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Aliases for CBLB Gene

Aliases for CBLB Gene

  • Cbl Proto-Oncogene B 2 3
  • Cbl Proto-Oncogene B, E3 Ubiquitin Protein Ligase 2 3 5
  • Cas-Br-M (Murine) Ecotropic Retroviral Transforming Sequence B 2 3
  • Casitas B-Lineage Lymphoma Proto-Oncogene B 3 4
  • Signal Transduction Protein CBL-B 3 4
  • SH3-Binding Protein CBL-B 3 4
  • RING Finger Protein 56 3 4
  • RNF56 3 4
  • Cas-Br-M (Murine) Ectropic Retroviral Transforming Sequence B 2
  • Cbl Proto-Oncogene, E3 Ubiquitin Protein Ligase B 3
  • EC 6.3.2.- 4
  • Nbla00127 3
  • EC 6.3.2 63
  • Cbl-B 3

External Ids for CBLB Gene

Previous GeneCards Identifiers for CBLB Gene

  • GC03M102013
  • GC03M104895
  • GC03M106658
  • GC03M106698
  • GC03M106859
  • GC03M105374
  • GC03M102751

Summaries for CBLB Gene

GeneCards Summary for CBLB Gene

CBLB (Cbl Proto-Oncogene B) is a Protein Coding gene. Among its related pathways are Bacterial invasion of epithelial cells and Antigen processing- Ubiquitination and Proteasome degradation. GO annotations related to this gene include calcium ion binding and ubiquitin-protein transferase activity. An important paralog of this gene is CBLC.

UniProtKB/Swiss-Prot for CBLB Gene

  • E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome. Negatively regulates TCR (T-cell receptor), BCR (B-cell receptor) and FCER1 (high affinity immunoglobulin epsilon receptor) signal transduction pathways. In naive T-cells, inhibits VAV1 activation upon TCR engagement and imposes a requirement for CD28 costimulation for proliferation and IL-2 production. Also acts by promoting PIK3R1/p85 ubiquitination, which impairs its recruitment to the TCR and subsequent activation. In activated T-cells, inhibits PLCG1 activation and calcium mobilization upon restimulation and promotes anergy. In B-cells, acts by ubiquitinating SYK and promoting its proteasomal degradation. Slightly promotes SRC ubiquitination. May be involved in EGFR ubiquitination and internalization. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3.

Gene Wiki entry for CBLB Gene

No data available for Entrez Gene Summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CBLB Gene

Genomics for CBLB Gene

Regulatory Elements for CBLB Gene

Enhancers for CBLB Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around CBLB on UCSC Golden Path with GeneCards custom track

Genomic Location for CBLB Gene

Chromosome:
3
Start:
105,655,461 bp from pter
End:
105,869,552 bp from pter
Size:
214,092 bases
Orientation:
Minus strand

Genomic View for CBLB Gene

Genes around CBLB on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for CBLB Gene

Proteins for CBLB Gene

  • Protein details for CBLB Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q13191-CBLB_HUMAN
    Recommended name:
    E3 ubiquitin-protein ligase CBL-B
    Protein Accession:
    Q13191
    Secondary Accessions:
    • A8K9S7
    • B7WNM4
    • Q13192
    • Q13193
    • Q3LIC0
    • Q63Z43
    • Q8IVC5

    Protein attributes for CBLB Gene

    Size:
    982 amino acids
    Molecular mass:
    109450 Da
    Quaternary structure:
    • Interacts with SH3 domain-containing proteins LCK, CRK and SORBS1. Interacts with LCP2 and ZAP70. May interact with CBL. Interacts with SH3 domain-containing proteins VAV1, FYN, FGR, PLCG1, GRB2, CRKL, PIK3R1 and SH3KBP1/CIN85. Identified in heterotrimeric complexes with SH3KBP1/CIN85, CD2AP and ARHGEF7, where one CBLB peptide binds two copies of the other protein. Interacts with poly-ubiquitinated proteins. Dimerization is required for the binding of poly-ubiquitin, but not for the binding of mono-ubiquitin. Interacts with EGFR (phosphorylated).
    Miscellaneous:
    • This protein has one functional calcium-binding site.
    SequenceCaution:
    • Sequence=BAE45748.1; Type=Erroneous termination; Positions=904; Note=Translated as Arg.; Evidence={ECO:0000305}; Sequence=CAH56175.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for CBLB Gene

    Alternative splice isoforms for CBLB Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CBLB Gene

Proteomics data for CBLB Gene at MOPED

Post-translational modifications for CBLB Gene

  • Auto-ubiquitinated upon EGF-mediated cell activation or upon T-cell costimulation by CD28; which promotes proteasomal degradation.
  • Phosphorylated on tyrosine and serine residues upon TCR or BCR activation, and upon various types of cell stimulation.
  • Ubiquitination at Lys 97 and Lys 516
  • Modification sites at PhosphoSitePlus

Domains & Families for CBLB Gene

Gene Families for CBLB Gene

Graphical View of Domain Structure for InterPro Entry

Q13191

UniProtKB/Swiss-Prot:

CBLB_HUMAN :
  • 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.
  • Contains 1 RING-type zinc finger.
Domain:
  • 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.
  • The UBA domain interacts with poly-ubiquitinated proteins.
  • Contains 1 Cbl-PTB (Cbl-type phosphotyrosine-binding) domain.
  • Contains 1 UBA domain.
Similarity:
  • Contains 1 RING-type zinc finger.
genes like me logo Genes that share domains with CBLB: view

Function for CBLB Gene

Molecular function for CBLB Gene

GENATLAS Biochemistry:
protein (109kDa),homolog to the proto-oncogene v-cbl,expressed in a variety of normal tissues,potentially interacting with signal transduction molecules,regulating in mouse,the CD28 dependence of T cell activation and putatively contributing to autoimmune diseases
UniProtKB/Swiss-Prot Function:
E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome. Negatively regulates TCR (T-cell receptor), BCR (B-cell receptor) and FCER1 (high affinity immunoglobulin epsilon receptor) signal transduction pathways. In naive T-cells, inhibits VAV1 activation upon TCR engagement and imposes a requirement for CD28 costimulation for proliferation and IL-2 production. Also acts by promoting PIK3R1/p85 ubiquitination, which impairs its recruitment to the TCR and subsequent activation. In activated T-cells, inhibits PLCG1 activation and calcium mobilization upon restimulation and promotes anergy. In B-cells, acts by ubiquitinating SYK and promoting its proteasomal degradation. Slightly promotes SRC ubiquitination. May be involved in EGFR ubiquitination and internalization. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3.

Enzyme Numbers (IUBMB) for CBLB Gene

Gene Ontology (GO) - Molecular Function for CBLB Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001784 phosphotyrosine binding IEA --
GO:0004842 ubiquitin-protein transferase activity IEA,TAS --
GO:0005509 calcium ion binding IEA --
GO:0005515 protein binding IEA,IPI 10022120
GO:0016874 ligase activity IEA --
genes like me logo Genes that share ontologies with CBLB: view
genes like me logo Genes that share phenotypes with CBLB: view

Animal Models for CBLB Gene

MGI Knock Outs for CBLB:

Animal Model Products

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

Localization for CBLB Gene

Subcellular locations from UniProtKB/Swiss-Prot for CBLB Gene

Cytoplasm. Note=Upon EGF stimulation, associates with endocytic vesicles.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for CBLB Gene COMPARTMENTS Subcellular localization image for CBLB gene
Compartment Confidence
cytosol 5
nucleus 5
plasma membrane 4

Gene Ontology (GO) - Cellular Components for CBLB Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IDA --
genes like me logo Genes that share ontologies with CBLB: view

Pathways & Interactions for CBLB Gene

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

UniProtKB/Swiss-Prot Q13191-CBLB_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

SIGNOR curated interactions for CBLB Gene

Inactivates:
Is inactivated by:

Gene Ontology (GO) - Biological Process for CBLB Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006607 NLS-bearing protein import into nucleus TAS 7784085
GO:0009629 response to gravity IEA --
genes like me logo Genes that share ontologies with CBLB: view

Drugs & Compounds for CBLB Gene

(4) Drugs for CBLB Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
calcium Nutra 0

(2) Additional Compounds for CBLB Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with CBLB: view

Transcripts for CBLB Gene

Unigene Clusters for CBLB Gene

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

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

ExUns: 1 ^ 2a · 2b · 2c · 2d · 2e ^ 3a · 3b ^ 4a · 4b ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13a · 13b ^ 14 ^ 15a · 15b ^ 16 ^ 17 ^ 18a ·
SP1: - -
SP2: - -
SP3: - -
SP4: - - - - - - - - - - - - - - - -
SP5: -
SP6: - -
SP7:
SP8: -
SP9: - - - - -
SP10:

ExUns: 18b ^ 19a · 19b ^ 20 ^ 21a · 21b ^ 22
SP1: - -
SP2:
SP3:
SP4: - -
SP5: - - -
SP6:
SP7: - - -
SP8:
SP9:
SP10:

Relevant External Links for CBLB Gene

GeneLoc Exon Structure for
CBLB
ECgene alternative splicing isoforms for
CBLB

Expression for CBLB Gene

mRNA expression in normal human tissues for CBLB Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for CBLB Gene

This gene is overexpressed in Peripheral blood mononuclear cells (23.7), CD8 Tcells (21.3), and Adrenal (12.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for CBLB Gene



SOURCE GeneReport for Unigene cluster for CBLB Gene Hs.430589

mRNA Expression by UniProt/SwissProt for CBLB Gene

Q13191-CBLB_HUMAN
Tissue specificity: Expressed in placenta, heart, lung, kidney, spleen, ovary and testis, as well as fetal brain and liver and hematopoietic cell lines, but not in adult brain, liver, pancreas, salivary gland, or skeletal muscle. Present in lymphocytes (at protein level).
genes like me logo Genes that share expression patterns with CBLB: view

Protein tissue co-expression partners for CBLB Gene

- Elite partner

Primer Products

No data available for mRNA differential expression in normal tissues for CBLB Gene

Orthologs for CBLB Gene

This gene was present in the common ancestor of animals.

Orthologs for CBLB Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia CBLB 35
  • 91.92 (n)
  • 97.25 (a)
CBLB 36
  • 97 (a)
OneToOne
dog
(Canis familiaris)
Mammalia CBLB 35
  • 91.48 (n)
  • 97.15 (a)
CBLB 36
  • 97 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Cblb 35
  • 87.62 (n)
  • 94.88 (a)
Cblb 16
Cblb 36
  • 96 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia CBLB 35
  • 99.56 (n)
  • 99.9 (a)
CBLB 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Cblb 35
  • 87.76 (n)
  • 95.2 (a)
oppossum
(Monodelphis domestica)
Mammalia CBLB 36
  • 92 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CBLB 36
  • 90 (a)
OneToOne
chicken
(Gallus gallus)
Aves CBLB 35
  • 79.87 (n)
  • 87.04 (a)
CBLB 36
  • 82 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia CBLB 36
  • 83 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia cblb 35
  • 73.77 (n)
  • 78.9 (a)
zebrafish
(Danio rerio)
Actinopterygii cblb 35
  • 65.17 (n)
  • 70.6 (a)
cblb 36
  • 69 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta Cbl 37
  • 72 (a)
Cbl 36
  • 41 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea sli-1 37
  • 56 (a)
sli-1 36
  • 42 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 66 (a)
OneToMany
Species with no ortholog for CBLB:
  • 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)
  • 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)
  • wheat (Triticum aestivum)

Evolution for CBLB Gene

ENSEMBL:
Gene Tree for CBLB (if available)
TreeFam:
Gene Tree for CBLB (if available)

Paralogs for CBLB Gene

Paralogs for CBLB Gene

(3) SIMAP similar genes for CBLB Gene using alignment to 7 proteins:

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

Variants for CBLB Gene

Sequence variations from dbSNP and Humsavar for CBLB Gene

SNP ID Clin Chr 03 pos Sequence Context AA Info Type
rs17853100 - 105,702,302(+) GGTCT(C/T)TGGAA nc-transcript-variant, reference, missense
rs35835913 - 105,670,275(-) AAACT(A/G)ACAGA nc-transcript-variant, downstream-variant-500B, reference, missense
rs726443 -- 105,719,476(+) TCCTA(C/T)AAGAT intron-variant
rs726444 -- 105,719,694(+) actta(C/T)tatac intron-variant
rs1020327 -- 105,715,322(-) GTGAT(A/T)CTAAC intron-variant

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

Variant ID Type Subtype PubMed ID
nsv525071 CNV Gain 19592680
nsv829651 CNV Loss 17160897
dgv5228n71 CNV Loss 21882294
nsv877309 CNV Loss 21882294
nsv877310 CNV Loss 21882294
nsv877311 CNV Loss 21882294
nsv511097 CNV Complex 20534489
nsv508234 CNV Loss 20534489
nsv877312 CNV Loss 21882294

Variation tolerance for CBLB Gene

Residual Variation Intolerance Score: 5.51% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.88; 59.04% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for CBLB Gene

Human Gene Mutation Database (HGMD)
CBLB

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

Disorders for CBLB Gene

Relevant External Links for CBLB

Genetic Association Database (GAD)
CBLB
Human Genome Epidemiology (HuGE) Navigator
CBLB
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
CBLB

No disorders were found for CBLB Gene.

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

Publications for CBLB Gene

  1. Cloning and characterization of cbl-b: a SH3 binding protein with homology to the c-cbl proto-oncogene. (PMID: 7784085) Keane M.M. … Lipkowitz S. (Oncogene 1995) 2 3 4 23 67
  2. [Expression of c-Cbl, Cbl-b, and epidermal growth factor receptor in gastric carcinoma and their clinical significance]. (PMID: 20038312) Dong Q. … Li L.L. (Chin J Cancer 2010) 3 23
  3. Cbl-b and itch: key regulators of peripheral T-cell tolerance. (PMID: 20395198) Venuprasad K. (Cancer Res. 2010) 3 23
  4. Novel insights into the mechanisms of CIN85 SH3 domains binding to Cbl proteins: solution-based investigations and in vivo implications. (PMID: 19268472) Ababou A. … Ladbury J.E. (J. Mol. Biol. 2009) 3 23
  5. Cbl negatively regulates JNK activation and cell death. (PMID: 19546888) Sproul A.A. … Greene L.A. (Cell Res. 2009) 3 23

Products for CBLB Gene

Sources for CBLB Gene

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