HNF4A and SMAD4

Data Source:
HPRD (in vitro, in vivo)

		HNF4A	SMAD4
Description		hepatocyte nuclear factor 4 alpha	SMAD family member 4
Image
GO Annotations	Cellular Component	Chromatin Nucleus Nucleoplasm Cytoplasm	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 RNA Polymerase II Activating Transcription Factor Binding DNA-binding Transcription Activator Activity, RNA Polymerase II-specific DNA Binding Chromatin Binding DNA-binding Transcription Factor Activity Nuclear Receptor Activity Signaling Receptor Binding Fatty Acid Binding Protein Binding Zinc Ion Binding Protein Homodimerization Activity Sequence-specific Double-stranded DNA 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	Type B Pancreatic Cell Development Regulation Of Transcription By RNA Polymerase II Transcription Initiation From RNA Polymerase II Promoter Ornithine Metabolic Process Lipid Metabolic Process Xenobiotic Metabolic Process Sex Differentiation Blood Coagulation Negative Regulation Of Cell Population Proliferation Response To Glucose Regulation Of Gastrulation Regulation Of Lipid Metabolic Process Signal Transduction Involved In Regulation Of Gene Expression Cell Differentiation Negative Regulation Of Cell Growth Intracellular Receptor Signaling Pathway Glucose Homeostasis Cholesterol Homeostasis Regulation Of Circadian Rhythm Negative Regulation Of Transcription, DNA-templated Positive Regulation Of Transcription, DNA-templated Positive Regulation Of Transcription By RNA Polymerase II Rhythmic Process Anatomical Structure Development Regulation Of Insulin Secretion Lipid Homeostasis Phospholipid Homeostasis SMAD Protein Signal Transduction Triglyceride Homeostasis Hepatocyte Differentiation	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		Nuclear Receptor transcription pathway	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		Lauric acid AVI-4557 Myristic acid
Diseases		Maturity onset diabetes of the young (MODY)	Colorectal cancer Hereditary hemorrhagic telangiectasia (HHT) Pancreatic cancer Juvenile polyposis syndrome
GWAS		Apolipoprotein A1 levels ( 32203549) Apolipoprotein B levels ( 32203549) C-reactive protein ( 22939635) C-reactive protein levels ( 30388399 21300955) C-reactive protein levels or HDL-cholesterol levels (pleiotropy) ( 27286809) C-reactive protein levels or LDL-cholesterol levels (pleiotropy) ( 27286809) C-reactive protein levels or total cholesterol levels (pleiotropy) ( 27286809) Cholesterol, total ( 24097068 20686565) Chronic inflammatory diseases (ankylosing spondylitis, Crohn's disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy) ( 26974007) Coenzyme Q10 levels ( 27149984) Estimated glomerular filtration rate ( 31152163) Factor VII activity ( 30642921) Fibrinogen levels ( 28107422 26561523) Gallstone disease ( 30504769) Granulocyte count ( 27863252) HDL cholesterol ( 24097068 19060906 30275531 25961943 20686565) HDL cholesterol levels ( 32203549 30698716) HDL cholesterol levels in current drinkers ( 30698716) HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df) ( 30698716) HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df) ( 30698716) HDL cholesterol levels x long total sleep time interaction (2df test) ( 31719535) HDL cholesterol levels x short total sleep time interaction (2df test) ( 31719535) Hematocrit ( 32888494 27863252) Hemoglobin ( 32888494) Hemoglobin levels ( 32327693) LDL cholesterol levels ( 32203549) LDL cholesterol levels in current drinkers ( 30698716) LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df) ( 30698716) LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df) ( 30698716) Low density lipoprotein cholesterol levels ( 32154731) Lymphocyte percentage of white cells ( 32888494) Medication use (drugs used in diabetes) ( 31015401) Metabolic syndrome ( 31589552) Myeloid white cell count ( 27863252) Neutrophil count ( 32888494 27863252) Neutrophil percentage of white cells ( 32888494 27863252) Pancreatic cancer ( 29422604) Red blood cell count ( 32888494) Serum uric acid levels ( 30993211) Sum basophil neutrophil counts ( 27863252) Sum neutrophil eosinophil counts ( 27863252) Type 2 diabetes ( 24509480 30054458 21874001 30297969 29632382 31118516 32499647 22158537 30718926 28869590) Type 2 diabetes (adjusted for BMI) ( 29632382) Ulcerative colitis ( 19915572 23128233) Urate levels ( 31578528) White blood cell count ( 32888494)	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		69 interacting genes: ANP32B ARNT COPS5 CREBBP DDX3X DMD EIF1AY ESR1 FOXO1 GTF2B GTF2H1 HDAC3 HDAC4 HIF1A HNF1A ISL1 MAPK1 MAPK14 MAPK3 MECR MED1 MED10 MED14 MED16 MED17 MED21 MED24 MED7 NCOA1 NCOA2 NCOA6 NCOR2 NPPA NR0B2 NR1I2 NR1I3 NR2C2 NR2F1 NRBF2 NRIP1 PCBD1 PIAS4 PLPP2 PNRC1 PNRC2 PPARGC1A PPARGC1B PRKAA2 PRKACA PRMT1 PROX1 RNF4 SIRT1 SMAD2 SMAD3 SMAD4 SP1 SREBF1 SREBF2 SUB1 TAF6 TAF9 TBP TGS1 TP53 TRIM24 UBE2I XPO1 ZNHIT3	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		3172	4089
HPRD ID		02612	02995
Ensembl ID		ENSG00000101076	ENSG00000141646
Uniprot IDs		A0A087WXV4 B9VVT8 F1D8S2 F1D8T0 F1D8T1 P41235	A0A024R274 Q13485
PDB IDs		1PZL 3CBB 3FS1 4B7W 4IQR 6CHT	1DD1 1G88 1MR1 1U7F 1U7V 1YGS 5C4V 5MEY 5MEZ 5MF0 5UWU
Enriched GO Terms of Interacting Partners?
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