Gene Report

Basic Information

Approved Symbol	CBLB
Approved Name	Cbl proto-oncogene, E3 ubiquitin protein ligase B
Previous Name	Cas-Br-M (murine) ectropic retroviral transforming sequence b, "Cas-Br-M (murine) ecotropic retroviral transforming sequence b"
Symbol Alias	RNF56, Cbl-b
Location	3q
Position	chr3:105377109-105587887 (-)
External Links	Entrez Gene: 868 Ensembl: ENSG00000114423 UCSC: uc003dwc.3 HGNC ID: 1542
No. of Studies (Positive/Negative)	1(1/0)
Type	Literature-origin

Positive relationships between CBLB and MDD (count: 0)

Positive relationships between CBLB and other components at different levels (count: 1)

Genetic/epigenetic locus					Protein and other molecule			Cell and molecular pathway			Neural system			Cognition and behavior		Symptoms and signs			Environment

Name in Literature	Level	Approved Name (Name in Literature)	Type	Reference	Research Type	Statistical Result	Relation Description	All
Name in Literature	Related Components
Cblb		Histone-lysine N-methyltransferase SETDB1(Setdb1 (Set domain, bifurcated 1))	protein	Jiang Y, 2010	animal model		Gene was occupied by Setdb1 in neuron Gene was occupied by Setdb1 in neuron

Positive relationship network of CBLB in MK4MDD

Network loading ...

Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between CBLB and MDD (count: 0)

Negative relationships between CBLB and other components at different levels (count: 0)

CBLB related SNPs in MK4MDD (count: 0)

CBLB related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
E3 ubiquitin-protein ligase CBL-B	Q13191	0(0/0)	Gene mapped

CBLB related GO terms (count: 21)

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0004871	signal transducer activity	molecular function	IEA
GO:0004842	ubiquitin-protein ligase activity	molecular function	IEA
GO:0001784	phosphotyrosine binding	molecular function	IEA
GO:0005634	nucleus	cellular component	IDA
GO:0008270	zinc ion binding	molecular function	IEA
GO:0005829	cytosol	cellular component	TAS
GO:0005515	protein binding	molecular function	IPI
GO:0005509	calcium ion binding	molecular function	IEA
GO:0005730	nucleolus	cellular component	IDA
GO:0002669	positive regulation of T cell anergy	biological process	IEA
GO:0005737	cytoplasm	cellular component	IDA
GO:0046642	negative regulation of alpha-beta T cell proliferation	biological process	IEA
GO:0042110	T cell activation	biological process	IEA
GO:0035556	intracellular signal transduction	biological process	IEA
GO:0006607	NLS-bearing substrate import into nucleus	biological process	TAS[7784085]
GO:0007166	cell surface receptor signaling pathway	biological process	IEA
GO:0045732	positive regulation of protein catabolic process	biological process	IEA
GO:0050860	negative regulation of T cell receptor signaling pathway	biological process	IEA
GO:0007165	signal transduction	biological process	TAS[7784085]
GO:0006955	immune response	biological process	IEA
GO:0005886	plasma membrane	cellular component	TAS

CBLB related KEGG pathways (count: 8)

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa04660	t cell_receptor_signaling_pathway	T cell receptor signaling pathway	Activation of T lymphocytes is a key event for an efficient ...... Activation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. Engagement of these receptors through the interaction with a foreign antigen associated with major histocompatibility complex molecules and CD28 counter-receptors B7.1/B7.2, respectively, results in a series of signaling cascades. These cascades comprise an array of protein-tyrosine kinases, phosphatases, GTP-binding proteins and adaptor proteins that regulate generic and specialised functions, leading to T-cell proliferation, cytokine production and differentiation into effector cells. More...
hsa04144	endocytosis	Endocytosis	Endocytosis is a mechanism for cells to remove ligands, nutr...... Endocytosis is a mechanism for cells to remove ligands, nutrients, and plasma membrane (PM) proteins, and lipids from the cell surface, bringing them into the cell interior. Transmembrane proteins entering through clathrin-dependent endocytosis (CDE) have sequences in their cytoplasmic domains that bind to the APs (adaptor-related protein complexes) and enable their rapid removal from the PM. In addition to APs and clathrin, there are numerous accessory proteins including dynamin. Depending on the various proteins that enter the endosome membrane, these cargoes are sorted to distinct destinations. Some cargoes, such as nutrient receptors, are recycled back to the PM. Ubiquitylated membrane proteins, such as activated growth-factor receptors, are sorted into intraluminal vesicles and eventually end up in the lysosome lumen via multivesicular endosomes (MVEs). There are distinct mechanisms of clathrin-independent endocytosis (CIE) depending upon the cargo and the cell type. More...
hsa04910	insulin signaling_pathway	Insulin signaling pathway	Insulin binding to its receptor results in the tyrosine phos...... Insulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the regulatory subunit of phosphoinositide 3-kinase (PI3K). PI3K activates 3-phosphoinositide-dependent protein kinase 1 (PDK1), which activates Akt, a serine kinase. Akt in turn deactivates glycogen synthase kinase 3 (GSK-3), leading to activation of glycogen synthase (GYS) and thus glycogen synthesis. Activation of Akt also results in the translocation of GLUT4 vesicles from their intracellular pool to the plasma membrane, where they allow uptake of glucose into the cell. Akt also leads to mTOR-mediated activation of protein synthesis by eIF4 and p70S6K. The translocation of GLUT4 protein is also elicited through the CAP/Cbl/TC10 pathway, once Cbl is phosphorylated by INSR. Other signal transduction proteins interact with IRS including GRB2. GRB2 is part of the cascade including SOS, RAS, RAF and MEK that leads to activation of mitogen-activated protein kinase (MAPK) and mitogenic responses in the form of gene transcription. SHC is another substrate of INSR. When tyrosine phosphorylated, SHC associates with GRB2 and can thus activate the RAS/MAPK pathway independently of IRS-1. More...
hsa04120	ubiquitin mediated_proteolysis	Ubiquitin mediated proteolysis	Protein ubiquitination plays an important role in eukaryotic...... Protein ubiquitination plays an important role in eukaryotic cellular processes. It mainly functions as a signal for 26S proteasome dependent protein degradation. The addition of ubiquitin to proteins being degraded is performed by a reaction cascade consisting of three enzymes, named E1 (ubiquitin activating enzyme), E2 (ubiquitin conjugating enzyme), and E3 (ubiquitin ligase). Each E3 has specificity to its substrate, or proteins to be targeted by ubiquitination. Many E3s are discovered in eukaryotes and they are classified into four types: HECT type, U-box type, single RING-finger type, and multi-subunit RING-finger type. Multi-subunit RING-finger E3s are exemplified by cullin-Rbx E3s and APC/C. They consist of a RING-finger-containing subunit (RBX1 or RBX2) that functions to bind E2s, a scaffold-like cullin molecule, adaptor proteins, and a target recognizing subunit that binds substrates. More...
hsa04012	erbb signaling_pathway	ErbB signaling pathway	The ErbB family of receptor tyrosine kinases (RTKs) couples ...... The ErbB family of receptor tyrosine kinases (RTKs) couples binding of extracellular growth factor ligands to intracellular signaling pathways regulating diverse biologic responses, including proliferation, differentiation, cell motility, and survival. Ligand binding to the four closely related members of this RTK family -epidermal growth factor receptor (EGFR, also known as ErbB-1 or HER1), ErbB-2 (HER2), ErbB-3 (HER3), and ErbB-4 (HER4)-induces the formation of receptor homo- and heterodimers and the activation of the intrinsic kinase domain, resulting in phosphorylation on specific tyrosine residues (pY) within the cytoplasmic tail. Signaling effectors containing binding pockets for pY-containing peptides are recruited to activated receptors and induce the various signaling pathways. The Shc- and/or Grb2-activated mitogen-activated protein kinase (MAPK) pathway is a common target downstream of all ErbB receptors. Similarly, the phosphatidylinositol-3-kinase (PI-3K) pathway is directly or indirectly activated by most ErbBs. Several cytoplasmic docking proteins appear to be recruited by specific ErbB receptors and less exploited by others. These include the adaptors Crk, Nck, the phospholipase C gamma (PLCgamma), the intracellular tyrosine kinase Src, or the Cbl E3 ubiquitin protein ligase. More...
hsa05220	chronic myeloid_leukemia	Chronic myeloid leukemia	Chronic myelogenous leukaemia (CML) is a biphasic disease, i...... Chronic myelogenous leukaemia (CML) is a biphasic disease, initiated by expression of the BCR/ABL fusion gene product in self-renewing, haematopoietic stem cells (HSCs). HSCs can differentiate into common myeloid progenitors (CMPs), which then differentiate into granulocyte/macrophage progenitors (GMPs). HSCs can also differentiate into common lymphoid progenitors (CLPs), which are the progenitors of lymphocytes such as T cells and B cells. The initial chronic phase of CML (CML-CP) is characterized by a massive expansion of the granulocytic-cell series. Acquisition of additional genetic mutations beyond expression of BCR/ABL causes the progression of CML from chronic phase to blast phase (CML-BP), characterized by an accumulation of myeloid or lymphoid blast cells. The BCR/ABL fusion gene encodes p210BCR/ABL, an oncoprotein, which, unlike the normal p145 c-Abl, has constitutive tyrosine kinase activity and is predominantly localized in the cytoplasm. The tyrosine kinase activity is essential for cell transformation and the cytoplasmic localization of BCR/ABL allows the assembly of phosphorylated substrates in multiprotein complexes that transmit mitogenic and antiapoptotic signals. Additional cytogenetic and molecular changes are frequently found in patients with CML during the progression of the disease from chronic to blast phase. Some of the genetic changes include mutations in TP53, RB, and CDKN2A (also known as p16INK4A), or overexpression of genes such as EVI1. Additional chromosome translocations are also observed, such as t(3;21)(q26;q22), which generates AML1/EVI1. AML1/EVI-1 represses TGF-beta-mediated growth inhibitory signal. More...
hsa04630	jak stat_signaling_pathway	Jak-STAT signaling pathway	The Janus kinase/signal transducers and activators of transc...... The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is one of a handful of pleiotropic cascades used to transduce a multitude of signals for development and homeostasis in animals, from humans to flies. In mammals, the JAK/STAT pathway is the principal signaling mechanism for a wide array of cytokines and growth factors. Following the binding of cytokines to their cognate receptor, STATs are activated by members of the JAK family of tyrosine kinases. Once activated, they dimerize and translocate to the nucleus and modulate the expression of target genes. In addition to the activation of STATs, JAKs mediate the recruitment of other molecules such as the MAP kinases, PI3 kinase etc. These molecules process downstream signals via the Ras-Raf-MAP kinase and PI3 kinase pathways which results in the activation of additional transcription factors. More...
hsa05200	pathways in_cancer	Pathways in cancer

CBLB related BioCarta pathways (count: 0)

CBLB related Reactome pathways (count: 0)

CBLB related interactors from protein-protein interaction data in HPRD (count: 26)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
CBLB	RET	No	in vivo	16525057
CBLB	ZAP70	No	in vivo	10074432
CBLB	RNF11	No	yeast 2-hybrid	15231748
CBLB	SPRY2	No	in vitro	11053437
CBLB	CRKL	No	in vitro;in vivo	10022120
CBLB	SHC1	No	in vitro;in vivo	9614102
CBLB	SH3KBP1	No	in vivo;yeast 2-hybrid	12218189
CBLB	EGFR	No	in vitro;in vivo	10086340
CBLB	SORBS3	No	yeast 2-hybrid	16189514
CBLB	NCK1	No	in vivo	16503409
CBLB	FYB	No	in vivo	16503409
CBLB	GORASP2	No	yeast 2-hybrid	16189514
CBLB	PLCG2	No	in vitro	12093870
CBLB	FYN	No	in vitro	16503409
CBLB	PIK3R1	Yes	in vitro;in vivo	10086340
CBLB	ARHGEF7	No	in vivo;yeast 2-hybrid	12935897
CBLB	GRB2	No	in vitro;in vivo	10086340
CBLB	VAV1	No	in vivo	11857085
CBLB	SYK	No	in vitro	10022120 , 12771181
CBLB	TNFRSF11A	No	in vivo	11406619
CBLB	BLNK	No	in vivo	12093870
CBLB	NEDD4	No	in vitro;in vivo	12907674
CBLB	FLT3	No	in vivo	9614102
CBLB	KIT	No	in vivo	15315962
CBLB	NCK2	No	yeast 2-hybrid	16189514
CBLB	CRY1	Yes	yeast 2-hybrid	16189514

Gene Report

Gene mapped GO terms

Gene mapped KEGG pathways