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deleted in colon cancer (DCC); netrin receptor DCC; tumor suppressor protein DCC; colorectal cancer suppressor; immunoglobulin superfamily DCC subclass member 1 (DCC, IGDCC1)
Function:
1) receptor for netrin required for axon guidance
2) mediates axon attraction of neuronal growth cones in the developing nervous system upon ligand binding
3) association with UNC5 proteins may trigger signaling for axon repulsion
4) required for apoptosis induction when not associated with netrin ligand
5) tumor suppressor gene
6) interacts with cytoplasmic part of UNC5A, UNC5B, UNC5C & probably UNC5D
7) ubiquitination mediated by SIAH1 or SIAH2, leading to its subsequent proteasomal degradation
Structure:
1) belongs to the immunoglobulin superfamily, DCC family
2) contains 6 fibronectin F3 modules
- contains 4 Ig-like C2-type domains (immunoglobulin-like)
Compartment: membrane
Expression:
- found in axons of the central & peripheral nervous system & in differentiated cell types of the intestine
Pathology:
1) colorectal tumors that lost their capacity to differentiate into mucus producing cells uniformly lack DCC expression
2) inactivation of DCC due to allelic deletion &/or point mutations may cause both lymphatic & hematogenous metastasis of esophageal squamous cell carcinomas
Related
Deleted in Colon Carcinoma [DCC] tumor suppressor gene
General
anti-oncoprotein (tumor suppressor protein)
glycoprotein
netrin receptor
Properties
SIZE: entity length = 1447 aa
MW = 158 kD
COMPARTMENT: cellular membrane
MOTIF: signal sequence {1-25}
immunoglobulin superfamily domain {26-135}
MOTIF: cysteine residue {C61}
MODIFICATION: cysteine residue {C117}
N-glycosylation site {N94}
cysteine residue {C117}
MODIFICATION: cysteine residue {C61}
immunoglobulin superfamily domain {139-229}
MOTIF: cysteine residue {C161}
MODIFICATION: cysteine residue {C212}
cysteine residue {C212}
MODIFICATION: cysteine residue {C161}
immunoglobulin superfamily domain {234-326}
MOTIF: cysteine residue {C261}
MODIFICATION: cysteine residue {C310}
N-glycosylation site {N299}
cysteine residue {C310}
MODIFICATION: cysteine residue {C261}
N-glycosylation site {N318}
immunoglobulin superfamily domain {331-416}
MOTIF: cysteine residue {C352}
MODIFICATION: cysteine residue {C400}
cysteine residue {C400}
MODIFICATION: cysteine residue {C352}
fibronectin type III domain or F3 module {429-520}
MOTIF: N-glycosylation site {N478}
fibronectin type III domain or F3 module {528-616}
fibronectin type III domain or F3 module {622-714}
MOTIF: N-glycosylation site {N628}
N-glycosylation site {N702}
fibronectin type III domain or F3 module {726-814}
fibronectin type III domain or F3 module {843-939}
fibronectin type III domain or F3 module {944-1041}
Ser phosphorylation site {S1073}
Thr phosphorylation site {T1074}
transmembrane domain {1098-1122}
Database Correlations
OMIM 120470
UniProt P43146
PFAM correlations
Entrez Gene 1630
Kegg hsa:1630
References
- Hunter T.
Cooperation between oncogenes.
Cell. 1991 Jan 25;64(2):249-70. Review.
PMID: 1988147
- FASEB 93
- Uniprot :accession P43146