CBL Cbl proto-oncogene, E3 ubiquitin protein ligase [ Homo sapiens ]

Gene ID: 867, updated on 19-May-2012

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Summary

Official Symbol: CBLprovided by HGNC
Official Full Name: Cbl proto-oncogene, E3 ubiquitin protein ligaseprovided by HGNC
Primary source: HGNC:1541
See related: Ensembl:ENSG00000110395; HPRD:01320; MIM:165360; Vega:OTTHUMG00000166170
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CBL2; NSLL; C-CBL; RNF55
Summary: 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. Mutations in this gene are also the cause of Noonan syndrome-like disorder. [provided by RefSeq, Mar 2012]

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Genomic context

Location :: 11q23.3

Sequence :: Chromosome: 11; NC_000011.9 (119076990..119178859)

See CBL in Epigenomics, MapViewer

Chromosome 11 - NC_000011.9 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Data show that TET2 and ASXL1 pathogenic mutations are found in 8% of myeloproliferative neoplasms lacking JAK2 and MPL mutations, whereas IDH1, IDH2, and c-CBL mutations are not detected in this subset of patients.
Title: TET2, ASXL1, IDH1, IDH2, and c-CBL genes in JAK2- and MPL-negative myeloproliferative neoplasms.
Met-dependent Cbl loss may also promote cross-talk through indirect enhancement of EGF receptor signaling.
Title: Met kinase-dependent loss of the E3 ligase Cbl in gastric cancer.
C-CBL mutations play a role at least in part in a subset of myelodysplastic syndrome patients during secondary acute myeloid leukemia transformation.
Title: A high occurrence of acquisition and/or expansion of C-CBL mutant clones in the progression of high-risk myelodysplastic syndrome to acute myeloid leukemia.
ITSN1 binds Pro-rich regions in both Cbl and Spry2, and interaction of ITSN1 with Spry2 disrupts Spry2-Cbl interaction, resulting in enhanced ubiquitylation of the EGFR.
Title: Intersectin 1 enhances Cbl ubiquitylation of epidermal growth factor receptor through regulation of Sprouty2-Cbl interaction.
Tyr371 phosphorylation activates CBL by inducing linker conformational changes that eliminate autoinhibition, flip the RING domain and E2 into proximity of the substrate-binding site and transform the RING domain into an enhanced E2-binding module.
Title: Structural basis for autoinhibition and phosphorylation-dependent activation of c-Cbl.
Data show that Down-regulation of c-Cbl in VHL-deficient ccRCC cells revealed that the c-Cbl and pVHL collaborated to down-regulate the activated EGFR.
Title: The von Hippel-Lindau tumor suppressor protein promotes c-Cbl-independent poly-ubiquitylation and degradation of the activated EGFR.
We demonstrate that CHIP and c-Cbl depletion have no effect on CFTR endocytosis.
Title: Dab2 is a key regulator of endocytosis and post-endocytic trafficking of the cystic fibrosis transmembrane conductance regulator.
the C-terminal region of c-Cbl plays a crucial role in the temporal and spatial control of 5-HT(2A)R recycling.
Title: Role of c-Cbl carboxyl terminus in serotonin 5-HT2A receptor recycling and resensitization.
Results indicate that c-Cbl and particularly its phosphorylated residue Y731 plays an important role in platelet outside-in signaling contributing to platelet-spreading and clot retraction.
Title: Tyrosine phosphorylated c-Cbl regulates platelet functional responses mediated by outside-in signaling.
Overexpressions of c-Cbl, Cbl-b, and EGFR are closely related to the invasion and progression of gastric carcinoma.
Title: [Expression of c-Cbl, Cbl-b, and epidermal growth factor receptor in gastric carcinoma and their clinical significance].

Submit: New GeneRIF Correction See all (126)

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Phenotypes

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Noonan syndrome-like disorder with or without juvenile meylomonocytic leukemia

MIM: 613563

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HIV-1 protein interactions

Protein	Gene	Interaction	Pubs
Nef	nef	HIV-1 Nef enhances the phosphorylation of c-Cbl in CD4+ T cells, an effect that requires the Src tyrosine kinase Lck	PubMed
	nef	In the presence of Nef, lipid raft Cdc42 is activated and forms a ternary complex between the c-Cbl-interacting protein p85Cool-1/betaPix and c-Cbl, displacing UbcH7 from rafts	PubMed

Go to the HIV-1, Human Protein Interaction Database

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_005179.2	NP_036252.1	CD2AP	BIND	PubMed	CMS interacts with Cbl. This interaction was modeled on a demonstrated interaction between CMS from an unspecified species and human Cbl.
NP_005179.2		EGFR	BIND	PubMed	An unspecified isoform of EGFR interacts with CBL.
NP_005179.2		EGFR	BIND	PubMed	c-Cbl ubiquitinates an unspecified isoform of EGFR. This interaction was modeled on a demonstrated interaction between c-Cbl and EGFR, both from an unspecified species.
NP_005179.2	NP_002077.1	GRB2	BIND	PubMed	c-Cbl interacts with Grb2. This interaction was modeled on a demonstrated interaction between human c-Cbl and Grb2 from an unspecified species.
NP_005179.2		GRB2	BIND	PubMed	Grb2 interacts with Cbl.
NP_005179.2	NP_000215.1	KRT18	BIND	PubMed	c-Cbl interacts with Keratin 18.
NP_005179.2	NP_000236.2	MET	BIND	PubMed	Met interacts with Cbl.
NP_005179.2	NP_036515.3	OSTF1	BIND	PubMed	Cbl interacts with SH3P2.
NP_005179.2	NP_002600.1	PDGFRB	BIND	PubMed	c-Cbl interacts with and ubiquitinates PDGF-R-beta. This interaction was modeled on a demonstrated interaction between human c-Cbl and PDGF-R-beta from an unspecified species.
NP_005179.2	NP_114098.1	SH3KBP1	BIND	PubMed	CIN85 interacts with Cbl.
NP_005179.2		SORBS1	BIND	PubMed	An unspecified isoform of CAP interacts with Cbl. This interaction was modeled on a demonstrated interaction between CAP from an unspecified species and human Cbl.
NP_005179.2	AAC05508.1	SORBS2	BIND	PubMed	ArgBP2 interacts with Cbl.
NP_005179.2	AAC05508.1	SORBS2	BIND	PubMed	ArgBP2-A interacts with Cbl.
NP_005179.2	NP_005833.1	SPRY2	BIND	PubMed	hSpry2 interacts with c-Cbl.
NP_005179.2	NP_005833.1	SPRY2	BIND	PubMed	c-Cbl interacts with hSpry2. This interaction was modeled on a demonstrated interaction between c-Cbl from an unspecified species and human hSpry2.
NP_005179.2	NP_005833.1	SPRY2	BIND	PubMed	SPRY2 interacts with c-Cbl.
NP_005179.2		SRC	BIND	PubMed	Cbl interacts with Src. This interaction was modeled on a demonstrated interaction between human Cbl and Src from unspecified species.
NP_005179.2	NP_003330.1	UBE2D2	BIND	PubMed	c-Cbl interacts with Ubc4.
NP_005179.2		UBE2L3	BIND	PubMed	c-Cbl interacts with an unspecified isoform of UbcH7. This interaction was modeled on a demonstrated interaction between c-Cbl from an unspecified species and human UbcH7.
NP_005179.2	NP_003395.1	YWHAB	BIND	PubMed	c-Cbl interacts with 14-3-3-beta.
NP_005179.2	NP_003397.1	YWHAZ	BIND	PubMed	c-Cbl interacts with 14-3-3-zeta.
NP_005179.2			BIND	PubMed	Endophilin A3/CIN85 interacts with Cbl.
P22681	P00519	ABL1	HPRD	PubMed
P22681	Q9ULH1	ASAP1	HPRD	PubMed
P22681	P30530	AXL	HPRD	PubMed
P22681	P51451	BLK	HPRD	PubMed
P22681	Q06187	BTK	HPRD	PubMed
P22681	P07384	CAPN1	HPRD	PubMed
P22681	P22681	CBL	HPRD	PubMed
P22681	P15391	CD19	HPRD	PubMed
P22681	Q9Y5K6	CD2AP	HPRD	PubMed
P22681	P25942	CD40	HPRD	PubMed
P22681	P06127	CD5	HPRD	PubMed
P22681	Q92772	CDKL2	HPRD	PubMed
P22681	P46108	CRK	HPRD	PubMed
P22681	P46109	CRKL	HPRD	PubMed
P22681	P07333	CSF1R	HPRD	PubMed
P22681	P00533	EGFR	HPRD	PubMed
P22681	O60841	EIF5B	HPRD	PubMed
P22681	P29317	EPHA2	HPRD	PubMed
P22681	O15197	EPHB6	HPRD	PubMed
P22681	P19235	EPOR	HPRD	PubMed
P22681	P55085	F2RL1	HPRD	PubMed
P22681	P09769	FGR	HPRD	PubMed
P22681	Q8WU20	FRS2	HPRD	PubMed
P22681	O15117	FYB	HPRD	PubMed
P22681	P06241	FYN	HPRD	PubMed
P22681	P08631	HCK	HPRD	PubMed
P22681	SHIP2	INPPL1	HPRD	PubMed
P22681	P06213	INSR	HPRD	PubMed
P22681	Q96J02	ITCH	HPRD	PubMed
P22681	Q08881	ITK	HPRD	PubMed
P22681	P35968	KDR	HPRD	PubMed
P22681	Q07666	KHDRBS1	HPRD	PubMed
P22681	P10721	KIT	HPRD	PubMed
P22681	P05783	KRT18	HPRD	PubMed
P22681	O43561	LAT	HPRD	PubMed
P22681	Q9GZY6	LAT2	HPRD	PubMed
P22681	P06239	LCK	HPRD	PubMed
P22681	Q13094	LCP2	HPRD	PubMed
P22681	P29376	LTK	HPRD	PubMed
P22681	P07948	LYN	HPRD	PubMed
P22681	P08581	MET	HPRD	PubMed
P22681	P16333	NCK1	HPRD	PubMed
P22681	P46531	NOTCH1	HPRD	PubMed
P22681	Q92882	OSTF1	HPRD	PubMed
P22681	P16234	PDGFRA	HPRD	PubMed
P22681	P09619	PDGFRB	HPRD	PubMed
P22681	P27986	PIK3R1	HPRD	PubMed
P22681	O00459	PIK3R2	HPRD	PubMed
P22681	P19174	PLCG1	HPRD	PubMed
P22681	P17252	PRKCA	HPRD	PubMed
P22681	Q14289	PTK2B	HPRD	PubMed
P22681	Q06124	PTPN11	HPRD	PubMed
P22681	Q9Y2R2	PTPN22	HPRD	PubMed
P22681	P29350	PTPN6	HPRD	PubMed
P22681	P07949	RET	HPRD	PubMed
P22681	Q14524	SCN5A	HPRD	PubMed
P22681	O14492	SH2B2	HPRD	PubMed
P22681	Q96B97	SH3KBP1	HPRD	PubMed
P22681	P29353	SHC1	HPRD	PubMed
P22681	Q13239	SLA	HPRD	PubMed
P22681	Q9H6Q3	SLA2	HPRD	PubMed
P22681	Q9BX66	SORBS1	HPRD	PubMed
P22681	Arg binding protein 2	SORBS2	HPRD	PubMed
P22681	O43597	SPRY2	HPRD	PubMed
P22681	P12931	SRC	HPRD	PubMed
P22681	P42229	STAT5A	HPRD	PubMed
P22681	P51692	STAT5B	HPRD	PubMed
P22681	P43405	SYK	HPRD	PubMed
P22681	Q9Y6Q6	TNFRSF11A	HPRD	PubMed
P22681	Q9Y4K3	TRAF6	HPRD	PubMed
P22681	P29597	TYK2	HPRD	PubMed
P22681	Suppressor of T-cell receptor signaling 1	UBASH3B	HPRD	PubMed
P22681	P62837	UBE2D2	HPRD	PubMed
P22681	P62253	UBE2G1	HPRD	PubMed
P22681	P60604	UBE2G2	HPRD	PubMed
P22681	P68036	UBE2L3	HPRD	PubMed
P22681	P15498	VAV1	HPRD	PubMed
P22681	P52735	VAV2	HPRD	PubMed
P22681	P31946	YWHAB	HPRD	PubMed
P22681	P61981	YWHAG	HPRD	PubMed
P22681	P27348	YWHAQ	HPRD	PubMed
P22681	P63104	YWHAZ	HPRD	PubMed
P22681	P43403	ZAP70	HPRD	PubMed
BioGRID:107315	BioGRID:106543	ABL1	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Far Western
BioGRID:107315	BioGRID:106573	ACTA1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:107315	BioGRID:106575	ACTB	BioGRID	PubMed	Affinity Capture-MS
BioGRID:107315	BioGRID:106587	ACTG2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:107315	BioGRID:114393	ARHGEF7	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:107315	BioGRID:107036	AXL	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:107049	BAG1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:107315	BioGRID:107083	BCR	BioGRID	PubMed	Biochemical Activity; Co-purification
BioGRID:107315	BioGRID:107160	BTK	BioGRID	PubMed	Reconstituted Complex
BioGRID:107315	BioGRID:107315	CBL	BioGRID	PubMed	Affinity Capture-Western; Co-crystal Structure
BioGRID:107315	BioGRID:107357	CD247	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:117140	CD2AP	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:107315	BioGRID:107383	CD33	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:107359	CD5	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:107433	CDC42	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:107315	BioGRID:107506	CFTR	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:107788	CRK	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:107789	CRKL	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Reconstituted Complex
BioGRID:107315	BioGRID:107822	CSF1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:107823	CSF1R	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:107315	BioGRID:107832	CSK	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:108237	EEF1A1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:107315	BioGRID:108276	EGFR	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Co-crystal Structure; Co-localization; Reconstituted Complex
BioGRID:107315	BioGRID:108360	EPHA8	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:108361	EPHB1	BioGRID	PubMed	Affinity Capture-Western; Co-localization; Reconstituted Complex
BioGRID:107315	BioGRID:108506	FCGR2A	BioGRID	PubMed	Co-fractionation
BioGRID:107315	BioGRID:108559	FGR	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:115506	FLOT1	BioGRID	PubMed	Reconstituted Complex
BioGRID:107315	BioGRID:116031	FRS2	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:107315	BioGRID:108810	FYN	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:107315	BioGRID:108868	GAPDH	BioGRID	PubMed	Affinity Capture-MS
BioGRID:107315	BioGRID:117568	GAPVD1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:109142	GRB2	BioGRID	PubMed	Affinity Capture-Western; FRET; Reconstituted Complex; Two-hybrid
BioGRID:107315	BioGRID:201466	Grap2	BioGRID	PubMed	Reconstituted Complex
BioGRID:107315	BioGRID:109305	HCK	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Far Western; Reconstituted Complex
BioGRID:107315	BioGRID:109540	HSPA4	BioGRID	PubMed	Affinity Capture-MS
BioGRID:107315	BioGRID:109541	HSPA5	BioGRID	PubMed	Affinity Capture-MS
BioGRID:107315	BioGRID:109701	IGF1R	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity
BioGRID:107315	BioGRID:109789	IL7R	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:109848	INPPL1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:109621	IRF8	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:109874	IRS1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:123747	ITCH	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:109884	ITGA5	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:109907	ITK	BioGRID	PubMed	Reconstituted Complex
BioGRID:107315	BioGRID:112351	ITSN1	BioGRID	PubMed	Far Western
BioGRID:107315	BioGRID:200643	Il6st	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:200851	Itsn1	BioGRID	PubMed	PCA
BioGRID:107315	BioGRID:109992	KDR	BioGRID	PubMed	Reconstituted Complex
BioGRID:107315	BioGRID:110015	KIT	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:110073	KRT18	BioGRID	PubMed	Two-hybrid
BioGRID:107315	BioGRID:110124	LCK	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:110129	LCP2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:117489	LRIG1	BioGRID	PubMed	Reconstituted Complex
BioGRID:107315	BioGRID:110236	LTK	BioGRID	PubMed	Biochemical Activity
BioGRID:107315	BioGRID:110245	LYN	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:110391	MET	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Co-crystal Structure; Reconstituted Complex
BioGRID:107315	BioGRID:110592	MST1R	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:110712	MYH9	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Reconstituted Complex
BioGRID:107315	BioGRID:110725	MYO1C	BioGRID	PubMed	Two-hybrid
BioGRID:107315	BioGRID:110770	NCK1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:110913	NOTCH1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:110969	NTRK1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:246737	Ngfr	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:107315	BioGRID:111182	PDGFRA	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:107315	BioGRID:111308	PIK3CA	BioGRID	PubMed	Co-purification
BioGRID:107315	BioGRID:111313	PIK3R1	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western
BioGRID:107315	BioGRID:111314	PIK3R2	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western
BioGRID:107315	BioGRID:111351	PLCG1	BioGRID	PubMed	Affinity Capture-Western; Far Western; Reconstituted Complex
BioGRID:107315	BioGRID:111678	PSMC5	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:111719	PTK2	BioGRID	PubMed	Co-localization
BioGRID:107315	BioGRID:108480	PTK2B	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:111745	PTPN11	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:111742	PTPN6	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:111787	PXN	BioGRID	PubMed	Affinity Capture-Western; Co-purification
BioGRID:107315	BioGRID:202089	Pdgfrb	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:202162	Pik3r1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:111911	RET	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:115850	SH2B2	BioGRID	PubMed	Affinity Capture-Western; Co-crystal Structure; Reconstituted Complex
BioGRID:107315	BioGRID:112350	SH3BP2	BioGRID	PubMed	Reconstituted Complex
BioGRID:107315	BioGRID:112353	SH3GL2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:112354	SH3GL3	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:119029	SH3KBP1	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western
BioGRID:107315	BioGRID:112361	SHC1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:112394	SLA	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:107315	BioGRID:123928	SLA2	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:107315	BioGRID:115831	SORBS1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:114047	SORBS2	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:107315	BioGRID:115547	SPRY2	BioGRID	PubMed	Affinity Capture-Western; Co-crystal Structure; FRET; Reconstituted Complex; Two-hybrid
BioGRID:107315	BioGRID:123599	SPRY4	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:112592	SRC	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:120759	STAP2	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:107315	BioGRID:112717	SYK	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Reconstituted Complex
BioGRID:107315	BioGRID:112869	TEK	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:112949	TLN1	BioGRID	PubMed	Co-purification
BioGRID:107315	BioGRID:114325	TNFRSF10A	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:114323	TNFRSF10B	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:113148	TYK2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:113165	UBA1	BioGRID	PubMed	Reconstituted Complex
BioGRID:107315	BioGRID:119748	UBASH3A	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Reconstituted Complex
BioGRID:107315	BioGRID:124390	UBASH3B	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:107315	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-Western; Co-crystal Structure; Reconstituted Complex
BioGRID:107315	BioGRID:113169	UBE2D1	BioGRID	PubMed	Reconstituted Complex
BioGRID:107315	BioGRID:113170	UBE2D2	BioGRID	PubMed	Reconstituted Complex
BioGRID:107315	BioGRID:113180	UBE2L3	BioGRID	PubMed	Affinity Capture-Western; Co-crystal Structure; Reconstituted Complex
BioGRID:107315	BioGRID:114504	UBE2M	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:115566	UBE4B	BioGRID	PubMed	Co-crystal Structure
BioGRID:107315	BioGRID:113252	VAV1	BioGRID	PubMed	Affinity Capture-Western; Far Western; Reconstituted Complex
BioGRID:107315	BioGRID:113253	VAV2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107315	BioGRID:113272	VIM	BioGRID	PubMed	Affinity Capture-MS
BioGRID:107315	BioGRID:113361	YWHAB	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:107315	BioGRID:116168	YWHAQ	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:107315	BioGRID:113366	YWHAZ	BioGRID	PubMed	Two-hybrid
BioGRID:107315	BioGRID:113367	ZAP70	BioGRID	PubMed	Affinity Capture-Western; Co-crystal Structure

Function	Evidence Code	Pubs
SH3 domain binding	IPI Inferred from Physical Interaction more info	PubMed
calcium ion binding	IEA Inferred from Electronic Annotation more info
ephrin receptor binding	IPI Inferred from Physical Interaction more info	PubMed
ligase activity	IEA Inferred from Electronic Annotation more info
phosphotyrosine binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
sequence-specific DNA binding transcription factor activity	TAS Traceable Author Statement more info	PubMed
signal transducer activity	IEA Inferred from Electronic Annotation more info
ubiquitin-protein ligase activity	TAS Traceable Author Statement more info	PubMed
zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
cell surface receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
epidermal growth factor receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
fibroblast growth factor receptor signaling pathway	TAS Traceable Author Statement more info
negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of epidermal growth factor receptor signaling pathway	TAS Traceable Author Statement more info
positive regulation of phosphatidylinositol 3-kinase cascade	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of receptor-mediated endocytosis	TAS Traceable Author Statement more info	PubMed
protein ubiquitination	TAS Traceable Author Statement more info	PubMed
regulation of signaling	IEA Inferred from Electronic Annotation more info
regulation of transcription, DNA-dependent	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytosol	TAS Traceable Author Statement more info
colocalizes_with flotillin complex	ISS Inferred from Sequence or Structural Similarity more info
nucleus	IEA Inferred from Electronic Annotation more info
plasma membrane	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	TAS Traceable Author Statement more info

General protein information

Preferred Names: E3 ubiquitin-protein ligase CBL

Names: E3 ubiquitin-protein ligase CBL; oncogene CBL2; proto-oncogene c-Cbl; RING finger protein 55; signal transduction protein CBL; casitas B-lineage lymphoma proto-oncogene; Cas-Br-M (murine) ecotropic retroviral transforming sequence

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_016808.1 RefSeqGene

Range

4997..106870

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_005188.3 → NP_005179.2 E3 ubiquitin-protein ligase CBL

Status: REVIEWED

Source sequence(s)

AA806454, AP002956, BC132733, DB457271

Consensus CDS

CCDS8418.1

UniProtKB/Swiss-Prot

P22681

Related

ENSP00000264033, OTTHUMP00000232087, ENST00000264033, OTTHUMT00000388219

Conserved Domains (5) summary

cd00162
Location:381 – 423
Blast Score: 132

RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...

cd00194
Location:861 – 894
Blast Score: 102

UBA; Ubiquitin Associated domain. The UBA domain is a commonly occurring sequence motif in some members of the ubiquitination pathway, UV excision repair proteins, and certain protein kinases. Although its specific role is so far unknown, it has been ...

pfam02262
Location:49 – 176
Blast Score: 650

Cbl_N; CBL proto-oncogene N-terminal domain 1

cd09920
Location:256 – 352
Blast Score: 537

SH2_Cbl-b_TKB; Src homology 2 (SH2) domain found in the Cbl-b TKB domain

pfam02761
Location:178 – 262
Blast Score: 438

Cbl_N2; CBL proto-oncogene N-terminus, EF hand-like domain

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000011.9 Reference GRCh37.p5 Primary Assembly

Range

119076990..119178859

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000143.1 Alternate HuRef

Range

115017377..115119562

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AP002956.1 (75549..177418)	None
genomic	CH471065.1	EAW67476.1
mRNA	AA806454.1	None
mRNA	AK092300.1	None
mRNA	BC132733.1	AAI32734.1
mRNA	BC136463.1	AAI36464.1
mRNA	BG722940.1	None
mRNA	DB457271.2	None
mRNA	X57110.1	CAA40393.1
mRNA	X69207.1	None
mRNA	AL832396.1	None
mRNA	BX648139.1	None