ITCH and NRAS

Number of citations of the paper that reports this interaction (PubMedID 31015455)
58

Data Source:
BioGRID (enzymatic study)

		ITCH	NRAS
Description		itchy E3 ubiquitin protein ligase	NRAS proto-oncogene, GTPase
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GO Annotations	Cellular Component	Nucleus Nucleoplasm Cytoplasm Mitochondrion Endosome Early Endosome Cytosol Plasma Membrane Cell Cortex Endosome Membrane Membrane Cytoplasmic Vesicle Early Endosome Membrane Protein-containing Complex Extracellular Exosome Cell Periphery	Golgi Membrane Endoplasmic Reticulum Membrane Golgi Apparatus Cytosol Plasma Membrane Membrane Extracellular Exosome Tertiary Granule Membrane
	Molecular Function	Ubiquitin-protein Transferase Activity Protein Binding Transferase Activity Ligase Activity Ubiquitin-like Protein Transferase Activity Ubiquitin-ubiquitin Ligase Activity Ribonucleoprotein Complex Binding Ubiquitin-like Protein Ligase Binding CXCR Chemokine Receptor Binding Ubiquitin Protein Ligase Activity Arrestin Family Protein Binding	Nucleotide Binding GTPase Activity G Protein Activity Protein Binding GTP Binding Hydrolase Activity GDP Binding Protein-containing Complex Binding
	Biological Process	Protein Polyubiquitination Regulation Of Cell Growth Immune System Process Positive Regulation Of T Cell Anergy Negative Regulation Of Immune System Process Positive Regulation Of Immune System Process Cytoplasmic Pattern Recognition Receptor Signaling Pathway T Cell Anergy Ubiquitin-dependent Protein Catabolic Process Protein Monoubiquitination Apoptotic Process Inflammatory Response Response To Oxidative Stress Positive Regulation Of Catabolic Process Regulation Of Gene Expression Positive Regulation Of Macromolecule Metabolic Process Protein Ubiquitination Protein Catabolic Process Receptor Internalization Negative Regulation Of Type I Interferon Production Protein K29-linked Ubiquitination CD4-positive, Alpha-beta T Cell Proliferation Nucleotide-binding Domain, Leucine Rich Repeat Containing Receptor Signaling Pathway CXCL12-activated CXCR4 Signaling Pathway Negative Regulation Of Cytoplasmic Pattern Recognition Receptor Signaling Pathway Negative Regulation Of Apoptotic Process Negative Regulation Of Canonical NF-kappaB Signal Transduction Proteasome-mediated Ubiquitin-dependent Protein Catabolic Process Innate Immune Response Positive Regulation Of Protein Catabolic Process Negative Regulation Of JNK Cascade Symbiont Entry Into Host Cell Negative Regulation Of Defense Response To Virus Negative Regulation Of Multicellular Organismal Process Defense Response To Virus Protein Autoubiquitination Regulation Of Necroptotic Process Protein K63-linked Ubiquitination Protein K48-linked Ubiquitination Regulation Of Protein Deubiquitination Protein Branched Polyubiquitination Regulation Of Hematopoietic Stem Cell Differentiation Negative Regulation Of Intracellular Signal Transduction Negative Regulation Of CD4-positive, Alpha-beta T Cell Proliferation Positive Regulation Of Receptor Catabolic Process	MAPK Cascade Positive Regulation Of Endothelial Cell Proliferation Signal Transduction Ras Protein Signal Transduction
Pathways		Downregulation of ERBB4 signaling NOD1/2 Signaling Pathway Activated NOTCH1 Transmits Signal to the Nucleus Activated NOTCH1 Transmits Signal to the Nucleus Degradation of GLI1 by the proteasome Hedgehog 'on' state Regulation of necroptotic cell death RUNX1 regulates transcription of genes involved in differentiation of HSCs Negative regulators of DDX58/IFIH1 signaling SARS-CoV-1 activates/modulates innate immune responses Antigen processing: Ubiquitination & Proteasome degradation	SOS-mediated signalling Activation of RAS in B cells Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants SHC1 events in ERBB2 signaling SHC1 events in ERBB4 signaling Signaling by SCF-KIT Signalling to RAS p38MAPK events p38MAPK events GRB2 events in EGFR signaling SHC1 events in EGFR signaling Downstream signal transduction GRB2 events in ERBB2 signaling GRB2 events in ERBB2 signaling Tie2 Signaling EGFR Transactivation by Gastrin DAP12 signaling SHC-related events triggered by IGF1R FCERI mediated MAPK activation NCAM signaling for neurite out-growth Ras activation upon Ca2+ influx through NMDA receptor VEGFR2 mediated cell proliferation CD209 (DC-SIGN) signaling Constitutive Signaling by EGFRvIII SHC-mediated cascade:FGFR1 FRS-mediated FGFR1 signaling SHC-mediated cascade:FGFR2 FRS-mediated FGFR2 signaling SHC-mediated cascade:FGFR3 FRS-mediated FGFR3 signaling FRS-mediated FGFR4 signaling SHC-mediated cascade:FGFR4 Signaling by FGFR2 in disease Signaling by FGFR4 in disease Signaling by FGFR1 in disease Signaling by FGFR3 in disease Regulation of RAS by GAPs RAF activation RAF/MAP kinase cascade MAP2K and MAPK activation Negative regulation of MAPK pathway Neutrophil degranulation Signaling by moderate kinase activity BRAF mutants Signaling by high-kinase activity BRAF mutants Signaling by BRAF and RAF1 fusions RAS signaling downstream of NF1 loss-of-function variants Paradoxical activation of RAF signaling by kinase inactive BRAF Insulin receptor signalling cascade PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases MET activates RAS signaling Activated NTRK2 signals through RAS Erythropoietin activates RAS Activated NTRK2 signals through FRS2 and FRS3 Activated NTRK3 signals through RAS FLT3 Signaling Constitutive Signaling by Overexpressed ERBB2 Estrogen-stimulated signaling through PRKCZ RAS processing Signaling downstream of RAS mutants Signaling by RAF1 mutants Signaling by ERBB2 KD Mutants Signaling by ERBB2 ECD mutants Signaling by ERBB2 TMD/JMD mutants Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants Signaling by PDGFRA extracellular domain mutants Signaling by FLT3 fusion proteins Signaling by FLT3 ITD and TKD mutants Signaling by RAS GAP mutants Signaling by RAS GTPase mutants
Drugs
Diseases			Adrenal carcinoma Acute myeloid leukemia (AML) Oral cancer Multiple myeloma Malignant melanoma Noonan syndrome and related disorders, including: Noonan syndrome (NS); Leopard syndrome (LS); Noonan syndrome-like with loose anagen hair (NS/LAH); CBL-mutation associated syndrome (CBL); Neurofibromatosis type 1 (NF1); Neurofibromatosis type 2 (NF2); Neurofibromatosis-Noonan syndrome (NFNS); Legius syndrome; Cardiofaciocutaneous syndrome (CFCS); Costello syndrome (CS) Hepatocellular carcinoma Thyroid cancer Autoimmune lymphoproliferative syndromes (ALPS), including the following five diseases: CD95 (Fas) defect, ALPS type 1a; CD95L (Fas ligand) defect, ALPS type 1b; Caspase 10 defect, ALPS type 2a; Caspase 8 defext, ALPS type 2b; Activaing N-Ras defect, N-Ras ALPS
GWAS		Appendicular lean mass ( 33097823) Bipolar disorder ( 31043756) Colorectal cancer or advanced adenoma ( 30510241) Estimated glomerular filtration rate ( 31015462 31152163) Fish- and plant-related diet ( 32066663) Heel bone mineral density ( 28869591) Hip circumference adjusted for BMI ( 34021172) Oily fish consumption ( 32066663) Pork consumption ( 32066663) Vitiligo ( 27723757)	Adult body size ( 32376654) Autism ( 24189344)
Interacting Genes		132 interacting genes: AGO2 AKT1 ARHGEF7 ARID1A ARRB2 ARRDC3 ATN1 BECN1 BIN1 BRAF CBL CBLC CDC34 CPSF6 CPSF7 CSNK2A1 CXCR4 CYLD DAZAP1 DSCR9 DTX1 DTX3L ERBB4 ESS2 EWSR1 FYN GJA1 GLIS3 GNAI2 H1-2 HNRNPUL1 JUN JUNB KIAA1210 KPNB1 KSR1 LAPTM5 LITAF LRRK1 MAP2 MAP2K1 MAP2K4 MAP3K2 MAPK8 MLANA MLKL MYCT1 N4BP1 NDFIP1 NDFIP2 NEDD9 NFE2 NOTCH1 NRAS NUDT21 NUMB PABPC1 PACSIN1 PIP4P2 POLR2A POLR2B POLR2C POLR2E POU5F1 PRKACA PRRG4 RAF1 RBM14 REPS2 RHBDD1 RIPK1 RNF11 RORA RPAP2 RPAP3 SCNN1A SCNN1B SF1 SGK3 SH3GL1 SH3GL2 SIK1 SMAD2 SMAD3 SMARCC1 SMARCC2 SMARCE1 SMN1 SNX9 SPART SPEN STAM2 STRIP2 SUFU TAB1 TAF15 TGFB1I1 TMEM51 TP73 TRERF1 TRPC4 TRPV1 TRPV4 TTYH3 UBAP2 UBAP2L UBC UBE2C UBE2D1 UBE2D2 UBE2D3 UBE2D4 UBE2E1 UBE2E2 UBE2E3 UBE2G1 UBE2J2 UBE2K UBE2L3 UBE2L6 UBE2M UBE2O UBE2Q1 UBE2Q2 UBE2R2 URI1 UVRAG WASL WBP2 YWHAQ YY1 ZC3H14	48 interacting genes: ACVR1 AKT1 ALDOB AOPEP ARAF ARHGAP4 BCL2 CCDC180 CORO2A CYLC2 DNAJB1 EEF1A1 FANCC FBP2 FRAT2 HEMGN HRAS ITCH LEF1 LZTR1 MAPK3 MAPKAP1 MTOR NEDD4 PIK3CA PIK3CG PLCE1 PPP2CB RACGAP1 RAF1 RAP1GDS1 RASGRP2 RASSF5 RGL2 RGL3 RPS20 SFRP4 SHOC2 SMAD1 SMAD4 SMURF2 SRI STX17 TDRD7 TRMO WDR76 XPA ZDHHC9
Entrez ID		83737	4893
HPRD ID		07565	01273
Ensembl ID		ENSG00000078747	ENSG00000213281
Uniprot IDs		Q96J02	P01111 Q5U091
PDB IDs		2DMV 2KYK 2NQ3 2P4R 2YSF 3TUG 4ROF 5C7M 5CQ2 5DWS 5DZD 5SXP	2N9C 3CON 5UHV 6E6H 6MPP 6ULI 6ULK 6ULN 6ULR 6UON 6WGH 6ZIO 6ZIR 6ZIZ 7F68 7OW3 7OW4 7OW5 7OW6 7PB2 8TBI 8VM2
Enriched GO Terms of Interacting Partners?		Ubiquitin Conjugating Enzyme Activity Ubiquitin-protein Transferase Activity Protein Polyubiquitination Protein K48-linked Ubiquitination Protein Ubiquitination Post-translational Protein Modification Protein Modification By Small Protein Conjugation Modification-dependent Protein Catabolic Process Ubiquitin Protein Ligase Binding Nucleus Cytosol Ubiquitin-dependent Protein Catabolic Process Macromolecule Catabolic Process Proteolysis Involved In Protein Catabolic Process ATP Binding Transferase Activity Regulation Of Macromolecule Metabolic Process Positive Regulation Of Metabolic Process Nucleoplasm Regulation Of Gene Expression Regulation Of Macromolecule Biosynthetic Process Regulation Of Metabolic Process Protein Modification Process Positive Regulation Of Macromolecule Metabolic Process Nucleotide Binding WW Domain Binding Regulation Of Primary Metabolic Process Protein Binding Intracellular Signal Transduction Regulation Of RNA Metabolic Process Positive Regulation Of Signal Transduction Regulation Of Protein Modification Process Regulation Of Nucleobase-containing Compound Metabolic Process Regulation Of DNA-templated Transcription Regulation Of RNA Biosynthetic Process Intracellular Signaling Cassette Cytoplasm Positive Regulation Of Intracellular Signal Transduction Positive Regulation Of Macromolecule Biosynthetic Process Positive Regulation Of Biosynthetic Process Regulation Of Cell Differentiation Macromolecule Metabolic Process Positive Regulation Of RNA Metabolic Process Protein K11-linked Ubiquitination Regulation Of Protein Metabolic Process Positive Regulation Of Protein Modification Process Negative Regulation Of Macromolecule Metabolic Process Negative Regulation Of Macromolecule Biosynthetic Process Regulation Of Protein Ubiquitination Negative Regulation Of Metabolic Process	Regulation Of Intracellular Signal Transduction Intracellular Signal Transduction Intracellular Signaling Cassette Insulin Receptor Signaling Pathway Signal Transduction Regulation Of Signal Transduction Cytosol Enzyme-linked Receptor Protein Signaling Pathway Regulation Of Cell Communication Regulation Of Signaling Positive Regulation Of Signal Transduction Insulin-like Growth Factor Receptor Signaling Pathway Positive Regulation Of Intracellular Signal Transduction Negative Regulation Of Apoptotic Process Negative Regulation Of Programmed Cell Death Positive Regulation Of Cell Communication Positive Regulation Of Signaling Cytoplasm Regulation Of Small GTPase Mediated Signal Transduction Cell Surface Receptor Protein Tyrosine Kinase Signaling Pathway Cell Population Proliferation Cell Surface Receptor Signaling Pathway Regulation Of Apoptotic Process Regulation Of Programmed Cell Death Positive Regulation Of Phosphatidylinositol 3-kinase/protein Kinase B Signal Transduction ERBB Signaling Pathway Ras Protein Signal Transduction Positive Regulation Of Cell Migration BMP Signaling Pathway MAPK Cascade Positive Regulation Of Cell Motility Anoikis Phosphatidylinositol 3-kinase/protein Kinase B Signal Transduction Positive Regulation Of Locomotion Regulation Of Cellular Component Organization Channel Inhibitor Activity Programmed Cell Death Cellular Response To Insulin Stimulus Regulation Of Protein Catabolic Process Regulation Of Autophagy Cell Death Small GTPase-mediated Signal Transduction Regulation Of Ras Protein Signal Transduction Cellular Response To Peptide Hormone Stimulus Gland Development Negative Regulation Of Autophagy Protein Serine/threonine Kinase Activity Regulation Of Cell Growth Lymphocyte Proliferation Schwann Cell Development
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