Search results for SLIT2

Showing 19 results out of 54

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Protein (3 results from a total of 3)

Identifier: R-HSA-375997
Species: Homo sapiens
Compartment: extracellular region
Primary external reference: UniProt: SLIT2: O94813
Identifier: R-HSA-426409
Species: Homo sapiens
Compartment: extracellular region
Primary external reference: UniProt: O94813
Identifier: R-HSA-426412
Species: Homo sapiens
Compartment: extracellular region
Primary external reference: UniProt: O94813

DNA Sequence (1 results from a total of 1)

Identifier: R-HSA-9010561
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: ENSEMBL: ENSG00000145147

Reaction (4 results from a total of 20)

Identifier: R-NUL-9010914
Species: Homo sapiens, Rattus norvegicus
Compartment: plasma membrane
Recombinant rat Robo2 receptor binds to recombinant human SLIT2 ligand (Brose et al. 1999, Nguyen Ba-Charvet et al. 2001).
Identifier: R-HSA-9010872
Species: Homo sapiens
Compartment: plasma membrane
SLIT2 binds to dystroglycan (DAG1). The interaction involves the C-terminal region of human SLIT2. The species origin of the DAG1 construct was not specified and is assumed to be human. Dystroglycan is required for proper SLIT2 localization within the basement membrane and the floor plate. Dystroglycan glycosylation, mediated at least in part by B4GAT1 (B3GNT1) and ISPD, is likely required for its interaction with SLIT2, but it has not been annotated. Mice mutant for B4gat1, Ispd or Dag1 have axon guidance defects similar to those observed in Slit or Robo mutant mice (Wright et al. 2012).
Identifier: R-HSA-9010898
Species: Homo sapiens
Compartment: plasma membrane
ROBO2 receptor binds to SLIT2 ligand (Brose et al. 1999, Nguyen Ba-Charvet et al. 2001).
Identifier: R-HSA-428518
Species: Homo sapiens
Compartment: plasma membrane
SLIT2 and both its natural cleavage products bind glypican-1 (GPC1), a glycosyl phosphatidyl inositol (GPI) anchored heparan sulfate proteoglycan (HSPG), through its C-terminus. Besides glypican-1, other HSPG may also be involved in SLIT2 binding. GPC1:HSPG is important for high affinity binding of SLIT to its receptor and for the repulsive activity of SLIT. SLIT-ROBO signaling strictly requires binding to heparan sulfate. HSPGs may also modulate the extracellular distribution or stability of SLIT proteins (Ronca et al. 2001, Zhang et al. 2004).

Set (2 results from a total of 2)

Identifier: R-HSA-9014805
Species: Homo sapiens
Compartment: extracellular region
Identifier: R-HSA-9010822
Species: Homo sapiens
Compartment: extracellular region

Complex (4 results from a total of 23)

Identifier: R-HSA-428489
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-390371
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-9010869
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-9010899
Species: Homo sapiens
Compartment: plasma membrane

Pathway (3 results from a total of 3)

Identifier: R-HSA-8985586
Species: Homo sapiens
ROBO1 receptor, activated by SLIT2, binds to MYO9B and inhibits its RHOA GAP activity. SLIT2-ROBO1 signaling thus results in increased RHOA activity, which is thought to negatively regulate invasiveness of lung cancer cells (Kong et al. 2015). ROCK-mediated signaling and phosphorylation of the myosin regulatory light chain (MLRC) downstream of activated RHOA is needed for SLIT-mediated axon pathfinding in cranial motor neurons (Murray et al. 2010).
Identifier: R-HSA-9010553
Species: Homo sapiens
Expression of SLIT and ROBO proteins is regulated at the level of transcription, translation and protein localization and stability. LIM-homeodomain transcription factors LHX2, LHX3, LHX4, LHX9 and ISL1 have so far been implicated in a cell type-dependent transcriptional regulation of ROBO1, ROBO2, ROBO3 and SLIT2 (Wilson et al. 2008, Marcos-Mondejar et al. 2012, Kim et al. 2016). Homeobox transcription factor HOXA2 is involved in transcriptional regulation of ROBO2 (Geisen et al. 2008). Transcription of SLIT1 during optic tract development in Xenopus is stimulated by FGF signaling and may also involve the transcription factor HOXA2, but the mechanism has not been established (Atkinson-Leadbeater et al. 2010). PAX6 and the homeodomain transcription factor NKX2.2 are also implicated in regulation of SLIT1 transcription (Genethliou et al. 2009). An RNA binding protein, MSI1, binds ROBO3 mRNA and promotes its translation, thus increasing ROBO3 protein levels (Kuwako et al. 2010). A poorly studied E3 ubiquitin ligase ZSWIM8 promotes degradation of ROBO3 (Wang et al. 2013). ROBO1 is protein half-life is increased via deubiquitination of ROBO1 by a ubiquitin protease USP33 (Yuasa-Kawada et al. 2009, Huang et al. 2015). Interaction of SLIT2 with DAG1 (dystroglycan) is important for proper localization of SLIT2 at the floor plate (Wright et al. 2012). Interaction of SLIT1 with a type IV collagen COL4A5 is important for localization of SLIT1 to the basement membrane of the optical tectum (Xiao et al. 2011).
Identifier: R-HSA-376176
Species: Homo sapiens
Compartment: plasma membrane
The Roundabout (ROBO) family encodes transmembrane receptors that regulate axonal guidance and cell migration. The major function of the Robo receptors is to mediate repulsion of the navigating growth cones. There are four human Robo homologues, ROBO1, ROBO2, ROBO3 and ROBO4. Most of the ROBOs have the similar ectodomain architecture as the cell adhesion molecules, with five Ig domains followed by three FN3 repeats, except for ROBO4. ROBO4 has two Ig and two FN3 repeats. The cytoplasmic domains of ROBO receptors are in general poorly conserved. However, there are four short conserved cytoplasmic sequence motifs, named CC0-3, that serve as binding sites for adaptor proteins. The ligands for the human ROBO1 and ROBO2 receptors are the three SLIT proteins SLIT1, SLIT2, and SLIT3; all of the SLIT proteins contain a tandem of four LRR (leucine rich repeat) domains at the N-terminus, termed D1-D4, followed by six EGF (epidermal growth factor)-like domains, a laminin G like domain (ALPS), three EGF-like domains, and a C-terminal cysteine knot domain. Most SLIT proteins are cleaved within the EGF-like region by unknown proteases (reviewed by Hohenster 2008, Ypsilanti and Chedotal 2014, Blockus and Chedotal 2016). NELL2 is a ligand for ROBO3 (Jaworski et al. 2015).

SLIT protein binding modulates ROBO interactions with the cytosolic adaptors. The cytoplasmic domain of ROBO1 and ROBO2 determines the repulsive responses of these receptors. Based on the studies from both invertebrate and vertebrate organisms it has been inferred that ROBO induces growth cone repulsion by controlling cytoskeletal dynamics via either Abelson kinase (ABL) and Enabled (Ena), or RAC1 activity (reviewed by Hohenster 2008, Ypsilanti and Chedotal 2014, Blockus and Chedotal 2016). While there is some redundancy in the function of ROBO receptors, ROBO1 is implicated as the predominant receptor for axon guidance in ventral tracts, and ROBO2 is the predominant receptor for axon guidance in dorsal tracts. ROBO2 also repels neuron cell bodies from the floor plate (Kim et al. 2011).

In addition to regulating axon guidance, ROBO1 and ROBO2 receptors are also implicated in regulation of proliferation and transition of primary to intermediate neuronal progenitors through a poorly characterized cross-talk with NOTCH-mediated activation of HES1 transcription (Borrell et al. 2012).

Thalamocortical axon extension is regulated by neuronal activity-dependent transcriptional regulation of ROBO1 transcription. Lower neuronal activity correlates with increased ROBO1 transcription, possibly mediated by the NFKB complex (Mire et al. 2012).

It is suggested that the homeodomain transcription factor NKX2.9 stimulates transcription of ROBO2, which is involved in regulation of motor axon exit from the vertebrate spinal code (Bravo-Ambrosio et al. 2012).

Of the four ROBO proteins, ROBO4 is not involved in neuronal system development but is, instead, involved in angiogenesis. The interaction of ROBO4 with SLIT3 is involved in proliferation, motility and chemotaxis of endothelial cells, and accelerates formation of blood vessels (Zhang et al. 2009).

Icon (2 results from a total of 2)

Species: Homo sapiens
Curator: Steve Jupe
Designer: Cristoffer Sevilla
SLIT2 icon
Slit homolog 2 protein
Species: Homo sapiens
Representation of Slit homolog 1, 2 and 3 proteins
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