CBL

Cbl proto-oncogene | RNF55, c-Cbl, CBL2

This gene is a proto-oncogene that encodes a RING finger E3 ubiquitin ligase. The encoded protein is one of the enzymes required for targeting substrates for degradation by the proteasome. This protein mediates the transfer of ubiquitin from ubiquitin conjugating enzymes (E2) to specific substrates. This protein also contains an N-terminal phosphotyrosine binding domain that allows it to interact with numerous tyrosine-phosphorylated substrates and target them for proteasome degradation. As such it functions as a negative regulator of many signal transduction pathways. This gene has been found to be mutated or translocated in many cancers including acute myeloid leukaemia, and expansion of CGG repeats in the 5' UTR has been associated with Jacobsen syndrome. Mutations in this gene are also the cause of Noonan syndrome-like disorder. [provided by RefSeq, Jul 2016]

Member of: DE-2

Biological processes 84 terms

DNA damage response (GO:0006974)Golgi apparatus (GO:0005794)Golgi apparatus (GO:0005794)SH3 domain binding (GO:0017124)SH3 domain binding (GO:0017124)axon (GO:0030424)cadherin binding (GO:0045296)calcium ion binding (GO:0005509)cell surface receptor signaling pathway (GO:0007166)cellular response to hypoxia (GO:0071456)cellular response to nerve growth factor stimulus (GO:1990090)cellular response to platelet-derived growth factor stimulus (GO:0036120)cilium (GO:0005929)cilium (GO:0005929)cytokine-mediated signaling pathway (GO:0019221)cytoplasm (GO:0005737)cytosol (GO:0005829)cytosol (GO:0005829)ephrin receptor binding (GO:0046875)ephrin receptor binding (GO:0046875)flotillin complex (GO:0016600)flotillin complex (GO:0016600)focal adhesion (GO:0005925)growth cone (GO:0030426)male gonad development (GO:0008584)mast cell degranulation (GO:0043303)membrane raft (GO:0045121)metal ion binding (GO:0046872)negative regulation of T cell activation (GO:0050868)negative regulation of T cell activation (GO:0050868)negative regulation of T cell receptor signaling pathway (GO:0050860)negative regulation of T cell receptor signaling pathway (GO:0050860)negative regulation of apoptotic process (GO:0043066)negative regulation of apoptotic process (GO:0043066)negative regulation of epidermal growth factor receptor signaling pathway (GO:0042059)negative regulation of epidermal growth factor receptor signaling pathway (GO:0042059)negative regulation of epidermal growth factor receptor signaling pathway (GO:0042059)negative regulation of epidermal growth factor receptor signaling pathway (GO:0042059)perinuclear region of cytoplasm (GO:0048471)phosphatidylinositol 3-kinase regulatory subunit binding (GO:0036312)phosphotyrosine residue binding (GO:0001784)plasma membrane (GO:0005886)plasma membrane (GO:0005886)plasma membrane (GO:0005886)plasma membrane (GO:0005886)plasma membrane (GO:0005886)plasma membrane (GO:0005886)positive regulation of epidermal growth factor receptor signaling pathway (GO:0045742)positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897)positive regulation of receptor-mediated endocytosis (GO:0048260)protein K63-linked ubiquitination (GO:0070534)protein K63-linked ubiquitination (GO:0070534)protein autoubiquitination (GO:0051865)protein binding (GO:0005515)protein kinase binding (GO:0019901)protein monoubiquitination (GO:0006513)protein polyubiquitination (GO:0000209)protein stabilization (GO:0050821)protein stabilization (GO:0050821)protein tyrosine kinase binding (GO:1990782)protein ubiquitination (GO:0016567)protein ubiquitination (GO:0016567)protein ubiquitination (GO:0016567)protein ubiquitination (GO:0016567)receptor tyrosine kinase binding (GO:0030971)regulation of platelet-derived growth factor receptor-alpha signaling pathway (GO:2000583)regulation of platelet-derived growth factor receptor-alpha signaling pathway (GO:2000583)regulation of signaling (GO:0023051)response to activity (GO:0014823)response to ethanol (GO:0045471)response to gamma radiation (GO:0010332)response to starvation (GO:0042594)response to testosterone (GO:0033574)signal transduction (GO:0007165)symbiont entry into host cell (GO:0046718)ubiquitin protein ligase activity (GO:0061630)ubiquitin protein ligase activity (GO:0061630)ubiquitin protein ligase activity (GO:0061630)ubiquitin protein ligase activity (GO:0061630)ubiquitin-dependent endocytosis (GO:0070086)ubiquitin-dependent protein catabolic process (GO:0006511)ubiquitin-dependent protein catabolic process (GO:0006511)ubiquitin-protein transferase activity (GO:0004842)ubiquitin-protein transferase activity (GO:0004842)

Expression (TPM)

TFs regulating CBL 0 TFs

Transcription factors with Perturb-seq knockdown data for CBL. The Binding column indicates whether any binding evidence exists for this TF–gene pair (ChIP-seq or motif footprint peaks). The Mean coef is the average Perturb-seq regression coefficient across active gRNAs (positive = CBL upregulated upon KD; negative = downregulated). The Outlier column indicates whether this gene is in the top or bottom 5% of all TF knockdown effects.

TF	Mean coef	Binding	Outlier	TF→Gene link

Rows:

Elements linked to CBL

Open chromatin peaks (ATAC-seq) in the genomic neighbourhood of CBL, linked by TSS proximity or chromatin conformation (Multiome / HiCAR). Each element overlaps at least one TF ChIP-seq binding site — the TFs column shows how many distinct TFs bind that element.

Element	Dist. to TSS	Link type	TFs
chr11:118,907,074–118,907,685	299.0 kb	Distal (>10kb) Multiome	491
chr11:118,909,181–118,909,816	297.0 kb	Distal (>10kb) Multiome	326
chr11:118,909,976–118,911,609	295.7 kb	Distal (>10kb) Multiome	652
chr11:118,911,717–118,912,963	294.1 kb	Distal (>10kb) Multiome	689
chr11:118,916,429–118,917,335	289.4 kb	Distal (>10kb) Multiome	355
chr11:118,917,640–118,918,851	287.9 kb	Distal (>10kb) Multiome	522
chr11:118,925,703–118,926,356	280.3 kb	Distal (>10kb) Multiome	595
chr11:118,927,947–118,930,852	276.9 kb	Distal (>10kb) Multiome	892
chr11:118,997,538–118,998,797	208.2 kb	Distal (>10kb) Multiome	798
chr11:119,018,081–119,019,265	187.8 kb	Distal (>10kb) Multiome	897
chr11:119,029,885–119,031,330	175.4 kb	Distal (>10kb) Multiome	876
chr11:119,056,436–119,057,778	149.1 kb	Distal (>10kb) Multiome	815
chr11:119,067,446–119,068,100	138.6 kb	Distal (>10kb) Multiome	762
chr11:119,084,563–119,085,756	121.3 kb	Distal (>10kb) Multiome	846
chr11:119,093,969–119,096,070	110.8 kb	Distal (>10kb) Multiome	1046
chr11:119,101,351–119,102,791	104.2 kb	Distal (>10kb) Multiome	871
chr11:119,106,906–119,107,993	99.0 kb	Distal (>10kb) Multiome	650
chr11:119,120,857–119,122,037	84.9 kb	Distal (>10kb) Multiome	787
chr11:119,144,795–119,145,355	61.3 kb	Distal (>10kb) Multiome	230
chr11:119,148,816–119,149,933	56.8 kb	Distal (>10kb) Multiome	262
chr11:119,168,601–119,169,645	37.4 kb	Distal (>10kb) Multiome	794
chr11:119,196,976–119,197,184	9.2 kb	Proximal (<10kb)	311
chr11:119,205,241–119,207,150	212 bp	At TSS Multiome	695
chr11:119,315,017–119,315,819	109.0 kb	Distal (>10kb) Multiome HiCAR	270
chr11:119,316,693–119,317,760	110.9 kb	Distal (>10kb) Multiome HiCAR	463
chr11:119,320,617–119,321,906	115.4 kb	Distal (>10kb) Multiome	516
chr11:119,334,140–119,334,815	128.1 kb	Distal (>10kb) Multiome	577
chr11:119,337,716–119,338,797	132.0 kb	Distal (>10kb) Multiome	412
chr11:119,339,587–119,340,902	133.8 kb	Distal (>10kb) Multiome	477
chr11:119,356,332–119,357,013	150.4 kb	Distal (>10kb) Multiome	366
chr11:119,361,041–119,361,699	155.0 kb	Distal (>10kb) Multiome	431
chr11:119,363,939–119,364,561	157.9 kb	Distal (>10kb) Multiome	255
chr11:119,377,954–119,379,307	172.2 kb	Distal (>10kb) Multiome	307
chr11:119,380,894–119,382,060	175.3 kb	Distal (>10kb) Multiome	800
chr11:119,422,349–119,423,771	216.9 kb	Distal (>10kb) Multiome	235
chr11:119,481,243–119,481,846	275.2 kb	Distal (>10kb) Multiome	592

Genome Browser

Genomic view of the CBL locus showing ATAC-seq accessibility and RNA-seq expression across the ESC → DE time course, together with TF binding peaks and element-to-TSS loop connections.