MET and CBL

Number of citations: 73 (PubMedID 35831314)
Data Source: BioGRID (biochemical), HPRD (two hybrid, in vivo, in vitro)

		MET	CBL
Name		MET proto-oncogene, receptor tyrosine kinase	Cbl proto-oncogene
Structure
GO Annotations	Cellular Component	Extracellular Region Plasma Membrane Basal Plasma Membrane Cell Surface Membrane Receptor Complex Postsynapse	Cytoplasm Golgi Apparatus Cytosol Plasma Membrane Focal Adhesion Cilium Membrane Flotillin Complex Axon Growth Cone Cell Projection Membrane Raft Perinuclear Region Of Cytoplasm
	Molecular Function	Nucleotide Binding Protein Kinase Activity Protein Tyrosine Kinase Activity Transmembrane Receptor Protein Tyrosine Kinase Activity Hepatocyte Growth Factor Receptor Activity Protein Binding ATP Binding Kinase Activity Transferase Activity Semaphorin Receptor Activity Protein Phosphatase Binding Identical Protein Binding Molecular Function Activator Activity	Phosphotyrosine Residue Binding Ubiquitin-protein Transferase Activity Calcium Ion Binding Protein Binding Zinc Ion Binding Transferase Activity SH3 Domain Binding Protein Kinase Binding Receptor Tyrosine Kinase Binding Phosphatidylinositol 3-kinase Regulatory Subunit Binding Cadherin Binding Metal Ion Binding Ephrin Receptor Binding Ubiquitin Protein Ligase Activity Protein Tyrosine Kinase Binding
	Biological Process	Endothelial Cell Morphogenesis Liver Development Signal Transduction Cell Surface Receptor Signaling Pathway Cell Surface Receptor Protein Tyrosine Kinase Signaling Pathway Regulation Of Gene Expression Negative Regulation Of Autophagy Neuron Differentiation Pancreas Development Positive Regulation Of Microtubule Polymerization Negative Regulation Of Rho Protein Signal Transduction Positive Regulation Of Transcription By RNA Polymerase II Hepatocyte Growth Factor Receptor Signaling Pathway Cell Development Animal Organ Development Branching Morphogenesis Of An Epithelial Tube Positive Chemotaxis Negative Regulation Of Stress Fiber Assembly Excitatory Postsynaptic Potential Establishment Of Skin Barrier Negative Regulation Of Thrombin-activated Receptor Signaling Pathway Semaphorin-plexin Signaling Pathway Negative Regulation Of Hydrogen Peroxide-mediated Programmed Cell Death Negative Regulation Of Guanyl-nucleotide Exchange Factor Activity Positive Regulation Of Endothelial Cell Chemotaxis	Protein Polyubiquitination Ubiquitin-dependent Protein Catabolic Process Protein Monoubiquitination DNA Damage Response Signal Transduction Cell Surface Receptor Signaling Pathway Male Gonad Development Response To Gamma Radiation Response To Activity Protein Ubiquitination Cytokine-mediated Signaling Pathway Regulation Of Signaling Regulation Of Rap Protein Signal Transduction Response To Testosterone Cellular Response To Platelet-derived Growth Factor Stimulus Negative Regulation Of Epidermal Growth Factor Receptor Signaling Pathway Response To Starvation Negative Regulation Of Apoptotic Process Mast Cell Degranulation Response To Ethanol Positive Regulation Of Epidermal Growth Factor Receptor Signaling Pathway Symbiont Entry Into Host Cell Positive Regulation Of Receptor-mediated Endocytosis Protein Autoubiquitination Positive Regulation Of Phosphatidylinositol 3-kinase/protein Kinase B Signal Transduction Ubiquitin-dependent Endocytosis Cellular Response To Hypoxia Regulation Of Intracellular Signal Transduction Cellular Response To Nerve Growth Factor Stimulus Regulation Of Platelet-derived Growth Factor Receptor-alpha Signaling Pathway
Pathways		PIP3 activates AKT signaling Constitutive Signaling by Aberrant PI3K in Cancer Sema4D mediated inhibition of cell attachment and migration RAF/MAP kinase cascade MET Receptor Activation Negative regulation of MET activity PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling MET activates RAS signaling MET activates PI3K/AKT signaling MET activates PTPN11 MET activates PTK2 signaling InlB-mediated entry of Listeria monocytogenes into host cell InlB-mediated entry of Listeria monocytogenes into host cell MET interacts with TNS proteins MET activates RAP1 and RAC1 MET receptor recycling MET activates STAT3 MECP2 regulates neuronal receptors and channels Drug-mediated inhibition of MET activation Regulation of MITF-M-dependent genes involved in cell cycle and proliferation	Interleukin-6 signaling Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants Spry regulation of FGF signaling Regulation of KIT signaling EGFR downregulation TGF-beta receptor signaling activates SMADs Constitutive Signaling by EGFRvIII Negative regulation of FGFR1 signaling Negative regulation of FGFR2 signaling Negative regulation of FGFR3 signaling Negative regulation of FGFR4 signaling Negative regulation of MET activity PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 Cargo recognition for clathrin-mediated endocytosis Clathrin-mediated endocytosis InlB-mediated entry of Listeria monocytogenes into host cell InlB-mediated entry of Listeria monocytogenes into host cell Regulation of signaling by CBL Regulation of signaling by CBL Signaling by CSF1 (M-CSF) in myeloid cells Negative regulation of FLT3 FLT3 signaling by CBL mutants
Drugs		Sunitinib K-252a SGX-523 1-(4-fluorophenyl)-N-[3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxamide N-({4-[(2-aminopyridin-4-yl)oxy]-3-fluorophenyl}carbamoyl)-2-(4-fluorophenyl)acetamide 2-(4-fluorophenyl)-N-{[3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl]carbamoyl}acetamide N-(3-chlorophenyl)-N-methyl-2-oxo-3-[(3,4,5-trimethyl-1H-pyrrol-2-yl)methyl]-2H-indole-5-sulfonamide 3-[3-(4-methylpiperazin-1-yl)-7-(trifluoromethyl)quinoxalin-5-yl]phenol AMG-208 1-[(2-NITROPHENYL)SULFONYL]-1H-PYRROLO[3,2-B]PYRIDINE-6-CARBOXAMIDE Crizotinib Cabozantinib Capmatinib Tivozanib Fostamatinib Tivantinib Brigatinib Amuvatinib Tepotinib Amivantamab	None
Diseases		Cholangiocarcinoma Gastric cancer Renal cell carcinoma	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)
GWAS		Age at first sexual intercourse ( 34211149 ) Alanine aminotransferase levels ( 33547301 ) Blood protein levels ( 30072576 ) Gamma glutamyl transferase levels ( 29403010 33339817 ) HDL cholesterol levels ( 28334899 ) Heel bone mineral density x serum urate levels interaction ( 34046847 ) Hematocrit ( 28017375 ) Lung function (FEV1/FVC) ( 30804560 ) Medication use (beta blocking agents) ( 31015401 ) Multiple sclerosis (severity) ( 19010793 ) PR segment duration ( 24850809 ) Pulse pressure ( 30578418 ) Resting heart rate ( 27798624 29769521 ) Triglyceride levels ( 28334899 ) Triglycerides ( 24097068 ) Waist-to-hip ratio adjusted for BMI ( 26426971 ) Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test) ( 26426971 )	High light scatter reticulocyte count ( 27863252 32888494 ) High light scatter reticulocyte percentage of red cells ( 32888494 27863252 ) Mean corpuscular volume ( 32888494 ) Mean spheric corpuscular volume ( 32888494 ) Platelet count ( 27863252 29403010 22139419 32888494 33545615 ) Plateletcrit ( 27863252 32888494 ) Reticulocyte count ( 27863252 32888494 ) Reticulocyte fraction of red cells ( 27863252 32888494 ) Triglyceride levels ( 33339817 )
Interacting Genes		112 interacting genes: ABL2 BAG1 BCAR3 BLK BTK CASP3 CBL CCND2 CD44 CDK4 CDK6 CDKN2B CNR1 CRK CTNNB1 CTTN DAPK3 DCN DNAJA3 EGFR EPHA2 ERBB2 FAS FES FGFR4 FGR FZR1 GAB1 GLIS2 GLMN GRB14 GRB2 GRB7 HCK HGF HGS HSH2D INPP5D INPPL1 ITGB1 ITGB4 ITK KDELR2 LATS2 LCK LYN MAP2K3 MAP2K5 MATK MUC20 MYC NCK1 NCK2 NF2 PCBD2 PIK3R1 PIK3R2 PIK3R3 PLCG1 PLCG2 PLXNB1 PTK6 PTPN11 PTPRB PTPRJ RAF1 RANBP10 RANBP9 RASA1 RASSF1 SH2B1 SH2B2 SH2B3 SH2D1A SH2D1B SH2D2A SH2D3C SH3BP2 SHB SHC1 SHC2 SHC3 SHC4 SHD SLA2 SMC1A SNAPIN SNX2 SOCS1 SOCS2 SOCS3 SOCS5 SOCS6 SPSB1 SRC STAP1 STAT3 STK11 SYK TEC TERT TNS1 TNS2 TNS3 TNS4 TP53 TXK VAV1 VAV2 VAV3 YES1 ZAP70	130 interacting genes: ABL1 APPL1 ASAP1 AXL BCR BLK BLNK BTK CAPN1 CBLIF CD19 CD2AP CD38 CD40 CD5 CDKL2 CRK CRKL CSF1R CTNNB1 CUBN EGFR EIF5B EPHA2 EPHB6 EPOR EPS8 F2RL1 FGR FLOT1 FLT3 FNBP1 FRS2 FYB1 FYN GRAP2 GRB2 HCK IGF1R INPPL1 INSR ITCH ITK ITSN2 JAK2 KDR KHDRBS1 KIT KRT18 LAT LAT2 LCK LCP2 LRIG1 LTK LYN MAPK8 MET MYH9 MYO1C MZF1 NCK1 NECTIN1 NOTCH1 OSTF1 PDGFRA PDGFRB PIK3R1 PIK3R2 PLCG1 PLK1 PRKCA PRKCQ PTEN PTK2B PTPN11 PTPN22 PTPN6 RET SCN5A SERPINA5 SH2B2 SH3KBP1 SHC1 SLA SLA2 SMAD7 SORBS1 SORBS2 SP7 SPRY2 SRC STAP2 STAT3 STAT5A STAT5B SYK TCN1 TCN2 TGM2 TNFRSF11A TRAF4 TRAF6 TRIM8 TYK2 UBASH3B UBC UBE2D1 UBE2D2 UBE2D3 UBE2E1 UBE2E2 UBE2E3 UBE2G1 UBE2G2 UBE2L3 UBE2M UBE2N UBE2U UBE2W USP21 VAV1 VAV2 WWP1 YES1 YWHAB YWHAG YWHAQ YWHAZ ZAP70
Entrez ID		4233	867
HPRD ID		01280	01320
Ensembl ID		ENSG00000105976	ENSG00000110395
Uniprot IDs		B4DLF5 E6Y365 P08581	P22681
PDB IDs		1FYR 1R0P 1R1W 1SHY 1SSL 2G15 2RFN 2RFS 2UZX 2UZY 2WD1 2WGJ 2WKM 3A4P 3BUX 3C1X 3CCN 3CD8 3CE3 3CTH 3CTJ 3DKC 3DKF 3DKG 3EFJ 3EFK 3F66 3F82 3I5N 3L8V 3LQ8 3Q6U 3Q6W 3QTI 3R7O 3RHK 3U6H 3U6I 3VW8 3ZBX 3ZC5 3ZCL 3ZXZ 3ZZE 4AOI 4AP7 4DEG 4DEH 4DEI 4EEV 4GG5 4GG7 4IWD 4K3J 4KNB 4MXC 4O3T 4O3U 4R1V 4R1Y 4XMO 4XYF 5DG5 5EOB 5EYC 5EYD 5HLW 5HNI 5HO6 5HOA 5HOR 5HTI 5LSP 5T3Q 5UAB 5UAD 5YA5 6GCU 6I04 6SD9 6SDC 6SDD 6SDE 6UBW 6WVZ 7B3Q 7B3T 7B3V 7B3W 7B3Z 7B40 7B41 7B42 7B43 7B44 7MO7 7MO8 7MO9 7MOA 7MOB 7V3R 7V3S 7Y4T 7Y4U 8AN8 8ANS 8AU3 8AU5 8AW1 8GVJ 8K78 8OUU 8OUV 8OV7 8OVZ 8OW3 8OWG 9C1R 9IVB	1B47 1FBV 1YVH 2CBL 2JUJ 2K4D 2OO9 2Y1M 2Y1N 3BUM 3BUN 3BUO 3BUW 3BUX 3OB1 3OB2 3PLF 4A49 4A4B 4A4C 4GPL 5HKW 5HKX 5HKY 5HKZ 5HL0 5J3X 5O76 6O02 6O03 6XAR 7SIY
GO Terms Enriched among Interactors		Phosphotyrosine Residue Binding Cell Surface Receptor Protein Tyrosine Kinase Signaling Pathway Cell Surface Receptor Signaling Pathway Enzyme-linked Receptor Protein Signaling Pathway Signal Transduction Non-membrane Spanning Protein Tyrosine Kinase Activity Protein Tyrosine Kinase Activity Intracellular Signal Transduction Immune Response-activating Cell Surface Receptor Signaling Pathway Regulation Of Signal Transduction Immune Response-regulating Cell Surface Receptor Signaling Pathway Regulation Of Signaling Regulation Of Cell Communication Regulation Of Cell Adhesion Cytosol ERBB Signaling Pathway Immune Response-activating Signaling Pathway Antigen Receptor-mediated Signaling Pathway Regulation Of Immune System Process Receptor Tyrosine Kinase Binding Epidermal Growth Factor Receptor Signaling Pathway Cell Activation Peptidyl-tyrosine Phosphorylation Leukocyte Activation Positive Regulation Of Immune System Process Immune Response-regulating Signaling Pathway Negative Regulation Of Signal Transduction Protein Kinase Activity Lymphocyte Activation Activation Of Immune Response Negative Regulation Of Cell Communication Negative Regulation Of Signaling Immune System Process Positive Regulation Of Signal Transduction Regulation Of Intracellular Signal Transduction Regulation Of Cell Activation Positive Regulation Of Immune Response Positive Regulation Of Intracellular Signal Transduction Regulation Of Immune Response Positive Regulation Of Cell Communication Positive Regulation Of Signaling Negative Regulation Of Immune System Process Fc Receptor Signaling Pathway Regulation Of Lymphocyte Activation Kinase Activity Regulation Of Cell Population Proliferation Regulation Of Multicellular Organismal Process Regulation Of Cell-cell Adhesion Regulation Of MAPK Cascade T Cell Activation	Cell Surface Receptor Protein Tyrosine Kinase Signaling Pathway Cell Surface Receptor Signaling Pathway Enzyme-linked Receptor Protein Signaling Pathway Signal Transduction Protein Tyrosine Kinase Activity Immune Response-regulating Cell Surface Receptor Signaling Pathway Immune Response-activating Cell Surface Receptor Signaling Pathway Regulation Of Immune Response Immune System Process Immune Response-regulating Signaling Pathway Regulation Of Immune System Process Antigen Receptor-mediated Signaling Pathway Positive Regulation Of Immune System Process Peptidyl-tyrosine Phosphorylation Immune Response-activating Signaling Pathway Phosphotyrosine Residue Binding Regulation Of MAPK Cascade Regulation Of Intracellular Signal Transduction Positive Regulation Of Immune Response Positive Regulation Of Intracellular Signal Transduction Plasma Membrane Activation Of Immune Response Cell Activation Leukocyte Activation Positive Regulation Of MAPK Cascade Protein Kinase Activity Intracellular Signal Transduction Regulation Of Signal Transduction Lymphocyte Activation Non-membrane Spanning Protein Tyrosine Kinase Activity ATP Binding Fc Receptor Signaling Pathway Positive Regulation Of Phosphatidylinositol 3-kinase/protein Kinase B Signal Transduction Transferase Activity Positive Regulation Of Signal Transduction Regulation Of Cell Adhesion Kinase Activity Regulation Of Signaling Regulation Of Cell Communication Protein Modification Process Positive Regulation Of Cell Adhesion Positive Regulation Of Cell Communication Positive Regulation Of Signaling Regulation Of Cell Activation Regulation Of Lymphocyte Activation Cell Migration Protein Phosphorylation Phosphorylation Nucleotide Binding Transmembrane Receptor Protein Tyrosine Kinase Activity