ID SLIT2_HUMAN Reviewed; 1529 AA. AC O94813; A0A0A6YYB8; B7ZLR5; O95710; Q17RU3; Q9Y5Q7; DT 19-JUL-2003, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1999, sequence version 1. DT 13-FEB-2019, entry version 191. DE RecName: Full=Slit homolog 2 protein; DE Short=Slit-2; DE Contains: DE RecName: Full=Slit homolog 2 protein N-product; DE Contains: DE RecName: Full=Slit homolog 2 protein C-product; DE Flags: Precursor; GN Name=SLIT2; Synonyms=SLIL3; 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 {ECO:0000312|EMBL:BAA35185.1}; RN [1] {ECO:0000305} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, AND RP VARIANTS PRO-636 AND PHE-1277. RC TISSUE=Fetal lung; RX PubMed=9813312; DOI=10.1016/S0169-328X(98)00224-1; RA Itoh A., Miyabayashi T., Ohno M., Sakano S.; RT "Cloning and expressions of three mammalian homologues of Drosophila RT slit suggest possible roles for Slit in the formation and maintenance RT of the nervous system."; RL Brain Res. Mol. Brain Res. 62:175-186(1998). RN [2] {ECO:0000305} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND TISSUE SPECIFICITY. RC TISSUE=Fetal brain, and Fetal kidney; RX PubMed=10349621; DOI=10.1016/S0925-4773(98)00174-9; RA Holmes G.P., Negus K., Burridge L., Raman S., Algar E., Yamada T., RA Little M.H.; RT "Distinct but overlapping expression patterns of two vertebrate slit RT homologs implies functional roles in CNS development and RT organogenesis."; RL Mech. Dev. 79:57-72(1998). RN [3] {ECO:0000305} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEIN SEQUENCE OF 1122-1129, RP FUNCTION, INTERACTION WITH ROBO1 AND ROBO2, AND SUBCELLULAR LOCATION. RC TISSUE=Fetal brain; RX PubMed=10102268; DOI=10.1016/S0092-8674(00)80590-5; RA Brose K., Bland K.S., Wang K.H., Arnott D., Henzel W., Goodman C.S., RA Tessier-Lavigne M., Kidd T.; RT "Slit proteins bind Robo receptors and have an evolutionarily RT conserved role in repulsive axon guidance."; RL Cell 96:795-806(1999). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., RA Waterston R.H., Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 RT and 4."; RL Nature 434:724-731(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP FUNCTION. RX PubMed=10975526; DOI=10.1016/S0092-8674(00)00041-6; RA Zou Y., Stoeckli E., Chen H., Tessier-Lavigne M.; RT "Squeezing axons out of the gray matter: a role for slit and RT semaphorin proteins from midline and ventral spinal cord."; RL Cell 102:363-375(2000). RN [8] RP FUNCTION. RX PubMed=10864954; RA Niclou S.P., Jia L., Raper J.A.; RT "Slit2 is a repellent for retinal ganglion cell axons."; RL J. Neurosci. 20:4962-4974(2000). RN [9] RP FUNCTION. RX PubMed=11309622; DOI=10.1038/35073616; RA Wu J.Y., Feng L., Park H.T., Havlioglu N., Wen L., Tang H., RA Bacon K.B., Jiang Z.H., Zhang X.C., Rao Y.; RT "The neuronal repellent Slit inhibits leukocyte chemotaxis induced by RT chemotactic factors."; RL Nature 410:948-952(2001). RN [10] RP DOMAIN. RX PubMed=11222645; RA Chen J.H., Wen L., Dupuis S., Wu J.Y., Rao Y.; RT "The N-terminal leucine-rich regions in Slit are sufficient to repel RT olfactory bulb axons and subventricular zone neurons."; RL J. Neurosci. 21:1548-1556(2001). RN [11] RP FUNCTION, AND INTERACTION WITH ROBO1 AND ROBO2. RX PubMed=11404413; RA Nguyen-Ba-Charvet K.T., Brose K., Ma L., Wang K.H., Marillat V., RA Sotelo C., Tessier-Lavigne M., Chedotal A.; RT "Diversity and specificity of actions of Slit2 proteolytic fragments RT in axon guidance."; RL J. Neurosci. 21:4281-4289(2001). RN [12] RP FUNCTION. RX PubMed=11239147; DOI=10.1126/science.1058445; RA Stein E., Tessier-Lavigne M.; RT "Hierarchical organization of guidance receptors: silencing of netrin RT attraction by slit through a Robo/DCC receptor complex."; RL Science 291:1928-1938(2001). RN [13] RP REVIEW. RX PubMed=12200164; DOI=10.1016/S0959-437X(02)00343-X; RA Wong K., Park H.T., Wu J.Y., Rao Y.; RT "Slit proteins: molecular guidance cues for cells ranging from neurons RT to leukocytes."; RL Curr. Opin. Genet. Dev. 12:583-591(2002). RN [14] RP X-RAY CRYSTALLOGRAPHY (3.01 ANGSTROMS) OF 504-716, AND DISULFIDE RP BONDS. RX PubMed=17704564; DOI=10.1107/S0907444907035470; RA Morlot C., Hemrika W., Romijn R.A., Gros P., Cusack S., McCarthy A.A.; RT "Production of Slit2 LRR domains in mammalian cells for structural RT studies and the structure of human Slit2 domain 3."; RL Acta Crystallogr. D 63:961-968(2007). RN [15] RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 271-480 IN COMPLEX WITH RP ROBO1, AND DISULFIDE BONDS. RX PubMed=17848514; DOI=10.1073/pnas.0705310104; RA Morlot C., Thielens N.M., Ravelli R.B., Hemrika W., Romijn R.A., RA Gros P., Cusack S., McCarthy A.A.; RT "Structural insights into the Slit-Robo complex."; RL Proc. Natl. Acad. Sci. U.S.A. 104:14923-14928(2007). RN [16] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 726-907, SUBUNIT, DISULFIDE RP BONDS, AND HEPARIN-BINDING. RX PubMed=19498462; DOI=10.1038/embor.2009.95; RA Seiradake E., von Philipsborn A.C., Henry M., Fritz M., RA Lortat-Jacob H., Jamin M., Hemrika W., Bastmeyer M., Cusack S., RA McCarthy A.A.; RT "Structure and functional relevance of the Slit2 homodimerization RT domain."; RL EMBO Rep. 10:736-741(2009). CC -!- FUNCTION: Thought to act as molecular guidance cue in cellular CC migration, and function appears to be mediated by interaction with CC roundabout homolog receptors. During neural development involved CC in axonal navigation at the ventral midline of the neural tube and CC projection of axons to different regions. SLIT1 and SLIT2 seem to CC be essential for midline guidance in the forebrain by acting as CC repulsive signal preventing inappropriate midline crossing by CC axons projecting from the olfactory bulb. In spinal chord CC development may play a role in guiding commissural axons once they CC reached the floor plate by modulating the response to netrin. In CC vitro, silences the attractive effect of NTN1 but not its growth- CC stimulatory effect and silencing requires the formation of a CC ROBO1-DCC complex. May be implicated in spinal chord midline post- CC crossing axon repulsion. In vitro, only commissural axons that CC crossed the midline responded to SLIT2. In the developing visual CC system appears to function as repellent for retinal ganglion axons CC by providing a repulsion that directs these axons along their CC appropriate paths prior to, and after passage through, the optic CC chiasm. In vitro, collapses and repels retinal ganglion cell CC growth cones. Seems to play a role in branching and arborization CC of CNS sensory axons, and in neuronal cell migration. In vitro, CC Slit homolog 2 protein N-product, but not Slit homolog 2 protein CC C-product, repels olfactory bulb (OB) but not dorsal root ganglia CC (DRG) axons, induces OB growth cones collapse and induces CC branching of DRG axons. Seems to be involved in regulating CC leukocyte migration. {ECO:0000269|PubMed:10102268, CC ECO:0000269|PubMed:10864954, ECO:0000269|PubMed:10975526, CC ECO:0000269|PubMed:11239147, ECO:0000269|PubMed:11309622, CC ECO:0000269|PubMed:11404413}. CC -!- SUBUNIT: Interacts with GREM1 (By similarity). Homodimer. Binds CC ROBO1 and ROBO2 with high affinity. {ECO:0000250, CC ECO:0000269|PubMed:10102268, ECO:0000269|PubMed:11404413, CC ECO:0000269|PubMed:17848514, ECO:0000269|PubMed:19498462}. CC -!- INTERACTION: CC Self; NbExp=2; IntAct=EBI-1236865, EBI-1236865; CC Q9Y6N7:ROBO1; NbExp=2; IntAct=EBI-1236865, EBI-399762; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10102268}. CC Note=The C-terminal cleavage protein is more diffusible than the CC larger N-terminal protein that is more tightly cell associated. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1 {ECO:0000305}; CC IsoId=O94813-1; Sequence=Displayed; CC Name=2 {ECO:0000305}; CC IsoId=O94813-2; Sequence=VSP_050035, VSP_050036; CC Name=3 {ECO:0000305}; CC IsoId=O94813-3; Sequence=VSP_050036; CC -!- TISSUE SPECIFICITY: Fetal lung and kidney, and adult spinal cord. CC Weak expression in adult adrenal gland, thyroid, trachea and other CC tissues examined. {ECO:0000269|PubMed:10349621, CC ECO:0000269|PubMed:9813312}. CC -!- DOMAIN: The leucine-rich repeat domain is sufficient for guiding CC both axon projection and neuronal migration, in vitro. CC {ECO:0000269|PubMed:11222645}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/SLIT2ID42328ch4p15.html"; 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; AB017168; BAA35185.1; -; mRNA. DR EMBL; AF055585; AAD04309.1; -; mRNA. DR EMBL; AF133270; AAD25539.1; -; mRNA. DR EMBL; AC021118; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC092577; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC096718; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC108011; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471069; EAW92793.1; -; Genomic_DNA. DR EMBL; BC117190; AAI17191.1; -; mRNA. DR EMBL; BC143978; AAI43979.1; -; mRNA. DR CCDS; CCDS3426.1; -. [O94813-1] DR CCDS; CCDS75110.1; -. [O94813-2] DR CCDS; CCDS75111.1; -. [O94813-3] DR RefSeq; NP_001276064.1; NM_001289135.2. [O94813-2] DR RefSeq; NP_001276065.1; NM_001289136.2. [O94813-3] DR RefSeq; NP_004778.1; NM_004787.3. [O94813-1] DR UniGene; Hs.29802; -. DR PDB; 2V70; X-ray; 3.01 A; A/B/C/D=504-714. DR PDB; 2V9S; X-ray; 2.00 A; A/B/C/D=271-480. DR PDB; 2V9T; X-ray; 1.70 A; B=271-479. DR PDB; 2WFH; X-ray; 1.80 A; A/B=726-907. DR PDBsum; 2V70; -. DR PDBsum; 2V9S; -. DR PDBsum; 2V9T; -. DR PDBsum; 2WFH; -. DR ProteinModelPortal; O94813; -. DR SMR; O94813; -. DR BioGrid; 114756; 18. DR DIP; DIP-38198N; -. DR IntAct; O94813; 10. DR MINT; O94813; -. DR STRING; 9606.ENSP00000422591; -. DR iPTMnet; O94813; -. DR PhosphoSitePlus; O94813; -. DR BioMuta; SLIT2; -. DR EPD; O94813; -. DR jPOST; O94813; -. DR MaxQB; O94813; -. DR PaxDb; O94813; -. DR PeptideAtlas; O94813; -. DR PRIDE; O94813; -. DR ProteomicsDB; 50454; -. DR ProteomicsDB; 50455; -. [O94813-2] DR ProteomicsDB; 50456; -. [O94813-3] DR Ensembl; ENST00000503823; ENSP00000427548; ENSG00000145147. [O94813-3] DR Ensembl; ENST00000503837; ENSP00000422261; ENSG00000145147. [O94813-2] DR Ensembl; ENST00000504154; ENSP00000422591; ENSG00000145147. [O94813-1] DR GeneID; 9353; -. DR KEGG; hsa:9353; -. DR UCSC; uc003gpr.3; human. [O94813-1] DR CTD; 9353; -. DR DisGeNET; 9353; -. DR EuPathDB; HostDB:ENSG00000145147.19; -. DR GeneCards; SLIT2; -. DR HGNC; HGNC:11086; SLIT2. DR HPA; CAB007590; -. DR HPA; HPA019511; -. DR HPA; HPA023088; -. DR MIM; 603746; gene. DR neXtProt; NX_O94813; -. DR OpenTargets; ENSG00000145147; -. DR PharmGKB; PA35939; -. DR eggNOG; KOG4237; Eukaryota. DR eggNOG; COG4886; LUCA. DR GeneTree; ENSGT00940000158402; -. DR HOGENOM; HOG000116120; -. DR HOVERGEN; HBG057959; -. DR InParanoid; O94813; -. DR KO; K06839; -. DR OrthoDB; 28488at2759; -. DR PhylomeDB; O94813; -. DR TreeFam; TF332887; -. DR Reactome; R-HSA-373752; Netrin-1 signaling. DR Reactome; R-HSA-376176; Signaling by ROBO receptors. DR Reactome; R-HSA-428540; Activation of RAC1. DR Reactome; R-HSA-428542; Regulation of commissural axon pathfinding by SLIT and ROBO. DR Reactome; R-HSA-428543; Inactivation of CDC42 and RAC1. DR Reactome; R-HSA-428890; Role of ABL in ROBO-SLIT signaling. DR Reactome; R-HSA-8985586; SLIT2:ROBO1 increases RHOA activity. DR Reactome; R-HSA-9010553; Regulation of expression of SLITs and ROBOs. DR SIGNOR; O94813; -. DR ChiTaRS; SLIT2; human. DR EvolutionaryTrace; O94813; -. DR GeneWiki; SLIT2; -. DR GenomeRNAi; 9353; -. DR PRO; PR:O94813; -. DR Proteomes; UP000005640; Chromosome 4. DR Bgee; ENSG00000145147; Expressed in 230 organ(s), highest expression level in upper lobe of lung. DR ExpressionAtlas; O94813; baseline and differential. DR Genevisible; O94813; HS. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; NAS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0005509; F:calcium ion binding; NAS:UniProtKB. DR GO; GO:0005095; F:GTPase inhibitor activity; IDA:UniProtKB. DR GO; GO:0008201; F:heparin binding; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0043237; F:laminin-1 binding; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0043394; F:proteoglycan binding; IPI:UniProtKB. DR GO; GO:0048495; F:Roundabout binding; IPI:UniProtKB. DR GO; GO:0003180; P:aortic valve morphogenesis; ISS:BHF-UCL. DR GO; GO:0061364; P:apoptotic process involved in luteolysis; IEP:UniProtKB. DR GO; GO:0048846; P:axon extension involved in axon guidance; IDA:UniProtKB. DR GO; GO:0007411; P:axon guidance; IDA:UniProtKB. DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; IDA:UniProtKB. DR GO; GO:0002042; P:cell migration involved in sprouting angiogenesis; IMP:BHF-UCL. DR GO; GO:0071504; P:cellular response to heparin; IDA:UniProtKB. DR GO; GO:0032870; P:cellular response to hormone stimulus; IEP:UniProtKB. DR GO; GO:0021836; P:chemorepulsion involved in postnatal olfactory bulb interneuron migration; IDA:UniProtKB. DR GO; GO:0021972; P:corticospinal neuron axon guidance through spinal cord; IMP:BHF-UCL. DR GO; GO:0050929; P:induction of negative chemotaxis; IDA:UniProtKB. DR GO; GO:0008045; P:motor neuron axon guidance; IDA:UniProtKB. DR GO; GO:0050919; P:negative chemotaxis; IDA:UniProtKB. DR GO; GO:0030837; P:negative regulation of actin filament polymerization; IDA:UniProtKB. DR GO; GO:0030308; P:negative regulation of cell growth; IMP:BHF-UCL. DR GO; GO:0030336; P:negative regulation of cell migration; IDA:UniProtKB. DR GO; GO:0090288; P:negative regulation of cellular response to growth factor stimulus; IDA:BHF-UCL. DR GO; GO:0070100; P:negative regulation of chemokine-mediated signaling pathway; IMP:BHF-UCL. DR GO; GO:0010596; P:negative regulation of endothelial cell migration; IDA:UniProtKB. DR GO; GO:0010593; P:negative regulation of lamellipodium assembly; IDA:UniProtKB. DR GO; GO:0002689; P:negative regulation of leukocyte chemotaxis; IDA:UniProtKB. DR GO; GO:0090027; P:negative regulation of monocyte chemotaxis; ISS:BHF-UCL. DR GO; GO:0071676; P:negative regulation of mononuclear cell migration; IDA:BHF-UCL. DR GO; GO:0090024; P:negative regulation of neutrophil chemotaxis; IDA:UniProtKB. DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IDA:UniProtKB. DR GO; GO:0090260; P:negative regulation of retinal ganglion cell axon guidance; IDA:UniProtKB. DR GO; GO:0051058; P:negative regulation of small GTPase mediated signal transduction; IDA:UniProtKB. DR GO; GO:0071672; P:negative regulation of smooth muscle cell chemotaxis; IDA:BHF-UCL. DR GO; GO:0014912; P:negative regulation of smooth muscle cell migration; IDA:BHF-UCL. DR GO; GO:0043116; P:negative regulation of vascular permeability; IDA:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:0050772; P:positive regulation of axonogenesis; TAS:UniProtKB. DR GO; GO:0003184; P:pulmonary valve morphogenesis; ISS:BHF-UCL. DR GO; GO:0051414; P:response to cortisol; IEP:UniProtKB. DR GO; GO:0031290; P:retinal ganglion cell axon guidance; IDA:UniProtKB. DR GO; GO:0035385; P:Roundabout signaling pathway; IMP:BHF-UCL. DR GO; GO:0001657; P:ureteric bud development; IMP:UniProtKB. DR GO; GO:0060412; P:ventricular septum morphogenesis; ISS:BHF-UCL. DR Gene3D; 3.80.10.10; -; 5. DR InterPro; IPR013320; ConA-like_dom_sf. DR InterPro; IPR000483; Cys-rich_flank_reg_C. DR InterPro; IPR006207; Cys_knot_C. DR InterPro; IPR001881; EGF-like_Ca-bd_dom. DR InterPro; IPR013032; EGF-like_CS. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site. DR InterPro; IPR018097; EGF_Ca-bd_CS. DR InterPro; IPR003645; Fol_N. DR InterPro; IPR001791; Laminin_G. DR InterPro; IPR001611; Leu-rich_rpt. DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp. DR InterPro; IPR032675; LRR_dom_sf. DR InterPro; IPR000372; LRRNT. DR Pfam; PF00008; EGF; 5. DR Pfam; PF12661; hEGF; 2. DR Pfam; PF00054; Laminin_G_1; 1. DR Pfam; PF13855; LRR_8; 7. DR Pfam; PF01463; LRRCT; 4. DR Pfam; PF01462; LRRNT; 4. DR SMART; SM00041; CT; 1. DR SMART; SM00181; EGF; 9. DR SMART; SM00179; EGF_CA; 7. DR SMART; SM00274; FOLN; 3. DR SMART; SM00282; LamG; 1. DR SMART; SM00369; LRR_TYP; 17. DR SMART; SM00082; LRRCT; 4. DR SMART; SM00013; LRRNT; 4. DR SUPFAM; SSF49899; SSF49899; 1. DR PROSITE; PS00010; ASX_HYDROXYL; 2. DR PROSITE; PS01185; CTCK_1; 1. DR PROSITE; PS01225; CTCK_2; 1. DR PROSITE; PS00022; EGF_1; 9. DR PROSITE; PS01186; EGF_2; 7. DR PROSITE; PS50026; EGF_3; 9. DR PROSITE; PS01187; EGF_CA; 2. DR PROSITE; PS50025; LAM_G_DOMAIN; 1. DR PROSITE; PS51450; LRR; 20. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Chemotaxis; Complete proteome; KW Developmental protein; Differentiation; Direct protein sequencing; KW Disulfide bond; EGF-like domain; Glycoprotein; Heparin-binding; KW Leucine-rich repeat; Neurogenesis; Polymorphism; Reference proteome; KW Repeat; Secreted; Signal. FT SIGNAL 1 30 {ECO:0000255}. FT CHAIN 31 1529 Slit homolog 2 protein. FT /FTId=PRO_0000007725. FT CHAIN 31 1121 Slit homolog 2 protein N-product. FT /FTId=PRO_0000007726. FT CHAIN 1122 1529 Slit homolog 2 protein C-product. FT /FTId=PRO_0000007727. FT DOMAIN 31 55 LRRNT. FT REPEAT 56 77 LRR 1. FT REPEAT 80 101 LRR 2. FT REPEAT 104 125 LRR 3. FT REPEAT 128 149 LRR 4. FT REPEAT 152 173 LRR 5. FT REPEAT 176 197 LRR 6. FT DOMAIN 209 259 LRRCT 1. FT DOMAIN 264 300 LRRNT 2. FT REPEAT 301 322 LRR 7. FT REPEAT 325 346 LRR 8. FT REPEAT 349 370 LRR 9. FT REPEAT 373 394 LRR 10. FT REPEAT 397 418 LRR 11. FT DOMAIN 430 480 LRRCT 2. FT DOMAIN 497 533 LRRNT 3. FT REPEAT 534 555 LRR 12. FT REPEAT 559 580 LRR 13. FT REPEAT 583 604 LRR 14. FT REPEAT 607 628 LRR 15. FT REPEAT 631 652 LRR 16. FT DOMAIN 664 714 LRRCT 3. FT DOMAIN 718 754 LRRNT 4. FT REPEAT 755 777 LRR 17. FT REPEAT 778 799 LRR 18. FT REPEAT 802 823 LRR 19. FT REPEAT 826 847 LRR 20. FT DOMAIN 859 909 LRRCT 4. FT DOMAIN 918 955 EGF-like 1. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 957 996 EGF-like 2. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 998 1034 EGF-like 3; calcium-binding. FT {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DOMAIN 1036 1074 EGF-like 4. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 1076 1112 EGF-like 5; calcium-binding. FT {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DOMAIN 1121 1157 EGF-like 6. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 1160 1333 Laminin G-like. {ECO:0000255|PROSITE- FT ProRule:PRU00122}. FT DOMAIN 1332 1368 EGF-like 7. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 1453 1528 CTCK. {ECO:0000255|PROSITE- FT ProRule:PRU00039, ECO:0000305}. FT SITE 1121 1122 Cleavage. FT CARBOHYD 66 66 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 186 186 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 564 564 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 623 623 N-linked (GlcNAc...) asparagine. FT CARBOHYD 794 794 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 799 799 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 1009 1009 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 1010 1010 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 1019 1019 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 1183 1183 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 1266 1266 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 1300 1300 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 277 286 FT DISULFID 434 457 FT DISULFID 436 478 FT DISULFID 506 512 FT DISULFID 510 519 FT DISULFID 668 691 FT DISULFID 670 712 FT DISULFID 727 733 FT DISULFID 731 740 FT DISULFID 863 886 FT DISULFID 865 907 FT DISULFID 922 933 {ECO:0000250}. FT DISULFID 927 943 {ECO:0000250}. FT DISULFID 945 954 {ECO:0000250}. FT DISULFID 961 972 {ECO:0000250}. FT DISULFID 966 984 {ECO:0000250}. FT DISULFID 986 995 {ECO:0000250}. FT DISULFID 1002 1013 {ECO:0000250}. FT DISULFID 1007 1022 {ECO:0000250}. FT DISULFID 1024 1033 {ECO:0000250}. FT DISULFID 1040 1053 {ECO:0000250}. FT DISULFID 1047 1062 {ECO:0000250}. FT DISULFID 1064 1073 {ECO:0000250}. FT DISULFID 1080 1091 {ECO:0000250}. FT DISULFID 1085 1100 {ECO:0000250}. FT DISULFID 1102 1111 {ECO:0000250}. FT DISULFID 1125 1136 {ECO:0000250}. FT DISULFID 1130 1145 {ECO:0000250}. FT DISULFID 1147 1156 {ECO:0000250}. FT DISULFID 1307 1333 {ECO:0000250}. FT DISULFID 1336 1346 {ECO:0000250}. FT DISULFID 1341 1356 {ECO:0000250}. FT DISULFID 1358 1367 {ECO:0000250}. FT DISULFID 1375 1385 {ECO:0000250}. FT DISULFID 1380 1395 {ECO:0000250}. FT DISULFID 1397 1406 {ECO:0000250}. FT DISULFID 1416 1426 {ECO:0000250}. FT DISULFID 1421 1436 {ECO:0000250}. FT DISULFID 1438 1447 {ECO:0000250}. FT DISULFID 1453 1492 {ECO:0000250}. FT DISULFID 1471 1506 {ECO:0000250}. FT DISULFID 1482 1522 {ECO:0000250}. FT DISULFID 1486 1524 {ECO:0000250}. FT VAR_SEQ 258 258 S -> SDEEE (in isoform 2). FT {ECO:0000303|PubMed:10102268, FT ECO:0000303|PubMed:9813312}. FT /FTId=VSP_050035. FT VAR_SEQ 480 487 Missing (in isoform 2 and isoform 3). FT {ECO:0000303|PubMed:10102268, FT ECO:0000303|PubMed:10349621, FT ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:9813312}. FT /FTId=VSP_050036. FT VARIANT 636 636 S -> P. {ECO:0000269|PubMed:9813312}. FT /FTId=VAR_018098. FT VARIANT 1277 1277 S -> F (in dbSNP:rs771375896). FT {ECO:0000269|PubMed:9813312}. FT /FTId=VAR_018099. FT CONFLICT 226 226 Q -> K (in Ref. 2; AAD25539). FT {ECO:0000305}. FT CONFLICT 607 610 SLKT -> KPQN (in Ref. 3; AAD04309). FT {ECO:0000305}. FT CONFLICT 634 634 L -> M (in Ref. 3; AAD04309). FT {ECO:0000305}. FT STRAND 277 280 {ECO:0000244|PDB:2V9T}. FT STRAND 283 285 {ECO:0000244|PDB:2V9T}. FT STRAND 304 306 {ECO:0000244|PDB:2V9T}. FT TURN 317 322 {ECO:0000244|PDB:2V9S}. FT STRAND 328 330 {ECO:0000244|PDB:2V9T}. FT TURN 341 346 {ECO:0000244|PDB:2V9T}. FT STRAND 352 354 {ECO:0000244|PDB:2V9T}. FT TURN 365 370 {ECO:0000244|PDB:2V9T}. FT STRAND 376 378 {ECO:0000244|PDB:2V9T}. FT TURN 389 394 {ECO:0000244|PDB:2V9T}. FT STRAND 400 402 {ECO:0000244|PDB:2V9T}. FT TURN 413 418 {ECO:0000244|PDB:2V9T}. FT STRAND 424 426 {ECO:0000244|PDB:2V9T}. FT HELIX 436 438 {ECO:0000244|PDB:2V9T}. FT HELIX 439 447 {ECO:0000244|PDB:2V9T}. FT STRAND 456 460 {ECO:0000244|PDB:2V9T}. FT HELIX 461 463 {ECO:0000244|PDB:2V9T}. FT HELIX 468 470 {ECO:0000244|PDB:2V9T}. FT HELIX 473 475 {ECO:0000244|PDB:2V9T}. FT STRAND 511 513 {ECO:0000244|PDB:2V70}. FT STRAND 516 518 {ECO:0000244|PDB:2V70}. FT STRAND 536 539 {ECO:0000244|PDB:2V70}. FT HELIX 554 556 {ECO:0000244|PDB:2V70}. FT STRAND 562 564 {ECO:0000244|PDB:2V70}. FT TURN 575 580 {ECO:0000244|PDB:2V70}. FT STRAND 586 588 {ECO:0000244|PDB:2V70}. FT HELIX 599 602 {ECO:0000244|PDB:2V70}. FT STRAND 610 612 {ECO:0000244|PDB:2V70}. FT STRAND 633 636 {ECO:0000244|PDB:2V70}. FT TURN 647 652 {ECO:0000244|PDB:2V70}. FT STRAND 658 660 {ECO:0000244|PDB:2V70}. FT HELIX 670 672 {ECO:0000244|PDB:2V70}. FT HELIX 673 681 {ECO:0000244|PDB:2V70}. FT STRAND 690 694 {ECO:0000244|PDB:2V70}. FT HELIX 695 697 {ECO:0000244|PDB:2V70}. FT HELIX 702 704 {ECO:0000244|PDB:2V70}. FT HELIX 707 709 {ECO:0000244|PDB:2V70}. FT STRAND 732 734 {ECO:0000244|PDB:2WFH}. FT STRAND 737 739 {ECO:0000244|PDB:2WFH}. FT STRAND 758 760 {ECO:0000244|PDB:2WFH}. FT HELIX 771 775 {ECO:0000244|PDB:2WFH}. FT STRAND 781 783 {ECO:0000244|PDB:2WFH}. FT TURN 794 799 {ECO:0000244|PDB:2WFH}. FT STRAND 805 807 {ECO:0000244|PDB:2WFH}. FT TURN 818 823 {ECO:0000244|PDB:2WFH}. FT STRAND 829 831 {ECO:0000244|PDB:2WFH}. FT TURN 842 847 {ECO:0000244|PDB:2WFH}. FT STRAND 853 855 {ECO:0000244|PDB:2WFH}. FT HELIX 865 867 {ECO:0000244|PDB:2WFH}. FT HELIX 868 876 {ECO:0000244|PDB:2WFH}. FT STRAND 885 889 {ECO:0000244|PDB:2WFH}. FT HELIX 890 892 {ECO:0000244|PDB:2WFH}. FT TURN 897 899 {ECO:0000244|PDB:2WFH}. FT HELIX 902 904 {ECO:0000244|PDB:2WFH}. SQ SEQUENCE 1529 AA; 169870 MW; 5D19CC5E7FD461BA CRC64; MRGVGWQMLS LSLGLVLAIL NKVAPQACPA QCSCSGSTVD CHGLALRSVP RNIPRNTERL DLNGNNITRI TKTDFAGLRH LRVLQLMENK ISTIERGAFQ DLKELERLRL NRNHLQLFPE LLFLGTAKLY RLDLSENQIQ AIPRKAFRGA VDIKNLQLDY NQISCIEDGA FRALRDLEVL TLNNNNITRL SVASFNHMPK LRTFRLHSNN LYCDCHLAWL SDWLRQRPRV GLYTQCMGPS HLRGHNVAEV QKREFVCSGH QSFMAPSCSV LHCPAACTCS NNIVDCRGKG LTEIPTNLPE TITEIRLEQN TIKVIPPGAF SPYKKLRRID LSNNQISELA PDAFQGLRSL NSLVLYGNKI TELPKSLFEG LFSLQLLLLN ANKINCLRVD AFQDLHNLNL LSLYDNKLQT IAKGTFSPLR AIQTMHLAQN PFICDCHLKW LADYLHTNPI ETSGARCTSP RRLANKRIGQ IKSKKFRCSA KEQYFIPGTE DYRSKLSGDC FADLACPEKC RCEGTTVDCS NQKLNKIPEH IPQYTAELRL NNNEFTVLEA TGIFKKLPQL RKINFSNNKI TDIEEGAFEG ASGVNEILLT SNRLENVQHK MFKGLESLKT LMLRSNRITC VGNDSFIGLS SVRLLSLYDN QITTVAPGAF DTLHSLSTLN LLANPFNCNC YLAWLGEWLR KKRIVTGNPR CQKPYFLKEI PIQDVAIQDF TCDDGNDDNS CSPLSRCPTE CTCLDTVVRC SNKGLKVLPK GIPRDVTELY LDGNQFTLVP KELSNYKHLT LIDLSNNRIS TLSNQSFSNM TQLLTLILSY NRLRCIPPRT FDGLKSLRLL SLHGNDISVV PEGAFNDLSA LSHLAIGANP LYCDCNMQWL SDWVKSEYKE PGIARCAGPG EMADKLLLTT PSKKFTCQGP VDVNILAKCN PCLSNPCKND GTCNSDPVDF YRCTCPYGFK GQDCDVPIHA CISNPCKHGG TCHLKEGEED GFWCICADGF EGENCEVNVD DCEDNDCENN STCVDGINNY TCLCPPEYTG ELCEEKLDFC AQDLNPCQHD SKCILTPKGF KCDCTPGYVG EHCDIDFDDC QDNKCKNGAH CTDAVNGYTC ICPEGYSGLF CEFSPPMVLP RTSPCDNFDC QNGAQCIVRI NEPICQCLPG YQGEKCEKLV SVNFINKESY LQIPSAKVRP QTNITLQIAT DEDSGILLYK GDKDHIAVEL YRGRVRASYD TGSHPASAIY SVETINDGNF HIVELLALDQ SLSLSVDGGN PKIITNLSKQ STLNFDSPLY VGGMPGKSNV ASLRQAPGQN GTSFHGCIRN LYINSELQDF QKVPMQTGIL PGCEPCHKKV CAHGTCQPSS QAGFTCECQE GWMGPLCDQR TNDPCLGNKC VHGTCLPINA FSYSCKCLEG HGGVLCDEEE DLFNPCQAIK CKHGKCRLSG LGQPYCECSS GYTGDSCDRE ISCRGERIRD YYQKQQGYAA CQTTKKVSRL ECRGGCAGGQ CCGPLRSKRR KYSFECTDGS SFVDEVEKVV KCGCTRCVS //