SLIT2_HUMAN
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 03-AUG-2022, entry version 210.
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="http://atlasgeneticsoncology.org/Genes/SLIT2ID42328ch4p15.html";
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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; 49.
DR DIP; DIP-38198N; -.
DR IntAct; O94813; 23.
DR MINT; O94813; -.
DR STRING; 9606.ENSP00000422591; -.
DR TCDB; 9.B.87.1.32; the selenoprotein p receptor (selp-receptor) family.
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; O94813; -.
DR PeptideAtlas; O94813; -.
DR PRIDE; O94813; -.
DR ProteomicsDB; 50454; -. [O94813-1]
DR ProteomicsDB; 50455; -. [O94813-2]
DR ProteomicsDB; 50456; -. [O94813-3]
DR Antibodypedia; 3487; 324 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 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 OMA; CQAIRCK; -.
DR OrthoDB; 28488at2759; -.
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 1079 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 196 other tissues.
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: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; cd00110; LamG; 1.
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; 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; 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; 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
