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FLASH GENE

Symbol

CBLC

contributors: mct - updated : 24-02-2015

HGNC name	Cas-Br-M (murine) ecotropic retroviral transforming sequence c
HGNC id	15961

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	19q13.32      Physical location : 45.281.125 - 45.303.902
Synonym name	CBL family-adaptor protein 3
	RING finger protein 57
	signal transduction protein CBL-C
	SH3-binding protein CBL-C
Synonym symbol(s)	CBL3, CBL-SL, RNF57

DNA

TYPE	functioning gene
STRUCTURE	22.78 kb     11 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_012116 11 - 1591 NP_036248 52 474 - 1999 10362357 long form NM_001130852 10 splicing 1453 NP_001124324 - 428 pancreatic adenocarcinoma 1999 10362357 short form

EXPRESSION

Type	restricted

constitutive of

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine large intestine colon       intestine small intestine         mouth         Respiratory lung           respiratory tract larynx

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular endocrine

cell lineage
cell lines	pancreatic adenocarcinoma
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	conserved N-terminal tyrosine kinase binding (TKB) domain showed restricted structural flexibility upon phosphopeptide binding, and mutation in CBLC TKB augmenting this flexibility enhanced its binding to target phosphoproteins
	a phosphotyrosine binding domain
	a catalytic RING finger domain
	C-terminal proline-rich domain that mediates interactions with SRC homology 3 (SH3) containing proteins

HOMOLOGY

interspecies

homolog to murine Cblc

Homologene

FAMILY	CBL family-adaptor protein 3
	RING finger ubiquitin ligases family

CATEGORY

adaptor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus

basic FUNCTION	regulating intracellular signaling mediated by various tyrosine kinase
	down-regulates receptor tyrosine kinases by conjugating ubiquitin to them, leading to receptor internalization and degradation
	CD2AP and CBLC, constitute a checkpoint that controls the extent of RET downregulation and, thereby, the sensitivity of neurons to glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs)

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	Src is a preferential target of CBLC for degradation
	RTK negative regulatory gene
	interacts with unphosphorylated RET and dissociates from RET after RET activation
	TGFB1I1 is a CBLC interacting protein (binding leads to an increase in the ubiquitin ligase activity of CBLC once CBLC has been activated by SRC phosphorylation or through an activating phosphomimetic mutation)
	PDLIM7 is a CBLC interacting protein, and binding of PDLIM7 to RET prevents CBLC recruitment to RET
	binds wild-type and MEN2A isoforms of the receptor tyrosine kinase, RET, and enhances ubiquitination and degradation of activated RET

cell & other

EGF receptor and Fyn tyrosine kinase binding

REGULATION

ASSOCIATED DISORDERS

ANIMAL & CELL MODELS