SMAD3 and SMAD4

Data Source:
BioGRID (affinity chromatography technology)
HPRD (in vivo, in vitro, two hybrid)

		SMAD3	SMAD4
Description		SMAD family member 3	SMAD family member 4
Image
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	Chromatin Nucleus Nucleoplasm Transcription Regulator Complex Cytoplasm Centrosome Cytosol Activin Responsive Factor Complex SMAD Protein Complex Heteromeric SMAD Protein Complex
	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	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 RNA Polymerase II Transcription Factor Binding Transcription Coactivator Binding DNA-binding Transcription Activator Activity, RNA Polymerase II-specific DNA Binding Chromatin Binding DNA-binding Transcription Factor Activity Protein Binding Collagen Binding Identical Protein Binding Protein Homodimerization Activity Sulfate Binding Sequence-specific DNA Binding Metal Ion Binding I-SMAD Binding R-SMAD Binding Transcription Regulator Activator Activity
	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	Negative Regulation Of Transcription By RNA Polymerase II Ovarian Follicle Development Branching Involved In Ureteric Bud Morphogenesis Response To Hypoxia In Utero Embryonic Development Gastrulation With Mouth Forming Second Outflow Tract Septum Morphogenesis Atrioventricular Valve Formation Epithelial To Mesenchymal Transition Involved In Endocardial Cushion Formation Left Ventricular Cardiac Muscle Tissue Morphogenesis Positive Regulation Of Cell Proliferation Involved In Heart Valve Morphogenesis Brainstem Development Regulation Of Transcription By RNA Polymerase II Cellular Iron Ion Homeostasis Transforming Growth Factor Beta Receptor Signaling Pathway SMAD Protein Complex Assembly Spermatogenesis Single Fertilization Axon Guidance Cell Population Proliferation Negative Regulation Of Cell Population Proliferation Anatomical Structure Morphogenesis Negative Regulation Of Cardiac Muscle Hypertrophy Positive Regulation Of Epithelial To Mesenchymal Transition Positive Regulation Of Pathway-restricted SMAD Protein Phosphorylation Neural Crest Cell Differentiation Protein Deubiquitination Regulation Of Transforming Growth Factor Beta Receptor Signaling Pathway Cell Differentiation Negative Regulation Of Cell Growth BMP Signaling Pathway Positive Regulation Of Transforming Growth Factor Beta Receptor Signaling Pathway Positive Regulation Of BMP Signaling Pathway Somite Rostral/caudal Axis Specification Regulation Of Transforming Growth Factor Beta2 Production Positive Regulation Of Luteinizing Hormone Secretion Somatic Stem Cell Population Maintenance Intracellular Signal Transduction Atrioventricular Canal Development Endothelial Cell Activation Embryonic Digit Morphogenesis Negative Regulation Of Transcription, DNA-templated Positive Regulation Of Transcription, DNA-templated Positive Regulation Of Transcription By RNA Polymerase II Positive Regulation Of Follicle-stimulating Hormone Secretion Mesendoderm Development Developmental Growth Neuron Fate Commitment Sebaceous Gland Development Formation Of Anatomical Boundary Regulation Of Binding Positive Regulation Of Histone H3-K4 Methylation Regulation Of Hair Follicle Development Uterus Development Positive Regulation Of SMAD Protein Signal Transduction SMAD Protein Signal Transduction Ventricular Septum Morphogenesis Negative Regulation Of Cell Death Endocardial Cell Differentiation Female Gonad Morphogenesis Secondary Palate Development Interleukin-6-mediated Signaling Pathway Negative Regulation Of ERK1 And ERK2 Cascade Response To Transforming Growth Factor Beta Cellular Response To BMP Stimulus Metanephric Mesenchyme Morphogenesis Nephrogenic Mesenchyme Morphogenesis Seminiferous Tubule Development Positive Regulation Of Transcription From RNA Polymerase II Promoter Involved In Cellular Response To Chemical Stimulus Positive Regulation Of Pri-miRNA Transcription By RNA Polymerase II Negative Regulation Of Cardiac Myofibril Assembly Positive Regulation Of Histone H3-K9 Acetylation
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	Signaling by NODAL Signaling by Activin Signaling by BMP 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 SMAD4 MH2 Domain Mutants in Cancer SMAD2/3 MH2 Domain Mutants in Cancer Transcriptional regulation of pluripotent stem cells Ub-specific processing proteases RUNX2 regulates bone development RUNX3 regulates CDKN1A transcription RUNX3 regulates BCL2L11 (BIM) 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
Drugs
Diseases			Colorectal cancer Hereditary hemorrhagic telangiectasia (HHT) Pancreatic cancer Juvenile polyposis syndrome
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)	Asthma ( 30929738 32296059) Asthma (childhood onset) ( 30929738) Asthma onset (childhood vs adult) ( 30929738) Immune response to anthrax vaccine ( 22658931) Metabolite levels ( 23823483) Oligoclonal band status in multiple sclerosis ( 25616667)
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	214 interacting genes: ACVR1B AKT1 ALDOB AOPEP AP2B1 APBB2 AR ARFRP1 ARL5B ATF2 ATF7IP BAAT BCAS3 BEX1 BRCA1 BTRC CAMK2G CCDC180 CD59 CDC14B CEBPA CEBPB CEBPD CHEK1 CITED1 CNKSR1 COPS5 CREBBP CSH1 CSH2 CTCF CTNNB1 CYFIP2 DACH1 DCP1A DCP1B DKK3 DLX1 DNAJB2 DNMT3L DVL1 ECSIT EEF1A1 EID2 EIF2AK4 EP300 ERBIN ESR1 ESR2 ETV4 EWSR1 FANCC FBLN1 FBP2 FBXO30 FBXO34 FHL2 FHL3 FN1 FOXG1 FOXH1 FOXO1 FOXO3 FOXO4 FSTL3 GATA2 GLI3 GPNMB GREB1 HDGF HDLBP HEMGN HMG20A HNF4A HOXA9 HOXC8 HRAS HYAL2 IL24 ITK JUN JUNB JUND LAMTOR5 LEF1 LMO4 LRATD2 LYPD3 MAPK1 MAPK13 MAX MDM4 MECOM MEF2A MEX3B MSANTD3 MYOD1 NAT8 NEK6 NELFCD NFIA NFKBID NKX3-2 NOTCH4 NR0B2 NRAS NUAK2 NUP214 OTUB1 PAK1 PAPPA2 PARD3 PBK PIAS1 PIAS2 PIAS3 PIAS4 PLG PLK4 PPP2CB PPP3R2 PRKAR1B PRKAR2A PRPF40A PSG2 PSG9 PSMD11 RAB13 RAB25 RAB2B RAB34 RAB38 RAB3B RAC2 RALA RASD2 RASL12 RASSF5 RBL1 RELA RFX1 RHEBL1 RHOD RHOG RHOJ RIPK2 RMND5B RPL28 RPS27A RRAS2 RSPH14 S100A14 SASH3 SERPINA1 SERPINB5 SFRP2 SFRP4 SHC1 SKI SKIL SKP2 SMAD1 SMAD2 SMAD3 SMAD5 SMAD7 SMAD9 SNIP1 SNRNP70 SNW1 SOX12 SP1 SPTBN1 SQSTM1 STK11IP STK35 STUB1 STX17 TCTA TDG TENM3 TFE3 TGFBR1 TGFBR2 TGFBRAP1 THRSP TIAF1 TLE5 TM9SF2 TOB1 TRAP1 TSSK3 TSTD2 UBA52 UBB UBE2I UBE2L3 UBE2Z UHRF2 USB1 USP10 USP4 USP9X WWOX XPO5 ZBED5 ZBTB7A ZIC1 ZMYM2 ZNF189 ZNF423 ZNF510 ZNF521 ZNF8
Entrez ID		4088	4089
HPRD ID		04380	02995
Ensembl ID		ENSG00000166949	ENSG00000141646
Uniprot IDs		A0A024R5Z3 P84022 Q9P0T0	A0A024R274 Q13485
PDB IDs		1MHD 1MJS 1MK2 1OZJ 1U7F 2LAJ 2LB2 5OD6 5ODG 5XOC 6ZMN	1DD1 1G88 1MR1 1U7F 1U7V 1YGS 5C4V 5MEY 5MEZ 5MF0 5UWU
Enriched GO Terms of Interacting Partners?
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