Q63155 (DCC_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Netrin receptor DCC

Alternative name(s):
Tumor suppressor protein DCC

Gene names

Name:

Dcc

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	1445 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

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 By similarity. Ref.1
Subunit structure	Interacts with the cytoplasmic part of UNC5A, UNC5B, UNC5C and probably UNC5D By similarity. Interacts with DSCAM. Interacts with PTK2/FAK1. Interacts with MYO10 By similarity. Interacts with MAPK1. Interacts with NTN1. Interacts with CBLN4; this interaction can be competed by NTN1 By similarity. Ref.1
Subcellular location	Membrane; Single-pass type I membrane protein Ref.1.
Tissue specificity	Detected in embryonic spinal cord, predominantly in axons of commissural neurons (at protein level). Detected in embryonic spinal cord. Ref.1
Post-translational modification	Ubiquitinated; mediated by SIAH1 or SIAH2 and leading to its subsequent proteasomal degradation By similarity.
Sequence similarities	Belongs to the immunoglobulin superfamily. DCC family. Contains 6 fibronectin type-III domains. Contains 4 Ig-like C2-type (immunoglobulin-like) domains.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Membrane
Disease	Tumor suppressor
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Molecular function	Developmental protein Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW axon guidance Inferred from mutant phenotype Ref.1. Source: RGD dorsal/ventral axon guidance Inferred from electronic annotation. Source: Compara neuron migration Inferred from electronic annotation. Source: Compara positive regulation of ERK1 and ERK2 cascade Inferred from mutant phenotype PubMed 15811950. Source: RGD positive regulation of neuron projection development Inferred from mutant phenotype PubMed 15737744. Source: RGD response to amphetamine Inferred from expression pattern PubMed 17996376. Source: RGD spinal cord ventral commissure morphogenesis Inferred from electronic annotation. Source: Compara
Cellular_component	axon Inferred from direct assay PubMed 12840034. Source: RGD growth cone membrane Inferred from direct assay PubMed 18691385. Source: RGD integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW membrane raft Inferred from direct assay PubMed 15811950. Source: RGD
Molecular_function	netrin receptor activity Inferred from mutant phenotype Ref.1. Source: RGD transcription coactivator activity Inferred from mutant phenotype PubMed 12840034. Source: RGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-1798965,EBI-1798965
Agap2	Q8CGU4	2	EBI-1798965,EBI-4409108
Dscam	Q9ERC8	4	EBI-1798965,EBI-1798601	From a different organism.
Robo1	O55005	2	EBI-1798965,EBI-3505237
RPL5	P46777	4	EBI-1798965,EBI-358018	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 25

25

Potential

Chain

26 – 1445

1420

Netrin receptor DCC

PRO_0000416246

Regions

Transmembrane

1100 – 1120

21

Helical; Potential

Domain

26 – 135

110

Ig-like C2-type 1

Domain

139 – 229

91

Ig-like C2-type 2

Domain

234 – 326

93

Ig-like C2-type 3

Domain

331 – 416

86

Ig-like C2-type 4

Domain

429 – 520

92

Fibronectin type-III 1

Domain

528 – 616

89

Fibronectin type-III 2

Domain

622 – 714

93

Fibronectin type-III 3

Domain

726 – 814

89

Fibronectin type-III 4

Domain

843 – 939

97

Fibronectin type-III 5

Domain

944 – 1041

98

Fibronectin type-III 6

Compositional bias

1252 – 1373

122

Pro-rich

Amino acid modifications

Modified residue

1178

1

Phosphoserine; by MAPK1 Ref.5

Modified residue

1187

1

Phosphothreonine; by MAPK1 Ref.5

Modified residue

1267

1

Phosphoserine; by MAPK1 Ref.5

Glycosylation

60

1

N-linked (GlcNAc...) Ref.4

Glycosylation

94

1

N-linked (GlcNAc...) Ref.4

Glycosylation

299

1

N-linked (GlcNAc...) Ref.4

Glycosylation

318

1

N-linked (GlcNAc...) Ref.4

Glycosylation

478

1

N-linked (GlcNAc...) Potential

Glycosylation

628

1

N-linked (GlcNAc...) Potential

Glycosylation

702

1

N-linked (GlcNAc...) Potential

Disulfide bond

61 ↔ 117

Ref.4

Disulfide bond

161 ↔ 212

Ref.4

Disulfide bond

261 ↔ 310

Ref.4

Disulfide bond

352 ↔ 400

Ref.4

Experimental info

Mutagenesis

1178

1

S → A: Abolishes phosphorylation by MAPK1; when associated with A-1187 and A-1267. Ref.5

Mutagenesis

1187

1

T → A: Abolishes phosphorylation by MAPK1; when associated with A-1178 and A-1267. Ref.5

Mutagenesis

1267

1

S → A: Abolishes phosphorylation by MAPK1; when associated with A-1178 and A-1187. Ref.5

Secondary structure

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1445

Helix Strand Turn

Details...

Beta strand

39 – 44

6

Beta strand

49 – 51

3

Beta strand

57 – 59

3

Beta strand

62 – 64

3

Beta strand

71 – 76

6

Beta strand

89 – 91

3

Beta strand

97 – 99

3

Beta strand

113 – 120

8

Helix

122 – 124

3

Beta strand

126 – 128

3

Beta strand

132 – 136

5

Beta strand

149 – 152

4

Beta strand

157 – 159

3

Beta strand

170 – 179

10

Beta strand

188 – 191

4

Beta strand

197 – 199

3

Helix

204 – 206

3

Beta strand

208 – 215

8

Beta strand

226 – 231

6

Beta strand

238 – 244

7

Beta strand

249 – 252

4

Beta strand

257 – 259

3

Beta strand

262 – 267

6

Beta strand

270 – 275

6

Beta strand

283 – 290

8

Turn

291 – 293

3

Beta strand

294 – 297

4

Helix

302 – 304

3

Beta strand

306 – 314

9

Beta strand

317 – 335

19

Beta strand

348 – 350

3

Beta strand

353 – 358

6

Beta strand

361 – 366

6

Beta strand

374 – 380

7

Turn

381 – 383

3

Beta strand

384 – 389

6

Helix

392 – 394

3

Beta strand

396 – 404

9

Beta strand

407 – 416

10

Sequences

	Sequence		Length	Mass (Da)
	Q63155 [UniParc]. Last modified January 1, 1998. Version 2. Checksum: 084F625954481988	FASTA	1,445	157,941
	10 20 30 40 50 60 MENSLGCVWV PKLAFVLFGA SLLSAHLQVT GFQIKPFTSL HFVSEPSDAV TMRGGNVLLN 70 80 90 100 110 120 CSAESDRGVP VIKWKKDGLI LALGMDDRKQ QLPNGSLLIQ NILHSRHHKP DEGLYQCEAS 130 140 150 160 170 180 LGDSGSIISR TAKVMVAGPL RFLSQTESIT AFMGDTVLLK CEVIGDPMPT IHWQKNQQDL 190 200 210 220 230 240 NPIPGDSRVV VLPSGALQIS RLQPGDSGVY RCSARNPAST RTGNEAEVRI LSDPGLHRQL 250 260 270 280 290 300 YFLQRPSNVI AIEGKDAVLE CCVSGYPPPS FTWLRGEEVI QLRSKKYSLL GGSNLLISNV 310 320 330 340 350 360 TDDDSGTYTC VVTYKNENIS ASAELTVLVP PWFLNHPSNL YAYESMDIEF ECAVSGKPVP 370 380 390 400 410 420 TVNWMKNGDV VIPSDYFQIV GGSNLRILGV VKSDEGFYQC VAENEAGNAQ SSAQLIVPKP 430 440 450 460 470 480 AIPSSSILPS APRDVVPVLV SSRFVRLSWR PPAEAKGNIQ TFTVFFSREG DNRERALNTT 490 500 510 520 530 540 QPGSLQLTVG NLKPEAMYTF RVVAYNEWGP GESSQPIKVA TQPELQVPGP VENLHAVSAS 550 560 570 580 590 600 PTSILITWEP PAYANGPVQG YRLFCTEVST GKEQNIEVDG LSYKLEGLKK FTEYTLRFLA 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 DDFPTSGPDV 850 860 870 880 890 900 STPMLPPVGV QAVALTHEAV RVSWADNSVP KNQKTSDVRL YTVRWRTSFS ASAKYKSEDT 910 920 930 940 950 960 TSLSYTATGL KPNTMYEFSV MVTKNRRSST WSMTAHATTY EAAPTSAPKD LTVITREGKP 970 980 990 1000 1010 1020 RAVIVSWQPP LEANGKITAY ILFYTLDKNI PIDDWIMETI SGDRLTHQIM DLSLDTMYYF 1030 1040 1050 1060 1070 1080 RIQARNAKGV GPLSDPILFR TLKVEHPDKM ANDQGRHGDG GYWPVDTNLI DRSTLNEPPI 1090 1100 1110 1120 1130 1140 GQMHPPHGSV TPQKNSNLLV ITVVTVGVLT VLVVVIVAVI CTRRSSAQQR KKRATHSASK 1150 1160 1170 1180 1190 1200 RKGSQKDLRP PDLWIHHEEM EMKNIEKPAG TDPAGRGSPI QSCQDLTPVS HSQSESQMGS 1210 1220 1230 1240 1250 1260 KSASHSGQDT EEAGSSMSTL ERSLAARRAT RTKLMIPMEA QSNNPAVVSA IPVPTLESAQ 1270 1280 1290 1300 1310 1320 YPGILPSPTC GYPHPQFTLR PVPFPTLSVD RGFGAGRTVS EGPTAQQQPM LPPAQPEHPS 1330 1340 1350 1360 1370 1380 SEEAPSRTIP TACVRPTHPL RSFANPLLPP PMSAIEPKVP YTPLLSQPGP TLPKTHVKTA 1390 1400 1410 1420 1430 1440 SLGLAGKARS PLLPVSVPTA PEVSEESHKP TEDPASVYEQ DDLSEQMASL EGLMKQLNAI TGSAF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH NTN1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]	"Genome sequence of the Brown Norway rat yields insights into mammalian evolution." Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M. , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S. Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Brown Norway.
[3]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Brown Norway.
[4]	"Structure of DCC and the prediction of N-terminal horseshoe configuration in other neural receptors." Chen Q., Liu J.-H., Wang J.-H. Submitted (JAN-2010) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 39-421, DISULFIDE BONDS, GLYCOSYLATION AT ASN-60; ASN-94; ASN-299 AND ASN-318.
[5]	"Phosphorylation of DCC by ERK2 is facilitated by direct docking of the receptor P1 domain to the kinase." Ma W., Shang Y., Wei Z., Wen W., Wang W., Zhang M. Structure 18:1502-1511(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 1140-1166 IN COMPLEX WITH MAPK1, PHOSPHORYLATION AT SER-1178; THR-1187 AND SER-1267, MUTAGENESIS OF SER-1178; THR-1187 AND SER-1267.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U68725 mRNA. Translation: AAB41099.1.
CH473971 Genomic DNA. Translation: EDM14792.1.

IPI

IPI00205910.

RefSeq

NP_036973.1. NM_012841.1.

UniGene

Rn.10666.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3LAF	X-ray	2.40	A	39-421	[»]
3O71	X-ray	1.95	B	1140-1166	[»]

ProteinModelPortal

Q63155.

SMR

Q63155. Positions 419-524, 531-818, 833-1047.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-46811N.

IntAct

Q63155. 9 interactions.

STRING

10116.ENSRNOP00000041438.

PTM databases

PhosphoSite

Q63155.

Proteomic databases

PRIDE

Q63155.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

25311.

KEGG

rno:25311.

Organism-specific databases

CTD

1630.

RGD

2492. Dcc.

Phylogenomic databases

HOGENOM

HOG000230686.

HOVERGEN

HBG005455.

InParanoid

Q63155.

KO

K06765.

Enzyme and pathway databases

Reactome

REACT_127416. Developmental Biology.
REACT_96538. Developmental Biology.

Gene expression databases

ArrayExpress

Q63155.

Genevestigator

Q63155.

Family and domain databases

Gene3D

2.60.40.10. 10 hits.

InterPro

IPR003961. Fibronectin_type3.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR010560. Neogenin_C.
[Graphical view]

Pfam

PF00041. fn3. 6 hits.
PF07679. I-set. 3 hits.
PF06583. Neogenin_C. 1 hit.
[Graphical view]

SMART

SM00060. FN3. 6 hits.
SM00409. IG. 1 hit.
SM00408. IGc2. 3 hits.
[Graphical view]

SUPFAM

SSF49265. FN_III-like. 6 hits.

PROSITE

PS50853. FN3. 6 hits.
PS50835. IG_LIKE. 4 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q63155.

NextBio

606123.

Entry information

Entry name

DCC_RAT

Accession

Primary (citable) accession number: Q63155

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 21, 2012
Last sequence update:	January 1, 1998
Last modified:	May 1, 2013
This is version 99 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program