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Reviewed, UniProtKB/Swiss-Prot P43146 (DCC_HUMAN)

Last modified June 16, 2009. Version 93. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Netrin receptor DCC
Alternative name(s):
    Tumor suppressor protein DCC
    Colorectal cancer suppressor
    Immunoglobulin superfamily DCC subclass member 1
Gene names
Name: DCC
Synonyms: IGDCC1
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length1447 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Receptor for netrin required for axon guidance. Mediates axon attraction of neuronal growth cones in the developing nervous system upon ligand binding. Its association with UNC5 proteins may trigger signaling for axon repulsion. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand. Implicated as a tumor suppressor gene. Ref.5

Subunit structure

Interacts with the cytoplasmic part of UNC5A, UNC5B, UNC5C and probably UNC5D By similarity.

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

Found in axons of the central and peripheral nervous system and in differentiated cell types of the intestine.

Post-translational modification

Ubiquitinated; mediated by SIAH1 or SIAH2 and leading to its subsequent proteasomal degradation Probable.

Involvement in disease

Colorectal tumors that lost their capacity to differentiate into mucus producing cells uniformly lack DCC expression. Inactivation of DCC due to allelic deletion and/or point mutations may cause both lymphatic and hematogenous metastasis of esophageal squamous cell carcinomas.

Sequence similarities

Belongs to the immunoglobulin superfamily. DCC family.

Contains 6 fibronectin type-III domains.

Contains 4 Ig-like C2-type (immunoglobulin-like) domains.

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Ontologies

Keywords
   Biological processApoptosis
Cell cycle
   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainImmunoglobulin domain
Repeat
Signal
Transmembrane
   Molecular functionAnti-oncogene
Developmental protein
Receptor
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Gene Ontology (GO)
   Biological processapoptosis

Inferred from electronic annotation. Source: UniProtKB-KW

cell cycle

Inferred from electronic annotation. Source: UniProtKB-KW

induction of apoptosis

Traceable author statement. Source: ProtInc

negative regulation of cell cycle

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular componentintegral to membrane

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

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Binary interactions

With

Entry

#Exp.

IntAct

Notes

MAZP562701EBI-1222919,EBI-1809742

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 Potential
Chain26 – 14471422Netrin receptor DCC
PRO_0000014744

Regions

Topological domain26 – 10971072Extracellular Potential
Transmembrane1098 – 112225 Potential
Topological domain1123 – 1447325Cytoplasmic Potential
Domain26 – 135110Ig-like C2-type 1
Domain139 – 22991Ig-like C2-type 2
Domain234 – 32693Ig-like C2-type 3
Domain331 – 41686Ig-like C2-type 4
Domain429 – 52092Fibronectin type-III 1
Domain528 – 61689Fibronectin type-III 2
Domain622 – 71493Fibronectin type-III 3
Domain726 – 81489Fibronectin type-III 4
Domain843 – 93997Fibronectin type-III 5
Domain944 – 104198Fibronectin type-III 6

Amino acid modifications

Modified residue10731Phosphoserine Ref.7
Modified residue10741Phosphothreonine Ref.7
Glycosylation941N-linked (GlcNAc...) Potential
Glycosylation2991N-linked (GlcNAc...) Potential
Glycosylation3181N-linked (GlcNAc...) Potential
Glycosylation4781N-linked (GlcNAc...) Potential
Glycosylation6281N-linked (GlcNAc...) Potential
Glycosylation7021N-linked (GlcNAc...) Potential
Disulfide bond61 ↔ 117 By similarity
Disulfide bond161 ↔ 212 By similarity
Disulfide bond261 ↔ 310 By similarity
Disulfide bond352 ↔ 400 By similarity

Natural variations

Natural variant1681M → T in a esophageal carcinoma. Ref.9
VAR_003909
Natural variant2011R → G: dbSNP rs2229080. Ref.9
VAR_003910
Natural variant7591I → M: dbSNP rs2278339.
VAR_056043
Natural variant10171M → V: dbSNP rs984274.
VAR_024495
Natural variant10391F → S in a colorectal cancer sample; somatic mutation. Ref.10
VAR_035511
Natural variant13751P → H in a colorectal carcinoma. Ref.4
VAR_003911

Experimental info

Sequence conflict1381Missing Ref.3
Sequence conflict233 – 32997Missing Ref.3
Sequence conflict4211Missing Ref.3

Secondary structure

1 ..................................................................................................... 1447
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
P43146-1 [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: 4A8612766ED0471F

FASTA1,447158,457
        10         20         30         40         50         60 
MENSLRCVWV PKLAFVLFGA SLLSAHLQVT GFQIKAFTAL RFLSEPSDAV TMRGGNVLLD 

        70         80         90        100        110        120 
CSAESDRGVP VIKWKKDGIH LALGMDERKQ QLSNGSLLIQ NILHSRHHKP DEGLYQCEAS 

       130        140        150        160        170        180 
LGDSGSIISR TAKVAVAGPL RFLSQTESVT AFMGDTVLLK CEVIGEPMPT IHWQKNQQDL 

       190        200        210        220        230        240 
TPIPGDSRVV VLPSGALQIS RLQPGDIGIY RCSARNPASS RTGNEAEVRI LSDPGLHRQL 

       250        260        270        280        290        300 
YFLQRPSNVV AIEGKDAVLE CCVSGYPPPS FTWLRGEEVI QLRSKKYSLL GGSNLLISNV 

       310        320        330        340        350        360 
TDDDSGMYTC VVTYKNENIS ASAELTVLVP PWFLNHPSNL YAYESMDIEF ECTVSGKPVP 

       370        380        390        400        410        420 
TVNWMKNGDV VIPSDYFQIV GGSNLRILGV VKSDEGFYQC VAENEAGNAQ TSAQLIVPKP 

       430        440        450        460        470        480 
AIPSSSVLPS APRDVVPVLV SSRFVRLSWR PPAEAKGNIQ TFTVFFSREG DNRERALNTT 

       490        500        510        520        530        540 
QPGSLQLTVG NLKPEAMYTF RVVAYNEWGP GESSQPIKVA TQPELQVPGP VENLQAVSTS 

       550        560        570        580        590        600 
PTSILITWEP PAYANGPVQG YRLFCTEVST GKEQNIEVDG LSYKLEGLKK FTEYSLRFLA 

       610        620        630        640        650        660 
YNRYGPGVST DDITVVTLSD VPSAPPQNVS LEVVNSRSIK VSWLPPPSGT QNGFITGYKI 

       670        680        690        700        710        720 
RHRKTTRRGE METLEPNNLW YLFTGLEKGS QYSFQVSAMT VNGTGPPSNW YTAETPENDL 

       730        740        750        760        770        780 
DESQVPDQPS SLHVRPQTNC IIMSWTPPLN PNIVVRGYII GYGVGSPYAE TVRVDSKQRY 

       790        800        810        820        830        840 
YSIERLESSS HYVISLKAFN NAGEGVPLYE SATTRSITDP TDPVDYYPLL DDFPTSVPDL 

       850        860        870        880        890        900 
STPMLPPVGV QAVALTHDAV RVSWADNSVP KNQKTSEVRL YTVRWRTSFS ASAKYKSEDT 

       910        920        930        940        950        960 
TSLSYTATGL KPNTMYEFSV MVTKNRRSST WSMTAHATTY EAAPTSAPKD FTVITREGKP 

       970        980        990       1000       1010       1020 
RAVIVSWQPP LEANGKITAY ILFYTLDKNI PIDDWIMETI SGDRLTHQIM DLNLDTMYYF 

      1030       1040       1050       1060       1070       1080 
RIQARNSKGV GPLSDPILFR TLKVEHPDKM ANDQGRHGDG GYWPVDTNLI DRSTLNEPPI 

      1090       1100       1110       1120       1130       1140 
GQMHPPHGSV TPQKNSNLLV IIVVTVGVIT VLVVVIVAVI CTRRSSAQQR KKRATHSAGK 

      1150       1160       1170       1180       1190       1200 
RKGSQKDLRP PDLWIHHEEM EMKNIEKPSG TDPAGRDSPI QSCQDLTPVS HSQSETQLGS 

      1210       1220       1230       1240       1250       1260 
KSTSHSGQDT EEAGSSMSTL ERSLAARRAP RAKLMIPMDA QSNNPAVVSA IPVPTLESAQ 

      1270       1280       1290       1300       1310       1320 
YPGILPSPTC GYPHPQFTLR PVPFPTLSVD RGFGAGRSQS VSEGPTTQQP PMLPPSQPEH 

      1330       1340       1350       1360       1370       1380 
SSSEEAPSRT IPTACVRPTH PLRSFANPLL PPPMSAIEPK VPYTPLLSQP GPTLPKTHVK 

      1390       1400       1410       1420       1430       1440 
TASLGLAGKA RSPLLPVSVP TAPEVSEESH KPTEDSANVY EQDDLSEQMA SLEGLMKQLN 


AITGSAF

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References

« Hide 'large scale' references
[1]"The DCC gene product in cellular differentiation and colorectal tumorigenesis."
Hedrick L., Cho K.R., Fearon E.R., Wu T.-C., Kinzler K.W., Vogelstein B.
Genes Dev. 8:1174-1183(1994) [PubMed: 7926722] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Identification of a chromosome 18q gene that is altered in colorectal cancers."
Fearon E.R., Cho K.R., Nigro J.M., Kern S.E., Simons J.W., Ruppert J.M., Hamilton S.R., Preisinger A.C., Thomas G., Kinzler K.W., Vogelstein B.
Science 247:49-56(1990) [PubMed: 2294591] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-750.
[3]"Scrambled exons."
Nigro J.M., Cho K.R., Fearon E.R., Kern S.E., Ruppert J.M., Oliner J.D., Kinzler K.W., Vogelstein B.
Cell 64:607-613(1991) [PubMed: 1991322] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 107-472 (SCRAMBELD EXONS).
[4]"The DCC gene: structural analysis and mutations in colorectal carcinomas."
Cho K.R., Oliner J.D., Simons J.W., Hedrick L., Fearon E.R., Preisinger A.C., Hedge P., Silverman G.A., Vogelstein B.
Genomics 19:525-531(1994) [PubMed: 8188295] [Abstract]
Cited for: GENE STRUCTURE, VARIANT CARCINOMA HIS-1375.
[5]"Deleted in Colorectal Cancer (DCC) encodes a netrin receptor."
Keino-Masu K., Masu M., Hinck L., Leonardo E.D., Chan S.S.-Y., Culotti J.G., Tessier-Lavigne M.
Cell 87:175-185(1996) [PubMed: 8861902] [Abstract]
Cited for: FUNCTION.
[6]"Mammalian homologs of seven in absentia regulate DCC via the ubiquitin-proteasome pathway."
Hu G., Zhang S., Vidal M., Baer J.L., Xu T., Fearon E.R.
Genes Dev. 11:2701-2714(1997) [PubMed: 9334332] [Abstract]
Cited for: INTERACTION WITH SIAH1 AND SIAH2, DEGRADATION.
[7]"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column."
Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y.
Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1073 AND THR-1074, MASS SPECTROMETRY.
[8]"Solution structure of the fibronectin type III domains of human netrin receptor DCC."
RIKEN structural genomics initiative (RSGI)
Submitted (MAR-2008) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 419-1047.
[9]"Point mutations and allelic deletion of tumor suppressor gene DCC in human esophageal squamous cell carcinomas and their relation to metastasis."
Miyake S., Nagai K., Yoshino K., Oto M., Endo M., Yuasa Y.
Cancer Res. 54:3007-3010(1994) [PubMed: 8187090] [Abstract]
Cited for: VARIANT CARCINOMA THR-168, VARIANT GLY-201.
[10]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed: 16959974] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] SER-1039.
+Additional computationally mapped references.

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Cross-references

Sequence databases

X76132 mRNA. Translation: CAA53735.1.
M32292 mRNA. Translation: AAA35751.1.
M32286 Genomic DNA. Translation: AAA52174.1.
M32288 Genomic DNA. Translation: AAA52175.1. Sequence problems.
M32290 Genomic DNA. Translation: AAA52176.1.
M63696 Genomic DNA. Translation: AAA52177.1.
M63700 Genomic DNA. Translation: AAA52178.1.
M63702 Genomic DNA. Translation: AAA52179.1.
M63718 Genomic DNA. Translation: AAA52180.1.
M63698 Genomic DNA. Translation: AAA52181.1.
IPIIPI00016422.
PIRA54100.
RefSeqNP_005206.2.
UniGeneHs.579550

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
2ED7NMR-A419-524[»]
2ED8NMR-A528-620[»]
2ED9NMR-A602-718[»]
2EDBNMR-A716-818[»]
2EDDNMR-A833-942[»]
2EDENMR-A944-1044[»]
ModBaseSearch...

Protein-protein interaction databases

IntActP43146. 2 interactions.

PTM databases

PhosphoSiteP43146.

Proteomic databases

PRIDEP43146.

Genome annotation databases

EnsemblENSG00000187323. Homo sapiens. [Contig view]
GeneID1630.
KEGGhsa:1630.

Organism-specific databases

GeneCardsGC18P048121.
H-InvDBHIX0039754.
HGNCHGNC:2701. DCC.
HPACAB002311.
MIM120470. gene.
PharmGKBPA27170.
GenAtlasSearch...

Phylogenomic databases

HOGENOMP43146.
HOVERGENP43146.

Gene expression databases

ArrayExpressP43146.
BgeeP43146.
CleanExHS_DCC.
GermOnlineENSG00000187323. Homo sapiens.

Family and domain databases

InterProIPR008957. Fibronectin_typ-III-like_fold.
IPR003961. FN_III.
IPR003962. FnIII_subd.
IPR007110. Ig-like.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR010560. Neogenin_C.
[Graphical view]
Gene3DG3DSA:2.60.40.30. FN_III-like. 6 hits.
G3DSA:2.60.40.10. Ig-like_fold. 4 hits.
PfamPF00041. fn3. 6 hits.
PF07679. I-set. 4 hits.
PF06583. Neogenin_C. 1 hit.
[Graphical view]
PRINTSPR00014. FNTYPEIII.
SMARTSM00060. FN3. 6 hits.
SM00409. IG. 1 hit.
SM00408. IGc2. 3 hits.
[Graphical view]
PROSITEPS50853. FN3. 6 hits.
PS50835. IG_LIKE. 4 hits.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio6688.
SOURCESearch...

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Entry information

Entry nameDCC_HUMAN
AccessionPrimary (citable) accession number: P43146
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: June 16, 2009
This is version 93 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents