SMAD3 and TLR4

Data Source:
BioGRID (two hybrid)

		SMAD3	TLR4
Description		SMAD family member 3	toll like receptor 4
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GO Annotations	Cellular Component	Chromatin Nucleus Nuclear Inner Membrane Nucleoplasm Transcription Regulator Complex Cytoplasm Cytosol Plasma Membrane Receptor Complex SMAD Protein Complex Heteromeric SMAD Protein Complex	Ruffle Phagocytic Cup Cytoplasm Early Endosome Golgi Apparatus Plasma Membrane Integral Component Of Plasma Membrane External Side Of Plasma Membrane Cell Surface Endosome Membrane Intrinsic Component Of Plasma Membrane Receptor Complex Lipopolysaccharide Receptor Complex Perinuclear Region Of Cytoplasm
	Molecular Function	Transcription Regulatory Region Sequence-specific DNA Binding RNA Polymerase II Cis-regulatory Region Sequence-specific DNA Binding DNA-binding Transcription Factor Activity, RNA Polymerase II-specific Cis-regulatory Region Sequence-specific DNA Binding RNA Polymerase II Activating Transcription Factor Binding Transcription Coactivator Binding DNA-binding Transcription Activator Activity, RNA Polymerase II-specific DNA-binding Transcription Factor Activity Transforming Growth Factor Beta Receptor Binding Protein Binding Collagen Binding Beta-catenin Binding Transcription Factor Binding Zinc Ion Binding DEAD/H-box RNA Helicase Binding Protein Kinase Binding Phosphatase Binding Chromatin DNA Binding Ubiquitin Protein Ligase Binding Mineralocorticoid Receptor Binding Glucocorticoid Receptor Binding Identical Protein Binding Protein Homodimerization Activity Ubiquitin Binding BHLH Transcription Factor Binding Sequence-specific DNA Binding Co-SMAD Binding I-SMAD Binding R-SMAD Binding	Lipopolysaccharide Binding Amyloid-beta Binding Lipopolysaccharide Immune Receptor Activity Transmembrane Signaling Receptor Activity Signaling Receptor Binding Protein Binding Signaling Receptor Activity Identical Protein Binding Protein Heterodimerization Activity NAD(P)+ Nucleosidase Activity NAD+ Nucleotidase, Cyclic ADP-ribose Generating
	Biological Process	Negative Regulation Of Transcription By RNA Polymerase II Ureteric Bud Development Response To Hypoxia In Utero Embryonic Development Mesoderm Formation Somitogenesis Liver Development Heart Looping Osteoblast Development Immune System Development Regulation Of Transcription By RNA Polymerase II Activation Of Cysteine-type Endopeptidase Activity Involved In Apoptotic Process Immune Response Cell Cycle Arrest Transforming Growth Factor Beta Receptor Signaling Pathway SMAD Protein Complex Assembly Endoderm Development Anatomical Structure Morphogenesis Embryonic Pattern Specification Positive Regulation Of Gene Expression Positive Regulation Of Alkaline Phosphatase Activity Positive Regulation Of Epithelial To Mesenchymal Transition Viral Process Regulation Of Striated Muscle Tissue Development Protein Deubiquitination Regulation Of Transforming Growth Factor Beta Receptor Signaling Pathway Signal Transduction Involved In Regulation Of Gene Expression Cell Differentiation Negative Regulation Of Cell Growth Adrenal Gland Development Positive Regulation Of Cell Migration Positive Regulation Of Bone Mineralization BMP Signaling Pathway Negative Regulation Of Transforming Growth Factor Beta Receptor Signaling Pathway Thyroid Gland Development Primary MiRNA Processing Positive Regulation Of Chondrocyte Differentiation Positive Regulation Of Interleukin-1 Beta Production Regulation Of Transforming Growth Factor Beta2 Production Positive Regulation Of Transforming Growth Factor Beta3 Production Activin Receptor Signaling Pathway Negative Regulation Of Osteoblast Proliferation Nodal Signaling Pathway Wound Healing T Cell Activation Negative Regulation Of Protein Catabolic Process Positive Regulation Of Protein Import Into Nucleus Negative Regulation Of Apoptotic Process Cell-cell Junction Organization Positive Regulation Of Nitric Oxide Biosynthetic Process Negative Regulation Of Fat Cell Differentiation Negative Regulation Of Osteoblast Differentiation Positive Regulation Of Transcription, DNA-templated Negative Regulation Of Mitotic Cell Cycle Positive Regulation Of Transcription By RNA Polymerase II Paraxial Mesoderm Morphogenesis Developmental Growth Embryonic Foregut Morphogenesis Embryonic Cranial Skeleton Morphogenesis Regulation Of Epithelial Cell Proliferation Negative Regulation Of Inflammatory Response Regulation Of Immune Response Protein Stabilization Positive Regulation Of Positive Chemotaxis Positive Regulation Of DNA-binding Transcription Factor Activity Regulation Of Binding Negative Regulation Of Cytosolic Calcium Ion Concentration Positive Regulation Of Stress Fiber Assembly Positive Regulation Of Focal Adhesion Assembly Pericardium Development Transdifferentiation SMAD Protein Signal Transduction Negative Regulation Of Wound Healing Negative Regulation Of Lung Blood Pressure Lens Fiber Cell Differentiation Cellular Response To Cytokine Stimulus Cellular Response To Transforming Growth Factor Beta Stimulus Positive Regulation Of Canonical Wnt Signaling Pathway Extrinsic Apoptotic Signaling Pathway Activation Of Cysteine-type Endopeptidase Activity Involved In Apoptotic Signaling Pathway Positive Regulation Of Extracellular Matrix Assembly Positive Regulation Of Pri-miRNA Transcription By RNA Polymerase II Negative Regulation Of Cardiac Muscle Hypertrophy In Response To Stress	Activation Of MAPK Activity Activation Of Innate Immune Response Toll-like Receptor Signaling Pathway B Cell Proliferation Involved In Immune Response Nitric Oxide Production Involved In Inflammatory Response Regulation Of Dendritic Cell Cytokine Production MyD88-dependent Toll-like Receptor Signaling Pathway MyD88-independent Toll-like Receptor Signaling Pathway Phagocytosis Inflammatory Response Immune Response I-kappaB Kinase/NF-kappaB Signaling I-kappaB Phosphorylation Positive Regulation Of Platelet Activation Positive Regulation Of Gene Expression Positive Regulation Of Keratinocyte Proliferation Astrocyte Development Detection Of Fungus Positive Regulation Of B Cell Proliferation Lipopolysaccharide-mediated Signaling Pathway Response To Lipopolysaccharide Detection Of Lipopolysaccharide Interleukin-1 Beta Production Negative Regulation Of Interferon-gamma Production Negative Regulation Of Interleukin-17 Production Negative Regulation Of Interleukin-23 Production Negative Regulation Of Interleukin-6 Production Negative Regulation Of Tumor Necrosis Factor Production Positive Regulation Of Chemokine Production Positive Regulation Of Interferon-alpha Production Positive Regulation Of Interferon-beta Production Positive Regulation Of Interferon-gamma Production Positive Regulation Of Interleukin-1 Beta Production Positive Regulation Of Interleukin-1 Production Positive Regulation Of Interleukin-10 Production Positive Regulation Of Interleukin-12 Production Positive Regulation Of Interleukin-6 Production Positive Regulation Of Interleukin-8 Production Positive Regulation Of Tumor Necrosis Factor Production Negative Regulation Of MyD88-independent Toll-like Receptor Signaling Pathway Toll-like Receptor 4 Signaling Pathway TRIF-dependent Toll-like Receptor Signaling Pathway T-helper 1 Type Immune Response Macrophage Activation Defense Response To Bacterium Positive Regulation Of Macrophage Activation Positive Regulation Of I-kappaB Kinase/NF-kappaB Signaling Innate Immune Response Positive Regulation Of MHC Class II Biosynthetic Process Positive Regulation Of Nitric Oxide Biosynthetic Process Negative Regulation Of Osteoclast Differentiation Positive Regulation Of Transcription By RNA Polymerase II Positive Regulation Of JNK Cascade Positive Regulation Of Inflammatory Response Defense Response To Gram-negative Bacterium Positive Regulation Of NF-kappaB Transcription Factor Activity Positive Regulation Of Nitric-oxide Synthase Biosynthetic Process Intestinal Epithelial Structure Maintenance Positive Regulation Of Macrophage Cytokine Production Necroptotic Process Negative Regulation Of ERK1 And ERK2 Cascade Positive Regulation Of ERK1 And ERK2 Cascade Positive Regulation Of Nucleotide-binding Oligomerization Domain Containing 1 Signaling Pathway Positive Regulation Of Nucleotide-binding Oligomerization Domain Containing 2 Signaling Pathway Cellular Response To Lipopolysaccharide Cellular Response To Lipoteichoic Acid Cellular Response To Mechanical Stimulus Cellular Response To Interferon-gamma Apoptotic Signaling Pathway Negative Regulation Of Cold-induced Thermogenesis Cellular Response To Oxidised Low-density Lipoprotein Particle Stimulus Positive Regulation Of Cytokine Production Involved In Inflammatory Response Positive Regulation Of NLRP3 Inflammasome Complex Assembly Positive Regulation Of NIK/NF-kappaB Signaling Positive Regulation Of Oxidative Stress-induced Neuron Death Positive Regulation Of Reactive Oxygen Species Biosynthetic Process Positive Regulation Of Cellular Response To Macrophage Colony-stimulating Factor Stimulus Positive Regulation Of Matrix Metallopeptidase Secretion Cellular Response To Amyloid-beta Positive Regulation Of Chemokine (C-X-C Motif) Ligand 2 Production
Pathways		Signaling by NODAL Signaling by NODAL Signaling by Activin Downregulation of TGF-beta receptor signaling TGF-beta receptor signaling activates SMADs Downregulation of SMAD2/3:SMAD4 transcriptional activity Downregulation of SMAD2/3:SMAD4 transcriptional activity SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription SMAD2/3 Phosphorylation Motif Mutants in Cancer SMAD4 MH2 Domain Mutants in Cancer SMAD2/3 MH2 Domain Mutants in Cancer TGFBR1 KD Mutants in Cancer Ub-specific processing proteases RUNX3 regulates CDKN1A transcription RUNX3 regulates BCL2L11 (BIM) transcription Interleukin-37 signaling NOTCH4 Intracellular Domain Regulates Transcription FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes FOXO-mediated transcription of cell cycle genes FOXO-mediated transcription of cell cycle genes	ER-Phagosome pathway Caspase activation via Death Receptors in the presence of ligand Toll Like Receptor 4 (TLR4) Cascade MyD88:MAL(TIRAP) cascade initiated on plasma membrane MyD88-independent TLR4 cascade TRIF-mediated programmed cell death MyD88 deficiency (TLR2/4) IRAK4 deficiency (TLR2/4) Regulation of TLR by endogenous ligand Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon IKK complex recruitment mediated by RIP1 TRAF6-mediated induction of TAK1 complex within TLR4 complex IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation
Drugs			Cyclobenzaprine Naloxone (R)-3-hydroxytetradecanoic acid Lauric acid Eritoran Golotimod E5531 Myristic acid Papain Mifamurtide
Diseases			Macular degeneration, including: Age-related macular degeneration (ARMD); Patterned dystrophy of retinal pigment epithelium (PDREP); Retinal macular dystrophy 2 (MCDR2); X-linked atrophic macular degeneration (MDXLA)
GWAS		Allergic disease (asthma, hay fever and/or eczema) (age of onset) ( 32603359) Allergic disease (asthma, hay fever and/or eczema) (multivariate analysis) ( 32603359) Allergic disease (asthma, hay fever or eczema) ( 29083406 29785011) Allergic rhinitis ( 30013184 31361310) Allergy ( 27182965) Appendicular lean mass ( 33097823) Asthma ( 31361310 31959851 30929738 20860503 27182965 32296059 31619474 29785011 29273806) Asthma (adult onset) ( 31036433 30929738) Asthma (childhood onset) ( 31036433 30929738) Asthma (moderate or severe) ( 30552067) Asthma and hay fever ( 24388013) Asthma onset (childhood vs adult) ( 30929738) Asthma or allergic disease (pleiotropy) ( 29785011) Bipolar disorder ( 31043756) Body fat distribution (leg fat ratio) ( 30664634) Body fat distribution (trunk fat ratio) ( 30664634) Central corneal thickness ( 32528159 31798171 29760442) Chronic inflammatory diseases (ankylosing spondylitis, Crohn's disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy) ( 26974007) Colorectal cancer or advanced adenoma ( 30510241) Corneal astigmatism ( 30306274) Corneal structure ( 23291589) Coronary artery disease ( 32469254 29212778 26343387 33020668) Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease) ( 28714975) Coronary heart disease ( 17634449) Crohn's disease ( 28067908 21102463) Dental caries (decayed and filled deciduous teeth) ( 31533690) Diverticular disease ( 30177863) Electrocardiogram morphology (amplitude at temporal datapoints) ( 32916098) Eosinophil counts ( 32888494 27863252) Eosinophil percentage of granulocytes ( 27863252) Eosinophil percentage of white cells ( 32888494 27863252) Estimated glomerular filtration rate ( 31152163 31015462) Femoral neck bone mineral density ( 29499414) HDL cholesterol levels ( 32203549) Heel bone mineral density ( 30598549 28869591) Height ( 28552196 31562340) Hematocrit ( 32888494) Inflammatory bowel disease ( 28067908 23128233) Intraocular pressure ( 29617998 31798171 29235454) Intraocular pressure and central corneal thickness (multi-trait analysis) ( 31798171) Lumbar spine bone mineral density ( 29499414) Lung cancer (smoking interaction) ( 24658283) Lung function (FVC) ( 30061609) Medication use (adrenergics, inhalants) ( 31015401) Medication use (glucocorticoids) ( 31015401) Metabolite levels ( 23823483) Myocardial infarction ( 26343387) Offspring birth weight ( 31043758) Osteoarthritis (hip) ( 30374069) Osteoarthritis of the hip or knee ( 30664745) Pediatric autoimmune diseases ( 26301688) Pulse pressure ( 27841878) Pursuit maintenance gain ( 29064472) Restless legs syndrome ( 29029846) Self-reported allergy ( 23817569) Spontaneous dizygotic twinning ( 27132594) Sum eosinophil basophil counts ( 27863252) Thyroid cancer ( 28195142) Ulcerative colitis ( 28067908) Waist circumference adjusted for BMI (adjusted for smoking behaviour) ( 28443625) Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction) ( 28443625) Waist circumference adjusted for BMI in non-smokers ( 28443625) Waist circumference adjusted for body mass index ( 25673412)	Adult body size ( 32376654) Blood protein levels ( 29875488 28240269) BMI (adjusted for smoking behaviour) ( 28443625) BMI in non-smokers ( 28443625) Body mass index ( 25673413 28448500) Body mass index (joint analysis main effects and physical activity interaction) ( 28448500) Body mass index (joint analysis main effects and smoking interaction) ( 28443625) Body mass index in physically active individuals ( 28448500) Body size at age 10 ( 32376654) Chronic inflammatory diseases (ankylosing spondylitis, Crohn's disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy) ( 26974007) Cognitive decline rate in late mild cognitive impairment ( 26252872) Experiencing mood swings ( 29500382) Feeling fed-up ( 29500382) Feeling guilty ( 29500382) Impulsivity (motor) ( 30718321) Irritable mood ( 29500382) Metabolite levels ( 23823483) Neurociticism ( 29500382) Neuroticism ( 29255261) Obesity-related traits ( 23251661) Osteoarthritis biomarkers ( 25057126) Plasma omega-6 polyunsaturated fatty acid levels (dihomo-gamma-linolenic acid) ( 24823311) Prostate-specific antigen levels ( 28139693) Voxel-wise structural brain imaging measurements in Alzheimerâ€™s disease ( 30584014)
Interacting Genes		282 interacting genes: AATF ACTB AKT1 ANAPC10 ANK3 APMAP APOB APP AR ARHGEF6 ATF2 ATF3 AXIN1 AXIN2 BLZF1 BPTF BRCA1 BRCA2 BTRC CAMK2G CCDC198 CCDC33 CDC16 CDC25A CDC27 CDK2 CDK4 CDK8 CDK9 CEBPA CEBPB CEBPD CFDP1 CFH CFLAR CHRD CLASRP CORO1A CPSF7 CPTP CREBBP CRX CSH2 CSNK1D CSNK1G2 CTCF CTNNB1 CUL1 CXXC5 CYP11A1 DAB2 DACH1 DDX5 DEDD DNAJB4 DNAJB5 DNMT3L DVL1 E2F4 E2F5 EBI3 EID2 EIF4B EIF4ENIF1 EP300 EPAS1 EPB41 ERBIN ESR1 ESR2 ETS1 FAM90A1 FBLN1 FHL2 FHL3 FLI1 FLNA FOS FOXG1 FOXH1 FOXO1 FOXO3 FOXO4 GGA1 GIT2 GLI3 GMEB1 GSC GSK3B GTF2IRD1 HDAC1 HDAC4 HDAC5 HEY1 HEYL HGS HIF1A HIPK2 HIVEP1 HMGA2 HNF4A HNRNPK HOXC11 HP HSPA4 HYAL2 IL37 ISL1 ITCH JPH3 JUN JUNB JUND KANSL1 KAT2B KDM2A KMT2B KPNB1 KRT10 KRT2 LBP LCK LEF1 LEMD3 LMNA MAGI2 MAP3K7 MAPK1 MAPK14 MAPK8 MAPK9 MAX MBD1 MCM3AP MDM4 MECOM MED15 MEN1 MEOX2 MTF2 MYC MYD88 MYO5B MYOCD MYOD1 NCOA6 NEDD4 NEDD4L NEDD9 NFIA NFYC NOTCH1 NOTCH4 NR3C1 NR4A1 NUP153 NUP214 OTUB1 PAEP PAPPA PARD3 PARP4 PAX8 PCDH1 PCK2 PEX6 PHC2 PIAS2 PIAS3 PIAS4 PIK3CA PIN1 PLAG1 PLAGL1 PLG PML PPM1A PPP1R12C PPP2R1A PRDM4 PRKAR1B PRKAR2A PROX1 PRTN3 PSMB1 PSMD11 RAB38 RANBP9 RARG RASD2 RASL12 RBL1 RBPMS RBX1 RCVRN RELA RIOK2 RIT1 RNF111 RNF31 RPA1 RPLP0 RRAS2 RUNX2 RUNX3 S100A4 SAP130 SBK3 SERTAD1 SETD2 SF3A1 SF3B2 SIN3A SKI SKIL SKOR2 SMAD1 SMAD2 SMAD4 SMAD7 SMAD9 SMURF1 SMURF2 SNRNP70 SNW1 SP1 SPTBN1 SQSTM1 SREBF2 SRY SS18L1 ST6GALNAC2 STRAP STUB1 SVEP1 TANK TDP2 TEKT4 TF TFE3 TGFBR1 TGFBR2 TGIF1 TGIF2 TGM2 TLE5 TLR4 TMED1 TOB1 TP53 TP73 TPM3 TRIM33 TSC2 TSC22D4 UBQLN4 UCHL5 USP7 VDR VIM VSIR WEE1 WWP1 WWP2 XPO6 XRCC6 YBX1 YY1 ZBTB16 ZBTB3 ZC3H12A ZCCHC14 ZDHHC4 ZEB1 ZEB2 ZFYVE9 ZMYM2 ZMYND11 ZNF329 ZNF774 ZNF8 ZNF83	25 interacting genes: BCL10 BTK CD14 CNPY4 DEFB4A HMGB1 HSP90B1 IRAK1 IRAK2 LY96 MAPK8IP3 MYD88 NOX4 RIPK2 RNF216 SERTAD1 SIGIRR SMAD3 SYK TICAM2 TIRAP TLR1 TLR5 TOLLIP UBQLN1
Entrez ID		4088	7099
HPRD ID		04380	04325
Ensembl ID		ENSG00000166949	ENSG00000136869
Uniprot IDs		A0A024R5Z3 P84022 Q9P0T0	O00206
PDB IDs		1MHD 1MJS 1MK2 1OZJ 1U7F 2LAJ 2LB2 5OD6 5ODG 5XOC 6ZMN	2Z62 2Z63 2Z65 2Z66 3FXI 3UL7 3UL8 3UL9 3ULA 4G8A 5NAM 5NAO
Enriched GO Terms of Interacting Partners?
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