CBL and TRAF6

Data Source:
BioGRID (affinity chromatography technology)
HPRD (in vivo)

		CBL	TRAF6
Description		Cbl proto-oncogene	TNF receptor associated factor 6
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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 Cytoplasm Lipid Droplet Cytosol Plasma Membrane Cell Cortex Cytoplasmic Side Of Plasma Membrane Endosome Membrane Protein-containing Complex CD40 Receptor Complex Perinuclear Region Of Cytoplasm Plasma Membrane Signaling Receptor 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	Ubiquitin-protein Transferase Activity Tumor Necrosis Factor Receptor Binding Protein Binding Zinc Ion Binding Protein Kinase Binding Mitogen-activated Protein Kinase Kinase Kinase Binding Ubiquitin Conjugating Enzyme Binding Ubiquitin Protein Ligase Binding Thioesterase Binding Identical Protein Binding Histone Deacetylase Binding Protein Kinase B Binding Protein N-terminus Binding Ubiquitin Protein Ligase Activity
	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	Negative Regulation Of Transcription By RNA Polymerase II Activation Of MAPK Activity Protein Polyubiquitination Ossification In Utero Embryonic Development Neural Tube Closure Stimulatory C-type Lectin Receptor Signaling Pathway Toll-like Receptor Signaling Pathway Regulation Of Immunoglobulin Production Positive Regulation Of T Cell Cytokine Production MyD88-dependent Toll-like Receptor Signaling Pathway Cellular Response To DNA Damage Stimulus I-kappaB Kinase/NF-kappaB Signaling Activation Of NF-kappaB-inducing Kinase Activity JNK Cascade Protein Deubiquitination Antigen Processing And Presentation Of Exogenous Peptide Antigen Via MHC Class II Osteoclast Differentiation Membrane Protein Intracellular Domain Proteolysis Positive Regulation Of Protein Ubiquitination Positive Regulation Of Lipopolysaccharide-mediated Signaling Pathway Activation Of Protein Kinase Activity Positive Regulation Of Interleukin-12 Production Positive Regulation Of Interleukin-2 Production Positive Regulation Of Interleukin-6 Production Tumor Necrosis Factor-mediated Signaling Pathway Toll-like Receptor 9 Signaling Pathway Fc-epsilon Receptor Signaling Pathway T-helper 1 Type Immune Response Positive Regulation Of T Cell Proliferation Odontogenesis Of Dentin-containing Tooth Myeloid Dendritic Cell Differentiation Positive Regulation Of Apoptotic Process Negative Regulation Of Apoptotic Process Regulation Of I-kappaB Kinase/NF-kappaB Signaling Positive Regulation Of I-kappaB Kinase/NF-kappaB Signaling Positive Regulation Of JUN Kinase Activity Bone Resorption Positive Regulation Of Osteoclast Differentiation Negative Regulation Of Transcription, DNA-templated Positive Regulation Of Transcription By RNA Polymerase II Positive Regulation Of JNK Cascade Cell Development Positive Regulation Of Smooth Muscle Cell Proliferation T Cell Receptor Signaling Pathway Positive Regulation Of DNA-binding Transcription Factor Activity Positive Regulation Of NF-kappaB Transcription Factor Activity Protein Autoubiquitination Nucleotide-binding Oligomerization Domain Containing Signaling Pathway Interleukin-1-mediated Signaling Pathway Protein K63-linked Ubiquitination Response To Interleukin-1 Cellular Response To Lipopolysaccharide Cellular Response To Cytokine Stimulus Positive Regulation Of NIK/NF-kappaB Signaling Positive Regulation Of Leukocyte Adhesion To Vascular Endothelial Cell Positive Regulation Of Transcription Regulatory Region DNA Binding
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	PIP3 activates AKT signaling MyD88:MAL(TIRAP) cascade initiated on plasma membrane NOD1/2 Signaling Pathway TICAM1, RIP1-mediated IKK complex recruitment Regulated proteolysis of p75NTR Downstream TCR signaling NRIF signals cell death from the nucleus NRIF signals cell death from the nucleus p75NTR recruits signalling complexes NF-kB is activated and signals survival FCERI mediated NF-kB activation TAK1 activates NFkB by phosphorylation and activation of IKKs complex activated TAK1 mediates p38 MAPK activation JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 CLEC7A (Dectin-1) signaling Ub-specific processing proteases Ovarian tumor domain proteases PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling TICAM1,TRAF6-dependent induction of TAK1 complex Interleukin-1 signaling TRAF6 mediated IRF7 activation TRAF6 mediated NF-kB activation TRAF6 mediated NF-kB activation IRAK1 recruits IKK complex IKK complex recruitment mediated by RIP1 IRAK2 mediated activation of TAK1 complex TRAF6-mediated induction of TAK1 complex within TLR4 complex Alpha-protein kinase 1 signaling pathway TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation MyD88 dependent cascade initiated on endosome IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation MyD88 cascade initiated on plasma membrane
Drugs
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)
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)	Idiopathic inflammatory myopathy ( 26362759) Metabolite levels ( 23823483) Rheumatoid arthritis ( 30423114 24390342)
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	174 interacting genes: ABL1 APP ATM ATP6V1E1 ATXN3 BANK1 BCL3 BEX3 BMPR1B BRSK2 CALCOCO2 CASP8 CAV1 CBL CD40 CUL5 CYLD DLG4 DNA2 ECSIT EDA2R EDARADD FHL2 FYN GART GSK3B GTF2I H2AX H2BC21 HNRNPA1 HSD17B10 HSPA4 IL17RB IPMK IQUB IRAK1 IRAK2 IRAK3 IRAK4 IRF5 IRF7 IRF8 JAK2 KCNQ1 LIMD1 LNX1 MALT1 MAP2K1 MAP2K6 MAP2K7 MAP3K11 MAP3K14 MAP3K3 MAP3K5 MAP3K7 MAP3K8 MAPK14 MAPK8 MAPT MAST2 MATR3 MAVS MBP MCL1 MEOX2 MTOR MTURN NEAT1 NGFR NTRK1 NTRK2 NUMBL OTUB1 OTUB2 OTUD7B PEDS1-UBE2V1 PELI3 PFN1 PINK1 PLEKHF2 PLEKHO1 POLI PPP4C PRKCZ PSMB5 PSMC1 PSMC2 PSMC3 PSMD1 PSMD12 PSMD13 PSMD6 PSMD7 PTPN6 RAD23A RIPK2 RNF114 RNF31 RPL3 RPS2 RPS20 RPS27A SIGIRR SPHK1 SPOP SQSTM1 SRC STAMBP STK26 STRADB STUB1 SYK TAB1 TAB2 TAB3 TANK TAX1BP1 TDP2 TGFBR1 TICAM1 TICAM2 TIFA TIRAP TLR3 TNFAIP3 TNFRSF11A TNFRSF13B TNFRSF19 TNFSF11 TRAF1 TRAF2 TRAF3IP1 TRAF3IP2 TRAF4 TRAF5 TRAF7 TRAFD1 TRAM1 TRIM17 TRIM25 TRIM37 TXNIP UBB UBC UBE2D1 UBE2D2 UBE2D3 UBE2D4 UBE2E1 UBE2I UBE2L3 UBE2N UBE2V1 UBOX5 UBTD1 UBXN7 UEVLD USP1 USP15 USP2 USP21 USP39 USP7 VPS52 XIAP YBX1 YES1 YOD1 YWHAQ ZBTB25 ZFAND5 ZMYND11 ZNF675 ZRANB1
Entrez ID		867	7189
HPRD ID		01320	03833
Ensembl ID		ENSG00000110395	ENSG00000175104
Uniprot IDs		P22681	Q9Y4K3
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	1LB4 1LB5 1LB6 2ECI 2JMD 3HCS 3HCT 3HCU 4Z8M 5ZUJ 6A33
Enriched GO Terms of Interacting Partners?
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