CBLC

Protein identityUniProt · HPA

UniProt accession

Q9ULV8

Gene

CBLC

Ensembl

ENSG00000142273

Chromosome

19

Canonical length

474 aa

Protein class

Cancer-related genes, Enzymes, Metabolic proteins, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Aggresome

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

474 residues, UniProt reviewed canonical sequence.

>Q9ULV8|CBLC
     1  MALAVAPWGR QWEEARALGR AVRMLQRLEE QCVDPRLSVS PPSLRDLLPR TAQLLREVAH
    61  SRRAAGGGGP GGPGGSGDFL LIYLANLEAK SRQVAALLPP RGRRSANDEL FRAGSRLRRQ
   121  LAKLAIIFSH MHAELHALFP GGKYCGHMYQ LTKAPAHTFW RESCGARCVL PWAEFESLLG
   181  TCHPVEPGCT ALALRTTIDL TCSGHVSIFE FDVFTRLFQP WPTLLKNWQL LAVNHPGYMA
   241  FLTYDEVQER LQACRDKPGS YIFRPSCTRL GQWAIGYVSS DGSILQTIPA NKPLSQVLLE
   301  GQKDGFYLYP DGKTHNPDLT ELGQAEPQQR IHVSEEQLQL YWAMDSTFEL CKICAESNKD
   361  VKIEPCGHLL CSCCLAAWQH SDSQTCPFCR CEIKGWEAVS IYQFHGQATA EDSGNSSDQE
   421  GRELELGQVP LSAPPLPPRP DLPPRKPRNA QPKVRLLKGN SPPAALGPQD PAPA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CBLC 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)

0.34

Highest tissue expression

48 nTPM

Expression across tissuesHPA

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)

1.14

gnomAD pLI

0

gnomAD missense Z

0.37

DepMap mean gene effect

-0.13

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell surface receptor signaling pathway
• negative regulation of epidermal growth factor receptor signaling pathway
• negative regulation of MAPK cascade
• negative regulation of neuron apoptotic process
• protein stabilization
• protein ubiquitination
• response to glial cell derived neurotrophic factor
• signal transduction
• ubiquitin-dependent protein catabolic process

Molecular functions

• calcium ion binding
• epidermal growth factor receptor binding
• phosphotyrosine residue binding
• receptor tyrosine kinase binding
• SH3 domain binding
• ubiquitin protein ligase activity
• zinc ion binding

Cellular components

• membrane raft
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Zinc finger, RING-type
• Adaptor protein Cbl, N-terminal helical
• EF-hand domain pair
• Zinc finger, RING/FYVE/PHD-type
• Adaptor protein Cbl, EF hand-like
• Adaptor protein Cbl, SH2-like domain
• Zinc finger, RING-type, conserved site
• Adaptor protein Cbl, PTB domain
• Adaptor protein Cbl
• Adaptor protein Cbl, N-terminal domain superfamily
• SH2 domain superfamily
• CBL proto-oncogene N-terminal domain 1
• CBL proto-oncogene N-terminus, EF hand-like domain
• CBL proto-oncogene N-terminus, SH2-like domain
• Zinc finger, C3HC4 type (RING finger)

KeywordsUniProt

• Calcium
• Metal-binding
• Phosphoprotein
• Repeat
• SH3-binding
• Transferase
• Ubl conjugation
• Ubl conjugation pathway
• Zinc
• Zinc-finger

InteractionsUniProt · HPA

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

• CRK
• EGFR
• RET
• SRC
• UBE2D3
• ITCH