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   27-MAR-2024, entry version 219.
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";
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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; 55.
DR   DIP; DIP-38198N; -.
DR   IntAct; O94813; 24.
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   EPD; O94813; -.
DR   jPOST; O94813; -.
DR   MassIVE; O94813; -.
DR   MaxQB; 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; 353 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   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   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.
DR   Genevisible; O94813; HS.
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; Reference proteome; Repeat; 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
//