Seroatlas · Human Serome Atlas

CBLB

E3 ubiquitin-protein ligase CBL-B

Also known as: Cbl-b, CBLB_HUMAN, RNF56

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q13191
Gene: CBLB
Ensembl: ENSG00000114423
Chromosome: 3
Canonical length: 982 aa
Protein class: Cancer-related genes, Enzymes, Metabolic proteins, Predicted intracellular proteins
Subcellular location: Nucleoplasm,Cytosol

OverviewNCBI Gene

This gene encodes an E3 ubiquitin-protein ligase which promotes proteosome-mediated protein degradation by transferring ubiquitin from an E2 ubiquitin-conjugating enzyme to a substrate. The encoded protein is involved in the regulation of immune response by limiting T-cell receptor, B-cell receptor, and high affinity immunoglobulin epsilon receptor activation. Studies in mouse suggest that this gene is involved in antifungal host defense and that its inhibition leads to increased fungal killing. Manipulation of this gene may be beneficial in implementing immunotherapies for a variety of conditions, including cancer, autoimmune diseases, allergies, and infections. [provided by RefSeq, Sep 2017]

Canonical amino-acid sequenceUniProt

982 residues, UniProt reviewed canonical sequence.

>Q13191|CBLB
     1  MANSMNGRNP GGRGGNPRKG RILGIIDAIQ DAVGPPKQAA ADRRTVEKTW KLMDKVVRLC
    61  QNPKLQLKNS PPYILDILPD TYQHLRLILS KYDDNQKLAQ LSENEYFKIY IDSLMKKSKR
   121  AIRLFKEGKE RMYEEQSQDR RNLTKLSLIF SHMLAEIKAI FPNGQFQGDN FRITKADAAE
   181  FWRKFFGDKT IVPWKVFRQC LHEVHQISSG LEAMALKSTI DLTCNDYISV FEFDIFTRLF
   241  QPWGSILRNW NFLAVTHPGY MAFLTYDEVK ARLQKYSTKP GSYIFRLSCT RLGQWAIGYV
   301  TGDGNILQTI PHNKPLFQAL IDGSREGFYL YPDGRSYNPD LTGLCEPTPH DHIKVTQEQY
   361  ELYCEMGSTF QLCKICAEND KDVKIEPCGH LMCTSCLTAW QESDGQGCPF CRCEIKGTEP
   421  IIVDPFDPRD EGSRCCSIID PFGMPMLDLD DDDDREESLM MNRLANVRKC TDRQNSPVTS
   481  PGSSPLAQRR KPQPDPLQIP HLSLPPVPPR LDLIQKGIVR SPCGSPTGSP KSSPCMVRKQ
   541  DKPLPAPPPP LRDPPPPPPE RPPPIPPDNR LSRHIHHVES VPSRDPPMPL EAWCPRDVFG
   601  TNQLVGCRLL GEGSPKPGIT ASSNVNGRHS RVGSDPVLMR KHRRHDLPLE GAKVFSNGHL
   661  GSEEYDVPPR LSPPPPVTTL LPSIKCTGPL ANSLSEKTRD PVEEDDDEYK IPSSHPVSLN
   721  SQPSHCHNVK PPVRSCDNGH CMLNGTHGPS SEKKSNIPDL SIYLKGDVFD SASDPVPLPP
   781  ARPPTRDNPK HGSSLNRTPS DYDLLIPPLG EDAFDALPPS LPPPPPPARH SLIEHSKPPG
   841  SSSRPSSGQD LFLLPSDPFV DLASGQVPLP PARRLPGENV KTNRTSQDYD QLPSCSDGSQ
   901  APARPPKPRP RRTAPEIHHR KPHGPEAALE NVDAKIAKLM GEGYAFEEVK RALEIAQNNV
   961  EVARSILREF AFPPPVSPRL NL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CBLB can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Intracellular
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.52
Highest tissue expression: 14 nTPM

Expression across tissuesHPA

Tissue

lymph node: 14 nTPM
bone marrow: 13 nTPM
adipose tissue: 12 nTPM
cerebellum: 10 nTPM
heart muscle: 10 nTPM
retina: 9.2 nTPM

Single-cell type

podocytes: 2,392 nCPM
cardiomyocytes: 1,315 nCPM
t-cells: 1,314 nCPM
nk-cells: 1,304 nCPM
thymic myoid cells: 1,195 nCPM
extravillous trophoblasts: 962 nCPM

Immune cell

NK-cell: 10 nTPM
gdT-cell: 9.2 nTPM
MAIT T-cell: 8 nTPM
naive CD8 T-cell: 7.2 nTPM
T-reg: 5.9 nTPM
memory CD8 T-cell: 5.3 nTPM

Brain region

cerebellum: 68 nTPM
hypothalamus: 45 nTPM
cerebral cortex: 44 nTPM
pons: 43 nTPM
basal ganglia: 43 nTPM
midbrain: 43 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CBLB.

Disease | AllUniProt

Conditions CBLB is implicated in, by any mechanism.

Autoimmune disease, multisystem, infantile-onset, 3 (ADMIO3) MIM:620430

Disease | GeneticClinVar

4 pathogenic / likely-pathogenic of 166 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Autoimmune disease, multisystem, infantile-onset, 3

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.27
gnomAD pLI: 1
gnomAD missense Z: 1.29
DepMap mean gene effect: -0.06
DepMap dependency class: none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of CBLB in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads CBLB as an antibody target. Whether an autoantibody or antibody against CBLB could matter depends on whether native CBLB is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

CBLB is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Source-annotated serology context

The source annotations explicitly mention antibody, autoantibody, autoantigen, or autoimmune context. This is biological context, not study-specific reactivity.

Manipulation of this gene may be beneficial in implementing immunotherapies for a variety of conditions, including cancer, autoimmune diseases, allergies, and infections.

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