Seroatlas · Human Serome Atlas

CBL

E3 ubiquitin-protein ligase CBL

Also known as: c-Cbl, CBL_HUMAN, CBL2, RNF55

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

Protein identityUniProt · HPA

UniProt accession: P22681
Gene: CBL
Ensembl: ENSG00000110395
Chromosome: 11
Canonical length: 906 aa
Protein class: Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins
Subcellular location: Cytosol,End piece
Quaternary structure: Homodimer

OverviewNCBI Gene

This gene is a proto-oncogene that encodes a RING finger E3 ubiquitin ligase. The encoded protein is one of the enzymes required for targeting substrates for degradation by the proteasome. This protein mediates the transfer of ubiquitin from ubiquitin conjugating enzymes (E2) to specific substrates. This protein also contains an N-terminal phosphotyrosine binding domain that allows it to interact with numerous tyrosine-phosphorylated substrates and target them for proteasome degradation. As such it functions as a negative regulator of many signal transduction pathways. This gene has been found to be mutated or translocated in many cancers including acute myeloid leukaemia, and expansion of CGG repeats in the 5' UTR has been associated with Jacobsen syndrome. Mutations in this gene are also the cause of Noonan syndrome-like disorder. [provided by RefSeq, Jul 2016]

Canonical amino-acid sequenceUniProt

906 residues, UniProt reviewed canonical sequence.

>P22681|CBL
     1  MAGNVKKSSG AGGGSGSGGS GSGGLIGLMK DAFQPHHHHH HHLSPHPPGT VDKKMVEKCW
    61  KLMDKVVRLC QNPKLALKNS PPYILDLLPD TYQHLRTILS RYEGKMETLG ENEYFRVFME
   121  NLMKKTKQTI SLFKEGKERM YEENSQPRRN LTKLSLIFSH MLAELKGIFP SGLFQGDTFR
   181  ITKADAAEFW RKAFGEKTIV PWKSFRQALH EVHPISSGLE AMALKSTIDL TCNDYISVFE
   241  FDIFTRLFQP WSSLLRNWNS LAVTHPGYMA FLTYDEVKAR LQKFIHKPGS YIFRLSCTRL
   301  GQWAIGYVTA DGNILQTIPH NKPLFQALID GFREGFYLFP DGRNQNPDLT GLCEPTPQDH
   361  IKVTQEQYEL YCEMGSTFQL CKICAENDKD VKIEPCGHLM CTSCLTSWQE SEGQGCPFCR
   421  CEIKGTEPIV VDPFDPRGSG SLLRQGAEGA PSPNYDDDDD ERADDTLFMM KELAGAKVER
   481  PPSPFSMAPQ ASLPPVPPRL DLLPQRVCVP SSASALGTAS KAASGSLHKD KPLPVPPTLR
   541  DLPPPPPPDR PYSVGAESRP QRRPLPCTPG DCPSRDKLPP VPSSRLGDSW LPRPIPKVPV
   601  SAPSSSDPWT GRELTNRHSL PFSLPSQMEP RPDVPRLGST FSLDTSMSMN SSPLVGPECD
   661  HPKIKPSSSA NAIYSLAARP LPVPKLPPGE QCEGEEDTEY MTPSSRPLRP LDTSQSSRAC
   721  DCDQQIDSCT YEAMYNIQSQ APSITESSTF GEGNLAAAHA NTGPEESENE DDGYDVPKPP
   781  VPAVLARRTL SDISNASSSF GWLSLDGDPT TNVTEGSQVP ERPPKPFPRR INSERKAGSC
   841  QQGSGPAASA ATASPQLSSE IENLMSQGYS YQDIQKALVI AQNNIEMAKN ILREFVSISS
   901  PAHVAT

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CBL 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: Cell surface
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.52
Highest tissue expression: 21 nTPM

Expression across tissuesHPA

Tissue

thymus: 21 nTPM
testis: 17 nTPM
blood vessel: 11 nTPM
tonsil: 11 nTPM
lymph node: 10 nTPM
spleen: 9.4 nTPM

Single-cell type

neutrophils: 712 nCPM
neutrophil progenitors: 369 nCPM
microglia: 210 nCPM
vascular smooth muscle cells: 198 nCPM
monocyte progenitors: 183 nCPM
platelets: 178 nCPM

Immune cell

neutrophil: 8.2 nTPM
intermediate monocyte: 2.7 nTPM
myeloid DC: 2.6 nTPM
non-classical monocyte: 2.4 nTPM
classical monocyte: 2.3 nTPM
eosinophil: 1.9 nTPM

Brain region

hypothalamus: 31 nTPM
pons: 28 nTPM
midbrain: 28 nTPM
thalamus: 28 nTPM
white matter: 27 nTPM
cerebral cortex: 27 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CBL.

Disease | AllUniProt

Conditions CBL is implicated in, by any mechanism.

Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL) MIM:613563

Disease | GeneticClinVar

35 pathogenic / likely-pathogenic of 2,439 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

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): 0.5
gnomAD pLI: 0
gnomAD missense Z: 1.03
DepMap mean gene effect: 0.06
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% 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 CBL 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 CBL as an antibody target. Whether an autoantibody or antibody against CBL could matter depends on whether native CBL is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

CBL is annotated at the cell surface, where native CBL is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label CBL as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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