Property Summary

NCBI Gene PubMed Count 62
PubMed Score 90.17
PubTator Score 59.62

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (13)

Disease log2 FC p
malignant mesothelioma -1.200 1.7e-06
psoriasis 1.300 8.9e-03
osteosarcoma 1.589 2.6e-02
group 4 medulloblastoma -1.900 5.5e-06
medulloblastoma, large-cell -1.500 3.3e-04
non-small cell lung cancer -2.321 7.7e-20
intraductal papillary-mucinous neoplasm ... 1.800 8.1e-03
colon cancer 1.500 1.2e-03
cystic fibrosis -1.200 2.8e-03
lung adenocarcinoma -1.344 1.5e-06
lung carcinoma -1.700 1.6e-08
ductal carcinoma in situ -1.200 3.7e-03
invasive ductal carcinoma -1.300 2.2e-02

Protein-protein Interaction (1)

Gene RIF (40)

PMID Text
24162774 HIV-1 gp120 upregulates the expression of SMAD family member 6 (SMAD6) in human B cells
23455153 monoubiquitinated SMAD6 impairs the binding affinity of non-modified SMAD6 to the BMP type I receptor. Moreover, UBE2O and SMAD6 cooperated in the regulation of BMP7-induced adipogenesis
23284751 Single Nucleotide Polymorphisms in SMAD6 gene is associated with brain metastasis in non-small-cell lung cancer
22705548 Smad6 indirectly maintains stemness by preventing spontaneous erythropoiesis in hematopoietic stem cells.
22275001 Congenital cardiovascular malformation is related to genetic variation in SMAD6
22223368 Loss of SMAD6 is associated with lung adenocarcinoma.
21984931 Haplotype analysis further revealed that two haplotype blocks within SMAD6 were significantly associated with decreased ovarian cancer risk, as compared to the most common haplotype.
21897371 results suggest that MyD88 degradation driven by the Smad6-Smurf pathway is a novel mechanism for TGF-beta1-mediated negative regulation of MyD88-dependent pro-inflammatory signalling
21576367 Data show that Runx1, in conjunction with Fli1, Gata2, and Scl, directly regulates the expression of Smad6 in the aorta-gonad-mesonephros region in the developing embryo, where hematopoietic stem cells originate.
20734064 Observational study of gene-disease association. (HuGE Navigator)
20658468 Smad6 and Smad7, inhibitors of BMP signaling, were up-regulated in HFE-mutant hereditary hemochromatosis compared to controls, disruptin bone morphogenic protein signaling.
20462450 Smad6 together with Smad2 may be prognostic factors, independent of nodal status in oral SCC after curative resection
19959123 Observational study of gene-disease association. (HuGE Navigator)
19688145 Study data demonstrates downregulated SMAD6 expression in psoriatic skin.
19277452 Smad6 gene is a candidate for the genetic determinants of bone mineral density in postmenopausal women.
19277452 Observational study of gene-disease association. (HuGE Navigator)
19211612 Observational study of gene-disease association. (HuGE Navigator)
19047146 Knockdown of SMAD6 led to the activation of TGF-beta signaling through up-regulation of plasminogen activator inhibitor-1 and phosphorylation of SMAD2/3 in NSCLC.
19032685 Splice variant Smad6B, in human prostatic and rodent testicular cell lines, exhibits a truncated C-terminus lacking the entire MH-2 domain and most parts of the linker region.
18445023 A case-control study in Afro-Caribbeans found SMAD6 SNPs were not strongly associated with increased risk of developing keloids.
18445023 Observational study of gene-disease association. (HuGE Navigator)
17934461 Observational study of gene-disease association. (HuGE Navigator)
17931948 Observational study of gene-disease association. (HuGE Navigator)
17850776 Stimulation of Smad 6 inhibits ERK activation and thus results in a negative feedback loop to fine-tune BMP signaling in human umbilical vein endothelial cells.
17359969 These data suggest autocrine TGF-beta1 antagonizes BMP signaling through modulation of inducible Smad6 and the activity of BMP specific Smad1/5.
16951688 Smad6 bound to Pellino-1 promoted TGF-beta-mediated anti-inflammatory effects.
16886151 Observational study of gene-disease association. (HuGE Navigator)
16687405 Smad6 appears to functionally interact with Dlx3, altering the ability of Dlx3 to bind target gene promoters.
16373339 OAZ can alter the intensity and duration of the BMP4 stimulus through Smad6
16299379 Smad6 interacts with Runx2 and mediates Smad ubiquitin regulatory factor 1-induced Runx2 degradation
16282533 HIV-1 gp120 upregulates the expression of SMAD family member 6 (SMAD6) in human B cells
16249187 appears that the anti-glucocorticoid actions of Smad6 may contribute to the neuroprotective, anticatabolic and pro-wound healing properties of the TGFbeta family of proteins
15736400 Smad6 and Smad7 expression affects the progression of early lesions of esophageal SCC and indicates a poor prognosis.
15716278 the level of Smad6s can alter the level of TGF-beta and the subsequent induction of PAI-1 via a FoxD1 transcription site
15665522 Adrenomedullin can attenuate TGF-beta1-mediated renal tubulointerstitial extracellular matrix turnover via an antagonistic mechanism of inhibitory Smad 6 in TGF-beta1-elicited signaling.
15529348 The regulation in chondrocytes of Smad6 and Smad7 expression by IL-1beta suggests a potentially important role of IL-1beta signaling in chondrocytes, via indirect influencing of the bone morphogenetic protein/TGFbeta signaling cascade.
15033458 tetradecanoylphorbol-13-acetate down-regulates Smad6 expression presumably via PKCmu-ERK-dependent pathway and up-regulates Smad7 expression via PKCmu-dependent mechanism(s) which need no MAPK and NF-kappaB activation
14645520 Smad6 repressed bone morphogenetic protein-induced Id1 transcription through recruiting transcriptional corepressor C-terminal binding protein (CtBP).
12407115 Smad6 and Smad7 regulate thrombomodulin-dependent activation of protein C
12397035 Smad6 has no role in TGF-beta response and injury in podocytes. In contrast, Smad6 is upregulated in the mesangium in human glomerular diseases and may be involved in functions independent of TGF-beta/Smad signaling.

AA Sequence

MFRSKRSGLVRRLWRSRVVPDREEGGSGGGGGGDEDGSLGSRAEPAPRAREGGGCGRSEVRPVAPRRPRD      1 - 70
AVGQRGAQGAGRRRRAGGPPRPMSEPGAGAGSSLLDVAEPGGPGWLPESDCETVTCCLFSERDAAGAPRD     71 - 140
ASDPLAGAALEPAGGGRSREARSRLLLLEQELKTVTYSLLKRLKERSLDTLLEAVESRGGVPGGCVLVPR    141 - 210
ADLRLGGQPAPPQLLLGRLFRWPDLQHAVELKPLCGCHSFAAAADGPTVCCNPYHFSRLCGPESPPPPYS    211 - 280
RLSPRDEYKPLDLSDSTLSYTETEATNSLITAPGEFSDASMSPDATKPSHWCSVAYWEHRTRVGRLYAVY    281 - 350
DQAVSIFYDLPQGSGFCLGQLNLEQRSESVRRTRSKIGFGILLSKEPDGVWAYNRGEHPIFVNSPTLDAP    351 - 420
GGRALVVRKVPPGYSIKVFDFERSGLQHAPEPDAADGPYDPNSVRISFAKGWGPCYSRQFITSCPCWLEI    421 - 490
LLNNPR                                                                    491 - 496
//

Text Mined References (63)

PMID Year Title
24658283 2014 A genome-wide gene-environment interaction analysis for tobacco smoke and lung cancer susceptibility.
23610558 2013 Rnf165/Ark2C enhances BMP-Smad signaling to mediate motor axon extension.
23455153 2013 Fine-tuning BMP7 signalling in adipogenesis by UBE2O/E2-230K-mediated monoubiquitination of SMAD6.
23284751 2012 SNPs in the TGF-? signaling pathway are associated with increased risk of brain metastasis in patients with non-small-cell lung cancer.
22705548 2012 Inhibition of erythropoiesis by Smad6 in human cord blood hematopoietic stem cells.
22589738 2012 Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.
22275001 2012 Nonsynonymous variants in the SMAD6 gene predispose to congenital cardiovascular malformation.
22223368 2012 Association of lung adenocarcinoma clinical stage with gene expression pattern in noninvolved lung tissue.
21984931 2011 Genetic variants in TGF-? pathway are associated with ovarian cancer risk.
21897371 2011 Smad6-specific recruitment of Smurf E3 ligases mediates TGF-?1-induced degradation of MyD88 in TLR4 signalling.
21576367 2011 A Runx1-Smad6 rheostat controls Runx1 activity during embryonic hematopoiesis.
20734064 2010 A large-scale candidate gene association study of age at menarche and age at natural menopause.
20658468 2010 Defective bone morphogenic protein signaling underlies hepcidin deficiency in HFE hereditary hemochromatosis.
20462450 2010 Smad2 and Smad6 as predictors of overall survival in oral squamous cell carcinoma patients.
19959123 2009 Association of TGFBR2 polymorphism with risk of sudden cardiac arrest in patients with coronary artery disease.
19688145 2009 Downregulation of SMAD2, 4 and 6 mRNA and TGFbeta receptor I mRNA in lesional and non-lesional psoriatic skin.
19277452 2009 Bone mass effects of a Smad6 gene polymorphism in Japanese postmenopausal women.
19211612 2009 A new nonsense mutation of SMAD8 associated with pulmonary arterial hypertension.
19047146 2008 SMAD6 contributes to patient survival in non-small cell lung cancer and its knockdown reestablishes TGF-beta homeostasis in lung cancer cells.
19032685 2008 Identification of a new human Smad6 splice variant.
19018011 2008 Holding their own: the noncanonical roles of Smad proteins.
18445023 2008 Genetic susceptibility to keloid scarring: SMAD gene SNP frequencies in Afro-Caribbeans.
17934461 2007 A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk.
17931948 2007 Minor contribution of SMAD7 and KLF10 variants to genetic susceptibility of type 2 diabetes.
17850776 2007 ERK signaling is a central regulator for BMP-4 dependent capillary sprouting.
17359969 2007 Antisense targeting of TGF-beta1 augments BMP-induced upregulation of osteopontin, type I collagen and Cbfa1 in human Saos-2 cells.
16951688 2006 Smad6 negatively regulates interleukin 1-receptor-Toll-like receptor signaling through direct interaction with the adaptor Pellino-1.
16886151 2006 Association of polymorphisms of IGF1R and genes in the transforming growth factor- beta /bone morphogenetic protein pathway with bacteremia in sickle cell anemia.
16687405 2006 Smad6 represses Dlx3 transcriptional activity through inhibition of DNA binding.
16601693 2006 Axin is a scaffold protein in TGF-beta signaling that promotes degradation of Smad7 by Arkadia.
16491121 2006 Smad6 is a protein kinase X phosphorylation substrate and is required for HL-60 cell differentiation.
16373339 2006 OAZ regulates bone morphogenetic protein signaling through Smad6 activation.
16299379 2006 Smad6 interacts with Runx2 and mediates Smad ubiquitin regulatory factor 1-induced Runx2 degradation.
16249187 2005 The Smad6-histone deacetylase 3 complex silences the transcriptional activity of the glucocorticoid receptor: potential clinical implications.
15736400 Prognostic value of the expression of Smad6 and Smad7, as inhibitory Smads of the TGF-beta superfamily, in esophageal squamous cell carcinoma.
15716278 2005 Smad6s regulates plasminogen activator inhibitor-1 through a protein kinase C-beta-dependent up-regulation of transforming growth factor-beta.
15665522 2005 Adrenomedullin impairs the profibrotic effects of transforming growth factor-beta1 through recruiting Smad6 protein in human renal tubular cells.
15621726 2004 Bone morphogenetic proteins.
15529348 2004 Bone morphogenetic protein and transforming growth factor beta inhibitory Smads 6 and 7 are expressed in human adult normal and osteoarthritic cartilage in vivo and are differentially regulated in vitro by interleukin-1beta.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15146197 2004 Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation.
15033458 2004 Expressions of inhibitory Smads, Smad6 and Smad7, are differentially regulated by TPA in human lung fibroblast cells.
14657019 2003 Arkadia amplifies TGF-beta superfamily signalling through degradation of Smad7.
14645520 2003 Smad6 recruits transcription corepressor CtBP to repress bone morphogenetic protein-induced transcription.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12407115 2002 Modulation of thrombomodulin-dependent activation of human protein C through differential expression of endothelial Smads.
12397035 2002 Inhibitory smads and tgf-Beta signaling in glomerular cells.
11737269 2001 Inhibition of BMP2-induced, TAK1 kinase-mediated neurite outgrowth by Smad6 and Smad7.
11483516 2001 Promoting bone morphogenetic protein signaling through negative regulation of inhibitory Smads.
11284962 2001 Human truncated Smad 6 (Smad 6s) inhibits the BMP pathway in Xenopus laevis.
11278251 2001 Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation.
10757800 2000 STRAP and Smad7 synergize in the inhibition of transforming growth factor beta signaling.
10748100 2000 BMP2-induced apoptosis is mediated by activation of the TAK1-p38 kinase pathway that is negatively regulated by Smad6.
10722652 2000 Smad6 as a transcriptional corepressor.
10708949 TGF-beta signaling by Smad proteins.
10708948 The Smad pathway.
10655064 2000 A role for smad6 in development and homeostasis of the cardiovascular system.
10647776 Remarkable versatility of Smad proteins in the nucleus of transforming growth factor-beta activated cells.
9759503 1998 TGF-beta signal transduction.
9712726 1998 Induction of inhibitory Smad6 and Smad7 mRNA by TGF-beta family members.
9436979 1998 Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor.
9256479 1997 Vascular MADs: two novel MAD-related genes selectively inducible by flow in human vascular endothelium.
8673135 1996 Mad-related genes in the human.