Aliases for CBLC Gene
Aliases for CBLC Gene
- Cbl Proto-Oncogene C 2 3 5
- Cas-Br-M (Murine) Ecotropic Retroviral Transforming Sequence C 2 3
- Cas-Br-M (Murine) Ectropic Retroviral Transforming Sequence C 2 3
- Cbl Proto-Oncogene C, E3 Ubiquitin Protein Ligase 2 3
- RING-Type E3 Ubiquitin Transferase CBL-C 3 4
- Signal Transduction Protein CBL-C 3 4
- SH3-Binding Protein CBL-3 3 4
- SH3-Binding Protein CBL-C 3 4
- RING Finger Protein 57 3 4
External Ids for CBLC Gene
- HGNC: 15961
- Entrez Gene: 23624
- Ensembl: ENSG00000142273
- OMIM: 608453
- UniProtKB: Q9ULV8
Previous GeneCards Identifiers for CBLC Gene
- GC19P045925
- GC19P045672
- GC19P049957
- GC19P049972
- GC19P045281
- GC19P041713
Summaries for CBLC Gene
-
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 cells, and alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]
GeneCards Summary for CBLC Gene
CBLC (Cbl Proto-Oncogene C) is a Protein Coding gene. Among its related pathways are EGF/EGFR Signaling Pathway and Ubiquitin mediated proteolysis. Gene Ontology (GO) annotations related to this gene include calcium ion binding and ubiquitin-protein transferase activity. An important paralog of this gene is CBLB.
UniProtKB/Swiss-Prot for CBLC Gene
-
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 ligases UB2D1, UB2D2 and UB2D3. Regulator of EGFR mediated signal transduction; upon EGF activation, ubiquitinates EGFR. Isoform 1, but not isoform 2, inhibits EGF stimulated MAPK1 activation. Promotes ubiquitination of SRC phosphorylated at Tyr-419. In collaboration with CD2AP may act as regulatory checkpoint for Ret signaling by modulating the rate of RET degradation after ligand activation; CD2AP converts it from an inhibitor to a promoter of RET degradation; the function limits the potency of GDNF on neuronal survival.
No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CBLC Gene
Genomics for CBLC Gene
GeneHancer (GH) Regulatory Elements for CBLC Gene
Promoters and enhancers for CBLC Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association
Download GeneHancer data dump
GeneHancers around CBLC on UCSC Golden Path with GeneCards custom track
Regulatory Element Products
Genomic Locations for CBLC Gene
Genomic Locations for CBLC Gene
- chr19:44,777,861-44,800,646
- (GRCh38/hg38)
- Size:
- 22,786 bases
- Orientation:
- Plus strand
- chr19:45,281,126-45,303,903
- (GRCh37/hg19)
Genomic View for CBLC Gene
Genes around CBLC on UCSC Golden Path with GeneCards custom track
- Cytogenetic band:
-
- 19q13.32 by Entrez Gene
- 19q13.32 by HGNC
- 19q13.32 by Ensembl
CBLC Gene in genomic location: bands according to
Ensembl, locations according to GeneLoc
(and/or Entrez Gene and/or Ensembl if different)
Genomic Neighborhood
• Exon Structure
• Gene Density
RefSeq DNA sequence for CBLC Gene
Proteins for CBLC Gene
-
Protein details for CBLC Gene (UniProtKB/Swiss-Prot)
- Protein Symbol:
- Q9ULV8-CBLC_HUMAN
- Recommended name:
- E3 ubiquitin-protein ligase CBL-C
- Protein Accession:
- Q9ULV8
- Q8N1E5
- Q9Y5Z2
- Q9Y5Z3
Protein attributes for CBLC Gene
- Size:
- 474 amino acids
- Molecular mass:
- 52456 Da
- Quaternary structure:
-
- Interacts with ubiquitin-conjugating enzyme E2 UBE2D2 and UBE2D3. Isoform 1 interacts with EGFR (tyrosine phosphorylated). Interacts with the SH3 domain proteins LYN and CRK. Interacts (via RING-type zinc finger) with TGFB1I1 (via LIM zinc-binding domain 2); the interaction is direct and enhances the E3 activity. Interacts directly with RET (inactive) and CD2AP; dissociates from RET upon RET activation by GDNF which also increases the interaction with CD2AP suggesting dissociation as CBLC:CD2AP complex. Interacts with SRC; the interaction is enhanced when SRC is phosphorylated at Tyr-419.
- Miscellaneous:
-
- This protein has one functional calcium-binding site.
Three dimensional structures from OCA and Proteopedia for CBLC Gene
Post-translational modifications for CBLC Gene
- Phosphorylated on multiple tyrosine residues by SRC. Isoform 1, but not isoform 2, is phosphorylated on tyrosines by EGFR.
- Autoubiquitinated when phosphorylated at Tyr-341, enhanced by SRC; suggesting proteasomal degradation.
- Modification sites at PhosphoSitePlus
- Modification sites at neXtProt
Other Protein References for CBLC Gene
- ENSEMBL proteins:
- REFSEQ proteins:
Antibody Products
-
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-
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-
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Assay Products
No data available for DME Specific Peptides for CBLC Gene
Domains & Families for CBLC Gene
Gene Families for CBLC Gene
- HGNC:
- Human Protein Atlas (HPA):
-
- Cancer-related genes
- Enzymes
- Predicted intracellular proteins
Protein Domains for CBLC Gene
Suggested Antigen Peptide Sequences for CBLC Gene
- GenScript: Design optimal peptide antigens:
Graphical View of Domain Structure for InterPro Entry
Q9ULV8UniProtKB/Swiss-Prot:
CBLC_HUMAN :- EF-hand-like and Sh2-like domains are required for N-terminal inhibition of E3 activity.
- Domain:
-
- EF-hand-like and Sh2-like domains are required for N-terminal inhibition of E3 activity.
- The N-terminus is composed of the phosphotyrosine binding (PTB) domain, a short linker region and the RING-type zinc finger. The PTB domain, which is also called TKB (tyrosine kinase binding) domain, is composed of three different subdomains: a four-helix bundle (4H), a calcium-binding EF hand and a divergent SH2 domain.
- The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme.
Function for CBLC Gene
Molecular function for CBLC Gene
- UniProtKB/Swiss-Prot 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 ligases UB2D1, UB2D2 and UB2D3. Regulator of EGFR mediated signal transduction; upon EGF activation, ubiquitinates EGFR. Isoform 1, but not isoform 2, inhibits EGF stimulated MAPK1 activation. Promotes ubiquitination of SRC phosphorylated at Tyr-419. In collaboration with CD2AP may act as regulatory checkpoint for Ret signaling by modulating the rate of RET degradation after ligand activation; CD2AP converts it from an inhibitor to a promoter of RET degradation; the function limits the potency of GDNF on neuronal survival.
- UniProtKB/Swiss-Prot CatalyticActivity:
- S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.
- UniProtKB/Swiss-Prot EnzymeRegulation:
- Phosphorylation at Tyr-341 is necessary and sufficient for the activation of E3 activity.
Enzyme Numbers (IUBMB) for CBLC Gene
Phenotypes From GWAS Catalog for CBLC Gene
| GO ID | Qualified GO term | Evidence | PubMed IDs |
|---|---|---|---|
| GO:0001784 | phosphotyrosine residue binding | IDA | 14661060 |
| GO:0004842 | ubiquitin-protein transferase activity | IEA | -- |
| GO:0004871 | obsolete signal transducer activity | IEA | -- |
| GO:0005154 | epidermal growth factor receptor binding | IDA | 10362357 |
| GO:0005509 | calcium ion binding | IEA | -- |
Phenotypes for CBLC Gene
- MGI mutant phenotypes for CBLC:
- inferred from 1 alleles
- GenomeRNAi human phenotypes for CBLC:
Animal Models for CBLC Gene
- MGI Knock Outs for CBLC:
-
- Cblc Cblc<tm1Pngr>
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-
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miRNA for CBLC Gene
- miRTarBase miRNAs that target CBLC
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-
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- CRISPR: plasmid gRNA, lentiviral gRNA, and donor plasmid
- Bacterial expression: pET, pBAD, and pCS
- Yeast expression
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-
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Cell Line Products
-
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No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for CBLC Gene
Localization for CBLC Gene
| Compartment | Confidence |
|---|---|
| extracellular | 5 |
| nucleus | 4 |
| plasma membrane | 3 |
| cytosol | 2 |
| lysosome | 1 |
- Nucleoplasm (2)
| GO ID | Qualified GO term | Evidence | PubMed IDs |
|---|---|---|---|
| GO:0005634 | nucleus | IEA | -- |
| GO:0005886 | plasma membrane | IBA | -- |
| GO:0045121 | membrane raft | IBA | -- |
| GO:0070062 | extracellular exosome | HDA | -- |
No data available for Subcellular locations from UniProtKB/Swiss-Prot for CBLC Gene
Pathways & Interactions for CBLC Gene
| SuperPathway | Contained pathways | ||
|---|---|---|---|
| 1 | Angiopoietin Like Protein 8 Regulatory Pathway | ||
| 2 | Endocytosis | ||
| 3 | Ubiquitin mediated proteolysis | ||
| 4 | EGF/EGFR Signaling Pathway | ||
| 5 | ErbB signaling pathway | ||
Pathways by source for CBLC Gene
4 BioSystems pathways for CBLC Gene
2 KEGG pathways for CBLC Gene
Interacting Proteins for CBLC Gene
GPS-Prot Interaction Network for CBLC
SIGNOR curated interactions for CBLC Gene
| GO ID | Qualified GO term | Evidence | PubMed IDs |
|---|---|---|---|
| GO:0006511 | ubiquitin-dependent protein catabolic process | IDA | 14661060 |
| GO:0007165 | signal transduction | IBA | -- |
| GO:0007166 | cell surface receptor signaling pathway | IEA | -- |
| GO:0007175 | negative regulation of epidermal growth factor-activated receptor activity | IDA | 10362357 |
| GO:0016567 | protein ubiquitination | IDA | 14661060 |
Drugs & Compounds for CBLC Gene
| Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
|---|---|---|---|---|---|---|
| pyrophosphate |
|
14000-31-8 |
|
Transcripts for CBLC Gene
mRNA/cDNA for CBLC Gene
- (38) Selected AceView cDNA sequences:
- (4) Additional mRNA sequences :
- (6) REFSEQ mRNAs :
- (4) Ensembl transcripts including schematic representations, and UCSC links where relevant :
-
- ENST00000270279 1579 bps (uc002ozs.4)
- ENST00000341505 1441 bps (uc010ejt.4)
- ENST00000647063 691 bps
- ENST00000647358 1531 bps
Unigene Clusters for CBLC Gene
CRISPR Products
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-
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Clone Products
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-
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- Mammalian expression: PiggyBac
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- Mammalian conditional (Cre-Lox): plasmid and PiggyBac
- Mammalian shRNA knockdown: lentiviral, adenoviral, AAV, and PiggyBac
- CRISPR: plasmid gRNA, lentiviral gRNA, and donor plasmid
- Bacterial expression: pET, pBAD, and pCS
- Yeast expression
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-
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| ExUns: | 1 | ^ | 2 | ^ | 3 | ^ | 4 | ^ | 5 | ^ | 6 | ^ | 7 | ^ | 8 | ^ | 9 | ^ | 10 | ^ | 11 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SP1: | |||||||||||||||||||||
| SP2: | - |
Expression for CBLC Gene
mRNA expression in embryonic tissues and stem cells from LifeMap Discovery
mRNA differential expression in normal tissues according to GTEx for CBLC Gene
This gene is overexpressed in Esophagus - Mucosa (x6.7), Skin - Not Sun Exposed (Suprapubic) (x6.5), Colon - Transverse (x6.3), and Skin - Sun Exposed (Lower leg) (x5.9).
NURSA nuclear receptor signaling pathways regulating expression of CBLC Gene:
CBLCSOURCE GeneReport for Unigene cluster for CBLC Gene:
Hs.466907mRNA Expression by UniProt/SwissProt for CBLC Gene:
Q9ULV8-CBLC_HUMAN
Tissue specificity:
Ubiquitous.
Evidence on tissue expression from TISSUES for CBLC Gene
- Skin(4.2)
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-
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Gene Expression Assay Products
No data available for Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for CBLC Gene
Orthologs for CBLC Gene
This gene was present in the common ancestor of animals.
| Organism | Taxonomy | Gene | Similarity | Type | Details |
|---|---|---|---|---|---|
| chimpanzee (Pan troglodytes) |
Mammalia | CBLC 34 33 |
|
OneToOne | |
| cow (Bos Taurus) |
Mammalia | CBLC 34 33 |
|
OneToOne | |
| dog (Canis familiaris) |
Mammalia | CBLC 34 33 |
|
OneToOne | |
| rat (Rattus norvegicus) |
Mammalia | Cblc 33 |
|
||
| mouse (Mus musculus) |
Mammalia | Cblc 16 34 33 |
|
||
| oppossum (Monodelphis domestica) |
Mammalia | CBLC 34 |
|
OneToOne | |
| platypus (Ornithorhynchus anatinus) |
Mammalia | CBLC 34 |
|
OneToOne | |
| lizard (Anolis carolinensis) |
Reptilia | CBLC 34 |
|
OneToOne | |
| zebrafish (Danio rerio) |
Actinopterygii | CBLC 34 |
|
OneToOne | |
| fruit fly (Drosophila melanogaster) |
Insecta | Cbl 34 |
|
OneToMany | |
| worm (Caenorhabditis elegans) |
Secernentea | sli-1 34 |
|
OneToMany | |
| sea squirt (Ciona savignyi) |
Ascidiacea | -- 34 |
|
OneToMany |
- Species where no ortholog for CBLC was found in the sources mined by GeneCards:
-
- A. gosspyii yeast (Ashbya gossypii)
- Actinobacteria (Mycobacterium tuberculosis)
- African clawed frog (Xenopus laevis)
- African malaria mosquito (Anopheles gambiae)
- Alicante grape (Vitis vinifera)
- alpha proteobacteria (Wolbachia pipientis)
- amoeba (Dictyostelium discoideum)
- Archea (Pyrococcus horikoshii)
- baker's yeast (Saccharomyces cerevisiae)
- barley (Hordeum vulgare)
- beta proteobacteria (Neisseria meningitidis)
- bread mold (Neurospora crassa)
- chicken (Gallus gallus)
- Chromalveolata (Phytophthora infestans)
- common water flea (Daphnia pulex)
- corn (Zea mays)
- E. coli (Escherichia coli)
- filamentous fungi (Aspergillus nidulans)
- Firmicute bacteria (Streptococcus pneumoniae)
- fission yeast (Schizosaccharomyces pombe)
- green algae (Chlamydomonas reinhardtii)
- honey bee (Apis mellifera)
- K. lactis yeast (Kluyveromyces lactis)
- loblloly pine (Pinus taeda)
- malaria parasite (Plasmodium falciparum)
- medicago trunc (Medicago Truncatula)
- moss (Physcomitrella patens)
- orangutan (Pongo pygmaeus)
- pig (Sus scrofa)
- rainbow trout (Oncorhynchus mykiss)
- rice (Oryza sativa)
- rice blast fungus (Magnaporthe grisea)
- schistosome parasite (Schistosoma mansoni)
- sea anemone (Nematostella vectensis)
- sea urchin (Strongylocentrotus purpuratus)
- sorghum (Sorghum bicolor)
- soybean (Glycine max)
- stem rust fungus (Puccinia graminis)
- sugarcane (Saccharum officinarum)
- thale cress (Arabidopsis thaliana)
- tomato (Lycopersicon esculentum)
- toxoplasmosis (Toxoplasma gondii)
- Trichoplax (Trichoplax adhaerens)
- tropical clawed frog (Silurana tropicalis)
- wheat (Triticum aestivum)
Evolution for CBLC Gene
- ENSEMBL:
- Gene Tree for CBLC (if available)
- TreeFam:
- Gene Tree for CBLC (if available)
- Aminode:
- Evolutionary constrained regions (ECRs) for CBLC: view image
Paralogs for CBLC Gene
Variants for CBLC Gene
| SNP ID | Clin | Chr 19 pos | Variation | AA Info | Type |
|---|---|---|---|---|---|
| rs1000151116 | -- | 44,783,862(+) | C/T | intron_variant | |
| rs1000593338 | -- | 44,778,172(+) | C/T | coding_sequence_variant, missense_variant, non_coding_transcript_variant | |
| rs1000666675 | -- | 44,777,999(+) | G/T | coding_sequence_variant, missense_variant, non_coding_transcript_variant | |
| rs1000690482 | -- | 44,798,287(+) | C/G | genic_downstream_transcript_variant, intron_variant | |
| rs1000755141 | -- | 44,792,976(+) | G/A | genic_downstream_transcript_variant, intron_variant |
Residual Variation Intolerance Score:
70.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score:
8.08;
84.44% of all genes are more intolerant (likely to be disease-causing)
Additional Variant Information for CBLC Gene
SNP Genotyping and Copy Number Assay Products
No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CBLC Gene
Disorders for CBLC Gene
Additional Disease Information for CBLC
No disorders were found for CBLC Gene.
No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for CBLC Gene
Publications for CBLC Gene
- cbl-3: a new mammalian cbl family protein. (PMID: 10362357) Keane MM … Lipkowitz S (Oncogene 1999) 2 3 4 22 58
- CD2AP and Cbl-3/Cbl-c constitute a critical checkpoint in the regulation of ret signal transduction. (PMID: 18753381) Tsui CC … Pierchala BA (The Journal of neuroscience : the official journal of the Society for Neuroscience 2008) 3 4 22 58
- Molecular cloning and characterization of a novel cbl-family gene, cbl-c. (PMID: 10571044) Kim M … Yamamoto T (Gene 1999) 2 3 4 58
- Structural flexibility regulates phosphopeptide-binding activity of the tyrosine kinase binding domain of Cbl-c. (PMID: 22888118) Takeshita K … Nakagawa A (Journal of biochemistry 2012) 3 4 58
- Cbl-c ubiquitin ligase activity is increased via the interaction of its RING finger domain with a LIM domain of the paxillin homolog, Hic 5. (PMID: 23145173) Ryan PE … Lipkowitz S (PloS one 2012) 3 4 58
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Sources for CBLC Gene
- (1) GeneCards
- (2) HGNC
- (3) EntrezGene
- (4) Swiss-Prot
- (5) Ensembl
- (6) OMIM
- (7) GeneLoc
- (8) Gene Wiki
- (9) UCSC
- (10) PhosphoSitePlus
- (11) GO
- (12) TrEMBL
- (13) InterPro
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