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CBLC Cbl proto-oncogene C [ Homo sapiens (human) ]

Gene ID: 23624, updated on 2-Nov-2024

Summary

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Official Symbol
CBLCprovided by HGNC
Official Full Name
Cbl proto-oncogene Cprovided by HGNC
Primary source
HGNC:HGNC:15961
See related
Ensembl:ENSG00000142273 MIM:608453; AllianceGenome:HGNC:15961
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CBL-3; RNF57; CBL-SL
Summary
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]
Expression
Biased expression in duodenum (RPKM 19.1), small intestine (RPKM 14.9) and 11 other tissues See more
Orthologs
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Genomic context

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See CBLC in Genome Data Viewer
Location:
19q13.32
Exon count:
13
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (44777869..44800652)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (47602623..47625402)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (45281126..45303909)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:45261851-45262500 Neighboring gene BCL3 transcription coactivator Neighboring gene uncharacterized LOC124900431 Neighboring gene microRNA 8085 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14771 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14772 Neighboring gene MPRA-validated peak3507 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14773 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:45315534-45316080 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:45316732-45317264 Neighboring gene Sharpr-MPRA regulatory region 5395 Neighboring gene basal cell adhesion molecule (Lutheran blood group) Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10740 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10741 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10742 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10743 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:45351264-45352246 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:45353716-45354627 Neighboring gene nectin cell adhesion molecule 2 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:45382143-45382992 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:45382993-45383842 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:45383843-45384692 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:45388007-45388506 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:45388826-45389326

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. A third human CBL gene is on chromosome 19. Ollendorff V, et al. Int J Oncol, 1998 Dec. PMID 9824625
  2. Comparative genomic organization of the cbl genes. Nau MM, et al. Gene, 2003 Apr 10. PMID 12711395
  3. Clinical presentation and outcome in a series of 88 patients with the cblC defect. Fischer S, et al. J Inherit Metab Dis, 2014 Sep. PMID 24599607
  4. Pathogenic mutations differentially affect the catalytic activities of the human B12-processing chaperone CblC and increase futile redox cycling. Gherasim C, et al. J Biol Chem, 2015 May 1. PMID 25809485, Free PMC Article
  5. The Ubiquitin Ligase CBLC Maintains the Network Organization of the Golgi Apparatus. Lee WY, et al. PLoS One, 2015. PMID 26393512, Free PMC Article

See all (48) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. CBLC inhibits the proliferation and metastasis of breast cancer cells via ubiquitination and degradation of CTTN.
    Title: CBLC inhibits the proliferation and metastasis of breast cancer cells via ubiquitination and degradation of CTTN.
  2. Stabilization of AURKA by the E3 ubiquitin ligase CBLC in lung adenocarcinoma.
    Title: Stabilization of AURKA by the E3 ubiquitin ligase CBLC in lung adenocarcinoma.
  3. Cbl-c is the most recently identified Cbl protein and is expressed exclusively in epithelial cells. Data mining reveals Cbl-c mutations associated with solid tumors. Subsequent cell-based analysis demonstrates a loss of E3 function and dominant negative effects for one of these mutations.
    Title: Loss of function Cbl-c mutations in solid tumors.
  4. ectopic expression of CBLC enhanced the activation of EGFR and downstream ERK1/2 signaling after ligand stimulation by competing with CBL for EGFR binding..
    Title: Upregulation of E3 Ubiquitin Ligase CBLC Enhances EGFR Dysregulation and Signaling in Lung Adenocarcinoma.
  5. Methylmalonic aciduria with homocystinuria cblC is a multisystemic metabolic disease affecting cobalamin metabolism. The presence of retinal alterations in cblC is a common feature and it is reported to develop more frequently and into a more severe form in the early-onset phenotype, suggesting to some extent a correlation with the biochemical phenotype
    Title: Optical coherence tomography morphology and evolution in cblC disease-related maculopathy in a case series of very young patients.
  6. Data suggest that ubiquitin ligase CBLC controls mostly network organization of the Golgi Apparatus.
    Title: The Ubiquitin Ligase CBLC Maintains the Network Organization of the Golgi Apparatus.
  7. Silencing of CBLC causes increased sensitivity to PARP1 inhibitor olaparib in breast cancer cell line models and that defective homologous recombination (HR) DNA repair is the likely cause.
    Title: Complementary genetic screens identify the E3 ubiquitin ligase CBLC, as a modifier of PARP inhibitor sensitivity.
  8. the effects of two pathogenic missense mutations on the the catalytic activities of the human B12-processing chaperone CblC
    Title: Pathogenic mutations differentially affect the catalytic activities of the human B12-processing chaperone CblC and increase futile redox cycling.
  9. This retrospective multicentre study evaluates clinical, biochemical and genetic findings in 88 cblC patients
    Title: Clinical presentation and outcome in a series of 88 patients with the cblC defect.
  10. The ubiquitin ligase activity of Cbl-c by the direct interaction of the LIM zinc coordinating domain of Hic5 is demonstrated.
    Title: 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.
Submit: New GeneRIF Correction See all GeneRIFs (15)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables SH3 domain binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables calcium ion binding IEA
Inferred from Electronic Annotation
more info
  
enables epidermal growth factor receptor binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables phosphotyrosine residue binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables receptor tyrosine kinase binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables ubiquitin protein ligase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables ubiquitin protein ligase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables zinc ion binding TAS
Traceable Author Statement
more info
 PubMed 
Process Evidence Code Pubs
involved_in cell surface receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of MAP kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of epidermal growth factor receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in negative regulation of epidermal growth factor receptor signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of epidermal growth factor-activated receptor activity IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of neuron apoptotic process IEA
Inferred from Electronic Annotation
more info
  
involved_in protein stabilization IEA
Inferred from Electronic Annotation
more info
  
involved_in protein ubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in response to glial cell derived neurotrophic factor IEA
Inferred from Electronic Annotation
more info
  
involved_in signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in ubiquitin-dependent protein catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
is_active_in membrane raft IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
E3 ubiquitin-protein ligase CBL-C
Names
Cas-Br-M (murine) ecotropic retroviral transforming sequence c
Cas-Br-M (murine) ectropic retroviral transforming sequence c
Cbl proto-oncogene C, E3 ubiquitin protein ligase
Cbl proto-oncogene, E3 ubiquitin protein ligase C
RING finger protein 57
RING-type E3 ubiquitin transferase CBL-C
SH3-binding protein CBL-3
SH3-binding protein CBL-C
signal transduction protein CBL-C
NP_001124324.1
NP_036248.3
XP_005258753.1
XP_011524990.1
XP_011524991.1
XP_011524992.1
XP_047294507.1
XP_047294508.1
XP_054176393.1
XP_054176394.1
XP_054176395.1
XP_054176396.1
XP_054176397.1
XP_054176398.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_054718.1 RefSeqGene

    Range
    5036..27798
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_1161

mRNA and Protein(s)

  1. NM_001130852.1 → NP_001124324.1  E3 ubiquitin-protein ligase CBL-C isoform 2

    See identical proteins and their annotated locations for NP_001124324.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) omits an in-frame coding exon compared to variant 1, resulting in a shorter protein (isoform 2).
    Source sequence(s)
    AF117647, BC028915, BF835530
    Consensus CDS
    CCDS46109.1
    UniProtKB/Swiss-Prot
    Q9ULV8
    Related
    ENSP00000340250.4, ENST00000341505.4
    Conserved Domains (3) summary
    cd09920
    Location:226 → 331
    SH2_Cbl-b_TKB; Src homology 2 (SH2) domain found in the Cbl-b TKB domain
    pfam02262
    Location:16 → 145
    Cbl_N; CBL proto-oncogene N-terminal domain 1
    pfam02761
    Location:149 → 232
    Cbl_N2; CBL proto-oncogene N-terminus, EF hand-like domain

  2. NM_012116.4 → NP_036248.3  E3 ubiquitin-protein ligase CBL-C isoform 1

    See identical proteins and their annotated locations for NP_036248.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes protein isoform 1.
    Source sequence(s)
    AC092066, AF117646, BC028915
    Consensus CDS
    CCDS12643.1
    UniProtKB/Swiss-Prot
    Q8N1E5, Q9ULV8, Q9Y5Z2, Q9Y5Z3
    Related
    ENSP00000494162.1, ENST00000647358.2
    Conserved Domains (4) summary
    cd09920
    Location:226 → 322
    SH2_Cbl-b_TKB; Src homology 2 (SH2) domain found in the Cbl-b TKB domain
    cd00162
    Location:351 → 393
    RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...
    pfam02262
    Location:16 → 145
    Cbl_N; CBL proto-oncogene N-terminal domain 1
    pfam02761
    Location:149 → 232
    Cbl_N2; CBL proto-oncogene N-terminus, EF hand-like domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

    Range
    44777869..44800652
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011526689.3 → XP_011524991.1  E3 ubiquitin-protein ligase CBL-C isoform X2

    Conserved Domains (3) summary
    cd09920
    Location:226 → 331
    SH2_Cbl-b_TKB; Src homology 2 (SH2) domain found in the Cbl-b TKB domain
    pfam02262
    Location:16 → 145
    Cbl_N; CBL proto-oncogene N-terminal domain 1
    pfam02761
    Location:149 → 232
    Cbl_N2; CBL proto-oncogene N-terminus, EF hand-like domain

  2. XM_011526688.3 → XP_011524990.1  E3 ubiquitin-protein ligase CBL-C isoform X1

    Conserved Domains (4) summary
    cd09920
    Location:226 → 322
    SH2_Cbl-b_TKB; Src homology 2 (SH2) domain found in the Cbl-b TKB domain
    cd00162
    Location:351 → 393
    RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...
    pfam02262
    Location:16 → 145
    Cbl_N; CBL proto-oncogene N-terminal domain 1
    pfam02761
    Location:149 → 232
    Cbl_N2; CBL proto-oncogene N-terminus, EF hand-like domain

  3. XM_005258696.4 → XP_005258753.1  E3 ubiquitin-protein ligase CBL-C isoform X3

    Conserved Domains (4) summary
    cd09920
    Location:226 → 322
    SH2_Cbl-b_TKB; Src homology 2 (SH2) domain found in the Cbl-b TKB domain
    cd00162
    Location:351 → 393
    RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...
    pfam02262
    Location:16 → 145
    Cbl_N; CBL proto-oncogene N-terminal domain 1
    pfam02761
    Location:149 → 232
    Cbl_N2; CBL proto-oncogene N-terminus, EF hand-like domain

  4. XM_011526690.3 → XP_011524992.1  E3 ubiquitin-protein ligase CBL-C isoform X5

    Conserved Domains (2) summary
    pfam02262
    Location:16 → 145
    Cbl_N; CBL proto-oncogene N-terminal domain 1
    pfam02761
    Location:149 → 219
    Cbl_N2; CBL proto-oncogene N-terminus, EF hand-like domain

  5. XM_047438552.1 → XP_047294508.1  E3 ubiquitin-protein ligase CBL-C isoform X6

  6. XM_047438551.1 → XP_047294507.1  E3 ubiquitin-protein ligase CBL-C isoform X4

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060943.1 Alternate T2T-CHM13v2.0

    Range
    47602623..47625402
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054320419.1 → XP_054176394.1  E3 ubiquitin-protein ligase CBL-C isoform X2

  2. XM_054320418.1 → XP_054176393.1  E3 ubiquitin-protein ligase CBL-C isoform X1

  3. XM_054320420.1 → XP_054176395.1  E3 ubiquitin-protein ligase CBL-C isoform X3

  4. XM_054320422.1 → XP_054176397.1  E3 ubiquitin-protein ligase CBL-C isoform X5

  5. XM_054320423.1 → XP_054176398.1  E3 ubiquitin-protein ligase CBL-C isoform X6

  6. XM_054320421.1 → XP_054176396.1  E3 ubiquitin-protein ligase CBL-C isoform X4

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9ULV8.3 GenPept UniProtKB/Swiss-Prot:Q9ULV8

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