Cblb Cbl proto-oncogene B [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Cblbprovided by RGD
Official Full Name: Cbl proto-oncogene Bprovided by RGD
Primary source: RGD:620535
See related: Ensembl:ENSRNOG00000001982 AllianceGenome:RGD:620535
Gene type: protein coding
RefSeq status: PROVISIONAL
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Summary: Enables protein kinase binding activity. Involved in response to gravity; response to hormone; and signal transduction. Located in membrane raft. Used to study type 1 diabetes mellitus. Human ortholog(s) of this gene implicated in lung non-small cell carcinoma and type 1 diabetes mellitus. Orthologous to human CBLB (Cbl proto-oncogene B). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in Spleen (RPKM 154.0), Adrenal (RPKM 135.4) and 9 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 11q21

Exon count:: 20

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	11	NC_086029.1 (62058829..62225904, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	11	NC_051346.1 (48589878..48756940, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	11	NC_005110.4 (51037383..51202761, complement)

Chromosome 11 - NC_086029.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Ubiquitination and functional modification of GluN2B subunit-containing NMDA receptors by Cbl-b in the spinal cord dorsal horn.
Title: Ubiquitination and functional modification of GluN2B subunit-containing NMDA receptors by Cbl-b in the spinal cord dorsal horn.
results suggest that ubiquitin and the E3 ubiquitin ligases c-Cbl and Cbl-b function as neuroimmune modulators in the subacute phase of neuropathic pain after nerve injury.
Title: Increased expression of the Cbl family of E3 ubiquitin ligases decreases Interleukin-2 production in a rat model of peripheral neuropathy.
Under microgravity conditions, elevated ROS may be a crucial mechanotransducer in skeletal muscle cells, regulating muscle mass through Cbl-b expression activated by the ERK-Egr signaling pathway.
Title: Reactive oxygen species upregulate expression of muscle atrophy-associated ubiquitin ligase Cbl-b in rat L6 skeletal muscle cells.
Cbl-b promotes chemotherapy-induced apoptosis in rat basophilic leukemia cells through inhibition of Akt and activation of ERK.
Title: Cbl-b promotes chemotherapy-induced apoptosis in rat basophilic leukemia cells by suppressing PI3K/Akt activation and enhancing MEK/ERK activation.
Results indicate that the Cbl-b-dependent destruction of IRS-1 is a critical dual mediator of both increased protein degradation and reduced protein synthesis observed in unloading-induced muscle atrophy.
Title: Ubiquitin ligase Cbl-b is a negative regulator for insulin-like growth factor 1 signaling during muscle atrophy caused by unloading.
Mechanism for lack of Cbl-b down-regulation may involve the proteasome since blocking proteasomal activity in young T-lymphocytes prevented Cbl-b down regulation while there was no effect in aged T-lymphocytes on Cbl-b expression.
Title: CD28 activation does not down-regulate Cbl-b expression in aged rat T-lymphocytes.
In the KDP rat, a nonsense mutation in the T-cell regulatory gene, Cblb, has been described as a major susceptibility locus.
Title: Haplotype tag single nucleotide polymorphism analysis of the human orthologues of the rat type 1 diabetes genes Ian4 (Lyp/Iddm1) and Cblb.
we report the positional cloning of Iddm/kdp1 and identify a nonsense mutation in Cblb, a member of the Cbl/Sli family of ubiquitin-protein ligases.Cblb is a major susceptibility gene for rat type 1 diabetes mellitus
Title: Cblb is a major susceptibility gene for rat type 1 diabetes mellitus.
Cbl-b is a negative regulator of both Lyn-Syk-LAT and Gab2mediated complementary signaling pathways in FcepsilonRI-mediated mast cell activation
Title: Negative regulation of FcepsilonRI-mediated mast cell activation by a ubiquitin-protein ligase Cbl-b.
c-Cbl protooncogene product is tyrosine- phosphorylated in rat cerebellum in response to ethanol administration.
Title: Phosphorylation of c-Cbl protooncogene product following ethanol administration in rat cerebellum: possible involvement of Fyn kinase.

Submit: New GeneRIF Correction See all GeneRIFs (12)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables SH3 domain binding	IBA Inferred from Biological aspect of Ancestor more info
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables phosphotyrosine residue binding	IEA Inferred from Electronic Annotation more info
enables protein kinase 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

Process	Evidence Code	Pubs
involved_in CD4-positive, alpha-beta T cell proliferation	IEA Inferred from Electronic Annotation more info
acts_upstream_of CD4-positive, alpha-beta T cell proliferation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within T cell activation	ISO Inferred from Sequence Orthology more info
involved_in T cell anergy	IEA Inferred from Electronic Annotation more info
acts_upstream_of T cell anergy	ISO Inferred from Sequence Orthology more info
involved_in T cell receptor signaling pathway	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within T cell receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in cell surface receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in cellular response to hydrogen peroxide	IEP Inferred from Expression Pattern more info	PubMed
involved_in immune response	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within immune response	ISO Inferred from Sequence Orthology more info
involved_in intracellular signal transduction	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within intracellular signal transduction	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of CD4-positive, alpha-beta T cell proliferation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of CD4-positive, alpha-beta T cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of T cell receptor signaling pathway	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of T cell receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of epidermal growth factor-activated receptor activity	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of T cell anergy	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of T cell anergy	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein catabolic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein ubiquitination	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of protein ubiquitination	ISO Inferred from Sequence Orthology more info
involved_in protein catabolic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in protein ubiquitination	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of cell adhesion	ISO Inferred from Sequence Orthology more info
involved_in regulation of platelet-derived growth factor receptor-alpha signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in regulation of platelet-derived growth factor receptor-alpha signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in regulation of platelet-derived growth factor receptor-alpha signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of signaling	IEA Inferred from Electronic Annotation more info
involved_in response to gravity	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to hormone	IEP Inferred from Expression Pattern more info	PubMed
involved_in signal transduction	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
is_active_in membrane raft	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleoplasm	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology 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-B

Names: Cas-Br-M (murine) ecotropic retroviral transforming sequence b; Cas-Br-M (murine) ectropic retroviral transforming sequence b; Casitas B-lineage lymphoma b; Cbl proto-oncogene B, E3 ubiquitin protein ligase; Cbl proto-oncogene, E3 ubiquitin protein ligase B; RING-type E3 ubiquitin transferase CBL-B; SH3-binding protein CBL-B; casitas B-lineage lymphoma proto-oncogene b; signal transduction protein CBL-B

NP_598285.1

EC 2.3.2.27

XP_006248320.1

EC 2.3.2.27

XP_006248321.1

EC 2.3.2.27

XP_008766848.1

EC 2.3.2.27

XP_063126330.1

EC 2.3.2.27

XP_063126331.1

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.

mRNA and Protein(s)

NM_133601.1 → NP_598285.1 E3 ubiquitin-protein ligase CBL-B

See identical proteins and their annotated locations for NP_598285.1

Status: PROVISIONAL

Source sequence(s)

AB071283

UniProtKB/Swiss-Prot

Q8K4S7, Q9QZ69

UniProtKB/TrEMBL

A6IQS7, G3V689

Related

ENSRNOP00000002719.3, ENSRNOT00000002719.5

Conserved Domains (5) summary

cd09920
Location:248 → 344

SH2_Cbl-b_TKB; Src homology 2 (SH2) domain found in the Cbl-b TKB domain

cd00162
Location:373 → 415

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 ...

cd14392
Location:887 → 927

UBA_Cbl-b; UBA domain found in E3 ubiquitin-protein ligase Cbl-b and similar proteins

pfam02262
Location:44 → 167

Cbl_N; CBL proto-oncogene N-terminal domain 1

pfam02761
Location:171 → 254

Cbl_N2; CBL proto-oncogene N-terminus, EF hand-like domain

RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

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

Reference GRCr8

Genomic

NC_086029.1 Reference GRCr8

Range

62058829..62225904 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006248258.5 → XP_006248320.1 E3 ubiquitin-protein ligase CBL-B isoform X1

See identical proteins and their annotated locations for XP_006248320.1

UniProtKB/TrEMBL

A0A0G2K8K2, A6IQS7, G3V689

Related

ENSRNOP00000074638.1

Conserved Domains (5) summary

cd09920
Location:248 → 344

SH2_Cbl-b_TKB; Src homology 2 (SH2) domain found in the Cbl-b TKB domain

cd00162
Location:373 → 415

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 ...

cd14392
Location:931 → 971

UBA_Cbl-b; UBA domain found in E3 ubiquitin-protein ligase Cbl-b and similar proteins

pfam02262
Location:44 → 167

Cbl_N; CBL proto-oncogene N-terminal domain 1

pfam02761
Location:171 → 254

Cbl_N2; CBL proto-oncogene N-terminus, EF hand-like domain
XM_063270261.1 → XP_063126331.1 E3 ubiquitin-protein ligase CBL-B isoform X3
XM_008768626.4 → XP_008766848.1 E3 ubiquitin-protein ligase CBL-B isoform X1

See identical proteins and their annotated locations for XP_008766848.1

UniProtKB/TrEMBL

A0A0G2K8K2, A6IQS7, G3V689

Conserved Domains (5) summary

cd09920
Location:248 → 344

SH2_Cbl-b_TKB; Src homology 2 (SH2) domain found in the Cbl-b TKB domain

cd00162
Location:373 → 415

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 ...

cd14392
Location:931 → 971

UBA_Cbl-b; UBA domain found in E3 ubiquitin-protein ligase Cbl-b and similar proteins

pfam02262
Location:44 → 167

Cbl_N; CBL proto-oncogene N-terminal domain 1

pfam02761
Location:171 → 254

Cbl_N2; CBL proto-oncogene N-terminus, EF hand-like domain
XM_063270260.1 → XP_063126330.1 E3 ubiquitin-protein ligase CBL-B isoform X2
XM_006248259.4 → XP_006248321.1 E3 ubiquitin-protein ligase CBL-B isoform X1

See identical proteins and their annotated locations for XP_006248321.1

UniProtKB/TrEMBL

A0A0G2K8K2, A6IQS7, G3V689

Conserved Domains (5) summary

cd09920
Location:248 → 344

SH2_Cbl-b_TKB; Src homology 2 (SH2) domain found in the Cbl-b TKB domain

cd00162
Location:373 → 415

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 ...

cd14392
Location:931 → 971

UBA_Cbl-b; UBA domain found in E3 ubiquitin-protein ligase Cbl-b and similar proteins

pfam02262
Location:44 → 167

Cbl_N; CBL proto-oncogene N-terminal domain 1

pfam02761
Location:171 → 254

Cbl_N2; CBL proto-oncogene N-terminus, EF hand-like domain