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Protein

Netrin-1

Gene

NTN1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Netrins control guidance of CNS commissural axons and peripheral motor axons. Its association with either DCC or some UNC5 receptors will lead to axon attraction or repulsion, respectively. It also serve as a survival factor via its association with its receptors which prevent the initiation of apoptosis. Involved in tumorigenesis by regulating apoptosis.1 Publication

GO - Biological processi

  1. anterior/posterior axon guidance Source: Ensembl
  2. apoptotic process Source: UniProtKB-KW
  3. axon guidance Source: Reactome
  4. establishment of nucleus localization Source: Ensembl
  5. inner ear morphogenesis Source: Ensembl
  6. mammary gland duct morphogenesis Source: Ensembl
  7. negative regulation of axon extension Source: Ensembl
  8. neuron migration Source: Ensembl
  9. positive regulation of axon extension Source: Ensembl
  10. positive regulation of cell proliferation Source: Ensembl
  11. regulation of cell migration Source: Ensembl
  12. single organismal cell-cell adhesion Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

ReactomeiREACT_22228. Role of second messengers in netrin-1 signaling.
REACT_22237. Netrin-1 signaling.
REACT_22351. DCC mediated attractive signaling.
REACT_22384. Netrin mediated repulsion signals.
REACT_25299. DSCAM interactions.

Names & Taxonomyi

Protein namesi
Recommended name:
Netrin-1
Alternative name(s):
Epididymis tissue protein Li 131P
Gene namesi
Name:NTN1
Synonyms:NTN1L
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 17

Organism-specific databases

HGNCiHGNC:8029. NTN1.

Subcellular locationi

GO - Cellular componenti

  1. basement membrane Source: Ensembl
  2. cytoplasm Source: Ensembl
  3. extracellular region Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA31813.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Sequence AnalysisAdd
BLAST
Chaini25 – 604580Netrin-1PRO_0000017082Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi95 – 951N-linked (GlcNAc...)Sequence Analysis
Glycosylationi116 – 1161N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi119 ↔ 152By similarity
Glycosylationi131 – 1311N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi285 ↔ 294By similarity
Disulfide bondi287 ↔ 304By similarity
Disulfide bondi306 ↔ 315By similarity
Disulfide bondi318 ↔ 338By similarity
Disulfide bondi341 ↔ 350By similarity
Disulfide bondi343 ↔ 368By similarity
Disulfide bondi371 ↔ 380By similarity
Disulfide bondi383 ↔ 401By similarity
Disulfide bondi404 ↔ 416By similarity
Disulfide bondi406 ↔ 423By similarity
Glycosylationi417 – 4171N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi425 ↔ 434By similarity
Disulfide bondi437 ↔ 451By similarity
Disulfide bondi472 ↔ 544By similarity
Disulfide bondi491 ↔ 601By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiO95631.
PaxDbiO95631.
PRIDEiO95631.

PTM databases

PhosphoSiteiO95631.

Expressioni

Tissue specificityi

Widely expressed in normal adult tissues with highest levels in heart, small intestine, colon, liver and prostate. Reduced expression in brain tumors and neuroblastomas. Expressed in epididymis (at protein level).2 Publications

Gene expression databases

BgeeiO95631.
CleanExiHS_NTN1.
ExpressionAtlasiO95631. baseline and differential.
GenevestigatoriO95631.

Organism-specific databases

HPAiHPA056419.

Interactioni

Subunit structurei

Binds to its receptors; DCC, DSCAM, UNC5A, UNC5B, UNC5C and probably UNC5D.

Protein-protein interaction databases

BioGridi114816. 2 interactions.
DIPiDIP-46273N.
IntActiO95631. 1 interaction.
STRINGi9606.ENSP00000173229.

Structurei

Secondary structure

1
604
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni58 – 614Combined sources
Beta strandi75 – 795Combined sources
Beta strandi83 – 864Combined sources
Beta strandi90 – 945Combined sources
Beta strandi96 – 994Combined sources
Helixi105 – 1073Combined sources
Beta strandi108 – 1103Combined sources
Beta strandi132 – 15322Combined sources
Beta strandi157 – 16610Combined sources
Beta strandi172 – 1798Combined sources
Helixi181 – 1844Combined sources
Helixi197 – 1993Combined sources
Beta strandi202 – 2043Combined sources
Beta strandi210 – 2123Combined sources
Beta strandi217 – 2215Combined sources
Turni222 – 2254Combined sources
Helixi227 – 2348Combined sources
Helixi236 – 2416Combined sources
Beta strandi243 – 2519Combined sources
Beta strandi257 – 2593Combined sources
Turni266 – 2683Combined sources
Helixi269 – 2713Combined sources
Beta strandi275 – 28511Combined sources
Beta strandi294 – 2963Combined sources
Beta strandi302 – 3043Combined sources
Beta strandi310 – 3123Combined sources
Beta strandi348 – 3525Combined sources
Helixi354 – 3596Combined sources
Beta strandi366 – 3705Combined sources
Turni372 – 3743Combined sources
Beta strandi375 – 3773Combined sources
Beta strandi387 – 3893Combined sources
Beta strandi401 – 4033Combined sources
Turni408 – 4103Combined sources
Beta strandi418 – 4203Combined sources
Beta strandi429 – 4313Combined sources
Beta strandi451 – 4533Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4URTX-ray3.10A39-453[»]
ProteinModelPortaliO95631.
SMRiO95631. Positions 39-453.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini47 – 284238Laminin N-terminalPROSITE-ProRule annotationAdd
BLAST
Domaini285 – 34056Laminin EGF-like 1PROSITE-ProRule annotationAdd
BLAST
Domaini341 – 40363Laminin EGF-like 2PROSITE-ProRule annotationAdd
BLAST
Domaini404 – 45350Laminin EGF-like 3PROSITE-ProRule annotationAdd
BLAST
Domaini472 – 601130NTRPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi530 – 5323Cell attachment siteSequence Analysis

Sequence similaritiesi

Contains 3 laminin EGF-like domains.PROSITE-ProRule annotation
Contains 1 laminin N-terminal domain.PROSITE-ProRule annotation
Contains 1 NTR domain.PROSITE-ProRule annotation

Keywords - Domaini

Laminin EGF-like domain, Repeat, Signal

Phylogenomic databases

eggNOGiNOG244580.
GeneTreeiENSGT00780000121873.
HOGENOMiHOG000286017.
HOVERGENiHBG006464.
InParanoidiO95631.
KOiK06843.
OMAiWQSENFV.
OrthoDBiEOG7SR4KJ.
PhylomeDBiO95631.
TreeFamiTF352481.

Family and domain databases

Gene3Di2.60.120.260. 1 hit.
InterProiIPR013032. EGF-like_CS.
IPR002049. EGF_laminin.
IPR008979. Galactose-bd-like.
IPR008211. Laminin_N.
IPR001134. Netrin_domain.
IPR018933. Netrin_module_non-TIMP.
IPR008993. TIMP-like_OB-fold.
[Graphical view]
PfamiPF00053. Laminin_EGF. 3 hits.
PF00055. Laminin_N. 1 hit.
PF01759. NTR. 1 hit.
[Graphical view]
SMARTiSM00643. C345C. 1 hit.
SM00180. EGF_Lam. 3 hits.
SM00136. LamNT. 1 hit.
[Graphical view]
SUPFAMiSSF49785. SSF49785. 1 hit.
SSF50242. SSF50242. 1 hit.
PROSITEiPS00022. EGF_1. 2 hits.
PS01248. EGF_LAM_1. 3 hits.
PS50027. EGF_LAM_2. 3 hits.
PS51117. LAMININ_NTER. 1 hit.
PS50189. NTR. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O95631-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MMRAVWEALA ALAAVACLVG AVRGGPGLSM FAGQAAQPDP CSDENGHPRR
60 70 80 90 100
CIPDFVNAAF GKDVRVSSTC GRPPARYCVV SERGEERLRS CHLCNASDPK
110 120 130 140 150
KAHPPAFLTD LNNPHNLTCW QSENYLQFPH NVTLTLSLGK KFEVTYVSLQ
160 170 180 190 200
FCSPRPESMA IYKSMDYGRT WVPFQFYSTQ CRKMYNRPHR APITKQNEQE
210 220 230 240 250
AVCTDSHTDM RPLSGGLIAF STLDGRPSAH DFDNSPVLQD WVTATDIRVA
260 270 280 290 300
FSRLHTFGDE NEDDSELARD SYFYAVSDLQ VGGRCKCNGH AARCVRDRDD
310 320 330 340 350
SLVCDCRHNT AGPECDRCKP FHYDRPWQRA TAREANECVA CNCNLHARRC
360 370 380 390 400
RFNMELYKLS GRKSGGVCLN CRHNTAGRHC HYCKEGYYRD MGKPITHRKA
410 420 430 440 450
CKACDCHPVG AAGKTCNQTT GQCPCKDGVT GITCNRCAKG YQQSRSPIAP
460 470 480 490 500
CIKIPVAPPT TAASSVEEPE DCDSYCKASK GKLKINMKKY CKKDYAVQIH
510 520 530 540 550
ILKADKAGDW WKFTVNIISV YKQGTSRIRR GDQSLWIRSR DIACKCPKIK
560 570 580 590 600
PLKKYLLLGN AEDSPDQSGI VADKSSLVIQ WRDTWARRLR KFQQREKKGK

CKKA
Length:604
Mass (Da):67,748
Last modified:May 5, 2009 - v2
Checksum:i9827C09D0D783B27
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti299 – 2991D → T in AAD09221 (PubMed:9950216).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti351 – 3511R → H in a neuroblastoma sample. 1 Publication
VAR_014279
Natural varianti489 – 4891K → E in a neuroblastoma sample. 1 Publication
VAR_014280

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U75586 mRNA. Translation: AAD09221.1.
GU727649 mRNA. Translation: ADU87650.1.
AC090610 Genomic DNA. No translation available.
AC005695 Genomic DNA. No translation available.
CCDSiCCDS11148.1.
RefSeqiNP_004813.2. NM_004822.2.
XP_006721658.1. XM_006721595.1.
UniGeneiHs.660885.

Genome annotation databases

EnsembliENST00000173229; ENSP00000173229; ENSG00000065320.
GeneIDi9423.
KEGGihsa:9423.
UCSCiuc002glw.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U75586 mRNA. Translation: AAD09221.1.
GU727649 mRNA. Translation: ADU87650.1.
AC090610 Genomic DNA. No translation available.
AC005695 Genomic DNA. No translation available.
CCDSiCCDS11148.1.
RefSeqiNP_004813.2. NM_004822.2.
XP_006721658.1. XM_006721595.1.
UniGeneiHs.660885.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4URTX-ray3.10A39-453[»]
ProteinModelPortaliO95631.
SMRiO95631. Positions 39-453.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114816. 2 interactions.
DIPiDIP-46273N.
IntActiO95631. 1 interaction.
STRINGi9606.ENSP00000173229.

PTM databases

PhosphoSiteiO95631.

Proteomic databases

MaxQBiO95631.
PaxDbiO95631.
PRIDEiO95631.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000173229; ENSP00000173229; ENSG00000065320.
GeneIDi9423.
KEGGihsa:9423.
UCSCiuc002glw.4. human.

Organism-specific databases

CTDi9423.
GeneCardsiGC17P008924.
H-InvDBHIX0039241.
HGNCiHGNC:8029. NTN1.
HPAiHPA056419.
MIMi601614. gene.
neXtProtiNX_O95631.
PharmGKBiPA31813.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG244580.
GeneTreeiENSGT00780000121873.
HOGENOMiHOG000286017.
HOVERGENiHBG006464.
InParanoidiO95631.
KOiK06843.
OMAiWQSENFV.
OrthoDBiEOG7SR4KJ.
PhylomeDBiO95631.
TreeFamiTF352481.

Enzyme and pathway databases

ReactomeiREACT_22228. Role of second messengers in netrin-1 signaling.
REACT_22237. Netrin-1 signaling.
REACT_22351. DCC mediated attractive signaling.
REACT_22384. Netrin mediated repulsion signals.
REACT_25299. DSCAM interactions.

Miscellaneous databases

ChiTaRSiNTN1. human.
GeneWikiiNTN1.
GenomeRNAii9423.
NextBioi35298.
PROiO95631.
SOURCEiSearch...

Gene expression databases

BgeeiO95631.
CleanExiHS_NTN1.
ExpressionAtlasiO95631. baseline and differential.
GenevestigatoriO95631.

Family and domain databases

Gene3Di2.60.120.260. 1 hit.
InterProiIPR013032. EGF-like_CS.
IPR002049. EGF_laminin.
IPR008979. Galactose-bd-like.
IPR008211. Laminin_N.
IPR001134. Netrin_domain.
IPR018933. Netrin_module_non-TIMP.
IPR008993. TIMP-like_OB-fold.
[Graphical view]
PfamiPF00053. Laminin_EGF. 3 hits.
PF00055. Laminin_N. 1 hit.
PF01759. NTR. 1 hit.
[Graphical view]
SMARTiSM00643. C345C. 1 hit.
SM00180. EGF_Lam. 3 hits.
SM00136. LamNT. 1 hit.
[Graphical view]
SUPFAMiSSF49785. SSF49785. 1 hit.
SSF50242. SSF50242. 1 hit.
PROSITEiPS00022. EGF_1. 2 hits.
PS01248. EGF_LAM_1. 3 hits.
PS50027. EGF_LAM_2. 3 hits.
PS51117. LAMININ_NTER. 1 hit.
PS50189. NTR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Netrin-1: interaction with deleted in colorectal cancer (DCC) and alterations in brain tumors and neuroblastomas."
    Meyerhardt J.A., Caca K., Eckstrand B.C., Hu G., Lengauer C., Banavali S., Look A.T., Fearon E.R.
    Cell Growth Differ. 10:35-42(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH DCC, TISSUE SPECIFICITY, VARIANTS HIS-351 AND GLU-489.
    Tissue: Brain stem and Liver.
  2. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
    Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
    , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
    Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "Systematic mapping and functional analysis of a family of human epididymal secretory sperm-located proteins."
    Li J., Liu F., Wang H., Liu X., Liu J., Li N., Wan F., Wang W., Zhang C., Jin S., Liu J., Zhu P., Liu Y.
    Mol. Cell. Proteomics 9:2517-2528(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
    Tissue: Epididymis.
  4. "Netrin-1 controls colorectal tumorigenesis by regulating apoptosis."
    Mazelin L., Bernet A., Bonod-Bidaud C., Pays L., Arnaud S., Gespach C., Bredesen D.E., Scoazec J.-Y., Mehlen P.
    Nature 431:80-84(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  5. "DSCAM functions as a netrin receptor in commissural axon pathfinding."
    Liu G., Li W., Wang L., Kar A., Guan K.L., Rao Y., Wu J.Y.
    Proc. Natl. Acad. Sci. U.S.A. 106:2951-2956(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH DSCAM.

Entry informationi

Entry nameiNET1_HUMAN
AccessioniPrimary (citable) accession number: O95631
Secondary accession number(s): E9KL51
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 15, 2002
Last sequence update: May 5, 2009
Last modified: February 4, 2015
This is version 124 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.