ID NET1_HUMAN Reviewed; 604 AA. AC O95631; E9KL51; DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot. DT 05-MAY-2009, sequence version 2. DT 13-FEB-2019, entry version 158. DE RecName: Full=Netrin-1; DE AltName: Full=Epididymis tissue protein Li 131P; DE Flags: Precursor; GN Name=NTN1; Synonyms=NTN1L; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH DCC, TISSUE SPECIFICITY, RP AND VARIANTS HIS-351 AND GLU-489. RC TISSUE=Brain stem, and Liver; RX PubMed=9950216; RA Meyerhardt J.A., Caca K., Eckstrand B.C., Hu G., Lengauer C., RA Banavali S., Look A.T., Fearon E.R.; RT "Netrin-1: interaction with deleted in colorectal cancer (DCC) and RT alterations in brain tumors and neuroblastomas."; RL Cell Growth Differ. 10:35-42(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in RT the human lineage."; RL Nature 440:1045-1049(2006). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC TISSUE=Epididymis; RX PubMed=20736409; DOI=10.1074/mcp.M110.001719; RA Li J., Liu F., Wang H., Liu X., Liu J., Li N., Wan F., Wang W., RA Zhang C., Jin S., Liu J., Zhu P., Liu Y.; RT "Systematic mapping and functional analysis of a family of human RT epididymal secretory sperm-located proteins."; RL Mol. Cell. Proteomics 9:2517-2528(2010). RN [4] RP FUNCTION. RX PubMed=15343335; DOI=10.1038/nature02788; RA Mazelin L., Bernet A., Bonod-Bidaud C., Pays L., Arnaud S., RA Gespach C., Bredesen D.E., Scoazec J.-Y., Mehlen P.; RT "Netrin-1 controls colorectal tumorigenesis by regulating apoptosis."; RL Nature 431:80-84(2004). RN [5] RP INTERACTION WITH DSCAM. RX PubMed=19196994; DOI=10.1073/pnas.0811083106; RA Liu G., Li W., Wang L., Kar A., Guan K.L., Rao Y., Wu J.Y.; RT "DSCAM functions as a netrin receptor in commissural axon RT pathfinding."; RL Proc. Natl. Acad. Sci. U.S.A. 106:2951-2956(2009). CC -!- FUNCTION: Netrins control guidance of CNS commissural axons and CC peripheral motor axons. Its association with either DCC or some CC UNC5 receptors will lead to axon attraction or repulsion, CC respectively. It also serve as a survival factor via its CC association with its receptors which prevent the initiation of CC apoptosis. Involved in tumorigenesis by regulating apoptosis. CC {ECO:0000269|PubMed:15343335}. CC -!- SUBUNIT: Binds to its receptors; DCC, DSCAM, UNC5A, UNC5B, UNC5C CC and probably UNC5D. CC -!- INTERACTION: CC P43146:DCC; NbExp=4; IntAct=EBI-2678626, EBI-1222919; CC Q8NBI3:DRAXIN; NbExp=3; IntAct=EBI-2678626, EBI-10827752; CC Q8IZJ1-2:UNC5B; NbExp=2; IntAct=EBI-2678626, EBI-10832046; CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular CC matrix {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Widely expressed in normal adult tissues with CC highest levels in heart, small intestine, colon, liver and CC prostate. Reduced expression in brain tumors and neuroblastomas. CC Expressed in epididymis (at protein level). CC {ECO:0000269|PubMed:20736409, ECO:0000269|PubMed:9950216}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; U75586; AAD09221.1; -; mRNA. DR EMBL; GU727649; ADU87650.1; -; mRNA. DR EMBL; AC090610; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC005695; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS11148.1; -. DR RefSeq; NP_004813.2; NM_004822.2. DR RefSeq; XP_006721658.1; XM_006721595.3. DR UniGene; Hs.660885; -. DR PDB; 4URT; X-ray; 3.10 A; A=39-453. DR PDB; 6FKQ; X-ray; 3.07 A; A=39-453. DR PDBsum; 4URT; -. DR PDBsum; 6FKQ; -. DR ProteinModelPortal; O95631; -. DR SMR; O95631; -. DR BioGrid; 114816; 6. DR DIP; DIP-46273N; -. DR IntAct; O95631; 7. DR STRING; 9606.ENSP00000173229; -. DR GlyConnect; 1542; -. DR iPTMnet; O95631; -. DR PhosphoSitePlus; O95631; -. DR BioMuta; NTN1; -. DR jPOST; O95631; -. DR MaxQB; O95631; -. DR PaxDb; O95631; -. DR PeptideAtlas; O95631; -. DR PRIDE; O95631; -. DR ProteomicsDB; 50967; -. DR Ensembl; ENST00000173229; ENSP00000173229; ENSG00000065320. DR GeneID; 9423; -. DR KEGG; hsa:9423; -. DR UCSC; uc002glw.4; human. DR CTD; 9423; -. DR DisGeNET; 9423; -. DR EuPathDB; HostDB:ENSG00000065320.8; -. DR GeneCards; NTN1; -. DR H-InvDB; HIX0039241; -. DR HGNC; HGNC:8029; NTN1. DR HPA; HPA056419; -. DR MalaCards; NTN1; -. DR MIM; 601614; gene. DR neXtProt; NX_O95631; -. DR OpenTargets; ENSG00000065320; -. DR Orphanet; 238722; Familial congenital mirror movements. DR PharmGKB; PA31813; -. DR eggNOG; KOG3512; Eukaryota. DR eggNOG; ENOG410XS7U; LUCA. DR GeneTree; ENSGT00940000153882; -. DR HOGENOM; HOG000286017; -. DR HOVERGEN; HBG006464; -. DR InParanoid; O95631; -. DR KO; K06843; -. DR OMA; DQFLWVR; -. DR OrthoDB; 858946at2759; -. DR PhylomeDB; O95631; -. DR TreeFam; TF352481; -. DR Reactome; R-HSA-373752; Netrin-1 signaling. DR Reactome; R-HSA-376172; DSCAM interactions. DR Reactome; R-HSA-418885; DCC mediated attractive signaling. DR Reactome; R-HSA-418886; Netrin mediated repulsion signals. DR Reactome; R-HSA-418890; Role of second messengers in netrin-1 signaling. DR Reactome; R-HSA-428542; Regulation of commissural axon pathfinding by SLIT and ROBO. DR SIGNOR; O95631; -. DR ChiTaRS; NTN1; human. DR GeneWiki; NTN1; -. DR GenomeRNAi; 9423; -. DR PRO; PR:O95631; -. DR Proteomes; UP000005640; Chromosome 17. DR Bgee; ENSG00000065320; Expressed in 168 organ(s), highest expression level in lower esophagus. DR ExpressionAtlas; O95631; baseline and differential. DR Genevisible; O95631; HS. DR GO; GO:0005604; C:basement membrane; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0033564; P:anterior/posterior axon guidance; IEA:Ensembl. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0032488; P:Cdc42 protein signal transduction; ISS:UniProtKB. DR GO; GO:0098609; P:cell-cell adhesion; IEA:Ensembl. DR GO; GO:0042472; P:inner ear morphogenesis; IEA:Ensembl. DR GO; GO:0060603; P:mammary gland duct morphogenesis; IEA:Ensembl. DR GO; GO:0030517; P:negative regulation of axon extension; IEA:Ensembl. DR GO; GO:1902842; P:negative regulation of netrin-activated signaling pathway; TAS:Reactome. DR GO; GO:0001764; P:neuron migration; IEA:Ensembl. DR GO; GO:0007097; P:nuclear migration; IEA:Ensembl. DR GO; GO:0045773; P:positive regulation of axon extension; ISS:UniProtKB. DR GO; GO:2000147; P:positive regulation of cell motility; ISS:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl. DR GO; GO:0007265; P:Ras protein signal transduction; ISS:UniProtKB. DR GO; GO:0030334; P:regulation of cell migration; IEA:Ensembl. DR GO; GO:0051963; P:regulation of synapse assembly; IEA:Ensembl. DR GO; GO:0006930; P:substrate-dependent cell migration, cell extension; ISS:UniProtKB. DR Gene3D; 2.60.120.1490; -; 1. DR InterPro; IPR008979; Galactose-bd-like_sf. DR InterPro; IPR002049; Laminin_EGF. DR InterPro; IPR008211; Laminin_N. DR InterPro; IPR038684; Laminin_N_sf. DR InterPro; IPR001134; Netrin_domain. DR InterPro; IPR018933; Netrin_module_non-TIMP. DR InterPro; IPR008993; TIMP-like_OB-fold. DR Pfam; PF00053; Laminin_EGF; 3. DR Pfam; PF00055; Laminin_N; 1. DR Pfam; PF01759; NTR; 1. DR SMART; SM00643; C345C; 1. DR SMART; SM00180; EGF_Lam; 3. DR SMART; SM00136; LamNT; 1. DR SUPFAM; SSF49785; SSF49785; 1. DR SUPFAM; SSF50242; SSF50242; 1. DR PROSITE; PS00022; EGF_1; 2. DR PROSITE; PS01248; EGF_LAM_1; 3. DR PROSITE; PS50027; EGF_LAM_2; 3. DR PROSITE; PS51117; LAMININ_NTER; 1. DR PROSITE; PS50189; NTR; 1. PE 1: Evidence at protein level; KW 3D-structure; Apoptosis; Complete proteome; Disulfide bond; KW Extracellular matrix; Glycoprotein; Laminin EGF-like domain; KW Polymorphism; Reference proteome; Repeat; Secreted; Signal. FT SIGNAL 1 24 {ECO:0000255}. FT CHAIN 25 604 Netrin-1. FT /FTId=PRO_0000017082. FT DOMAIN 47 284 Laminin N-terminal. {ECO:0000255|PROSITE- FT ProRule:PRU00466}. FT DOMAIN 285 340 Laminin EGF-like 1. {ECO:0000255|PROSITE- FT ProRule:PRU00460}. FT DOMAIN 341 403 Laminin EGF-like 2. {ECO:0000255|PROSITE- FT ProRule:PRU00460}. FT DOMAIN 404 453 Laminin EGF-like 3. {ECO:0000255|PROSITE- FT ProRule:PRU00460}. FT DOMAIN 472 601 NTR. {ECO:0000255|PROSITE- FT ProRule:PRU00295}. FT MOTIF 530 532 Cell attachment site. {ECO:0000255}. FT CARBOHYD 95 95 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 116 116 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 131 131 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 417 417 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 119 152 {ECO:0000250}. FT DISULFID 285 294 {ECO:0000250}. FT DISULFID 287 304 {ECO:0000250}. FT DISULFID 306 315 {ECO:0000250}. FT DISULFID 318 338 {ECO:0000250}. FT DISULFID 341 350 {ECO:0000250}. FT DISULFID 343 368 {ECO:0000250}. FT DISULFID 371 380 {ECO:0000250}. FT DISULFID 383 401 {ECO:0000250}. FT DISULFID 404 416 {ECO:0000250}. FT DISULFID 406 423 {ECO:0000250}. FT DISULFID 425 434 {ECO:0000250}. FT DISULFID 437 451 {ECO:0000250}. FT DISULFID 472 544 {ECO:0000250}. FT DISULFID 491 601 {ECO:0000250}. FT VARIANT 351 351 R -> H (in a neuroblastoma sample; FT dbSNP:rs531668666). FT {ECO:0000269|PubMed:9950216}. FT /FTId=VAR_014279. FT VARIANT 489 489 K -> E (in a neuroblastoma sample). FT {ECO:0000269|PubMed:9950216}. FT /FTId=VAR_014280. FT CONFLICT 299 299 D -> T (in Ref. 1; AAD09221). FT {ECO:0000305}. FT STRAND 44 46 {ECO:0000244|PDB:6FKQ}. FT TURN 58 61 {ECO:0000244|PDB:6FKQ}. FT STRAND 65 67 {ECO:0000244|PDB:6FKQ}. FT STRAND 75 83 {ECO:0000244|PDB:6FKQ}. FT STRAND 86 94 {ECO:0000244|PDB:6FKQ}. FT HELIX 99 101 {ECO:0000244|PDB:6FKQ}. FT HELIX 106 109 {ECO:0000244|PDB:6FKQ}. FT STRAND 132 153 {ECO:0000244|PDB:6FKQ}. FT STRAND 156 166 {ECO:0000244|PDB:6FKQ}. FT STRAND 172 179 {ECO:0000244|PDB:6FKQ}. FT HELIX 181 185 {ECO:0000244|PDB:6FKQ}. FT HELIX 197 199 {ECO:0000244|PDB:4URT}. FT STRAND 202 204 {ECO:0000244|PDB:4URT}. FT STRAND 212 215 {ECO:0000244|PDB:6FKQ}. FT STRAND 217 221 {ECO:0000244|PDB:6FKQ}. FT TURN 222 225 {ECO:0000244|PDB:4URT}. FT HELIX 232 234 {ECO:0000244|PDB:6FKQ}. FT HELIX 236 241 {ECO:0000244|PDB:6FKQ}. FT STRAND 243 254 {ECO:0000244|PDB:6FKQ}. FT STRAND 257 259 {ECO:0000244|PDB:4URT}. FT HELIX 265 269 {ECO:0000244|PDB:6FKQ}. FT STRAND 275 285 {ECO:0000244|PDB:6FKQ}. FT STRAND 292 296 {ECO:0000244|PDB:6FKQ}. FT STRAND 302 305 {ECO:0000244|PDB:6FKQ}. FT STRAND 310 312 {ECO:0000244|PDB:6FKQ}. FT TURN 344 346 {ECO:0000244|PDB:6FKQ}. FT STRAND 350 352 {ECO:0000244|PDB:6FKQ}. FT HELIX 354 359 {ECO:0000244|PDB:6FKQ}. FT STRAND 366 368 {ECO:0000244|PDB:6FKQ}. FT TURN 372 374 {ECO:0000244|PDB:6FKQ}. FT STRAND 375 380 {ECO:0000244|PDB:6FKQ}. FT STRAND 387 389 {ECO:0000244|PDB:6FKQ}. FT STRAND 391 393 {ECO:0000244|PDB:6FKQ}. FT STRAND 401 403 {ECO:0000244|PDB:6FKQ}. FT TURN 408 410 {ECO:0000244|PDB:6FKQ}. FT TURN 418 420 {ECO:0000244|PDB:6FKQ}. FT TURN 431 434 {ECO:0000244|PDB:6FKQ}. FT STRAND 447 449 {ECO:0000244|PDB:6FKQ}. FT STRAND 451 453 {ECO:0000244|PDB:4URT}. SQ SEQUENCE 604 AA; 67748 MW; 9827C09D0D783B27 CRC64; MMRAVWEALA ALAAVACLVG AVRGGPGLSM FAGQAAQPDP CSDENGHPRR CIPDFVNAAF GKDVRVSSTC GRPPARYCVV SERGEERLRS CHLCNASDPK KAHPPAFLTD LNNPHNLTCW QSENYLQFPH NVTLTLSLGK KFEVTYVSLQ FCSPRPESMA IYKSMDYGRT WVPFQFYSTQ CRKMYNRPHR APITKQNEQE AVCTDSHTDM RPLSGGLIAF STLDGRPSAH DFDNSPVLQD WVTATDIRVA FSRLHTFGDE NEDDSELARD SYFYAVSDLQ VGGRCKCNGH AARCVRDRDD SLVCDCRHNT AGPECDRCKP FHYDRPWQRA TAREANECVA CNCNLHARRC RFNMELYKLS GRKSGGVCLN CRHNTAGRHC HYCKEGYYRD MGKPITHRKA CKACDCHPVG AAGKTCNQTT GQCPCKDGVT GITCNRCAKG YQQSRSPIAP CIKIPVAPPT TAASSVEEPE DCDSYCKASK GKLKINMKKY CKKDYAVQIH ILKADKAGDW WKFTVNIISV YKQGTSRIRR GDQSLWIRSR DIACKCPKIK PLKKYLLLGN AEDSPDQSGI VADKSSLVIQ WRDTWARRLR KFQQREKKGK CKKA //