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FLASH GENE

Symbol

DCC

contributors: mct - updated : 22-06-2016

HGNC name	deleted in colorectal carcinoma
HGNC id	2701

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	1191.21 kb     29 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

Map	see TTR ,SERPINB2

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005215 29 - 10210 NP_005206 - 1447 - 1998 9796814

EXPRESSION

Type

widely

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 esophagus       highly   intestine large intestine colon       intestine large intestine rectum     Endocrine neuroendocrine pituitary     highly Hearing/Equilibrium ear       highly Nervous brain       highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial         Nervous peripherous

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	four Ig-like C2-type domains
	six fibronectin type III-like extracellular domains

conjugated

GlycoP , PhosphoP

HOMOLOGY

interspecies	homolog to murine Dcc (96.5pc)
	homolog to rattus Dcc (96.5pc)

Homologene

FAMILY	immunoglobulin superfamily
	DCC family

CATEGORY

adhesion , tumor suppressor , receptor membrane

SUBCELLULAR LOCALIZATION	plasma membrane
text	spinal commissural axons
	partially located to lipid rafts

basic FUNCTION	part of NTN1 receptor, inducing apoptosis in a caspase 9 dependent pathway by a mechanism independent of the intrinsic (mitochondria-dependent) apoptotic pathway, antagonized by NTN1
	inducing attraction in axon guidance through its cytoplasmic tail
	inducing apoptosis in the absence of its ligand
	dependence receptor that may require lipid raft localization for cell death signaling
	may function as a tumor suppressor gene in the esophagus
	associating with protein synthesis machinery and regulating translation
	its association with UNC5 proteins may trigger signaling for axon repulsion
	DCC functions as a tumour suppressor via its ability to trigger tumour cell apoptosis
	unction of DCC as a dependence receptor and a conditional tumour suppressor seems to represent an important safeguard mechanism, limiting tumour progression by engaging the apoptotic process
	function of DCC as a context-dependent tumour suppressor that limits survival of disseminated tumour cells
	NTN1/DCC/UNC5C chemotropism contributes to axonal confinement within the CNS

CELLULAR PROCESS	cell life, cell death/apoptosis
	cell life, antiapoptosis

PHYSIOLOGICAL PROCESS

nervous system

text	dependence receptor inducing apoptosis when unoccuped by ligand but inhibiting apoptosis in the presence of ligand

PATHWAY

metabolism

signaling

a component	forming a ROBO/DCC receptor complex, silencing netrin NTN1 attraction
	forming a binding complex containing multiple translation components

INTERACTION

DNA

RNA

small molecule

protein	caspase 9, caspase 3
	NTN1/DCC pair may also regulate neuron survival during nervous system development
	activating MAPK signaling, required for NTN1 mediated axon outgrowth and guidance
	DCC could regulate cell adhesion and migration through its association with ERM-M (ezrin/radixin/moesin and merlin) proteins
	interacting with SRC and FAK to mediate axon attraction
	interacting with UNC5A, UNC5B, UNC5C and probably with UNC5D
	ROBO1 interacts with the full-length DCC receptor
	DCC promotes movement of MYO10 along basal actin filaments and enhances MYO10-mediated basal filopodium elongation
	NTN1 binds to DCC and DSCAM mediating axon attraction, and UNC5 mediating axon repulsion
	MAPK8 is important in the coordination of DCC and DSCAM in NTN1-mediated attractive signaling
	DCC cooperates with DSCAM through regulating JNK activity in NTN1 signaling
	combination of DSCAM with DCC or UNC5C plays an important role in NTN1-mediated axon attraction or repulsion
	NTN1-UNC5C/DCC interaction is involved in controlling the interhemispherical projection in a subset of early born, deep layer callosal neurons
	NTN1, a canonical guidance cue, induced the interaction of TUBB3 with the netrin receptor DCC

cell & other

potentially involed in cell-cell or cell-matrix interactions

REGULATION

activated by

cleavage (apoptosis defect) by caspase

Other

ubiquitinated, mediated by SIAH1 or SIAH2, leading to its subsequent proteasomal degradation

ASSOCIATED DISORDERS

corresponding disease(s)

MMVC

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   deletion     homozygously deleted in colorectal cancer cell lines and other tumor types including stomach, pancreas, esophagus, prostate carcinomas tumoral     --low   by promoter hypermethylation in esophageal squamous cell carcinoma tumoral     --low   in more than 50p100 of colorectal tumours, as well as in many other neoplasms

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

unc5c haploinsufficiency results in diminished amphetamine-induced locomotion in male and female mice and this phenotype is identical to that produced by dcc haploinsufficiency and observed after adolescence