CBL and PTPN11

Data Source:
HPRD (in vivo)

		CBL	PTPN11
Description		Cbl proto-oncogene	protein tyrosine phosphatase non-receptor type 11
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GO Annotations	Cellular Component	Golgi Apparatus Cytosol Plasma Membrane Focal Adhesion Cilium Flotillin Complex Growth Cone Membrane Raft Perinuclear Region Of Cytoplasm	Nucleus Nucleoplasm Cytoplasm Mitochondrion Cytosol Protein-containing Complex
	Molecular Function	Phosphotyrosine Residue Binding Ubiquitin-protein Transferase Activity Epidermal Growth Factor Receptor Binding Calcium Ion Binding Protein Binding SH3 Domain Binding Receptor Tyrosine Kinase Binding Phosphatidylinositol 3-kinase Regulatory Subunit Binding Cadherin Binding Ephrin Receptor Binding Ubiquitin Protein Ligase Activity	Phosphotyrosine Residue Binding Phosphoprotein Phosphatase Activity Protein Tyrosine Phosphatase Activity Non-membrane Spanning Protein Tyrosine Phosphatase Activity Insulin Receptor Binding Protein Binding Protein Kinase Binding Protein Domain Specific Binding Signaling Receptor Complex Adaptor Activity Receptor Tyrosine Kinase Binding D1 Dopamine Receptor Binding Phospholipase Binding Insulin Receptor Substrate Binding Cadherin Binding Cell Adhesion Molecule Binding Peptide Hormone Receptor Binding Protein Tyrosine Kinase Binding
	Biological Process	Protein Polyubiquitination Ubiquitin-dependent Protein Catabolic Process Protein Monoubiquitination Cellular Response To DNA Damage Stimulus Signal Transduction Cell Surface Receptor Signaling Pathway Epidermal Growth Factor Receptor Signaling Pathway Negative Regulation Of Epidermal Growth Factor-activated Receptor Activity Transforming Growth Factor Beta Receptor Signaling Pathway Fibroblast Growth Factor Receptor Signaling Pathway Male Gonad Development Response To Gamma Radiation Positive Regulation Of Phosphatidylinositol 3-kinase Signaling Response To Activity Protein Ubiquitination Cytokine-mediated Signaling Pathway Regulation Of Rap Protein Signal Transduction Response To Testosterone Entry Of Bacterium Into Host Cell 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 Response To Antibiotic Positive Regulation Of Receptor-mediated Endocytosis Membrane Organization Interleukin-6-mediated Signaling Pathway Neuron Death Cellular Response To Epidermal Growth Factor Stimulus Cellular Response To Oxygen-glucose Deprivation Negative Regulation Of Neuron Death Cellular Response To Nerve Growth Factor Stimulus Regulation Of Platelet-derived Growth Factor Receptor-alpha Signaling Pathway	DNA Damage Checkpoint Activation Of MAPK Activity Triglyceride Metabolic Process Epidermal Growth Factor Receptor Signaling Pathway Integrin-mediated Signaling Pathway Axon Guidance Brain Development Heart Development Fibroblast Growth Factor Receptor Signaling Pathway Hormone-mediated Signaling Pathway Cytokine-mediated Signaling Pathway Cerebellar Cortex Formation Platelet Activation Platelet Formation T Cell Costimulation Negative Regulation Of Chondrocyte Differentiation Microvillus Organization Positive Regulation Of Interferon-beta Production Positive Regulation Of Interleukin-6 Production Positive Regulation Of Tumor Necrosis Factor Production Abortive Mitotic Cell Cycle Regulation Of Cell Adhesion Mediated By Integrin Negative Regulation Of Cell Adhesion Mediated By Integrin Multicellular Organism Growth Organ Growth Peptidyl-tyrosine Dephosphorylation Megakaryocyte Development Atrioventricular Canal Development ERBB Signaling Pathway Hormone Metabolic Process Glucose Homeostasis Regulation Of Protein-containing Complex Assembly Positive Regulation Of Ossification Positive Regulation Of Mitotic Cell Cycle Positive Regulation Of Glucose Import Positive Regulation Of Insulin Receptor Signaling Pathway Negative Regulation Of Insulin Secretion Regulation Of Protein Export From Nucleus Positive Regulation Of Hormone Secretion Platelet-derived Growth Factor Receptor Signaling Pathway Neurotrophin TRK Receptor Signaling Pathway Ephrin Receptor Signaling Pathway Multicellular Organismal Reproductive Process Genitalia Development Inner Ear Development Homeostasis Of Number Of Cells Within A Tissue Positive Regulation Of Peptidyl-tyrosine Phosphorylation Leukocyte Migration Negative Regulation Of Cortisol Secretion Positive Regulation Of Protein Kinase B Signaling Bergmann Glial Cell Differentiation Negative Regulation Of Growth Hormone Secretion Face Morphogenesis Regulation Of Type I Interferon-mediated Signaling Pathway Intestinal Epithelial Cell Migration Interleukin-6-mediated Signaling Pathway Positive Regulation Of ERK1 And ERK2 Cascade Cellular Response To Mechanical Stimulus Cellular Response To Cytokine Stimulus Cellular Response To Epidermal Growth Factor Stimulus
Pathways		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 Negative regulation of FLT3 FLT3 signaling by CBL mutants	Interleukin-6 signaling PI3K Cascade MAPK3 (ERK1) activation MAPK1 (ERK2) activation GPVI-mediated activation cascade Prolactin receptor signaling PIP3 activates AKT signaling Spry regulation of FGF signaling Signaling by SCF-KIT GAB1 signalosome Downstream signal transduction PECAM1 interactions Tie2 Signaling Constitutive Signaling by Aberrant PI3K in Cancer Signaling by Leptin Costimulation by the CD28 family CTLA4 inhibitory signaling PD-1 signaling Signal regulatory protein family interactions Netrin mediated repulsion signals Platelet sensitization by LDL Interleukin-3, Interleukin-5 and GM-CSF signaling Interleukin-3, Interleukin-5 and GM-CSF signaling PI-3K cascade:FGFR1 FRS-mediated FGFR1 signaling PI-3K cascade:FGFR2 FRS-mediated FGFR2 signaling FRS-mediated FGFR3 signaling PI-3K cascade:FGFR3 FRS-mediated FGFR4 signaling PI-3K cascade:FGFR4 Negative regulation of FGFR1 signaling Negative regulation of FGFR2 signaling Negative regulation of FGFR3 signaling Negative regulation of FGFR4 signaling PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling Regulation of IFNG signaling RET signaling Interleukin-20 family signaling MET activates PTPN11 Regulation of RUNX1 Expression and Activity Interleukin-37 signaling Activated NTRK2 signals through FRS2 and FRS3 Interferon alpha/beta signaling Regulation of IFNA signaling Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon FLT3 Signaling STAT5 Activation STAT5 activation downstream of FLT3 ITD mutants Signaling by FLT3 ITD and TKD mutants
Drugs			Dodecyltrimethylammonium
Diseases		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)	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) Metachondromatosis
GWAS		High light scatter reticulocyte count ( 32888494 27863252) High light scatter reticulocyte percentage of red cells ( 32888494 27863252) Mean corpuscular volume ( 32888494) Mean spheric corpuscular volume ( 32888494) Platelet count ( 22139419 29403010 32888494 27863252) Plateletcrit ( 32888494 27863252) Reticulocyte count ( 32888494 27863252) Reticulocyte fraction of red cells ( 32888494 27863252)	Alcohol consumption (max-drinks) ( 29460428) Alcohol dependence symptom count ( 29460428) Apolipoprotein A1 levels ( 32203549) Blood pressure ( 21572416) Body mass index ( 26426971) Diastolic blood pressure ( 26390057) Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test) ( 29455858) Diastolic blood pressure x smoking status (ever vs never) interaction (2df test) ( 29455858) HDL cholesterol levels ( 32203549) Hematological parameters ( 19820697) Hypothyroidism ( 22493691) Low HDL-cholesterol levels ( 31006500) Mean arterial pressure ( 27618448) Medication use (agents acting on the renin-angiotensin system) ( 31015401) Medication use (beta blocking agents) ( 31015401) Medication use (diuretics) ( 31015401) Medication use (thyroid preparations) ( 31015401) Multiple sclerosis ( 31604244) Peripheral artery disease ( 31285632) Platelet count ( 22139419 32888494) Reaction time ( 29844566) Response to alcohol consumption (flushing response) ( 29460428) Retinal vascular caliber ( 21060863) Rheumatoid arthritis ( 30423114 24390342) Systemic seropositive rheumatic diseases (Systemic sclerosis or systemic lupus erythematosus or rheumatoid arthritis or idiopathic inflammatory myopathies) ( 30573655) Systolic blood pressure ( 26390057 30578418) Systolic blood pressure x smoking status (current vs non-current) interaction (2df test) ( 29455858) Systolic blood pressure x smoking status (ever vs never) interaction (2df test) ( 29455858) Tetralogy of Fallot ( 23297363) Type 1 diabetes ( 17554300) Urate levels ( 23263486)
Interacting Genes		128 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 PRKCA PRKCQ 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 TNS4 TRAF4 TRAF6 TRIM8 TYK2 UBASH3B UBC UBE2D1 UBE2D2 UBE2D3 UBE2E1 UBE2E2 UBE2E3 UBE2G1 UBE2G2 UBE2L3 UBE2M UBE2N UBE2U UBE2W USP21 VAV1 VAV2 YES1 YWHAB YWHAG YWHAQ YWHAZ ZAP70	166 interacting genes: AATK ACTN4 AKT1 AR ARHGAP1 AXL BCR BDKRB2 BEX1 BEX2 BLZF1 BTLA CALR CAT CAV1 CBL CCKBR CD33 CDH5 CEACAM1 CHUK CRKL CSF2RB CSF3R CTDSP1 CTLA4 CXCR4 DAB1 DDR1 DMRTC1 EGFR EPHA1 EPHA2 EPOR ERBB2 ERBB3 ERBB4 FAM71E1 FBXW7 FCGR1B FCGR2B FCRL3 FGFR2 FGFR4 FLT1 FLT3 FLT4 FRS2 FRS3 FYN GAB1 GAB2 GAB3 GHR GMNN GOLGA2 GRB2 GRIN2B GTF2A2 HNRNPU HSP90B1 HSPA5 HSPA9 HSPD1 IFNAR1 IFNGR1 IGF1R IL4R IL6ST ILK INPP5D INSR IRS1 IRS2 IRS4 JAK1 JAK2 KDR KIR2DL5A KIT KLRC1 LAIR1 LCK LEPR LIFR LILRB4 LINC01558 LINC02907 LNX1 LRP1 MAP3K4 MAP3K5 MAPK3 MAPT MET MPIG6B MPL MPZL1 MS4A2 MVP NEB NEDD9 NOX4 NSUN5 NSUN5P2 NTRK1 NTRK2 ORMDL3 PAG1 PDGFRA PDGFRB PECAM1 PIK3CA PIK3CG PIK3R1 PILRA PILRB PLCG1 PNCK POU2AF1 PRKCA PRKCB PRKCH PRLR PTK2 PTK2B PTK7 PTPN6 PXN RANGRF RET ROR2 ROS1 RPIA SELE SERF2 SERPINF1 SHC1 SIGLEC11 SIGLEC12 SIGLEC7 SIRPA SIT1 SLAMF1 SLAMF6 SLC38A1 SLN SOCS3 SOS1 SPRY2 SRC SRSF10 STAT1 STAT3 STAT5A STAT5B SYNCRIP TEK TIE1 TLK1 TNFRSF1A TREML1 TRIM32 TRMT2B TSC2 TXNIP
Entrez ID		867	5781
HPRD ID		01320	01470
Ensembl ID		ENSG00000110395	ENSG00000179295
Uniprot IDs		P22681	Q06124
PDB IDs		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	2SHP 3B7O 3MOW 3O5X 3TKZ 3TL0 3ZM0 3ZM1 3ZM2 3ZM3 4DGP 4DGX 4GWF 4H1O 4H34 4JE4 4JEG 4JMG 4NWF 4NWG 4OHD 4OHE 4OHH 4OHI 4OHL 4PVG 4QSY 4RDD 5BK8 5DF6 5EHP 5EHR 5I6V 5IBM 5IBS 5X7B 5X94 5XZR 6ATD 6BMR 6BMU 6BMV 6BMW 6BMX 6BMY 6BN5 6CMP 6CMQ 6CMR 6CMS 6CRF 6CRG 6IHZ 6MD7 6MD9 6MDA 6MDB 6MDC 6MDD 6R5G 7JVM 7JVN
Enriched GO Terms of Interacting Partners?
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