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SLIT3 (slit homolog 3 (Drosophila))

Written2012-09Kim Brussen
Sanquin Research, Landsteiner Laboratory, Department of Hematopoiesis, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

(Note : for Links provided by Atlas : click)

Identity

Alias_namesSLIL2
slit (Drosophila) homolog 3
slit homolog 3 (Drosophila)
Alias_symbol (synonym)slit2
MEGF5
SLIT1
Slit-3
Other alias
HGNC (Hugo) SLIT3
LocusID (NCBI) 6586
Atlas_Id 50515
Location 5q34  [Link to chromosome band 5q34]
Location_base_pair Starts at 168661733 and ends at 169301129 bp from pter ( according to hg19-Feb_2009)  [Mapping SLIT3.png]
 
  Genomic localization of SLIT3. The SLIT3 gene is shown in red, the surrounding genes in grey. The arrows indicate the direction of transcription (NCBI, version 27 nov 11). Adapted from NCBI map viewer.
Fusion genes
(updated 2016)
CREBRF (5q35.1) / SLIT3 (5q34)FSTL4 (5q31.1) / SLIT3 (5q34)NCKAP5 (2q21.2) / SLIT3 (5q34)
SLIT3 (5q34) / HSD17B4 (5q23.1)SLIT3 (5q34) / MAGED2 (Xp11.21)

DNA/RNA

 
  Map of the SLIT3 gene, direction from 5'UTR till 3'UTR. The direction of transcription is indicated by the arrow. Exons are depicted as blue boxes. Within the first and the last exon, the 5'UTR and 3'UTR are depicted in yellow. The length of the exons and introns is roughly indicated, but is not up to scale. The size of the exons ranges from 72 base pairs up to 4950 base pairs, the size of the introns ranges from 605 base pairs up to 310141 base pairs. For clarity, the exons are depicted larger than the introns. Below is indicated which protein domains are encoded by particular exons. Based on ENSEMBL version 68 Juli 2012 transcript ENST00000519560. Information on protein domains encoded by particular exons was obtained from Little et al., 2002.
Description 36 coding exons spanning 600 kb of the genome. All SLIT genes contain CpG islands in their promoter regions and intron length and exon-intron boundaries are highly similar (Little et al., 2002; Dallol et al., 2005).
Transcription The leucine rich repeat regions of the three human SLIT genes contain a large number of very small exons, mostly encoding for one individual leucine rich repeat. This allows alternative splicing of the exons, without altering the frame (Little et al., 2002). 8 mRNA transcript variants were reported in ENSEMBL, of which 3 transcript variants encode for a protein. The relevance of the differently spliced variants is unclear. Only one variant of SLIT3 was identified after screening of a human fetal brain cDNA library or by nucleotide database searching (Little et al., 2002).
Pseudogene None known.

Protein

Note The extracellular matrix protein SLIT was first identified in a genetic screen for mutations that affected the dorsal-ventral patterning or the development of the central nervous system in Drosophila (Anderson et al., 1984; Seeger et al., 1993). SLIT homologues have since been found in C. elegans and in vertebrates, including mammals (Holmes et al., 1998; Itoh et al., 1998; Brose et al., 1999; Holmes et al., 2001; Vargesson et al., 2001; Gilthorpe et al., 2002). The cognate receptor of the SLIT proteins is Roundabout or ROBO (Kidd et al., 1999; Huminiecki et al., 2002).
 
  Domain organization of the SLIT protein from N-terminus to C-terminus. SS: N-terminal signal peptide; LRR: leucin-rich repeat; EGF-like: epidermal growth factor-like domain; Lam-G like: Agrin, Laminin, Perlecan and SLIT (ALPS) or laminin G-like module; Cystein knot: C-terminal cystein knot. The sciccors represent a proteolytic cleavage site. Adapted from figure created by dr. S.B. Geutskens (Leiden University Medical Center; Department of Immunohematology and Blood Transfusion & Einthoven laboratory for Experimental Vascular Medicine; Leiden; The Netherlands).
Description In mammals there are three SLIT genes which encode large ECM glycoproteins of about 200 kDa, comprising a stretch of four leucine rich repeats (LRR) connected by disulphide bonds, seven to nine epidermal growth factor (EGF)-like domains, a domain named Agrin, Laminin, Perlecan and SLIT (ALPS) or laminin G-like module, and a C-terminal cystein knot (Rothberg and Artavanis-Tsakonas, 1992; Hohenester et al., 1999; Nguyen-Ba-Charvet and Chedotal, 2002). SLIT proteins can be proteolytically cleaved within the EGF-like region, this has been shown to occur for SLIT2 and for SLIT3 (Brose et al., 1999; Patel et al., 2001; Condac et al., 2012). Three different transcripts of SLIT3, all containing 36 exons, encode for a protein. These proteins are 1530, 1523, and 1472 amino acids long (ENSEMBL ENSP00000430333, ENSP00000332164, ENSP00000384890 respectively). The protein of 1472 amino acids lacks the cysteine knot, while the other two proteins contain all protein domains, although some domains differ slightly in amino acid position and length. The SLIT3 protein of 1523 amino acids is the major expressed protein (NCBI accession AAQ89243).
Expression In humans, SLIT3 is expressed both during embryonic development and during adult life. During embryogenesis, it is expressed in the fetal kidney, the fetal lung (Itoh et al., 1998) and to a lower extent in the fetal brain and the fetal liver (Dickinson et al., 2004). Thereafter, it is expressed in the kidney, the lung (Itoh et al., 1998), the female reproductive tract (endometrium, fallopian tube, ovaries, mammary gland, placenta) ( Dickinson et al., 2004; Dickinson et al., 2008; Duncan et al., 2010; Dickinson et al., 2011), the prostate (Dickinson et al., 2004), the heart, the lymph nodes, the thyroid, the adrenal gland, the digestive tract (stomach, small intestine, colon), the brain, the spinal cord (Itoh et al., 1998; Dickinson et al., 2004), the spleen, the thymus, the skin and in bone marrow stromal and endothelial cells (Dickinson et al., 2004; Geutskens et al., 2012).
Localisation SLIT is a secreted extra-cellular matrix protein that is bound to the surface of the cell by the extracellular matrix, mainly by heparan sulfates (Liang et al., 1999; Ronca et al., 2001). It has been reported that both the N-terminal part of SLIT2 (Hussain et al., 2006) and the C-terminal part of SLIT2 and SLIT3 bind to heparin and heparan sulfates (Ronca et al., 2001; Condac et al., 2012). The interaction between SLIT proteins and heparan-sulfates is not only important for the binding of SLIT proteins to the extracellular matrix, but can also increase the affinity of SLIT for ROBO (Hu et al., 2001). Removal of heparan sulfates from the cell surface abolishes the response to SLIT2 (Hu et al., 2001; Hussain et al., 2006). Therefore, heparan-sulfates are considered as important co-receptors in SLIT-ROBO signalling (Inatani et al., 2003; Steigemann et al., 2004; Hussain et al., 2006). The SLIT2 and the SLIT3 protein can be proteolytically cleaved. Following proteolytic cleavage of SLIT2, the 140kDa N-terminal fragment remains tightly associated to the cell surface, while the 50-60kDa C-terminal fragment is more loosely attached and can also be detected in conditioned medium (Brose et al., 1999; Wang et al., 1999).
Function The extra-cellular matrix protein SLIT binds to the transmembrane receptor Roundabout or ROBO and has a conserved role in axon guidance in the central nervous system (CNS), where SLIT functions as a repellent for ROBO-expressing axons (Brose et al., 1999; Kidd et al., 1999; Long et al., 2004). Outside the CNS, SLIT plays an important role during embryonic development and in human pathology.
Neuronal guidance: Several types of axons and neurons with different origins form a complex neuronal circuitry that allows proper functioning of the brain. Vertebrate commissural neurons first arise in the dorsal spinal cord. Their axons are directed to the midline/ floorplate by the chemoattractants netrin and sonic hedgehog. When these axons have reached the midline, they cross it and turn longitudinally on the opposite side, growing right alongside the midline/ floor plate (reviewed by Dickson and Gilestro, 2006). SLIT proteins function as chemorepellents throughout the central nervous system, thereby restricting the positioning of axons to their proper sites. Commisural axons defects have been reported in several studies. In Slit3 knockout mice, commisural axons stalled at the midline or projected aberrantly, although to a lesser extent as for the other Slit proteins (Unni et al., 2012). In Slit1,2,3 triple knockout mice embryos, the phenotype was more severe. 72% of the axons failed to leave the midline and 20% recrossed the midline (Long et al., 2004).
Angiogenesis: In the early developing diaphragm, SLIT3 promotes vascular development. Slit3 homozygous knockout mice had reduced vascular density and branching points. These data are subtantiated by research on endothelial cell lines. In HUVECs, SLIT3 functioned as a chemoattractant that induced endothelial cell chemotaxis and tube formation, RhoGTPase activation and modulation of the actin cytoskeleton. The vascular defects in Slit3 homozygous knockout mice occured before the onset of congenital diaphragmatic hernia (Zhang et al., 2009).
Migration: SLIT is required for proper directional migration and for the regulation of proliferation and differentiation of various cell types during embryogenesis. SLITs not only regulate migration during embryogenesis, but also during adult life. SLIT3 increases the migration of monocytes, macrophages and endothelial cells both in vitro and in vivo (Tanno et al., 2007; Zhang et al., 2009; Geutskens et al., 2010), while it inhibits the migration of hematopoietic stem and progenitor cells (HSPC) in vitro (Geutskens et al., 2012). The differential response of cells to SLIT3 may be explained by the level of ROBO1 expression; the level of ROBO1 is lower in monocytes than in HSPC (Geutskens et al., 2012). Cell-specific downstream signaling cues may also play a role. SLIT3 treatment of monocytes activates the GTPase RhoA to enhance migration (Geutskens et al., 2010). In contrast, SLIT3 inactivates RhoA in HSPC and inhibits their migration (Geutskens et al., 2012). HSPC that were pretreated with SLIT3 and transplanted into NOD-SCID mice showed increased homing to the bone marrow, which could be explained by modulation of SLIT/ ROBO signaling in the bone marrow environment. This is supported by the fact that SLIT3 does not inhibit transendothelial migration of HSPC in vitro (Geutskens et al., 2012). Thus, the response to SLIT3 proteins may be dependent on the level of ROBO expression, downstream cell-specific signaling cues and on the environment.
Homology A single slit gene was isolated in invertebrates, whereas there are three SLIT genes in mammals. The human SLIT3 protein shows 41,1% sequence homology with Drosophila slit (Itoh et al., 1998; Brose et al., 1999), 66% homology to human SLIT2 (NCBI accession AAD25539.1, NCBI protein blast) and 60% homology to human SLIT1 (NCBI accession BAA35184.1, NCBI protein blast).

Implicated in

Note
  
Entity Invasive ductal breast carcinoma
Note Methylation of the 5'CpG islands in the SLIT3 gene was detected in 41% of breast tumor cell lines and in 16% of primary human breast tumors. The methylation resulted in reduced SLIT3 expression. The methylation frequency was significantly lower than for SLIT2 (Dickinson et al., 2004). Marlow et al. reported that loss of SLIT2 and SLIT3 expression correlated with the upregulation of CXCR4 in human breast tumors. In mouse mammary gland and in human MCF7 breast cancer cells, this resulted in hyperplastic lesions and in desmoplastic stroma. Overexpression of SLIT2 or SLIT3 in human breast carcinoma MDA-MB-231 cells resulted in a down-regulation of CXCR4 expression, reduced colony formation in vitro and in inhibition of tumor growth in a xenograft model in vivo. Inhibition of tumor growth and down-regulation of CXCR4 expression in SLIT-expressing tumor cells was the most prominent with overexpression of SLIT3 (Marlow et al., 2008).
  
  
Entity Glioma
Note Methylation of the 5'CpG islands in the SLIT3 gene was detected in 29% of glioma tumor cell lines and in 35% of gliomas. 66,7% of the gliomas were classified as gliomblastoma multiforme, the rest was randomly collected. No methylation was found in normal tissue from glioma patients (Dickinson et al., 2004).
  
  
Entity Neurological diseases
Hybrid/Mutated Gene It is not known whether the neuronal guidance defects cause neurological diseases in mice. However, it was reported that SLIT3 may be associated with neurological diseases in humans. Single nucleotide polymorphisms and duplications of the chromosomal region harboring the SLIT3 gene were identified. Locus 5q35.1, encompassing the genes coding for SLIT3, CCDC99 and DOCK2, had significant copy number variation in patients with major depressive disorder. In 0,7% of these cases, there was a duplication of 5q35.1 (Glessner et al., 2010). Furthermore, some of the SNPs located in introns and exons of the SLIT3 gene showed significant association with Schizophrenia in the Chinese Han population (Shi et al., 2004).
  
  
Entity Congenital diaphragmatic hernia
Note Slit3 homozygous knockout mice suffered from diaphragmatic hernia. This was caused by a central tendon that remained fused to the liver. In the defective tendon, the collagen fibers did not form tight bundles. Due to the herniation, the orientation of the heart was twisted. The right ventricle faced ventrally and was enlarged (Liu et al., 2003).
Disease Congenital diaphragmatic hernia is a rare anatomical defect in the diaphragm. As a result, abdominal organs can be herniated inside the thoracic cavity, which results in severe respiratory complications. Malformations in the heart and the vascular system are also commonly reported, resulting in cardiovascular defects (reviewed in Tovar, 2012).
Prognosis Congenital diaphragmatic hernia is associated with a high morbidity and a mortality rate of around 50% (reviewed in Tovar, 2012).
  
  
Entity Renal agenesis
Note In approximately 20% of Slit3 homozygous knockout mice that were born and in 40% of homozygous mice that died before birth, unilateral or bilateral kidney and ureter agenesis was found (Liu et al., 2003). In addition, in one mouse one kidney was smaller than normal while the other kidney appeared normal in size. In another mouse, the kidneys were abnormally shaped and the left kidney extended to the right side and appeared to be connected with the right kidney (Liu et al., 2003).
Disease During renal agenesis one (unilateral) or two (bilateral) kidneys do not develop. Unilateral agenesis occurs more frequently than bilateral agenesis. Unilateral renal agenesis is usually accompanied by an enlargement of cells in the developed kidney. When the kidney fails to develop, the ureter often also fails to develop. Alternatively, the ureter may be dilated (Mishra, 2007).
  

Bibliography

Information for the dorsal--ventral pattern of the Drosophila embryo is stored as maternal mRNA.
Anderson KV, Nusslein-Volhard C.
Nature. 1984 Sep 20-26;311(5983):223-7.
PMID 6434989
 
The role of Slit-Robo signaling in the generation, migration and morphological differentiation of cortical interneurons.
Andrews W, Barber M, Hernadez-Miranda LR, Xian J, Rakic S, Sundaresan V, Rabbitts TH, Pannell R, Rabbitts P, Thompson H, Erskine L, Murakami F, Parnavelas JG.
Dev Biol. 2008 Jan 15;313(2):648-58. Epub 2007 Nov 13.
PMID 18054781
 
SLIT2 promoter methylation analysis in neuroblastoma, Wilms' tumour and renal cell carcinoma.
Astuti D, Da Silva NF, Dallol A, Gentle D, Martinsson T, Kogner P, Grundy R, Kishida T, Yao M, Latif F, Maher ER.
Br J Cancer. 2004 Jan 26;90(2):515-21.
PMID 14735202
 
Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance.
Brose K, Bland KS, Wang KH, Arnott D, Henzel W, Goodman CS, Tessier-Lavigne M, Kidd T.
Cell. 1999 Mar 19;96(6):795-806.
PMID 10102268
 
The C-terminal fragment of axon guidance molecule Slit3 binds heparin and neutralizes heparin's anticoagulant activity.
Condac E, Strachan H, Gutierrez-Sanchez G, Brainard B, Giese C, Heiss C, Johnson D, Azadi P, Bergmann C, Orlando R, Esmon CT, Harenberg J, Moremen K, Wang L.
Glycobiology. 2012 Sep;22(9):1183-92. doi: 10.1093/glycob/cws087. Epub 2012 May 28.
PMID 22641771
 
SLIT2, a human homologue of the Drosophila Slit2 gene, has tumor suppressor activity and is frequently inactivated in lung and breast cancers.
Dallol A, Da Silva NF, Viacava P, Minna JD, Bieche I, Maher ER, Latif F.
Cancer Res. 2002 Oct 15;62(20):5874-80.
PMID 12384551
 
DNA Methylation, Epigenetics and Metastasis.
Dallol A, Dickinson RE, Latif F.
Series: Cancer Metastasis - Biology and Treatment, Vol. 7, DNA Methylation, Epigenetics and Metastasis, 191-214. Esteller, Manel (Ed.) 2005, XII, 310 p.
 
Frequent epigenetic inactivation of the SLIT2 gene in gliomas.
Dallol A, Krex D, Hesson L, Eng C, Maher ER, Latif F.
Oncogene. 2003 Jul 17;22(29):4611-6.
PMID 12881718
 
SLIT2 axon guidance molecule is frequently inactivated in colorectal cancer and suppresses growth of colorectal carcinoma cells.
Dallol A, Morton D, Maher ER, Latif F.
Cancer Res. 2003 Mar 1;63(5):1054-8.
PMID 12615722
 
Glucocorticoid regulation of SLIT/ROBO tumour suppressor genes in the ovarian surface epithelium and ovarian cancer cells.
Dickinson RE, Fegan KS, Ren X, Hillier SG, Duncan WC.
PLoS One. 2011;6(11):e27792. doi: 10.1371/journal.pone.0027792. Epub 2011 Nov 23.
PMID 22132142
 
Regulation of commissural axon pathfinding by slit and its Robo receptors.
Dickson BJ, Gilestro GF.
Annu Rev Cell Dev Biol. 2006;22:651-75. (REVIEW)
PMID 17029581
 
Expression of the repulsive SLIT/ROBO pathway in the human endometrium and Fallopian tube.
Duncan WC, McDonald SE, Dickinson RE, Shaw JL, Lourenco PC, Wheelhouse N, Lee KF, Critchley HO, Horne AW.
Mol Hum Reprod. 2010 Dec;16(12):950-9. doi: 10.1093/molehr/gaq055. Epub 2010 Jul 22.
PMID 20651036
 
Frequent epigenetic inactivation of the SLIT2 gene in chronic and acute lymphocytic leukemia.
Dunwell TL, Dickinson RE, Stankovic T, Dallol A, Weston V, Austen B, Catchpoole D, Maher ER, Latif F.
Epigenetics. 2009 May 16;4(4):265-9. Epub 2009 May 1.
PMID 19550140
 
Control of human hematopoietic stem/progenitor cell migration by the extracellular matrix protein Slit3.
Geutskens SB, Andrews WD, van Stalborch AM, Brussen K, Holtrop-de Haan SE, Parnavelas JG, Hordijk PL, van Hennik PB.
Lab Invest. 2012 Aug;92(8):1129-39. doi: 10.1038/labinvest.2012.81. Epub 2012 May 21.
PMID 22614124
 
The migration of cerebellar rhombic lip derivatives.
Gilthorpe JD, Papantoniou EK, Chedotal A, Lumsden A, Wingate RJ.
Development. 2002 Oct;129(20):4719-28.
PMID 12361964
 
Duplication of the SLIT3 locus on 5q35.1 predisposes to major depressive disorder.
Glessner JT, Wang K, Sleiman PM, Zhang H, Kim CE, Flory JH, Bradfield JP, Imielinski M, Frackelton EC, Qiu H, Mentch F, Grant SF, Hakonarson H.
PLoS One. 2010 Dec 1;5(12):e15463. doi: 10.1371/journal.pone.0015463.
PMID 21152026
 
SLIT2-mediated ROBO2 signaling restricts kidney induction to a single site.
Grieshammer U, Le Ma, Plump AS, Wang F, Tessier-Lavigne M, Martin GR.
Dev Cell. 2004 May;6(5):709-17.
PMID 15130495
 
The crystal structure of a laminin G-like module reveals the molecular basis of alpha-dystroglycan binding to laminins, perlecan, and agrin.
Hohenester E, Tisi D, Talts JF, Timpl R.
Mol Cell. 1999 Nov;4(5):783-92.
PMID 10619025
 
Expression of slit-2 and slit-3 during chick development.
Holmes G, Niswander L.
Dev Dyn. 2001 Oct;222(2):301-7.
PMID 11668607
 
Distinct but overlapping expression patterns of two vertebrate slit homologs implies functional roles in CNS development and organogenesis.
Holmes GP, Negus K, Burridge L, Raman S, Algar E, Yamada T, Little MH.
Mech Dev. 1998 Dec;79(1-2):57-72.
PMID 10349621
 
Cell-surface heparan sulfate is involved in the repulsive guidance activities of Slit2 protein.
Hu H.
Nat Neurosci. 2001 Jul;4(7):695-701.
PMID 11426225
 
A molecular mechanism for the heparan sulfate dependence of slit-robo signaling.
Hussain SA, Piper M, Fukuhara N, Strochlic L, Cho G, Howitt JA, Ahmed Y, Powell AK, Turnbull JE, Holt CE, Hohenester E.
J Biol Chem. 2006 Dec 22;281(51):39693-8. Epub 2006 Oct 24.
PMID 17062560
 
Mammalian brain morphogenesis and midline axon guidance require heparan sulfate.
Inatani M, Irie F, Plump AS, Tessier-Lavigne M, Yamaguchi Y.
Science. 2003 Nov 7;302(5647):1044-6.
PMID 14605369
 
Cloning and expressions of three mammalian homologues of Drosophila slit suggest possible roles for Slit in the formation and maintenance of the nervous system.
Itoh A, Miyabayashi T, Ohno M, Sakano S.
Brain Res Mol Brain Res. 1998 Nov 20;62(2):175-86.
PMID 9813312
 
Slit is the midline repellent for the robo receptor in Drosophila.
Kidd T, Bland KS, Goodman CS.
Cell. 1999 Mar 19;96(6):785-94.
PMID 10102267
 
Mammalian homologues of the Drosophila slit protein are ligands of the heparan sulfate proteoglycan glypican-1 in brain.
Liang Y, Annan RS, Carr SA, Popp S, Mevissen M, Margolis RK, Margolis RU.
J Biol Chem. 1999 Jun 18;274(25):17885-92.
PMID 10364234
 
Conserved modularity and potential for alternate splicing in mouse and human Slit genes.
Little M, Rumballe B, Georgas K, Yamada T, Teasdale RD.
Int J Dev Biol. 2002;46(4):385-91.
PMID 12141424
 
Congenital diaphragmatic hernia, kidney agenesis and cardiac defects associated with Slit3-deficiency in mice.
Liu J, Zhang L, Wang D, Shen H, Jiang M, Mei P, Hayden PS, Sedor JR, Hu H.
Mech Dev. 2003 Sep;120(9):1059-70.
PMID 14550534
 
Conserved roles for Slit and Robo proteins in midline commissural axon guidance.
Long H, Sabatier C, Ma L, Plump A, Yuan W, Ornitz DM, Tamada A, Murakami F, Goodman CS, Tessier-Lavigne M.
Neuron. 2004 Apr 22;42(2):213-23.
PMID 15091338
 
SLITs suppress tumor growth in vivo by silencing Sdf1/Cxcr4 within breast epithelium.
Marlow R, Strickland P, Lee JS, Wu X, Pebenito M, Binnewies M, Le EK, Moran A, Macias H, Cardiff RD, Sukumar S, Hinck L.
Cancer Res. 2008 Oct 1;68(19):7819-27. doi: 10.1158/0008-5472.CAN-08-1357.
PMID 18829537
 
Renal agenesis: report of an interesting case.
Mishra A.
Br J Radiol. 2007 Aug;80(956):e167-9.
PMID 17762048
 
Role of Slit proteins in the vertebrate brain.
Nguyen-Ba-Charvet KT, Chedotal A.
J Physiol Paris. 2002 Jan-Mar;96(1-2):91-8. (REVIEW)
PMID 11755787
 
Slit proteins are not dominant chemorepellents for olfactory tract and spinal motor axons.
Patel K, Nash JA, Itoh A, Liu Z, Sundaresan V, Pini A.
Development. 2001 Dec;128(24):5031-7.
PMID 11748139
 
Slit1 and Slit2 cooperate to prevent premature midline crossing of retinal axons in the mouse visual system.
Plump AS, Erskine L, Sabatier C, Brose K, Epstein CJ, Goodman CS, Mason CA, Tessier-Lavigne M.
Neuron. 2002 Jan 17;33(2):219-32.
PMID 11804570
 
Slit protein-mediated inhibition of CXCR4-induced chemotactic and chemoinvasive signaling pathways in breast cancer cells.
Prasad A, Fernandis AZ, Rao Y, Ganju RK.
J Biol Chem. 2004 Mar 5;279(10):9115-24. Epub 2003 Nov 26.
PMID 14645233
 
Slit-2 induces a tumor-suppressive effect by regulating beta-catenin in breast cancer cells.
Prasad A, Paruchuri V, Preet A, Latif F, Ganju RK.
J Biol Chem. 2008 Sep 26;283(39):26624-33. doi: 10.1074/jbc.M800679200. Epub 2008 Jul 8.
PMID 18611862
 
Characterization of Slit protein interactions with glypican-1.
Ronca F, Andersen JS, Paech V, Margolis RU.
J Biol Chem. 2001 Aug 3;276(31):29141-7. Epub 2001 May 25.
PMID 11375980
 
Modularity of the slit protein. Characterization of a conserved carboxy-terminal sequence in secreted proteins and a motif implicated in extracellular protein interactions.
Rothberg JM, Artavanis-Tsakonas S.
J Mol Biol. 1992 Sep 20;227(2):367-70.
PMID 1404356
 
Mutations affecting growth cone guidance in Drosophila: genes necessary for guidance toward or away from the midline.
Seeger M, Tear G, Ferres-Marco D, Goodman CS.
Neuron. 1993 Mar;10(3):409-26.
PMID 8461134
 
Genetic structure adds power to detect schizophrenia susceptibility at SLIT3 in the Chinese Han population.
Shi Y, Zhao X, Yu L, Tao R, Tang J, La Y, Duan Y, Gao B, Gu N, Xu Y, Feng G, Zhu S, Liu H, Salter H, He L.
Genome Res. 2004 Jul;14(7):1345-9.
PMID 15231749
 
Heparan sulfate proteoglycan syndecan promotes axonal and myotube guidance by slit/robo signaling.
Steigemann P, Molitor A, Fellert S, Jackle H, Vorbruggen G.
Curr Biol. 2004 Feb 3;14(3):225-30.
PMID 14761655
 
Slit3 regulates cell motility through Rac/Cdc42 activation in lipopolysaccharide-stimulated macrophages.
Tanno T, Fujiwara A, Sakaguchi K, Tanaka K, Takenaka S, Tsuyama S.
FEBS Lett. 2007 Mar 6;581(5):1022-6. Epub 2007 Feb 12.
PMID 17306799
 
Congenital diaphragmatic hernia.
Tovar JA.
Orphanet J Rare Dis. 2012 Jan 3;7:1. doi: 10.1186/1750-1172-7-1. (REVIEW)
PMID 22214468
 
SLIT2 attenuation during lung cancer progression deregulates beta-catenin and E-cadherin and associates with poor prognosis.
Tseng RC, Lee SH, Hsu HS, Chen BH, Tsai WC, Tzao C, Wang YC.
Cancer Res. 2010 Jan 15;70(2):543-51. doi: 10.1158/0008-5472.CAN-09-2084. Epub 2010 Jan 12.
PMID 20068157
 
Multiple Slits regulate the development of midline glial populations and the corpus callosum.
Unni DK, Piper M, Moldrich RX, Gobius I, Liu S, Fothergill T, Donahoo AL, Baisden JM, Cooper HM, Richards LJ.
Dev Biol. 2012 May 1;365(1):36-49. doi: 10.1016/j.ydbio.2012.02.004. Epub 2012 Feb 11.
PMID 22349628
 
Expression patterns of Slit and Robo family members during vertebrate limb development.
Vargesson N, Luria V, Messina I, Erskine L, Laufer E.
Mech Dev. 2001 Aug;106(1-2):175-80.
PMID 11472852
 
Induction of tumor angiogenesis by Slit-Robo signaling and inhibition of cancer growth by blocking Robo activity.
Wang B, Xiao Y, Ding BB, Zhang N, Yuan Xb, Gui L, Qian KX, Duan S, Chen Z, Rao Y, Geng JG.
Cancer Cell. 2003 Jul;4(1):19-29.
PMID 12892710
 
Biochemical purification of a mammalian slit protein as a positive regulator of sensory axon elongation and branching.
Wang KH, Brose K, Arnott D, Kidd T, Goodman CS, Henzel W, Tessier-Lavigne M.
Cell. 1999 Mar 19;96(6):771-84.
PMID 10102266
 
Inhibition of medulloblastoma cell invasion by Slit.
Werbowetski-Ogilvie TE, Seyed Sadr M, Jabado N, Angers-Loustau A, Agar NY, Wu J, Bjerkvig R, Antel JP, Faury D, Rao Y, Del Maestro RF.
Oncogene. 2006 Aug 24;25(37):5103-12. Epub 2006 Apr 24.
PMID 16636676
 
A genetic model for a central (septum transversum) congenital diaphragmatic hernia in mice lacking Slit3.
Yuan W, Rao Y, Babiuk RP, Greer JJ, Wu JY, Ornitz DM.
Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5217-22. Epub 2003 Apr 17.
PMID 12702769
 
Repulsive axon guidance molecule Slit3 is a novel angiogenic factor.
Zhang B, Dietrich UM, Geng JG, Bicknell R, Esko JD, Wang L.
Blood. 2009 Nov 5;114(19):4300-9. doi: 10.1182/blood-2008-12-193326. Epub 2009 Sep 9.
PMID 19741192
 

Citation

This paper should be referenced as such :
Brussen, K
SLIT3 (slit homolog 3 (Drosophila))
Atlas Genet Cytogenet Oncol Haematol. 2013;17(3):161-166.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/SLIT3ID50515ch5q34.html


External links

Nomenclature
HGNC (Hugo)SLIT3   11087
Cards
AtlasSLIT3ID50515ch5q34
Entrez_Gene (NCBI)SLIT3  6586  slit guidance ligand 3
AliasesMEGF5; SLIL2; SLIT1; Slit-3; 
slit2
GeneCards (Weizmann)SLIT3
Ensembl hg19 (Hinxton)ENSG00000184347 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000184347 [Gene_View]  chr5:168661733-169301129 [Contig_View]  SLIT3 [Vega]
ICGC DataPortalENSG00000184347
TCGA cBioPortalSLIT3
AceView (NCBI)SLIT3
Genatlas (Paris)SLIT3
WikiGenes6586
SOURCE (Princeton)SLIT3
Genetics Home Reference (NIH)SLIT3
Genomic and cartography
GoldenPath hg38 (UCSC)SLIT3  -     chr5:168661733-169301129 -  5q34-q35.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)SLIT3  -     5q34-q35.1   [Description]    (hg19-Feb_2009)
EnsemblSLIT3 - 5q34-q35.1 [CytoView hg19]  SLIT3 - 5q34-q35.1 [CytoView hg38]
Mapping of homologs : NCBISLIT3 [Mapview hg19]  SLIT3 [Mapview hg38]
OMIM603745   
Gene and transcription
Genbank (Entrez)AB011538 AB017169 AF075240 AF086552 AI741785
RefSeq transcript (Entrez)NM_001271946 NM_003062
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)SLIT3
Cluster EST : UnigeneHs.552087 [ NCBI ]
CGAP (NCI)Hs.552087
Alternative Splicing GalleryENSG00000184347
Gene ExpressionSLIT3 [ NCBI-GEO ]   SLIT3 [ EBI - ARRAY_EXPRESS ]   SLIT3 [ SEEK ]   SLIT3 [ MEM ]
Gene Expression Viewer (FireBrowse)SLIT3 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)6586
GTEX Portal (Tissue expression)SLIT3
Protein : pattern, domain, 3D structure
UniProt/SwissProtO75094   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO75094  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO75094
Splice isoforms : SwissVarO75094
PhosPhoSitePlusO75094
Domaine pattern : Prosite (Expaxy)CTCK_1 (PS01185)    CTCK_2 (PS01225)    EGF_1 (PS00022)    EGF_2 (PS01186)    EGF_3 (PS50026)    EGF_CA (PS01187)    LAM_G_DOMAIN (PS50025)    LRR (PS51450)   
Domains : Interpro (EBI)ConA-like_dom    Cys-rich_flank_reg_C    Cys_knot_C    EGF-like_Ca-bd_dom    EGF-like_CS    EGF-like_dom    EGF-type_Asp/Asn_hydroxyl_site    EGF_Ca-bd_CS    Growth_fac_rcpt_    L_dom-like    Laminin_G    Leu-rich_rpt    Leu-rich_rpt_typical-subtyp    LRRNT   
Domain families : Pfam (Sanger)EGF (PF00008)    Laminin_G_2 (PF02210)    LRR_8 (PF13855)    LRRCT (PF01463)    LRRNT (PF01462)   
Domain families : Pfam (NCBI)pfam00008    pfam02210    pfam13855    pfam01463    pfam01462   
Domain families : Smart (EMBL)CT (SM00041)  EGF (SM00181)  EGF_CA (SM00179)  LamG (SM00282)  LRR_TYP (SM00369)  LRRCT (SM00082)  LRRNT (SM00013)  
Conserved Domain (NCBI)SLIT3
DMDM Disease mutations6586
Blocks (Seattle)SLIT3
SuperfamilyO75094
Human Protein AtlasENSG00000184347
Peptide AtlasO75094
HPRD04775
IPIIPI00983148   IPI00409709   IPI00409710   IPI00017640   
Protein Interaction databases
DIP (DOE-UCLA)O75094
IntAct (EBI)O75094
FunCoupENSG00000184347
BioGRIDSLIT3
STRING (EMBL)SLIT3
ZODIACSLIT3
Ontologies - Pathways
QuickGOO75094
Ontology : AmiGOcalcium ion binding  extracellular space  mitochondrion  axon guidance  negative regulation of cell proliferation  animal organ morphogenesis  negative regulation of gene expression  chemorepulsion involved in embryonic olfactory bulb interneuron precursor migration  negative regulation of cell growth  cellular response to hormone stimulus  Roundabout signaling pathway  Roundabout binding  axon extension involved in axon guidance  negative chemotaxis  response to cortisol  apoptotic process involved in luteolysis  negative regulation of chemokine-mediated signaling pathway  
Ontology : EGO-EBIcalcium ion binding  extracellular space  mitochondrion  axon guidance  negative regulation of cell proliferation  animal organ morphogenesis  negative regulation of gene expression  chemorepulsion involved in embryonic olfactory bulb interneuron precursor migration  negative regulation of cell growth  cellular response to hormone stimulus  Roundabout signaling pathway  Roundabout binding  axon extension involved in axon guidance  negative chemotaxis  response to cortisol  apoptotic process involved in luteolysis  negative regulation of chemokine-mediated signaling pathway  
Pathways : KEGGAxon guidance   
REACTOMEO75094 [protein]
REACTOME PathwaysR-HSA-373752 [pathway]   
NDEx NetworkSLIT3
Atlas of Cancer Signalling NetworkSLIT3
Wikipedia pathwaysSLIT3
Orthology - Evolution
OrthoDB6586
GeneTree (enSembl)ENSG00000184347
Phylogenetic Trees/Animal Genes : TreeFamSLIT3
HOVERGENO75094
HOGENOMO75094
Homologs : HomoloGeneSLIT3
Homology/Alignments : Family Browser (UCSC)SLIT3
Gene fusions - Rearrangements
Fusion : MitelmanCREBRF/SLIT3 [5q35.1/5q34]  [t(5;5)(q35;q35)]  
Fusion : MitelmanFSTL4/SLIT3 [5q31.1/5q34]  [t(5;5)(q31;q35)]  
Fusion : MitelmanSLIT3/HSD17B4 [5q34/5q23.1]  [t(5;5)(q23;q35)]  
Fusion: TCGAC5orf41 SLIT3 5q34 LUAD
Fusion: TCGAFSTL4 5q31.1 SLIT3 5q34 BRCA
Fusion: TCGASLIT3 5q34 HSD17B4 5q23.1 BRCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSLIT3 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SLIT3
dbVarSLIT3
ClinVarSLIT3
1000_GenomesSLIT3 
Exome Variant ServerSLIT3
ExAC (Exome Aggregation Consortium)SLIT3 (select the gene name)
Genetic variants : HAPMAP6586
Genomic Variants (DGV)SLIT3 [DGVbeta]
DECIPHERSLIT3 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisSLIT3 
Mutations
ICGC Data PortalSLIT3 
TCGA Data PortalSLIT3 
Broad Tumor PortalSLIT3
OASIS PortalSLIT3 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICSLIT3  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDSLIT3
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch SLIT3
DgiDB (Drug Gene Interaction Database)SLIT3
DoCM (Curated mutations)SLIT3 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)SLIT3 (select a term)
intoGenSLIT3
NCG5 (London)SLIT3
Cancer3DSLIT3(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM603745   
Orphanet
MedgenSLIT3
Genetic Testing Registry SLIT3
NextProtO75094 [Medical]
TSGene6586
GENETestsSLIT3
Target ValidationSLIT3
Huge Navigator SLIT3 [HugePedia]
snp3D : Map Gene to Disease6586
BioCentury BCIQSLIT3
ClinGenSLIT3
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD6586
Chemical/Pharm GKB GenePA35940
Clinical trialSLIT3
Miscellaneous
canSAR (ICR)SLIT3 (select the gene name)
Probes
Litterature
PubMed40 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineSLIT3
EVEXSLIT3
GoPubMedSLIT3
iHOPSLIT3
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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