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FLASH GENE
Symbol DCC contributors: mct - updated : 22-06-2014
HGNC name deleted in colorectal carcinoma
HGNC id 2701
Corresponding disease
MMVC mirror movements, congenital
Location 18q21.2      Physical location : 49.866.541 - 51.062.273
Synonym name
  • colorectal cancer-related chromosome sequence 18
  • netrin-1 receptor
  • immunoglobulin superfamily, DCC subclass, member 1
  • colorectal tumor suppressor
  • Synonym symbol(s) CRC18, CRCR1, IGDCC1
    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
    Physical map
    MADH7 18q21.1 MAD, mothers against decapentaplegic homolog 7 (Drosophila) FLJ20071 RPL17 18q21.1 ribosomal protein L17 LOC390852 18 similar to signal recognition particle 72kDa LIPG 18q21.1 lipase, endothelial ACAA2 18q21.1 acetyl-Coenzyme A acyltransferase 2 (mitochondrial 3-oxoacyl-Coenzyme A thiolase) MYO5B 18q12 myosin VB FLJ32743 18q21.1 hypothetical protein FLJ32743 MBD1 18q21 methyl-CpG binding domain protein 1 CGBP 18q12 methyl-CpG binding domain protein 1 MGC10200 18q21.1 hypothetical protein MGC:10200 LOC390853 18 similar to acidic ribosomal phosphoprotein P0 MAPK4 18q21.2-q21.3 mitogen-activated protein kinase 4 B29 18q21 mitogen-activated protein kinase 4 ME2 18q21 malic enzyme 2, NAD(+)-dependent, mitochondrial ELAC1 18q21 elaC homolog 1 (E. coli) MADH4 18q21.1 MAD, mothers against decapentaplegic homolog 4 (Drosophila) LOC51320 18q21.1 hypothetical protein LOC51320 LOC390854 18 similar to neuroepithelial cell transforming gene 1; guanine nucleotide regulatory protein (oncogene); Rho guanine nucleotide exchange factor (GEF) 8 LOC390855 18 similar to 40S ribosomal protein S8 DCC 18q21.1 deleted in colorectal carcinoma LOC390856 18 similar to ribosomal protein L29 MBD2 18q21.1 methyl-CpG binding domain protein 2 POLI 18q21.1 polymerase (DNA directed) iota STARD6 18q21.2 START domain containing 6 MGC33382 18q21.2 hypothetical protein MGC33382 FLJ39106 18q21.2 hypothetical protein FLJ39106 LOC390857 18 similar to protein 40kD RAB27B 18q12.3-q21 RAB27B, member RAS oncogene family SE57-1 18q21 CTCL tumor antigen se57-1 TCF4 18q21.1 transcription factor 4
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    29 - 10210 - 1447 - 1998 9796814
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
     intestinelarge intestinecolon  
     intestinelarge intestinerectum  
    Endocrineneuroendocrinepituitary  highly
    Hearing/Equilibriumear   highly
    Nervousbrain   highly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelial    
    Nervousperipherous   
    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
  • 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)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein 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