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

Summary

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

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_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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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

EC 2.3.2.27

NP_036248.3

EC 2.3.2.27

XP_005258753.1

EC 2.3.2.27

XP_011524990.1

EC 2.3.2.27

XP_011524991.1

EC 2.3.2.27

XP_011524992.1

EC 2.3.2.27

XP_047294507.1

EC 2.3.2.27

XP_047294508.1

EC 2.3.2.27

XP_054176393.1

EC 2.3.2.27

XP_054176394.1

EC 2.3.2.27

XP_054176395.1

EC 2.3.2.27

XP_054176396.1

EC 2.3.2.27

XP_054176397.1

EC 2.3.2.27

XP_054176398.1

EC 2.3.2.27

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

NG_054718.1 RefSeqGene

Range

5036..27798

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1161

mRNA and Protein(s)

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
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

NC_000019.10 Reference GRCh38.p14 Primary Assembly

Range

44777869..44800652

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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
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
XM_047438552.1 → XP_047294508.1 E3 ubiquitin-protein ligase CBL-C isoform X6
XM_047438551.1 → XP_047294507.1 E3 ubiquitin-protein ligase CBL-C isoform X4