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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
  • 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
  • RNF57 3 4
  • Cbl Proto-Oncogene, E3 Ubiquitin Protein Ligase C 3
  • E3 Ubiquitin-Protein Ligase CBL-C 3
  • EC 6.3.2.- 4
  • CBL-SL 3
  • CBL-3 3
  • 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]

GeneCards Summary for CBLC Gene

CBLC (Cbl Proto-Oncogene C) is a Protein Coding gene. Among its related pathways are EGFR1 Signaling Pathway and Pathways in cancer. 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 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 , fRNAdb sequence ontologies and piRNA Summary for CBLC Gene

Genomics for CBLC Gene

Regulatory Elements for CBLC Gene

Enhancers for CBLC Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH19F044772 1.6 FANTOM5 Ensembl ENCODE 13.8 -2.5 -2474 6.1 MLX ZFP64 ARID4B DMAP1 ZNF48 YY1 FOS MXD4 NFIL3 SMARCA4 CBLC CEACAM19 BCAM ENSG00000236807
GH19F044740 1.6 FANTOM5 ENCODE 5.4 -28.2 -28191 18.7 CREB3L1 FEZF1 YBX1 YY1 ZNF143 ZNF548 ZNF263 SP3 TBX21 MEF2D ZNF155 ZNF45 ZNF180 ZNF224 ZNF234 ZNF284 FBXO46 RELB BCL3 ENSG00000266958
GH19F045418 1.1 Ensembl ENCODE 4.9 +641.8 641840 2.2 HDGF PKNOX1 TBL1XR1 SCRT2 ZNF143 ZNF207 ETV6 CREM EGR2 ZNF263 CD3EAP CBLC PIR48099 MIR6088
GH19F044769 1.3 Ensembl ENCODE 0.4 -7.3 -7261 1.6 HDGF PKNOX1 ARNT MLX ARID4B DMAP1 YY1 SLC30A9 ZNF143 SP3 ZNF155 CBLC ENSG00000236807
GH19F044767 1.3 FANTOM5 Ensembl ENCODE 0.4 -9.8 -9799 1.1 SMARCA5 BCOR CBX3 ZNF280D ZMYM3 USF2 ZBTB40 ZNF664 RAD51 HDAC2 RELB BCL3 CLASRP BLOC1S3 ENSG00000236807 CBLC
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around CBLC on UCSC Golden Path with GeneCards custom track

Promoters for CBLC Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000347254 239 1001 CTCF SAP130 ZFP64 ARID4B DMAP1 ZNF48 RAD21 TEAD3 POLR2A TCF7L2

Genomic Location for CBLC Gene

Chromosome:
19
Start:
44,777,861 bp from pter
End:
44,800,646 bp from pter
Size:
22,786 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

  • Autoubiquitinated when phosphorylated at Tyr-341, enhanced by SRC; suggesting proteasomal degradation.
  • Phosphorylated on multiple tyrosine residues by SRC. Isoform 1, but not isoform 2, is phosphorylated on tyrosines by EGFR.
  • 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

Suggested Antigen Peptide Sequences for CBLC Gene

GenScript: Design optimal peptide antigens:

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.
  • Contains 1 RING-type zinc finger.
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.
  • Contains 1 Cbl-PTB (Cbl-type phosphotyrosine-binding) domain.
Similarity:
  • Contains 1 RING-type zinc finger.
genes like me logo Genes that share domains with CBLC: view

Function for CBLC Gene

Molecular function for CBLC Gene

UniProtKB/Swiss-Prot EnzymeRegulation:
Phosphorylation at Tyr-341 is necessary and sufficient for the activation of E3 activity.
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.

Enzyme Numbers (IUBMB) for CBLC Gene

Gene Ontology (GO) - Molecular Function for CBLC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001784 phosphotyrosine binding IDA 14661060
GO:0004842 ubiquitin-protein transferase activity IEA --
GO:0004871 signal transducer activity IEA --
GO:0005154 epidermal growth factor receptor binding IDA 10362357
GO:0005509 calcium ion binding IEA --
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:

Animal Model Products

miRNA for CBLC Gene

miRTarBase miRNAs that target CBLC

Inhibitory RNA Products

Flow Cytometry Products

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
extracellular 5
nucleus 4
plasma membrane 3
cytosol 2
lysosome 1

Gene Ontology (GO) - Cellular Components for CBLC Gene

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 IDA 23376485
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

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: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
GO:0023051 regulation of signaling IEA --
GO:0042059 negative regulation of epidermal growth factor receptor signaling pathway IDA 10362357
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 Nutra 0
Adenosine triphosphate Approved Nutra 0
calcium Nutra 0

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

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
pyrophosphate
  • (4-)Diphosphoric acid ion
  • (P2O74-)Diphosphate
  • Diphosphate
  • Diphosphoric acid
  • PPi
14000-31-8
genes like me logo Genes that share compounds with CBLC: view

Transcripts for CBLC Gene

Unigene Clusters for CBLC Gene

Cbl proto-oncogene, E3 ubiquitin protein ligase C:
Representative Sequences:

Inhibitory RNA Products

Flow Cytometry Products

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
ECgene alternative splicing isoforms 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).

NURSA nuclear receptor signaling pathways regulating expression of CBLC Gene:

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.
genes like me logo Genes that share expression patterns with CBLC: view

Primer Products

No data available for Protein differential expression in normal tissues , Protein expression and Protein tissue co-expression partners 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 34 35
  • 90.19 (n)
cow
(Bos Taurus)
Mammalia CBLC 34 35
  • 86.21 (n)
dog
(Canis familiaris)
Mammalia CBLC 34 35
  • 83.57 (n)
rat
(Rattus norvegicus)
Mammalia Cblc 34
  • 80.22 (n)
mouse
(Mus musculus)
Mammalia Cblc 34 16 35
  • 80.02 (n)
oppossum
(Monodelphis domestica)
Mammalia CBLC 35
  • 57 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CBLC 35
  • 31 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia CBLC 35
  • 55 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii CBLC 35
  • 40 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta Cbl 35
  • 22 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea sli-1 35
  • 32 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 47 (a)
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)

Paralogs for CBLC Gene

Paralogs for CBLC Gene

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

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

Variants for CBLC Gene

Sequence variations from dbSNP and Humsavar for CBLC Gene

SNP ID Clin Chr 19 pos Sequence Context AA Info Type
rs10401942 -- 44,789,178(+) gttct(C/T)ggtct intron-variant
rs10405573 -- 44,793,077(+) aacct(C/G)ggagg intron-variant
rs10416628 -- 44,782,477(+) TGCAG(A/G)GACAA intron-variant, nc-transcript-variant, reference, synonymous-codon
rs10418198 -- 44,800,054(+) CTAGG(A/G)ACAAG intron-variant
rs10419669 -- 44,794,812(+) acctc(A/G)gggcc intron-variant

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

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

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)

Relevant External Links for CBLC Gene

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

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

Disorders for CBLC Gene

Relevant External Links for CBLC

Atlas of Genetics and Cytogenetics in Oncology and Haematology:
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

  1. cbl-3: a new mammalian cbl family protein. (PMID: 10362357) Keane M.M. … Lipkowitz S. (Oncogene 1999) 2 3 4 22 64
  2. CD2AP and Cbl-3/Cbl-c constitute a critical checkpoint in the regulation of ret signal transduction. (PMID: 18753381) Tsui C.C. … Pierchala B.A. (J. Neurosci. 2008) 3 4 22 64
  3. Molecular cloning and characterization of a novel cbl-family gene, cbl-c. (PMID: 10571044) Kim M. … Yamamoto T. (Gene 1999) 2 3 4 64
  4. Structural flexibility regulates phosphopeptide-binding activity of the tyrosine kinase binding domain of Cbl-c. (PMID: 22888118) Takeshita K. … Nakagawa A. (J. Biochem. 2012) 3 4 64
  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 P.E. … Lipkowitz S. (PLoS ONE 2012) 3 4 64

Products for CBLC Gene

Sources for CBLC Gene

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