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 02-OCT-2024, entry version 222. 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; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC 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 slit RT suggest possible roles for Slit in the formation and maintenance of the RT 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 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 conserved RT 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., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., 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., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., 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., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 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., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., 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 project: RT 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 semaphorin RT proteins from midline and ventral spinal cord."; RL Cell 102:363-375(2000). RN [8] RP FUNCTION. RX PubMed=10864954; DOI=10.1523/jneurosci.20-13-04962.2000; 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., Bacon K.B., RA 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; DOI=10.1523/jneurosci.21-05-01548.2001; 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; DOI=10.1523/jneurosci.21-12-04281.2001; RA Nguyen-Ba-Charvet K.T., Brose K., Ma L., Wang K.H., Marillat V., Sotelo C., RA Tessier-Lavigne M., Chedotal A.; RT "Diversity and specificity of actions of Slit2 proteolytic fragments in RT 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 to RT leukocytes."; RL Curr. Opin. Genet. Dev. 12:583-591(2002). RN [14] RP X-RAY CRYSTALLOGRAPHY (3.01 ANGSTROMS) OF 504-716, AND DISULFIDE 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 studies RT 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 ROBO1, AND RP DISULFIDE BONDS. RX PubMed=17848514; DOI=10.1073/pnas.0705310104; RA Morlot C., Thielens N.M., Ravelli R.B., Hemrika W., Romijn R.A., Gros P., RA 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 BONDS, RP AND HEPARIN-BINDING. RX PubMed=19498462; DOI=10.1038/embor.2009.95; RA Seiradake E., von Philipsborn A.C., Henry M., Fritz M., Lortat-Jacob H., RA Jamin M., Hemrika W., Bastmeyer M., Cusack S., McCarthy A.A.; RT "Structure and functional relevance of the Slit2 homodimerization 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 in CC axonal navigation at the ventral midline of the neural tube and CC projection of axons to different regions. SLIT1 and SLIT2 seem to be CC essential for midline guidance in the forebrain by acting as repulsive CC signal preventing inappropriate midline crossing by axons projecting CC from the olfactory bulb. In spinal cord development may play a role in CC guiding commissural axons once they reached the floor plate by CC modulating the response to netrin. In vitro, silences the attractive CC effect of NTN1 but not its growth-stimulatory effect and silencing CC requires the formation of a ROBO1-DCC complex. May be implicated in CC spinal cord midline post-crossing axon repulsion. In vitro, only CC commissural axons that crossed the midline responded to SLIT2. In the CC developing visual system appears to function as repellent for retinal CC ganglion axons by providing a repulsion that directs these axons along CC their appropriate paths prior to, and after passage through, the optic CC chiasm. In vitro, collapses and repels retinal ganglion cell growth CC cones. Seems to play a role in branching and arborization of CNS CC sensory axons, and in neuronal cell migration. In vitro, Slit homolog 2 CC protein N-product, but not Slit homolog 2 protein C-product, repels CC olfactory bulb (OB) but not dorsal root ganglia (DRG) axons, induces OB CC growth cones collapse and induces branching of DRG axons. Seems to be CC involved in regulating leukocyte migration. CC {ECO:0000269|PubMed:10102268, ECO:0000269|PubMed:10864954, CC ECO:0000269|PubMed:10975526, ECO:0000269|PubMed:11239147, CC ECO:0000269|PubMed:11309622, ECO:0000269|PubMed:11404413}. CC -!- SUBUNIT: Interacts with GREM1 (By similarity). Homodimer. Binds ROBO1 CC 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 O94813; Q9Y6N7: ROBO1; NbExp=2; IntAct=EBI-1236865, EBI-399762; CC O94813; O94813: SLIT2; NbExp=2; IntAct=EBI-1236865, EBI-1236865; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10102268}. Note=The CC C-terminal cleavage protein is more diffusible than the larger N- CC 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. Weak CC expression in adult adrenal gland, thyroid, trachea and other tissues CC examined. {ECO:0000269|PubMed:10349621, ECO:0000269|PubMed:9813312}. CC -!- DOMAIN: The leucine-rich repeat domain is sufficient for guiding both CC axon projection and neuronal migration, in vitro. CC {ECO:0000269|PubMed:11222645}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/42328/SLIT2"; 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 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 AlphaFoldDB; O94813; -. DR SMR; O94813; -. DR BioGRID; 114756; 57. DR DIP; DIP-38198N; -. DR IntAct; O94813; 39. DR MINT; O94813; -. DR STRING; 9606.ENSP00000422591; -. DR TCDB; 9.B.87.1.32; the selenoprotein p receptor (selp-receptor) family. DR GlyCosmos; O94813; 12 sites, No reported glycans. DR GlyGen; O94813; 12 sites. DR iPTMnet; O94813; -. DR PhosphoSitePlus; O94813; -. DR BioMuta; SLIT2; -. DR jPOST; O94813; -. DR MassIVE; O94813; -. DR PaxDb; 9606-ENSP00000422591; -. DR PeptideAtlas; O94813; -. DR ProteomicsDB; 50454; -. [O94813-1] DR ProteomicsDB; 50455; -. [O94813-2] DR ProteomicsDB; 50456; -. [O94813-3] DR Pumba; O94813; -. DR Antibodypedia; 3487; 348 antibodies from 40 providers. DR DNASU; 9353; -. DR Ensembl; ENST00000503823.5; ENSP00000427548.1; ENSG00000145147.20. [O94813-3] DR Ensembl; ENST00000503837.5; ENSP00000422261.1; ENSG00000145147.20. [O94813-2] DR Ensembl; ENST00000504154.6; ENSP00000422591.1; ENSG00000145147.20. [O94813-1] DR GeneID; 9353; -. DR KEGG; hsa:9353; -. DR MANE-Select; ENST00000504154.6; ENSP00000422591.1; NM_004787.4; NP_004778.1. DR UCSC; uc003gpr.3; human. [O94813-1] DR AGR; HGNC:11086; -. DR CTD; 9353; -. DR DisGeNET; 9353; -. DR GeneCards; SLIT2; -. DR HGNC; HGNC:11086; SLIT2. DR HPA; ENSG00000145147; Low tissue specificity. DR MalaCards; SLIT2; -. DR MIM; 603746; gene. DR neXtProt; NX_O94813; -. DR OpenTargets; ENSG00000145147; -. DR PharmGKB; PA35939; -. DR VEuPathDB; HostDB:ENSG00000145147; -. DR eggNOG; KOG4237; Eukaryota. DR GeneTree; ENSGT00940000158402; -. DR InParanoid; O94813; -. DR OrthoDB; 5475408at2759; -. DR PhylomeDB; O94813; -. DR TreeFam; TF332887; -. DR PathwayCommons; O94813; -. 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 Reactome; R-HSA-9830674; Formation of the ureteric bud. DR SignaLink; O94813; -. DR SIGNOR; O94813; -. DR BioGRID-ORCS; 9353; 7 hits in 1158 CRISPR screens. DR ChiTaRS; SLIT2; human. DR EvolutionaryTrace; O94813; -. DR GeneWiki; SLIT2; -. DR GenomeRNAi; 9353; -. DR Pharos; O94813; Tbio. DR PRO; PR:O94813; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; O94813; protein. DR Bgee; ENSG00000145147; Expressed in lower lobe of lung and 198 other cell types or tissues. DR ExpressionAtlas; O94813; baseline and differential. 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: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 CDD; cd00054; EGF_CA; 6. DR CDD; cd00110; LamG; 1. DR Gene3D; 2.60.120.200; -; 1. DR Gene3D; 2.10.25.10; Laminin; 8. DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 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 InterPro; IPR051355; Notch/Slit_guidance. DR PANTHER; PTHR45836:SF23; LRRCT DOMAIN-CONTAINING PROTEIN; 1. DR PANTHER; PTHR45836; SLIT HOMOLOG; 1. DR Pfam; PF00008; EGF; 5. DR Pfam; PF12661; hEGF; 2. DR Pfam; PF00054; Laminin_G_1; 1. DR Pfam; PF00560; LRR_1; 1. DR Pfam; PF13855; LRR_8; 7. DR Pfam; PF01463; LRRCT; 4. DR Pfam; PF01462; LRRNT; 3. 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; SM00365; LRR_SD22; 6. DR SMART; SM00369; LRR_TYP; 17. DR SMART; SM00082; LRRCT; 4. DR SMART; SM00013; LRRNT; 4. DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 1. DR SUPFAM; SSF57196; EGF/Laminin; 6. DR SUPFAM; SSF52058; L domain-like; 2. 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; Developmental protein; KW Differentiation; Direct protein sequencing; Disulfide bond; KW EGF-like domain; Glycoprotein; Heparin-binding; Leucine-rich repeat; KW Neurogenesis; Proteomics identification; Reference proteome; Repeat; KW Secreted; Signal. FT SIGNAL 1..30 FT /evidence="ECO:0000255" FT CHAIN 31..1529 FT /note="Slit homolog 2 protein" FT /id="PRO_0000007725" FT CHAIN 31..1121 FT /note="Slit homolog 2 protein N-product" FT /id="PRO_0000007726" FT CHAIN 1122..1529 FT /note="Slit homolog 2 protein C-product" FT /id="PRO_0000007727" FT DOMAIN 31..55 FT /note="LRRNT" FT REPEAT 56..77 FT /note="LRR 1" FT REPEAT 80..101 FT /note="LRR 2" FT REPEAT 104..125 FT /note="LRR 3" FT REPEAT 128..149 FT /note="LRR 4" FT REPEAT 152..173 FT /note="LRR 5" FT REPEAT 176..197 FT /note="LRR 6" FT DOMAIN 209..259 FT /note="LRRCT 1" FT DOMAIN 264..300 FT /note="LRRNT 2" FT REPEAT 301..322 FT /note="LRR 7" FT REPEAT 325..346 FT /note="LRR 8" FT REPEAT 349..370 FT /note="LRR 9" FT REPEAT 373..394 FT /note="LRR 10" FT REPEAT 397..418 FT /note="LRR 11" FT DOMAIN 430..480 FT /note="LRRCT 2" FT DOMAIN 497..533 FT /note="LRRNT 3" FT REPEAT 534..555 FT /note="LRR 12" FT REPEAT 559..580 FT /note="LRR 13" FT REPEAT 583..604 FT /note="LRR 14" FT REPEAT 607..628 FT /note="LRR 15" FT REPEAT 631..652 FT /note="LRR 16" FT DOMAIN 664..714 FT /note="LRRCT 3" FT DOMAIN 718..754 FT /note="LRRNT 4" FT REPEAT 755..777 FT /note="LRR 17" FT REPEAT 778..799 FT /note="LRR 18" FT REPEAT 802..823 FT /note="LRR 19" FT REPEAT 826..847 FT /note="LRR 20" FT DOMAIN 859..909 FT /note="LRRCT 4" FT DOMAIN 918..955 FT /note="EGF-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 957..996 FT /note="EGF-like 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 998..1034 FT /note="EGF-like 3; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1036..1074 FT /note="EGF-like 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1076..1112 FT /note="EGF-like 5; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1121..1157 FT /note="EGF-like 6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1160..1333 FT /note="Laminin G-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122" FT DOMAIN 1332..1368 FT /note="EGF-like 7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1453..1528 FT /note="CTCK" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039, FT ECO:0000305" FT SITE 1121..1122 FT /note="Cleavage" FT CARBOHYD 66 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 186 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 564 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 623 FT /note="N-linked (GlcNAc...) asparagine" FT CARBOHYD 794 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 799 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1009 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1010 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1019 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1183 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1266 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1300 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="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 FT /evidence="ECO:0000250" FT DISULFID 927..943 FT /evidence="ECO:0000250" FT DISULFID 945..954 FT /evidence="ECO:0000250" FT DISULFID 961..972 FT /evidence="ECO:0000250" FT DISULFID 966..984 FT /evidence="ECO:0000250" FT DISULFID 986..995 FT /evidence="ECO:0000250" FT DISULFID 1002..1013 FT /evidence="ECO:0000250" FT DISULFID 1007..1022 FT /evidence="ECO:0000250" FT DISULFID 1024..1033 FT /evidence="ECO:0000250" FT DISULFID 1040..1053 FT /evidence="ECO:0000250" FT DISULFID 1047..1062 FT /evidence="ECO:0000250" FT DISULFID 1064..1073 FT /evidence="ECO:0000250" FT DISULFID 1080..1091 FT /evidence="ECO:0000250" FT DISULFID 1085..1100 FT /evidence="ECO:0000250" FT DISULFID 1102..1111 FT /evidence="ECO:0000250" FT DISULFID 1125..1136 FT /evidence="ECO:0000250" FT DISULFID 1130..1145 FT /evidence="ECO:0000250" FT DISULFID 1147..1156 FT /evidence="ECO:0000250" FT DISULFID 1307..1333 FT /evidence="ECO:0000250" FT DISULFID 1336..1346 FT /evidence="ECO:0000250" FT DISULFID 1341..1356 FT /evidence="ECO:0000250" FT DISULFID 1358..1367 FT /evidence="ECO:0000250" FT DISULFID 1375..1385 FT /evidence="ECO:0000250" FT DISULFID 1380..1395 FT /evidence="ECO:0000250" FT DISULFID 1397..1406 FT /evidence="ECO:0000250" FT DISULFID 1416..1426 FT /evidence="ECO:0000250" FT DISULFID 1421..1436 FT /evidence="ECO:0000250" FT DISULFID 1438..1447 FT /evidence="ECO:0000250" FT DISULFID 1453..1492 FT /evidence="ECO:0000250" FT DISULFID 1471..1506 FT /evidence="ECO:0000250" FT DISULFID 1482..1522 FT /evidence="ECO:0000250" FT DISULFID 1486..1524 FT /evidence="ECO:0000250" FT VAR_SEQ 258 FT /note="S -> SDEEE (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10102268, FT ECO:0000303|PubMed:9813312" FT /id="VSP_050035" FT VAR_SEQ 480..487 FT /note="Missing (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:10102268, FT ECO:0000303|PubMed:10349621, ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:9813312" FT /id="VSP_050036" FT VARIANT 636 FT /note="S -> P" FT /evidence="ECO:0000269|PubMed:9813312" FT /id="VAR_018098" FT VARIANT 1277 FT /note="S -> F (in dbSNP:rs771375896)" FT /evidence="ECO:0000269|PubMed:9813312" FT /id="VAR_018099" FT CONFLICT 226 FT /note="Q -> K (in Ref. 2; AAD25539)" FT /evidence="ECO:0000305" FT CONFLICT 607..610 FT /note="SLKT -> KPQN (in Ref. 3; AAD04309)" FT /evidence="ECO:0000305" FT CONFLICT 634 FT /note="L -> M (in Ref. 3; AAD04309)" FT /evidence="ECO:0000305" FT STRAND 277..280 FT /evidence="ECO:0007829|PDB:2V9T" FT STRAND 283..285 FT /evidence="ECO:0007829|PDB:2V9T" FT STRAND 304..306 FT /evidence="ECO:0007829|PDB:2V9T" FT TURN 317..322 FT /evidence="ECO:0007829|PDB:2V9S" FT STRAND 328..330 FT /evidence="ECO:0007829|PDB:2V9T" FT TURN 341..346 FT /evidence="ECO:0007829|PDB:2V9T" FT STRAND 352..354 FT /evidence="ECO:0007829|PDB:2V9T" FT TURN 365..370 FT /evidence="ECO:0007829|PDB:2V9T" FT STRAND 376..378 FT /evidence="ECO:0007829|PDB:2V9T" FT TURN 389..394 FT /evidence="ECO:0007829|PDB:2V9T" FT STRAND 400..402 FT /evidence="ECO:0007829|PDB:2V9T" FT TURN 413..418 FT /evidence="ECO:0007829|PDB:2V9T" FT STRAND 424..426 FT /evidence="ECO:0007829|PDB:2V9T" FT HELIX 436..438 FT /evidence="ECO:0007829|PDB:2V9T" FT HELIX 439..447 FT /evidence="ECO:0007829|PDB:2V9T" FT STRAND 456..460 FT /evidence="ECO:0007829|PDB:2V9T" FT HELIX 461..463 FT /evidence="ECO:0007829|PDB:2V9T" FT HELIX 468..470 FT /evidence="ECO:0007829|PDB:2V9T" FT HELIX 473..475 FT /evidence="ECO:0007829|PDB:2V9T" FT STRAND 511..513 FT /evidence="ECO:0007829|PDB:2V70" FT STRAND 516..518 FT /evidence="ECO:0007829|PDB:2V70" FT STRAND 536..539 FT /evidence="ECO:0007829|PDB:2V70" FT HELIX 554..556 FT /evidence="ECO:0007829|PDB:2V70" FT STRAND 562..564 FT /evidence="ECO:0007829|PDB:2V70" FT TURN 575..580 FT /evidence="ECO:0007829|PDB:2V70" FT STRAND 586..588 FT /evidence="ECO:0007829|PDB:2V70" FT HELIX 599..602 FT /evidence="ECO:0007829|PDB:2V70" FT STRAND 610..612 FT /evidence="ECO:0007829|PDB:2V70" FT STRAND 633..636 FT /evidence="ECO:0007829|PDB:2V70" FT TURN 647..652 FT /evidence="ECO:0007829|PDB:2V70" FT STRAND 658..660 FT /evidence="ECO:0007829|PDB:2V70" FT HELIX 670..672 FT /evidence="ECO:0007829|PDB:2V70" FT HELIX 673..681 FT /evidence="ECO:0007829|PDB:2V70" FT STRAND 690..694 FT /evidence="ECO:0007829|PDB:2V70" FT HELIX 695..697 FT /evidence="ECO:0007829|PDB:2V70" FT HELIX 702..704 FT /evidence="ECO:0007829|PDB:2V70" FT HELIX 707..709 FT /evidence="ECO:0007829|PDB:2V70" FT STRAND 732..734 FT /evidence="ECO:0007829|PDB:2WFH" FT STRAND 737..739 FT /evidence="ECO:0007829|PDB:2WFH" FT STRAND 758..760 FT /evidence="ECO:0007829|PDB:2WFH" FT HELIX 771..775 FT /evidence="ECO:0007829|PDB:2WFH" FT STRAND 781..783 FT /evidence="ECO:0007829|PDB:2WFH" FT TURN 794..799 FT /evidence="ECO:0007829|PDB:2WFH" FT STRAND 805..807 FT /evidence="ECO:0007829|PDB:2WFH" FT TURN 818..823 FT /evidence="ECO:0007829|PDB:2WFH" FT STRAND 829..831 FT /evidence="ECO:0007829|PDB:2WFH" FT TURN 842..847 FT /evidence="ECO:0007829|PDB:2WFH" FT STRAND 853..855 FT /evidence="ECO:0007829|PDB:2WFH" FT HELIX 865..867 FT /evidence="ECO:0007829|PDB:2WFH" FT HELIX 868..876 FT /evidence="ECO:0007829|PDB:2WFH" FT STRAND 885..889 FT /evidence="ECO:0007829|PDB:2WFH" FT HELIX 890..892 FT /evidence="ECO:0007829|PDB:2WFH" FT TURN 897..899 FT /evidence="ECO:0007829|PDB:2WFH" FT HELIX 902..904 FT /evidence="ECO:0007829|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 //