
65. Oncopreventive effects of theanine and theobromine on dimethylhydrazine-induced colon cancer model. Shojaei-Zarghani S, etal., Biomed Pharmacother. 2021 Feb;134:111140. doi: 10.1016/j.biopha.2020.111140. Epub 2020 Dec 24.
66. Association between Altered Expression and Genetic Variations of Transforming Growth Factor ß-Smad Pathway with Chronic Myeloid Leukemia. Shokeen Y, etal., Int J Hematol Oncol Stem Cell Res. 2018 Jan 1;12(1):14-22.
67. Smad4 mediates activation of mitogen-activated protein kinases by TGF-beta in pancreatic acinar cells. Simeone DM, etal., Am J Physiol Cell Physiol. 2001 Jul;281(1):C311-9.
68. Expression profiling identifies altered expression of genes that contribute to the inhibition of transforming growth factor-beta signaling in ovarian cancer. Sunde JS, etal., Cancer Res. 2006 Sep 1;66(17):8404-12.
69. SMAD4 haploinsufficiency associates with augmented colonic inflammation in select humans and mice. Szigeti R, etal., Ann Clin Lab Sci. 2012 Fall;42(4):401-8.
70. Localization of 54 rat genes, and definition of new synteny groups conserved in the human and the rat. Szpirer C, etal., Mamm Genome 2000 Sep;11(9):729-35
71. Biologically different subgroups of invasive ductal carcinoma of the pancreas: Dpc4 status according to the ratio of intraductal carcinoma components. Takahashi H, etal., Clin Cancer Res. 2004 Jun 1;10(11):3772-9. doi: 10.1158/1078-0432.CCR-03-0120.
72. Allelic imbalance in chromosome band 18q21 and SMAD4 mutations in ovarian cancers. Takakura S, etal., Genes Chromosomes Cancer. 1999 Mar;24(3):264-71.
73. Inhibiting scar formation in vitro and in vivo by adenovirus-mediated mutant Smad4: a preliminary report. Tan WQ, etal., Exp Dermatol. 2011 Feb;20(2):119-24. doi: 10.1111/j.1600-0625.2010.01186.x.
74. [Smad4 and TGF-beta1 expression and clinical significance in bladder transitional cell carcinoma] Tang ZY, etal., Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2006 Jun;31(3):363-6.
75. Tentative Sequence Identification Numbers Tentative Sequence Data IDs. TIGR Gene Index, Rat Data
76. Activin signal transduction in the fetal rat adrenal gland and in human H295R cells. Wang EY, etal., J Endocrinol 2003 Jul;178(1):137-48.
77. MicroRNA-224 targets SMAD family member 4 to promote cell proliferation and negatively influence patient survival. Wang Y, etal., PLoS One. 2013 Jul 29;8(7):e68744. doi: 10.1371/journal.pone.0068744. Print 2013.
78. [Expressions of transforming growth factor-beta(1) and Smad4 in rat models of chronic nonbacterial prostatitis and their clinical significance]. Wang YM, etal., Zhonghua Nan Ke Xue. 2010 Jun;16(6):490-4.
79. Treatment with cardiotonic pills(®) after ischemia-reperfusion ameliorates myocardial fibrosis in rats. Wei XH, etal., Microcirculation. 2013 Jan;20(1):17-29. doi: 10.1111/micc.12002.
80. Targeting RICTOR Sensitizes SMAD4-Negative Colon Cancer to Irinotecan. Wong CK, etal., Mol Cancer Res. 2020 Mar;18(3):414-423. doi: 10.1158/1541-7786.MCR-19-0525. Epub 2020 Jan 13.
81. Pancreatic cancer: molecular pathogenesis and new therapeutic targets. Wong HH and Lemoine NR, Nat Rev Gastroenterol Hepatol. 2009 Jul;6(7):412-22. Epub 2009 Jun 9.
82. Comprehensive analysis of SMAD4 mutations and protein expression in juvenile polyposis: evidence for a distinct genetic pathway and polyp morphology in SMAD4 mutation carriers. Woodford-Richens KL, etal., Am J Pathol. 2001 Oct;159(4):1293-300.
83. Alterations of Smad signaling in human breast carcinoma are associated with poor outcome: a tissue microarray study. Xie W, etal., Cancer Res. 2002 Jan 15;62(2):497-505.
84. TGF-beta signaling alterations and susceptibility to colorectal cancer. Xu Y and Pasche B, Hum Mol Genet. 2007 Apr 15;16 Spec No 1:R14-20.
85. Non-virus-mediated transfer of siRNAs against Runx2 and Smad4 inhibit heterotopic ossification in rats. Xue T, etal., Gene Ther. 2010 Mar;17(3):370-9. doi: 10.1038/gt.2009.154. Epub 2009 Nov 26.
86. Reduced Expression of SMAD4 Is Associated with Poor Survival in Colon Cancer. Yan P, etal., Clin Cancer Res. 2016 Jun 15;22(12):3037-47. doi: 10.1158/1078-0432.CCR-15-0939. Epub 2016 Feb 9.
87. Inactivation of Smad4 is a prognostic factor in intrahepatic cholangiocarcinoma. Yan XQ, etal., Chin Med J (Engl). 2013 Aug;126(16):3039-43.
88. Smad4 expression in hepatocellular carcinoma differs by hepatitis status. Yao L, etal., Asian Pac J Cancer Prev. 2012;13(4):1297-303. doi: 10.7314/apjcp.2012.13.4.1297.
89. Apoptosis incidence and protein expression of p53, TGF-beta receptor II, p27Kip1, and Smad4 in benign, premalignant, and malignant human prostate. Zeng L, etal., Hum Pathol. 2004 Mar;35(3):290-7.
90. Smad3 prevents beta-catenin degradation and facilitates beta-catenin nuclear translocation in chondrocytes. Zhang M, etal., J Biol Chem. 2010 Mar 19;285(12):8703-10. doi: 10.1074/jbc.M109.093526. Epub 2010 Jan 22.
91. [High glucose induces sumoylation of Smad4 via SUMO2/3 in glomerular mesangial cells]. Zhou XQ, etal., Sichuan Da Xue Xue Bao Yi Xue Ban. 2014 May;45(3):380-5.
92. Involvement of mutations in the DPC4 promoter in endometrial carcinoma development. Zhou Y, etal., Mol Carcinog. 1999 May;25(1):64-72.
Additional References at PubMed
PMID:8774881   PMID:9111321   PMID:9256479   PMID:9288972   PMID:9311995   PMID:9389648   PMID:9420335   PMID:9506519   PMID:9702197   PMID:9707553   PMID:9732876   PMID:10626800  
PMID:10647180   PMID:10670756   PMID:10708962   PMID:10823886   PMID:11197776   PMID:11809702   PMID:12161428   PMID:12270938   PMID:12374795   PMID:12411310   PMID:12943993   PMID:14559231  
PMID:14633973   PMID:14691138   PMID:14764653   PMID:15215210   PMID:15282343   PMID:15342483   PMID:15344310   PMID:15459107   PMID:15657445   PMID:15925496   PMID:16007207   PMID:16151019  
PMID:16330325   PMID:16556916   PMID:16777850   PMID:17159989   PMID:17438144   PMID:17568773   PMID:17628518   PMID:17698011   PMID:18212064   PMID:18539898   PMID:18692037   PMID:18832382  
PMID:18986983   PMID:19251704   PMID:19328798   PMID:19366691   PMID:19366699   PMID:19415695   PMID:19793887   PMID:19796622   PMID:20926379   PMID:21300867   PMID:21330551   PMID:21724602  
PMID:21828274   PMID:21988832   PMID:22316667   PMID:22506032   PMID:22507670   PMID:22735812   PMID:23034633   PMID:23426367   PMID:24739304   PMID:24866243   PMID:24971350   PMID:25178280  
PMID:25514493   PMID:25609649   PMID:26494787   PMID:26699655   PMID:28791348   PMID:29183317   PMID:29199336   PMID:31346987   PMID:31582430   PMID:34889563  


Genomics

Comparative Map Data
Smad4
(Rattus norvegicus - Norway rat)
Rat AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
GRCr81869,518,988 - 69,549,684 (-)NCBIGRCr8GRCr8GRCr8
GRCr8 Ensembl1869,518,988 - 69,549,684 (-)EnsemblGRCr8
mRatBN7.21867,243,742 - 67,274,438 (-)NCBImRatBN7.2mRatBN7.2
mRatBN7.2 Ensembl1867,243,742 - 67,274,438 (-)EnsemblmRatBN7.2
UTH_Rnor_SHR_Utx1869,351,818 - 69,382,528 (-)NCBIUTH_Rnor_SHR_UtxUTH_Rnor_SHR_Utx
UTH_Rnor_SHRSP_BbbUtx_1.01870,026,538 - 70,057,217 (-)NCBIUTH_Rnor_SHRSP_BbbUtx_1.0UTH_Rnor_SHRSP_BbbUtx_1.0
UTH_Rnor_WKY_Bbb_1.01867,891,801 - 67,922,479 (-)NCBIUTH_Rnor_WKY_Bbb_1.0UTH_Rnor_WKY_Bbb_1.0
Rnor_6.01869,626,682 - 69,657,373 (-)NCBIRnor_6.0Rnor_6.0rn6Rnor6.0
Rnor_6.0 Ensembl1869,627,757 - 69,671,199 (-)Ensemblrn6Rnor6.0
Rnor_5.01868,773,326 - 68,802,354 (-)NCBIRnor_5.0Rnor_5.0rn5
RGSC_v3.41870,432,705 - 70,461,541 (-)NCBIRGSC_v3.4RGSC_v3.4rn4
Celera1865,246,042 - 65,276,480 (-)NCBICelera
RGSC_v3.11870,504,785 - 70,534,814 (-)NCBI
Cytogenetic Map18q12.2NCBI
SMAD4
(Homo sapiens - human)
Human AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
GRCh381851,030,213 - 51,085,042 (+)NCBIGRCh38GRCh38hg38GRCh38
GRCh38.p14 Ensembl1851,028,528 - 51,085,045 (+)Ensemblhg38GRCh38
GRCh371848,556,583 - 48,611,412 (+)NCBIGRCh37GRCh37hg19GRCh37
Build 361846,810,611 - 46,860,145 (+)NCBIBuild 36Build 36hg18NCBI36
Build 341846,810,610 - 46,860,144NCBI
Celera1845,413,367 - 45,468,195 (+)NCBICelera
Cytogenetic Map18q21.2NCBI
HuRef1845,411,927 - 45,466,923 (+)NCBIHuRef
CHM1_11848,551,997 - 48,606,836 (+)NCBICHM1_1
T2T-CHM13v2.01851,231,926 - 51,286,759 (+)NCBIT2T-CHM13v2.0
Smad4
(Mus musculus - house mouse)
Mouse AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
GRCm391873,767,861 - 73,836,862 (-)NCBIGRCm39GRCm39mm39
GRCm39 Ensembl1873,772,080 - 73,836,851 (-)EnsemblGRCm39 EnsemblGRCm39
GRCm381873,634,790 - 73,703,791 (-)NCBIGRCm38GRCm38mm10GRCm38
GRCm38.p6 Ensembl1873,639,009 - 73,703,780 (-)Ensemblmm10GRCm38
MGSCv371873,798,667 - 73,863,395 (-)NCBIMGSCv37MGSCv37mm9NCBIm37
MGSCv361873,764,382 - 73,829,110 (-)NCBIMGSCv36mm8
Celera1874,884,056 - 74,923,073 (-)NCBICelera
Cytogenetic Map18E2NCBI
cM Map1849.51NCBI
Smad4
(Chinchilla lanigera - long-tailed chinchilla)
Chinchilla AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
ChiLan1.0 EnsemblNW_00495540235,961,165 - 35,994,538 (+)Ensembl
ChiLan1.0NW_00495540235,956,080 - 36,001,746 (+)NCBIChiLan1.0ChiLan1.0
SMAD4
(Pan paniscus - bonobo/pygmy chimpanzee)
Bonobo AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
NHGRI_mPanPan1-v21768,549,261 - 68,603,954 (+)NCBINHGRI_mPanPan1-v2
NHGRI_mPanPan11854,241,866 - 54,296,559 (+)NCBINHGRI_mPanPan1
Mhudiblu_PPA_v01844,402,112 - 44,456,779 (+)NCBIMhudiblu_PPA_v0Mhudiblu_PPA_v0panPan3
PanPan1.11847,692,311 - 47,802,530 (+)NCBIPanPan1.1PanPan1.1panPan2
PanPan1.1 Ensembl1847,764,568 - 47,797,359 (+)EnsemblpanPan2panpan1.1
SMAD4
(Canis lupus familiaris - dog)
Dog AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
CanFam3.1123,875,989 - 23,930,027 (-)NCBICanFam3.1CanFam3.1canFam3CanFam3.1
CanFam3.1 Ensembl123,882,139 - 23,969,405 (-)EnsemblcanFam3CanFam3.1
Dog10K_Boxer_Tasha124,868,005 - 24,956,178 (-)NCBIDog10K_Boxer_TashaDog10K_Boxer_Tasha
ROS_Cfam_1.0123,767,402 - 23,821,366 (-)NCBIROS_Cfam_1.0ROS_Cfam_1.0
ROS_Cfam_1.0 Ensembl123,772,519 - 23,821,180 (-)EnsemblROS_Cfam_1.0 Ensembl
UMICH_Zoey_3.1123,833,038 - 23,921,205 (-)NCBIUMICH_Zoey_3.1
UNSW_CanFamBas_1.0123,719,264 - 23,807,404 (-)NCBIUNSW_CanFamBas_1.0
UU_Cfam_GSD_1.0123,987,158 - 24,041,139 (-)NCBIUU_Cfam_GSD_1.0UU_Cfam_GSD_1.0
Smad4
(Ictidomys tridecemlineatus - thirteen-lined ground squirrel)
Squirrel AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
HiC_Itri_2NW_02440494437,008,523 - 37,038,961 (-)NCBIHiC_Itri_2
SpeTri2.0 EnsemblNW_00493649712,249,140 - 12,278,123 (-)EnsemblSpeTri2.0 Ensembl
SpeTri2.0NW_00493649712,242,869 - 12,278,012 (-)NCBISpeTri2.0SpeTri2.0SpeTri2.0
SMAD4
(Sus scrofa - pig)
Pig AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
Sscrofa11.1 Ensembl1100,589,850 - 100,628,029 (+)EnsemblsusScr11Sscrofa11.1
Sscrofa11.11100,521,843 - 100,633,501 (+)NCBISscrofa11.1Sscrofa11.1susScr11Sscrofa11.1
Sscrofa10.21110,456,997 - 110,568,659 (+)NCBISscrofa10.2Sscrofa10.2susScr3
SMAD4
(Chlorocebus sabaeus - green monkey)
Green Monkey AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
ChlSab1.11829,894,157 - 29,951,445 (-)NCBIChlSab1.1ChlSab1.1chlSab2
ChlSab1.1 Ensembl1829,897,621 - 29,934,478 (-)EnsemblChlSab1.1 EnsemblchlSab2Vervet-AGM
Vero_WHO_p1.0NW_0236660504,018,900 - 4,079,370 (-)NCBIVero_WHO_p1.0Vero_WHO_p1.0
Smad4
(Heterocephalus glaber - naked mole-rat)
Naked Mole-Rat AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
HetGla_female_1.0 EnsemblNW_00462477814,570,348 - 14,630,325 (+)EnsemblHetGla_female_1.0 EnsemblhetGla2HetGla_female_1.0 Ensembl
HetGla 1.0NW_00462477814,570,025 - 14,629,950 (+)NCBIHetGla 1.0HetGla 1.0hetGla2
Smad4
(Rattus rattus - black rat)
Black Rat AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
Rrattus_CSIRO_v11558,292,542 - 58,337,603 (+)NCBIRrattus_CSIRO_v1

Variants

.
Variants in Smad4
284 total Variants
miRNA Target Status (No longer updated)

Confirmed Target Of
miRNA GeneMature miRNAMethod NameResult TypeData TypeSupport TypePMID
Mir146arno-miR-146a-5pMirtarbaseexternal_infoqRT-PCR//Western blotFunctional MTI22735812
Mir29arno-miR-29a-3pMirtarbaseexternal_infoLuciferase reporter assay//Microarray//Northern blFunctional MTI22506032

Predicted Target Of
Summary Value
Count of predictions:120
Count of miRNA genes:104
Interacting mature miRNAs:110
Transcripts:ENSRNOT00000021113
Prediction methods:Microtar, Miranda, Rnahybrid
Result types:miRGate_prediction

The detailed report is available here: Full Report CSV TAB Printer

miRNA Target Status data imported from miRGate (http://mirgate.bioinfo.cnio.es/).
For more information about miRGate, see PMID:25858286 or access the full paper here.


QTLs in Region (GRCr8)
The following QTLs overlap with this region.    Full Report CSV TAB Printer Gviewer
RGD IDSymbolNameLODP ValueTraitSub TraitChrStartStopSpecies
1331733Bp233Blood pressure QTL 2333.97196arterial blood pressure trait (VT:2000000)mean arterial blood pressure (CMO:0000009)182507112683910656Rat
1331730Scl27Serum cholesterol level QTL 273.826blood HDL cholesterol amount (VT:0000184)serum high density lipoprotein cholesterol level (CMO:0000361)185449080186134022Rat
1331741Bp232Blood pressure QTL 2323.59112arterial blood pressure trait (VT:2000000)diastolic blood pressure (CMO:0000005)182349405785487725Rat
1331742Bp228Blood pressure QTL 2283.88752arterial blood pressure trait (VT:2000000)mean arterial blood pressure (CMO:0000009)183161050577371277Rat
1298072Cia26Collagen induced arthritis QTL 263.6joint integrity trait (VT:0010548)joint inflammation composite score (CMO:0000919)186438376279484311Rat
631834Sach3Saccharin preference QTL 33.90.01consumption behavior trait (VT:0002069)calculated saccharin drink intake volume (CMO:0001600)183857591983575919Rat
12904668Bw188Body weight QTL 1880.03body mass (VT:0001259)body weight (CMO:0000012)182682218671822186Rat
12904669Cm125Cardiac mass QTL 1250.001heart mass (VT:0007028)heart wet weight to body weight ratio (CMO:0002408)182682218671822186Rat
12904670Cm126Cardiac mass QTL 1260.001heart left ventricle mass (VT:0007031)heart left ventricle weight to body weight ratio (CMO:0000530)182682218671822186Rat
6893683Bw110Body weight QTL 1102.70.002body mass (VT:0001259)body weight (CMO:0000012)184562030686134022Rat
7794793Mcs34Mammary carcinoma susceptibility QTL 341.54mammary gland integrity trait (VT:0010552)mammary tumor incidence/prevalence measurement (CMO:0000946)186563556785897775Rat
12904677Kidm72Kidney mass QTL 720.001kidney mass (VT:0002707)both kidneys wet weight to body weight ratio (CMO:0000340)182682218671822186Rat
9589041Epfw12Epididymal fat weight QTL 1217.080.001epididymal fat pad mass (VT:0010421)epididymal fat pad weight to body weight ratio (CMO:0000658)184891573786134022Rat
8694432Bw165Body weight QTL 1653.810.001body lean mass (VT:0010483)lean tissue morphological measurement (CMO:0002184)184891573786134022Rat
12904673Cm127Cardiac mass QTL 1270.005heart right ventricle mass (VT:0007033)heart right ventricle weight to body weight ratio (CMO:0000914)182682218671822186Rat
12904675Am19Aortic mass QTL 190.001aorta mass (VT:0002845)aorta weight to aorta length to body weight ratio (CMO:0002722)182682218671822186Rat
1331774Bp226Blood pressure QTL 2264.41065arterial blood pressure trait (VT:2000000)mean arterial blood pressure (CMO:0000009)183161050577371277Rat
9589816Gluco68Glucose level QTL 687.250.001blood glucose amount (VT:0000188)plasma glucose level (CMO:0000042)183199089176990891Rat
1331770Bp234Blood pressure QTL 2343.807arterial blood pressure trait (VT:2000000)mean arterial blood pressure (CMO:0000009)184562030686134022Rat
2301969Bp324Blood pressure QTL 3244.05arterial blood pressure trait (VT:2000000)systolic blood pressure (CMO:0000004)186198220476619168Rat
1578667Bss21Bone structure and strength QTL 213.5femur morphology trait (VT:0000559)femoral neck cortical cross-sectional area (CMO:0001702)181206648285493247Rat
2303120Mamtr8Mammary tumor resistance QTL 80.001mammary gland integrity trait (VT:0010552)mammary tumor growth rate (CMO:0000344)183161050585493247Rat
12880368Bw187Body weight QTL 1870.045body mass (VT:0001259)body weight (CMO:0000012)183337915878379158Rat
724542Kidm2Kidney mass QTL 22.6kidney mass (VT:0002707)calculated kidney weight (CMO:0000160)186144685386134022Rat
61367Iddm4Insulin dependent diabetes mellitus QTL 42.330.0074blood glucose amount (VT:0000188)plasma glucose level (CMO:0000042)184046238385462383Rat
1359020Ppulsi2Prepulse inhibition QTL 22.71prepulse inhibition trait (VT:0003088)acoustic startle response measurement (CMO:0001519)185449080176272247Rat
2312600Bp341Blood pressure QTL 3410.05arterial blood pressure trait (VT:2000000)systolic blood pressure (CMO:0000004)186160038472538878Rat
9590318Scort22Serum corticosterone level QTL 227.640.001blood corticosterone amount (VT:0005345)plasma corticosterone level (CMO:0001173)183199089176990891Rat
1578661Bss20Bone structure and strength QTL 203.7femur morphology trait (VT:0000559)femoral neck cross-sectional area (CMO:0001697)181206648285493247Rat
1331754Bp230Blood pressure QTL 2304.61609arterial blood pressure trait (VT:2000000)mean arterial blood pressure (CMO:0000009)181564228086134022Rat
12904069Cm123Cardiac mass QTL 1230.001heart left ventricle mass (VT:0007031)heart left ventricle weight to body weight ratio (CMO:0000530)183337915878379158Rat
1331798Bp224Blood pressure QTL 2243.53873arterial blood pressure trait (VT:2000000)mean arterial blood pressure (CMO:0000009)183161050577371277Rat
12904070Cm124Cardiac mass QTL 1240.01heart right ventricle mass (VT:0007033)heart right ventricle weight to body weight ratio (CMO:0000914)183337915878379158Rat
12904071Am18Aortic mass QTL 180.001aorta mass (VT:0002845)aorta weight to aorta length to body weight ratio (CMO:0002722)183337915878379158Rat
2303584Gluco55Glucose level QTL 552blood glucose amount (VT:0000188)blood glucose level (CMO:0000046)185079521286134022Rat
2301413Bp318Blood pressure QTL 3180.002arterial blood pressure trait (VT:2000000)mean arterial blood pressure (CMO:0000009)182682218671822186Rat
61383Bp47Blood pressure QTL 4717.3arterial blood pressure trait (VT:2000000)systolic blood pressure (CMO:0000004)183152278376522783Rat
12904067Cm122Cardiac mass QTL 1220.001heart mass (VT:0007028)heart wet weight to body weight ratio (CMO:0002408)183337915878379158Rat
61384Bp48Blood pressure QTL 4819.4arterial blood pressure trait (VT:2000000)systolic blood pressure (CMO:0000004)186289225779484461Rat
2301417Bp319Blood pressure QTL 3190.002arterial blood pressure trait (VT:2000000)mean arterial blood pressure (CMO:0000009)183337915878379158Rat
12904073Kidm71Kidney mass QTL 710.001kidney mass (VT:0002707)both kidneys wet weight to body weight ratio (CMO:0000340)183337915878379158Rat
738008Hcar14Hepatocarcinoma resistance QTL 144.3liver integrity trait (VT:0010547)liver nonremodeling tumorous lesion number (CMO:0001462)185782524385493247Rat
1331776Bp225Blood pressure QTL 2252.829arterial blood pressure trait (VT:2000000)diastolic blood pressure (CMO:0000005)183161050577371277Rat
631518Bw11Body weight QTL 112.8body mass (VT:0001259)body weight (CMO:0000012)183612162681121626Rat
1641923Colcr8Colorectal carcinoma resistance QTL 83.10.0014intestine integrity trait (VT:0010554)poorly differentiated malignant colorectal tumor number (CMO:0002076)183199089176990891Rat
8694366Abfw8Abdominal fat weight QTL 86.380.001visceral adipose mass (VT:0010063)abdominal fat pad weight to body weight ratio (CMO:0000095)184891573786134022Rat
631509Sald2Serum aldosterone level QTL 22.9blood aldosterone amount (VT:0005346)serum aldosterone level (CMO:0000487)182641582171415821Rat
631274Sprol1Serum protein level QTL 15.3blood total protein amount (VT:0005567)serum total protein level (CMO:0000661)183164450879484311Rat
1358193Emca2Estrogen-induced mammary cancer QTL 21.6mammary gland integrity trait (VT:0010552)post-insult time to mammary tumor formation (CMO:0000345)186584644786134022Rat
1598832Glom11Glomerulus QTL 112.9kidney glomerulus morphology trait (VT:0005325)index of glomerular damage (CMO:0001135)185326667186134022Rat
1600373Mamtr6Mammary tumor resistance QTL 6mammary gland integrity trait (VT:0010552)mammary tumor number (CMO:0000343)181955353285493247Rat
8694378Bw157Body weight QTL 1573.590.001body lean mass (VT:0010483)lean tissue morphological measurement (CMO:0002184)183199089176990891Rat
2303571Bw92Body weight QTL 923body mass (VT:0001259)body weight (CMO:0000012)185079521286134022Rat
631675Iddm15Insulin dependent diabetes mellitus QTL 15urine glucose amount (VT:0001758)percentage of study population developing diabetes mellitus during a period of time (CMO:0001114)186289225779484461Rat
61429Cia17Collagen induced arthritis QTL 174.6joint integrity trait (VT:0010548)joint inflammation composite score (CMO:0000919)183161050572538878Rat

Markers in Region
PMC86557P1  
Rat AssemblyChrPosition (strand)SourceJBrowse
mRatBN7.21867,260,537 - 67,260,816 (+)MAPPERmRatBN7.2
Rnor_6.01869,643,478 - 69,643,756NCBIRnor6.0
Rnor_5.01868,788,748 - 68,789,026UniSTSRnor5.0
RGSC_v3.41870,448,115 - 70,448,393UniSTSRGSC3.4
Celera1865,262,730 - 65,263,008UniSTS
Cytogenetic Map18q12.3UniSTS
D18Wsu70e  
Rat AssemblyChrPosition (strand)SourceJBrowse
mRatBN7.21867,243,804 - 67,244,056 (+)MAPPERmRatBN7.2
Rnor_6.01869,626,745 - 69,626,996NCBIRnor6.0
Rnor_5.01868,772,247 - 68,772,498UniSTSRnor5.0
RGSC_v3.41870,431,626 - 70,431,877UniSTSRGSC3.4
Celera1865,246,105 - 65,246,356UniSTS
Cytogenetic Map18q12.3UniSTS
RH129873  
Rat AssemblyChrPosition (strand)SourceJBrowse
mRatBN7.21867,243,837 - 67,244,052 (+)MAPPERmRatBN7.2
Rnor_6.01869,626,778 - 69,626,992NCBIRnor6.0
Rnor_5.01868,772,280 - 68,772,494UniSTSRnor5.0
RGSC_v3.41870,431,659 - 70,431,873UniSTSRGSC3.4
Celera1865,246,138 - 65,246,352UniSTS
Cytogenetic Map18q12.3UniSTS
RH143443  
Rat AssemblyChrPosition (strand)SourceJBrowse
mRatBN7.2X24,734,938 - 24,735,040 (+)MAPPERmRatBN7.2
mRatBN7.21867,244,710 - 67,244,812 (+)MAPPERmRatBN7.2
Rnor_6.01869,627,651 - 69,627,752NCBIRnor6.0
Rnor_6.0X26,090,613 - 26,090,714NCBIRnor6.0
Rnor_5.01868,773,153 - 68,773,254UniSTSRnor5.0
Rnor_5.0X26,494,877 - 26,494,978UniSTSRnor5.0
RGSC_v3.4X45,395,750 - 45,395,851UniSTSRGSC3.4
RGSC_v3.41870,432,532 - 70,432,633UniSTSRGSC3.4
Celera1865,247,011 - 65,247,112UniSTS
CeleraX25,153,772 - 25,153,873UniSTS
Cytogenetic Map18q12.3UniSTS
PMC324399P2  
Rat AssemblyChrPosition (strand)SourceJBrowse
mRatBN7.21867,244,543 - 67,245,043 (+)MAPPERmRatBN7.2
Rnor_6.01869,627,484 - 69,627,983NCBIRnor6.0
Rnor_5.01868,772,986 - 68,773,485UniSTSRnor5.0
RGSC_v3.41870,432,365 - 70,432,864UniSTSRGSC3.4
Celera1865,246,844 - 65,247,343UniSTS
Cytogenetic Map18q12.3UniSTS
AF010230  
Rat AssemblyChrPosition (strand)SourceJBrowse
mRatBN7.21867,251,904 - 67,252,073 (+)MAPPERmRatBN7.2
Rnor_6.01869,634,845 - 69,635,013NCBIRnor6.0
Rnor_5.01868,780,115 - 68,780,283UniSTSRnor5.0
RGSC_v3.41870,439,482 - 70,439,650UniSTSRGSC3.4
Celera1865,254,097 - 65,254,265UniSTS
Cytogenetic Map18q12.3UniSTS


Expression

RNA-SEQ Expression

alimentary part of gastrointestinal system
appendage
circulatory system
ectoderm
endocrine system
endoderm
exocrine system
hemolymphoid system
hepatobiliary system
integumental system
mesenchyme
mesoderm
musculoskeletal system
nervous system
renal system
reproductive system
respiratory system
sensory system
visual system
16 12 67 165 91 90 59 92 59 6 356 192 11 144 81 92 31 17 17

Sequence


Ensembl Acc Id: ENSRNOT00000082484   ⟹   ENSRNOP00000074882
Type: CODING
Position:
Rat AssemblyChrPosition (strand)Source
GRCr8 Ensembl1869,518,988 - 69,549,684 (-)Ensembl
mRatBN7.2 Ensembl1867,243,742 - 67,274,438 (-)Ensembl
Rnor_6.0 Ensembl1869,627,757 - 69,671,199 (-)Ensembl
Ensembl Acc Id: ENSRNOT00000090198   ⟹   ENSRNOP00000070425
Type: CODING
Position:
Rat AssemblyChrPosition (strand)Source
GRCr8 Ensembl1869,520,262 - 69,549,684 (-)Ensembl
mRatBN7.2 Ensembl1867,245,016 - 67,274,438 (-)Ensembl
Rnor_6.0 Ensembl1869,627,824 - 69,657,301 (-)Ensembl
Ensembl Acc Id: ENSRNOT00000103096   ⟹   ENSRNOP00000079042
Type: CODING
Position:
Rat AssemblyChrPosition (strand)Source
mRatBN7.2 Ensembl1867,243,742 - 67,274,438 (-)Ensembl
Ensembl Acc Id: ENSRNOT00000116718   ⟹   ENSRNOP00000091850
Type: CODING
Position:
Rat AssemblyChrPosition (strand)Source
mRatBN7.2 Ensembl1867,244,625 - 67,274,438 (-)Ensembl
RefSeq Acc Id: NM_019275   ⟹   NP_062148
RefSeq Status: VALIDATED
Type: CODING
Position:
Rat AssemblyChrPosition (strand)Source
GRCr81869,518,988 - 69,549,684 (-)NCBI
mRatBN7.21867,243,742 - 67,274,438 (-)NCBI
Rnor_6.01869,626,682 - 69,657,373 (-)NCBI
Rnor_5.01868,773,326 - 68,802,354 (-)NCBI
RGSC_v3.41870,432,705 - 70,461,541 (-)RGD
Celera1865,246,042 - 65,276,480 (-)NCBI
Sequence:
Protein Sequences
Protein RefSeqs NP_062148 (Get FASTA)   NCBI Sequence Viewer  
GenBank Protein AAC12781 (Get FASTA)   NCBI Sequence Viewer  
  BAA83092 (Get FASTA)   NCBI Sequence Viewer  
  EDM14795 (Get FASTA)   NCBI Sequence Viewer  
  EDM14796 (Get FASTA)   NCBI Sequence Viewer  
  EDM14797 (Get FASTA)   NCBI Sequence Viewer  
Ensembl Protein ENSRNOP00000074882
  ENSRNOP00000074882.2
GenBank Protein O70437 (Get FASTA)   NCBI Sequence Viewer  
RefSeq Acc Id: NP_062148   ⟸   NM_019275
- UniProtKB: O70437 (UniProtKB/Swiss-Prot),   A6IY15 (UniProtKB/TrEMBL),   A0A8I5ZMM9 (UniProtKB/TrEMBL)
- Sequence:
Ensembl Acc Id: ENSRNOP00000070425   ⟸   ENSRNOT00000090198
Ensembl Acc Id: ENSRNOP00000074882   ⟸   ENSRNOT00000082484
Ensembl Acc Id: ENSRNOP00000079042   ⟸   ENSRNOT00000103096
Ensembl Acc Id: ENSRNOP00000091850   ⟸   ENSRNOT00000116718
Protein Domains
MH1   MH2

Protein Structures
Name Modeler Protein Id AA Range Protein Structure
AF-O70437-F1-model_v2 AlphaFold O70437 1-552 view protein structure

Transcriptome

eQTL   View at Phenogen
WGCNA   View at Phenogen
Tissue/Strain Expression   View at Phenogen


Additional Information

Database Acc Id Source(s)
AGR Gene RGD:3033 AgrOrtholog
BioCyc Gene G2FUF-7058 BioCyc
Ensembl Genes ENSRNOG00000051965 Ensembl, ENTREZGENE, UniProtKB/Swiss-Prot
Ensembl Transcript ENSRNOT00000082484 ENTREZGENE
  ENSRNOT00000082484.2 UniProtKB/Swiss-Prot
Gene3D-CATH 2.60.200.10 UniProtKB/Swiss-Prot
  3.90.520.10 UniProtKB/Swiss-Prot
InterPro Dwarfin UniProtKB/Swiss-Prot
  MAD_homology1_Dwarfin-type UniProtKB/Swiss-Prot
  MAD_homology_MH1 UniProtKB/Swiss-Prot
  SMAD-like_dom_sf UniProtKB/Swiss-Prot
  SMAD_dom_Dwarfin-type UniProtKB/Swiss-Prot
  SMAD_FHA_dom_sf UniProtKB/Swiss-Prot
  SMAD_MH1_sf UniProtKB/Swiss-Prot
KEGG Report rno:50554 UniProtKB/Swiss-Prot
NCBI Gene 50554 ENTREZGENE
PANTHER MOTHERS AGAINST DECAPENTAPLEGIC HOMOLOG 4 UniProtKB/Swiss-Prot
  PTHR13703 UniProtKB/Swiss-Prot
Pfam MH1 UniProtKB/Swiss-Prot
  MH2 UniProtKB/Swiss-Prot
PhenoGen Smad4 PhenoGen
PROSITE MH1 UniProtKB/Swiss-Prot
  MH2 UniProtKB/Swiss-Prot
RatGTEx ENSRNOG00000051965 RatGTEx
SMART DWA UniProtKB/Swiss-Prot
  DWB UniProtKB/Swiss-Prot
Superfamily-SCOP SSF49879 UniProtKB/Swiss-Prot
  SSF56366 UniProtKB/Swiss-Prot
TIGR TC217262
UniProt A0A0G2JXW2_RAT UniProtKB/TrEMBL
  A0A0G2K970_RAT UniProtKB/TrEMBL
  A0A8I5ZMM9 ENTREZGENE
  A6IY14_RAT UniProtKB/TrEMBL
  A6IY15 ENTREZGENE, UniProtKB/TrEMBL
  A6IY16_RAT UniProtKB/TrEMBL
  O70437 ENTREZGENE, UniProtKB/Swiss-Prot


Nomenclature History
Date Current Symbol Current Name Previous Symbol Previous Name Description Reference Status
2008-10-23 Smad4  SMAD family member 4  Smad4  MAD homolog 4 (Drosophila)  Nomenclature updated to reflect human and mouse nomenclature 1299863 APPROVED
2008-03-19 Smad4  MAD homolog 4 (Drosophila)  Smad4  SMAD family member 4  Nomenclature updated to reflect human and mouse nomenclature 1299863 APPROVED
2008-02-14 Smad4  SMAD family member 4  Smad4  MAD homolog 4 (Drosophila)  Nomenclature updated to reflect human and mouse nomenclature 1299863 APPROVED
2005-11-17 Smad4  MAD homolog 4 (Drosophila)  Madh4  MAD homolog 4 (Drosophila)  Symbol updated 1299863 APPROVED

RGD Curation Notes
Note Type Note Reference
gene_disease deletions in human gene are associated with pancreatic carcinomas 734492