SHC1 and SMAD4

Data Source:
BioGRID (two hybrid)

		SHC1	SMAD4
Description		SHC adaptor protein 1	SMAD family member 4
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GO Annotations	Cellular Component	Mitochondrial Matrix Cytosol Plasma Membrane Shc-EGFR Complex	Chromatin Nucleus Nucleoplasm Transcription Regulator Complex Cytoplasm Centrosome Cytosol Activin Responsive Factor Complex SMAD Protein Complex Heteromeric SMAD Protein Complex
	Molecular Function	Phosphotyrosine Residue Binding Transmembrane Receptor Protein Tyrosine Kinase Adaptor Activity Epidermal Growth Factor Receptor Binding Insulin Receptor Binding Insulin-like Growth Factor Receptor Binding Neurotrophin TRKA Receptor Binding Protein Binding Phospholipid Binding Protein Kinase Binding Receptor Tyrosine Kinase Binding Ephrin Receptor Binding Epidermal Growth Factor 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	MAPK Cascade Activation Of MAPK Activity Angiogenesis Transmembrane Receptor Protein Tyrosine Kinase Signaling Pathway Epidermal Growth Factor Receptor Signaling Pathway Regulation Of Epidermal Growth Factor-activated Receptor Activity Ras Protein Signal Transduction Axon Guidance Heart Development Positive Regulation Of Cell Population Proliferation Insulin Receptor Signaling Pathway Viral Process Cytokine-mediated Signaling Pathway Actin Cytoskeleton Reorganization Interleukin-15-mediated Signaling Pathway IRE1-mediated Unfolded Protein Response Fc-epsilon Receptor Signaling Pathway Interleukin-2-mediated Signaling Pathway ERBB2 Signaling Pathway Regulation Of Growth Defense Response To Bacterium Negative Regulation Of Apoptotic Process Positive Regulation Of MAPK Cascade Negative Regulation Of Transcription, DNA-templated Positive Regulation Of Transcription, DNA-templated Positive Regulation Of Ras Protein Signal Transduction Leukocyte Migration Positive Regulation Of ERK1 And ERK2 Cascade Cellular Response To Growth Factor Stimulus Cell-cell Adhesion	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		Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants SHC1 events in ERBB2 signaling SHC1 events in ERBB2 signaling SHC1 events in ERBB4 signaling Signalling to RAS Signalling to RAS SHC1 events in EGFR signaling Tie2 Signaling Integrin signaling XBP1(S) activates chaperone genes Interleukin-3, Interleukin-5 and GM-CSF signaling Constitutive Signaling by EGFRvIII RAF/MAP kinase cascade Signal attenuation Insulin receptor signalling cascade Insulin receptor signalling cascade RET signaling Interleukin-15 signaling Interleukin-15 signaling Interleukin-2 signaling Erythropoietin activates RAS Erythropoietin activates RAS Interleukin receptor SHC signaling Constitutive Signaling by Overexpressed ERBB2 Signaling by ERBB2 KD Mutants Signaling by ERBB2 ECD mutants Signaling by ERBB2 TMD/JMD mutants	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		Bipolar disorder ( 31043756) Body fat distribution (leg fat ratio) ( 30664634) Body fat distribution (trunk fat ratio) ( 30664634) Eosinophil counts ( 29403010) Hemoglobin levels ( 32327693) Inflammatory bowel disease ( 27569725) Prostate cancer ( 23535732)	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		143 interacting genes: ALK AP2A1 AP2A2 APP AR AXL BCL3 BCR BUB1 C11orf58 CALCOCO2 CALD1 CBL CBLB CBLC CD22 CD247 CD3E CD81 CDH5 CEACAM1 CRK CRKL CSF1R CSF2RB CSF3R CSK DAG1 DDR1 DDR2 DOK1 DUSP23 EGFR EPHA2 EPOR EPS8 ERBB2 ERBB3 ERBB4 ESR1 FAM118B FBXW7 FCGR2A FCGR3A FGFR1 FGFR2 FLT1 FLT4 FYN GAB1 GAB2 GEMIN7 GH1 GHR GRAP GRAP2 GRB2 GRB7 HMOX2 IGF1R IL2 IL2RB IL2RG IL4R IL6ST ILK INPP5D INPPL1 INSR IRS1 IRS2 ITGB3 ITGB4 JAK2 KDR KIT KRT18 LCK LCP2 LRP1 LTK LYN MAP4K1 MAPK1 MAPK14 MAPK6 MAPK8 MAPKAPK2 MET MME MPL MRPL44 MST1R NGFR NPM1 NTRK1 NTRK2 NTRK3 NUDT21 OSGEP PAG1 PAK1 PDGFRB PIK3C2B PIK3R1 PIK3R2 PLCG1 PLCG2 PLPP3 PLSCR1 PPP2R5A PRKCA PRKCD PRKRA PTK2 PTK2B PTPN11 PTPN12 PTPN2 PTPN6 RAPGEF1 RASA1 RB1 RET SH2B2 SHCBP1 SMAD4 SOS1 SOS2 SP1 SRC STAT5A STAT5B SUV39H2 SYK TEC TEK TPR TRIM15 UBASH3B VAV1 VAV3 ZAP70	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		6464	4089
HPRD ID		02780	02995
Ensembl ID		ENSG00000160691	ENSG00000141646
Uniprot IDs		P29353	A0A024R274 Q13485
PDB IDs		1MIL 1N3H 1OY2 1QG1 1SHC 1TCE 1WCP 2L1C 4JMH 4XWX 5CZI 6DM4	1DD1 1G88 1MR1 1U7F 1U7V 1YGS 5C4V 5MEY 5MEZ 5MF0 5UWU
Enriched GO Terms of Interacting Partners?
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