CBLC (Cbl proto-oncogene C)

Gene

• Entrez ID: 23624
• Gene name: Cbl proto-oncogene C
• Gene symbol: CBLC
• Synonyms (NCBI Gene): CBL-3, CBL-SL, RNF57
• Chromosome: 19
• Chromosome location: 19q13.32
• Summary: This gene encodes a member of the Cbl family of E3 ubiquitin ligases. Cbl proteins play important roles in cell signaling through the ubiquitination and subsequent downregulation of tyrosine kinases. Expression of this gene may be restricted to epithelial

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT029439	hsa-miR-26b-5p	Microarray	19088304

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001784	Function	Phosphotyrosine residue binding	IDA	14661060
GO:0001784	Function	Phosphotyrosine residue binding	IEA
GO:0004842	Function	Ubiquitin-protein transferase activity	IEA
GO:0005154	Function	Epidermal growth factor receptor binding	IDA	10362357
GO:0005509	Function	Calcium ion binding	IEA
GO:0005515	Function	Protein binding	IPI	32296183, 32814053
GO:0005886	Component	Plasma membrane	IBA
GO:0006511	Process	Ubiquitin-dependent protein catabolic process	IDA	14661060
GO:0007165	Process	Signal transduction	IBA
GO:0007166	Process	Cell surface receptor signaling pathway	IEA
GO:0008270	Function	Zinc ion binding	IEA
GO:0008270	Function	Zinc ion binding	TAS	10362357
GO:0016567	Process	Protein ubiquitination	IDA	14661060
GO:0016740	Function	Transferase activity	IEA
GO:0017124	Function	SH3 domain binding	IDA	10362357
GO:0017124	Function	SH3 domain binding	IEA
GO:0023051	Process	Regulation of signaling	IEA
GO:0030163	Process	Protein catabolic process	IEA
GO:0030163	Process	Protein catabolic process	IEA
GO:0030971	Function	Receptor tyrosine kinase binding	IBA
GO:0042059	Process	Negative regulation of epidermal growth factor receptor signaling pathway	IBA
GO:0042059	Process	Negative regulation of epidermal growth factor receptor signaling pathway	IDA	10362357
GO:0043409	Process	Negative regulation of MAPK cascade	IDA	10362357
GO:0043524	Process	Negative regulation of neuron apoptotic process	IEA
GO:0045121	Component	Membrane raft	IBA
GO:0046872	Function	Metal ion binding	IEA
GO:0050821	Process	Protein stabilization	IEA
GO:0061630	Function	Ubiquitin protein ligase activity	IBA
GO:0061630	Function	Ubiquitin protein ligase activity	IDA	14661060
GO:0061630	Function	Ubiquitin protein ligase activity	IEA
GO:1990790	Process	Response to glial cell derived neurotrophic factor	IEA

Other IDs

• MIM: 608453
• HGNC: 15961
• e!Ensembl: ENSG00000142273

Protein

• UniProt ID: Q9ULV8
• Protein name: E3 ubiquitin-protein ligase CBL-C (EC 2.3.2.27) (RING finger protein 57) (RING-type E3 ubiquitin transferase CBL-C) (SH3-binding protein CBL-3) (SH3-binding protein CBL-C) (Signal transduction protein CBL-C)
• Protein function: Acts as an E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Functionally coupled with the E2 ubiquitin-protein
• PDB: 3OP0, 3VRN, 3VRO, 3VRP, 3VRQ, 3VRR
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02262	Cbl_N	13 → 145	CBL proto-oncogene N-terminal domain 1	Domain
  PF02761	Cbl_N2	149 → 232	CBL proto-oncogene N-terminus, EF hand-like domain	Domain
  PF02762	Cbl_N3	234 → 319	CBL proto-oncogene N-terminus, SH2-like domain	Domain
  PF14447	Prok-RING_4	351 → 398		Family

• Tissue specificity: TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:10362357}.
• Sequence:

  MALAVAPWGRQWEEARALGRAVRMLQRLEEQCVDPRLSVSPPSLRDLLPRTAQLLREVAH
  SRRAAGGGGPGGPGGSGDFLLIYLANLEAKSRQVAALLPPRGRRSANDELFRAGSRLRRQ
  LAKLAIIFSHMHAELHALFPGGKYCGHMYQLTKAPAHTFWRESCGARCVLPWAEFESLLG
  TCHPVEPGCTALALRTTIDLTCSGHVSIFEFDVFTRLFQPWPTLLKNWQLLAVNHPGYMA
  FLTYDEVQERLQACRDKPGSYIFRPSCTRLGQWAIGYVSSDGSILQTIPANKPLSQVLLE
  GQKDGFYLYPDGKTHNPDLTELGQAEPQQRIHVSEEQLQLYWAMDSTFELCKICAESNKD
  VKIEPCGHLLCSCCLAAWQHSDSQTCPFCRCEIKGWEAVSIYQFHGQATAEDSGNSSDQE
  GRELELGQVPLSAPPLPPRPDLPPRKPRNAQPKVRLLKGNSPPAALGPQDPAPA

• Sequence length: 474

Pathways

KEGG:

Ubiquitin mediated proteolysis
Endocytosis

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CROHN'S DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FAMILIAL HYPERLIPIDEMIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Relationship Type	References	Evidence Score
Acute Kidney Injury	Associate	38178022	★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Associate	37386009	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Anemia Megaloblastic	Associate	21497120	★☆☆☆☆ Found in Text Mining only
Aortic Dissection	Associate	38178022	★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Associate	24466333, 25883215, 36043996	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Associate	29377892	★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Associate	36385010	★☆☆☆☆ Found in Text Mining only
Cardiomyopathies	Associate	38168585	★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Associate	21497120, 32068834	★☆☆☆☆ Found in Text Mining only
Cognition Disorders	Associate	21497120	★☆☆☆☆ Found in Text Mining only
Cyanosis	Associate	32443968	★☆☆☆☆ Found in Text Mining only
Death	Associate	34655177	★☆☆☆☆ Found in Text Mining only
Dyspnea	Associate	32443968	★☆☆☆☆ Found in Text Mining only
Heart Failure	Associate	32443968	★☆☆☆☆ Found in Text Mining only
Homocystinuria	Associate	15292234, 20696242, 32457044	★☆☆☆☆ Found in Text Mining only
Hyperhomocysteinemia	Associate	21497120	★☆☆☆☆ Found in Text Mining only
Hypertension Pulmonary	Associate	32443968, 38168585	★☆☆☆☆ Found in Text Mining only
Melanoma	Associate	29377892	★☆☆☆☆ Found in Text Mining only
Methylcobalamin Deficiency CblG Type	Associate	32068834, 38168585	★☆☆☆☆ Found in Text Mining only
Methylmalonic acidemia	Associate	15292234, 20696242, 32457044, 33797888, 33982424	★☆☆☆☆ Found in Text Mining only
Methylmalonic acidemia	Stimulate	21497120	★☆☆☆☆ Found in Text Mining only
Methylmalonic acidemia	Inhibit	32443968	★☆☆☆☆ Found in Text Mining only
Methylmalonic acidemia with homocystinuria	Associate	25809485, 34655177	★☆☆☆☆ Found in Text Mining only
Methylmalonic acidemia with homocystinuria	Inhibit	32443968	★☆☆☆☆ Found in Text Mining only
Methylmalonic Aciduria and Homocystinuria CblF Type	Inhibit	21497120	★☆☆☆☆ Found in Text Mining only
Methylmalonic Aciduria and Homocystinuria CblF Type	Associate	32068834, 33797888	★☆☆☆☆ Found in Text Mining only
Muscular Dystrophies	Associate	21497120	★☆☆☆☆ Found in Text Mining only
Myotonia with Skeletal Abnormalities and Mental Retardation	Associate	21497120	★☆☆☆☆ Found in Text Mining only
Neoplasm Metastasis	Inhibit	36043996	★☆☆☆☆ Found in Text Mining only
Neoplasms	Associate	29377892	★☆☆☆☆ Found in Text Mining only
Neoplasms	Inhibit	36043996	★☆☆☆☆ Found in Text Mining only
Neurologic Manifestations	Associate	21497120, 32068834, 38178022	★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Associate	21497120	★☆☆☆☆ Found in Text Mining only
Peripheral Nervous System Diseases	Associate	38168585	★☆☆☆☆ Found in Text Mining only
Vitamin B 12 Deficiency	Associate	29302025	★☆☆☆☆ Found in Text Mining only