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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
    mouse all
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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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