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 ... See more...

Aliases for CBLC Gene

Aliases for CBLC Gene

  • Cbl Proto-Oncogene C 2 3 5
  • RNF57 2 3 4
  • 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
  • E3 Ubiquitin-Protein Ligase 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
  • CBL-SL 2 3
  • CBL-3 2 3
  • Cbl Proto-Oncogene, E3 Ubiquitin Protein Ligase C 3
  • EC 2.3.2.27 4
  • CBLC 5
  • CBL3 4

External Ids for CBLC Gene

Previous GeneCards Identifiers for CBLC Gene

  • GC19P045925
  • GC19P045672
  • GC19P049957
  • GC19P049972
  • GC19P045281
  • GC19P041713

Summaries for CBLC Gene

Entrez Gene Summary 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]

CIViC Summary for CBLC Gene

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 ErbB signaling pathway. Gene Ontology (GO) annotations related to this gene include calcium ion binding and ubiquitin-protein transferase activity. An important paralog of this gene is CBL.

UniProtKB/Swiss-Prot Summary 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.

Gene Wiki entry for CBLC Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CBLC Gene

Genomics for CBLC Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for CBLC Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH19J044772 Promoter/Enhancer 2 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 613.7 -1.9 -1880 7.3 GATAD2A REST IKZF1 ZNF7 ZSCAN4 RBFOX2 ZNF740 SP1 POLR2A SOX6 CBLC CEACAM19 BCAM ENSG00000236807 lnc-BCL3-4 BCL3
GH19J044740 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 5.4 -28.1 -28085 18.9 ARHGAP35 CEBPG SP1 HNRNPL CREB1 GATAD2A YBX1 PRDM10 ZNF629 REST BCL3 lnc-CEACAM20-2 ZNF45 ZNF224 ZNF155 ZNF180 ZNF284 ZNF225 ZNF234 CLASRP
GH19J045418 Promoter/Enhancer 1.3 Ensembl ENCODE dbSUPER 4.9 +642.0 641995 1.9 SP1 POLR2A BACH1 STAT3 ZNF143 TCF12 IKZF2 RCOR1 TRIM22 PKNOX1 AB372689-001 RF00017-3005 POLR1G CBLC lnc-PPP1R13L-3 PPP1R13L FOSB ERCC1 lnc-ERCC1-1
GH19J044716 Enhancer 0.4 dbSUPER 12.8 -61.1 -61093 0.2 CEBPB HLF CEBPG ENSG00000266903 BCL3 ENSG00000236807 ENSG00000253027 CBLC LOC107985305 CEACAM16
GH19J044781 Enhancer 0.4 Ensembl dbSUPER 5 +3.0 3046 0.6 MGA CBLC ENSG00000285128 BCAM
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CBLC on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CBLC

Top Transcription factor binding sites by QIAGEN in the CBLC gene promoter:
  • AP-2gamma
  • AP-4
  • GCNF
  • GCNF-1
  • GCNF-2
  • HEN1
  • HTF
  • NRF-2
  • p300
  • XBP-1

Genomic Locations for CBLC Gene

Genomic Locations for CBLC Gene
chr19:44,777,855-44,800,652
(GRCh38/hg38)
Size:
22,798 bases
Orientation:
Plus strand
chr19:45,281,126-45,303,903
(GRCh37/hg19)
Size:
22,778 bases
Orientation:
Plus strand

Genomic View for CBLC Gene

Genes around CBLC on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CBLC Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CBLC Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene 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
    Secondary Accessions:
    • 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

    Alternative splice isoforms for CBLC Gene

    UniProtKB/Swiss-Prot:

neXtProt entry 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

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:
  • SH3-binding protein CBL-C (CBLC_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9ULV8

UniProtKB/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.
genes like me logo Genes that share domains with CBLC: view

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:
Reaction=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.; EC=2.3.2.27; Evidence={ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:20525694, ECO:0000269|PubMed:23145173};.
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

Gene Ontology (GO) - Molecular Function for CBLC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001784 phosphotyrosine residue binding IEA,IDA 14661060
GO:0004842 ubiquitin-protein transferase activity IEA --
GO:0005154 epidermal growth factor receptor binding IDA 10362357
GO:0005509 calcium ion binding IEA --
GO:0008270 zinc ion binding TAS 10362357
genes like me logo Genes that share ontologies with CBLC: view
genes like me logo Genes that share phenotypes with CBLC: view

Animal Models for CBLC Gene

MGI Knock Outs for CBLC:
  • Cblc Cblc<tm1Pngr>

Animal Model Products

CRISPR Products

miRNA for CBLC Gene

miRTarBase miRNAs that target CBLC

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CBLC

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for CBLC Gene

Localization for CBLC Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CBLC gene
Compartment Confidence
plasma membrane 3
nucleus 3
cytosol 2
extracellular 1
endosome 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for CBLC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane IBA 21873635
GO:0045121 membrane raft IBA 21873635
genes like me logo Genes that share ontologies with CBLC: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for CBLC Gene

Pathways & Interactions for CBLC Gene

genes like me logo Genes that share pathways with CBLC: view

Pathways by source for CBLC Gene

SIGNOR curated interactions for CBLC Gene

Inactivates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process 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 21873635
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 IEA,IDA 14661060
genes like me logo Genes that share ontologies with CBLC: view

Drugs & Compounds for CBLC Gene

(5) Drugs for CBLC Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Phosphoric acid Approved Pharma 0
Adenosine monophosphate Approved, Investigational Nutra 0
ATP Investigational Nutra Agonist, Activator, Partial agonist, Antagonist, Full agonist, Gating inhibitor, Pore Blocker, Potentiation 0
Calcium Nutra 6556

(1) Additional Compounds for CBLC Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
pyrophosphate
  • [(ho)2P(O)OP(O)(OH)2]
  • Acide diphosphorique
  • Diphosphorsaeure
  • H4P2O7
  • PYROphosphATE
14000-31-8
genes like me logo Genes that share compounds with CBLC: view

Transcripts for CBLC Gene

mRNA/cDNA for CBLC Gene

2 REFSEQ mRNAs :
5 NCBI additional mRNA sequence :
3 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CBLC

Alternative Splicing Database (ASD) splice patterns (SP) for CBLC Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11
SP1:
SP2: -

Relevant External Links for CBLC Gene

GeneLoc Exon Structure for
CBLC

Expression for CBLC Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE 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).

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CBLC

SOURCE GeneReport for Unigene cluster for CBLC Gene:

Hs.466907

mRNA Expression by UniProt/SwissProt for CBLC Gene:

Q9ULV8-CBLC_HUMAN
Tissue specificity: Ubiquitous.

Evidence on tissue expression from TISSUES for CBLC Gene

  • Skin(4.3)
genes like me logo Genes that share expression patterns with CBLC: view

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.

Orthologs for CBLC Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia CBLC 30 31
  • 90.19 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia CBLC 30 31
  • 86.21 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia CBLC 30 31
  • 83.57 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Cblc 30
  • 80.22 (n)
Mouse
(Mus musculus)
Mammalia Cblc 30 17 31
  • 80.02 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia CBLC 31
  • 57 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia CBLC 31
  • 31 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia CBLC 31
  • 55 (a)
OneToOne
Zebrafish
(Danio rerio)
Actinopterygii CBLC 31
  • 40 (a)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta Cbl 31
  • 22 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea sli-1 31
  • 32 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 47 (a)
OneToMany
Species where no ortholog for CBLC was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium 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 Vase (Ciona intestinalis)
  • 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

Paralogs for CBLC Gene

(2) SIMAP similar genes for CBLC Gene using alignment to 1 proteins:

  • CBLC_HUMAN
genes like me logo Genes that share paralogs with CBLC: view

Variants for CBLC Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CBLC Gene

SNP ID Clinical significance and condition Chr 19 pos Variation AA Info Type
763536 Likely Benign: not provided 44,778,294(+) C/G INTRON_VARIANT
rs3208856 - p.His405Tyr

Additional dbSNP identifiers (rs#s) for CBLC Gene

Structural Variations from Database of Genomic Variants (DGV) for CBLC Gene

Variant ID Type Subtype PubMed ID
nsv2506 CNV deletion 18451855
nsv833841 CNV loss 17160897

Variation tolerance for CBLC Gene

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

Human Gene Mutation Database (HGMD)
CBLC
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CBLC

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CBLC Gene

Disorders for CBLC Gene

No disorders were found for CBLC Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for CBLC Gene

Publications for CBLC Gene

  1. cbl-3: a new mammalian cbl family protein. (PMID: 10362357) Keane MM … Lipkowitz S (Oncogene 1999) 2 3 4 23
  2. 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 23
  3. Molecular cloning and characterization of a novel cbl-family gene, cbl-c. (PMID: 10571044) Kim M … Yamamoto T (Gene 1999) 2 3 4
  4. 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
  5. 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

Products for CBLC Gene

Sources for CBLC Gene