O95631 (NET1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Netrin-1

Alternative name(s):
Epididymis tissue protein Li 131P

Gene names

Name:	NTN1
Synonyms:	NTN1L

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	604 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	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. Ref.4
Subunit structure	Binds to its receptors; DCC, DSCAM, UNC5A, UNC5B, UNC5C and probably UNC5D. Ref.1 Ref.5
Subcellular location	Secreted › extracellular space › extracellular matrix By similarity.
Tissue specificity	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). Ref.1 Ref.3
Sequence similarities	Contains 3 laminin EGF-like domains. Contains 1 laminin N-terminal domain. Contains 1 NTR domain.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Extracellular matrix Secreted
Coding sequence diversity	Polymorphism
Domain	Laminin EGF-like domain Repeat Signal
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW axon guidance Traceable author statement. Source: Reactome cell-cell adhesion Inferred from electronic annotation. Source: Compara establishment of nucleus localization Inferred from electronic annotation. Source: Compara inner ear morphogenesis Inferred from electronic annotation. Source: Compara mammary gland duct morphogenesis Inferred from electronic annotation. Source: Compara negative regulation of axon extension Inferred from electronic annotation. Source: Compara neuron migration Inferred from electronic annotation. Source: Compara positive regulation of axon extension Inferred from electronic annotation. Source: Compara positive regulation of cell proliferation Inferred from electronic annotation. Source: Compara regulation of cell migration Inferred from electronic annotation. Source: Compara
Cellular_component	basement membrane Inferred from electronic annotation. Source: Compara cytoplasm Inferred from electronic annotation. Source: Compara extracellular region Traceable author statement. Source: Reactome
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 24	24	Potential
	Chain	25 – 604	580	Netrin-1		PRO_0000017082
Regions
	Domain	47 – 284	238	Laminin N-terminal
	Domain	285 – 340	56	Laminin EGF-like 1
	Domain	341 – 403	63	Laminin EGF-like 2
	Domain	404 – 453	50	Laminin EGF-like 3
	Domain	472 – 601	130	NTR
	Motif	530 – 532	3	Cell attachment site Potential
Amino acid modifications
	Glycosylation	95	1	N-linked (GlcNAc...) Potential
	Glycosylation	116	1	N-linked (GlcNAc...) Potential
	Glycosylation	131	1	N-linked (GlcNAc...) Potential
	Glycosylation	417	1	N-linked (GlcNAc...) Potential
	Disulfide bond	119 ↔ 152		By similarity
	Disulfide bond	285 ↔ 294		By similarity
	Disulfide bond	287 ↔ 304		By similarity
	Disulfide bond	306 ↔ 315		By similarity
	Disulfide bond	318 ↔ 338		By similarity
	Disulfide bond	341 ↔ 350		By similarity
	Disulfide bond	343 ↔ 368		By similarity
	Disulfide bond	371 ↔ 380		By similarity
	Disulfide bond	383 ↔ 401		By similarity
	Disulfide bond	404 ↔ 416		By similarity
	Disulfide bond	406 ↔ 423		By similarity
	Disulfide bond	425 ↔ 434		By similarity
	Disulfide bond	437 ↔ 451		By similarity
	Disulfide bond	472 ↔ 544		By similarity
	Disulfide bond	491 ↔ 601		By similarity
Natural variations
	Natural variant	351	1	R → H in a neuroblastoma sample. Ref.1		VAR_014279
	Natural variant	489	1	K → E in a neuroblastoma sample. Ref.1		VAR_014280
Experimental info
	Sequence conflict	299	1	D → T in AAD09221. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O95631 [UniParc]. Last modified May 5, 2009. Version 2. Checksum: 9827C09D0D783B27	FASTA	604	67,748
	10 20 30 40 50 60 MMRAVWEALA ALAAVACLVG AVRGGPGLSM FAGQAAQPDP CSDENGHPRR CIPDFVNAAF 70 80 90 100 110 120 GKDVRVSSTC GRPPARYCVV SERGEERLRS CHLCNASDPK KAHPPAFLTD LNNPHNLTCW 130 140 150 160 170 180 QSENYLQFPH NVTLTLSLGK KFEVTYVSLQ FCSPRPESMA IYKSMDYGRT WVPFQFYSTQ 190 200 210 220 230 240 CRKMYNRPHR APITKQNEQE AVCTDSHTDM RPLSGGLIAF STLDGRPSAH DFDNSPVLQD 250 260 270 280 290 300 WVTATDIRVA FSRLHTFGDE NEDDSELARD SYFYAVSDLQ VGGRCKCNGH AARCVRDRDD 310 320 330 340 350 360 SLVCDCRHNT AGPECDRCKP FHYDRPWQRA TAREANECVA CNCNLHARRC RFNMELYKLS 370 380 390 400 410 420 GRKSGGVCLN CRHNTAGRHC HYCKEGYYRD MGKPITHRKA CKACDCHPVG AAGKTCNQTT 430 440 450 460 470 480 GQCPCKDGVT GITCNRCAKG YQQSRSPIAP CIKIPVAPPT TAASSVEEPE DCDSYCKASK 490 500 510 520 530 540 GKLKINMKKY CKKDYAVQIH ILKADKAGDW WKFTVNIISV YKQGTSRIRR GDQSLWIRSR 550 560 570 580 590 600 DIACKCPKIK PLKKYLLLGN AEDSPDQSGI VADKSSLVIQ WRDTWARRLR KFQQREKKGK CKKA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U75586 mRNA. Translation: AAD09221.1. GU727649 mRNA. Translation: ADU87650.1. AC090610 Genomic DNA. No translation available. AC005695 Genomic DNA. No translation available.
IPI	IPI00006732.
RefSeq	NP_004813.2. NM_004822.2.
UniGene	Hs.660885.
3D structure databases
ProteinModelPortal	O95631.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-46273N.
IntAct	O95631. 1 interaction.
STRING	9606.ENSP00000173229.
PTM databases
PhosphoSite	O95631.
Proteomic databases
PaxDb	O95631.
PRIDE	O95631.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000173229; ENSP00000173229; ENSG00000065320. ENST00000538852; ENSP00000443259; ENSG00000065320. ENST00000546090; ENSP00000441611; ENSG00000065320.
GeneID	9423.
KEGG	hsa:9423.
UCSC	uc002glw.4. human.
Organism-specific databases
CTD	9423.
GeneCards	GC17P008865.
H-InvDB	HIX0039241.
HGNC	HGNC:8029. NTN1.
MIM	601614. gene.
neXtProt	NX_O95631.
PharmGKB	PA31813.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG244580.
HOGENOM	HOG000286017.
HOVERGEN	HBG006464.
InParanoid	O95631.
KO	K06843.
OMA	NCHTCDA.
OrthoDB	EOG4H19V9.
PhylomeDB	O95631.
Enzyme and pathway databases
Reactome	REACT_111045. Developmental Biology. REACT_111155. Cell-Cell communication.
Gene expression databases
ArrayExpress	O95631.
Bgee	O95631.
CleanEx	HS_NTN1.
Genevestigator	O95631.
GermOnline	ENSG00000065320. Homo sapiens.
Family and domain databases
InterPro	IPR013032. EGF-like_CS. IPR002049. EGF_laminin. IPR008211. Laminin_N. IPR001134. Netrin_domain. IPR018933. Netrin_module_non-TIMP. IPR008993. TIMP-like_OB-fold. [Graphical view]
Pfam	PF00053. Laminin_EGF. 3 hits. PF00055. Laminin_N. 1 hit. PF01759. NTR. 1 hit. [Graphical view]
SMART	SM00643. C345C. 1 hit. SM00180. EGF_Lam. 3 hits. SM00136. LamNT. 1 hit. [Graphical view]
SUPFAM	SSF50242. TIMP_like. 1 hit.
PROSITE	PS00022. EGF_1. 2 hits. PS01186. EGF_2. False negative. PS01248. EGF_LAM_1. 3 hits. PS50027. EGF_LAM_2. 3 hits. PS51117. LAMININ_NTER. 1 hit. PS50189. NTR. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL1741307.
GenomeRNAi	9423.
NextBio	35298.
SOURCE	Search...

Entry information

Entry name

NET1_HUMAN

Accession

Primary (citable) accession number: O95631
Secondary accession number(s): E9KL51

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 15, 2002
Last sequence update:	May 5, 2009
Last modified:	May 1, 2013
This is version 107 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.