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Aliases for CBLC Gene

Aliases for CBLC Gene

  • Cbl Proto-Oncogene C, E3 Ubiquitin Protein Ligase 2 3
  • Cas-Br-M (Murine) Ecotropic Retroviral Transforming Sequence C 2 3
  • Cas-Br-M (Murine) Ectropic Retroviral Transforming Sequence C 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
  • 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, E3 Ubiquitin Protein Ligase) is a Protein Coding gene. Among its related pathways are Pathways in cancer and Endocytosis. 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.

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

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

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
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

Proteomics data for CBLC Gene at MOPED

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

ENSEMBL proteins:
REFSEQ proteins:

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:0004871 signal transducer activity IEA --
GO:0005154 epidermal growth factor receptor binding IDA 10362357
GO:0005509 calcium ion binding IEA --
GO:0005515 protein binding --
genes like me logo Genes that share ontologies with CBLC: view

Phenotypes for CBLC Gene

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

Animal Model Products

miRNA for CBLC Gene

miRTarBase miRNAs that target CBLC

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for CBLC

In Situ Assay Products

Flow Cytometry Products

No data available for Animal Models , Transcription Factor Targets and HOMER Transcription for CBLC Gene

Localization for CBLC Gene

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for CBLC Gene COMPARTMENTS Subcellular localization image for CBLC gene
Compartment Confidence
extracellular 5
nucleus 2
lysosome 1
vacuole 1

Gene Ontology (GO) - Cellular Components for CBLC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
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

PCR Array Products

  • Pathway & Disease-focused RT² Profiler PCR Arrays

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:0042059 negative regulation of epidermal growth factor receptor signaling pathway IDA 10362357
GO:0042787 protein ubiquitination involved in ubiquitin-dependent protein catabolic process 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
Adenosine monophosphate Approved Nutra 0
Adenosine triphosphate Approved Nutra 0
Diphosphate Experimental Pharma 0
Calcium Nutra 0
tyrosine Nutra 547

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

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
phosphoric acid
  • Acide phosphorique (FRENCH)
  • Acido fosforico [Italian]
  • Acidum phosphoricum
  • Diphosphate tetrasodium
  • Fosforzuuroplossingen [Dutch]
7664-38-2
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:

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for CBLC

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 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).

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

In Situ Assay 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
cow
(Bos Taurus)
Mammalia CBLC 35
  • 86.21 (n)
  • 83.64 (a)
CBLC 36
  • 74 (a)
OneToOne
dog
(Canis familiaris)
Mammalia CBLC 35
  • 83.57 (n)
  • 79.58 (a)
CBLC 36
  • 71 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Cblc 35
  • 80.02 (n)
  • 75.69 (a)
Cblc 16
Cblc 36
  • 67 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia CBLC 35
  • 90.19 (n)
  • 88.61 (a)
CBLC 36
  • 94 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Cblc 35
  • 80.22 (n)
  • 77.14 (a)
oppossum
(Monodelphis domestica)
Mammalia CBLC 36
  • 57 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CBLC 36
  • 31 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia CBLC 36
  • 55 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii CBLC 36
  • 40 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta Cbl 36
  • 22 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea sli-1 36
  • 32 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 47 (a)
OneToMany
Species with no ortholog for CBLC:
  • 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 MAF
rs748913 -- 44,800,321(-) TCTGC(C/G)CCTCT intron-variant, utr-variant-3-prime
rs899087 -- 44,791,300(-) gggac(A/G)gagcc intron-variant
rs1079419 -- 44,778,981(-) GGGTG(C/T)CCAAG intron-variant
rs1382090 -- 44,784,417(-) CCTAC(C/G/T)AGAAT intron-variant, missense, reference, nc-transcript-variant
rs1809335 -- 44,780,734(-) gcact(C/T)tggga intron-variant

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

Variant ID Type Subtype PubMed ID
nsv912116 CNV Loss 21882294
nsv833841 CNV Loss 17160897
nsv2506 CNV Loss 18451855
dgv3945n71 CNV Gain 21882294

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

HapMap Linkage Disequilibrium report
CBLC
Human Gene Mutation Database (HGMD)
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
genes like me logo Genes that share disorders with CBLC: view

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 23 67
  2. Mutations of e3 ubiquitin ligase cbl family members constitute a novel common pathogenic lesion in myeloid malignancies. (PMID: 19901108) Makishima H. … Maciejewski J.P. (J. Clin. Oncol. 2009) 23 67
  3. 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) 23 67
  4. Regulation of peripheral T cell tolerance by the E3 ubiquitin ligase Cbl-b. (PMID: 17391982) Loeser S. … Penninger J.M. (Semin. Immunol. 2007) 23 67
  5. EGFRvIII undergoes activation-dependent downregulation mediated by the Cbl proteins. (PMID: 16702950) Davies G.C. … Lipkowitz S. (Oncogene 2006) 23 67

Products for CBLC Gene

Sources for CBLC Gene

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