Tbio SLIT2 Slit homolog 2 protein

Protein Summary

Description

Thought to act as molecular guidance cue in cellular migration, and function appears to be mediated by interaction with roundabout homolog receptors. During neural development involved in axonal navigation at the ventral midline of the neural tube and projection of axons to different regions. SLIT1 and SLIT2 seem to be essential for midline guidance in the forebrain by acting as repulsive signal preventing inappropriate midline crossing by axons projecting from the olfactory bulb. In spinal chord development may play a role in guiding commissural axons once they reached the floor plate by modulating the response to netrin. In vitro, silences the attractive effect of NTN1 but not its growth-stimulatory effect and silencing requires the formation of a ROBO1-DCC complex. May be implicated in spinal chord midline post-crossing axon repulsion. In vitro, only commissural axons that crossed the midline responded to SLIT2. In the developing visual system appears to function as repellent for retinal ganglion axons by providing a repulsion that directs these axons along their appropriate paths prior to, and after passage through, the optic chiasm. In vitro, collapses and repels retinal ganglion cell growth cones. Seems to play a role in branching and arborization of CNS sensory axons, and in neuronal cell migration. In vitro, Slit homolog 2 protein N-product, but not Slit homolog 2 protein C-product, repels olfactory bulb (OB) but not dorsal root ganglia (DRG) axons, induces OB growth cones collapse and induces branching of DRG axons. Seems to be involved in regulating leukocyte migration. This gene encodes a member of the slit family of secreted glycoproteins, which are ligands for the Robo family of immunoglobulin receptors. Slit proteins play highly conserved roles in axon guidance and neuronal migration and may also have functions during other cell migration processes including leukocyte migration. Members of the slit family are characterized by an N-terminal signal peptide, four leucine-rich repeats, nine epidermal growth factor repeats, and a C-terminal cysteine knot. Proteolytic processing of this protein gives rise to an N-terminal fragment that contains the four leucine-rich repeats and five epidermal growth factor repeats and a C-terminal fragment that contains four epidermal growth factor repeats and the cysteine knot. Both full length and cleaved proteins are secreted extracellularly and can function in axon repulsion as well as other specific processes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

Uniprot Accession IDs

• O94813
• A0A0A6YYB8
• B7ZLR5
• O95710
• Q17RU3
• Q9Y5Q7
• Slit-2

Gene Name

• SLIT2

Ensembl ID

• ENST00000503823
• ENSP00000427548
• ENSG00000145147
• ENST00000503837
• ENSP00000422261
• ENST00000504154
• ENSP00000422591

Symbol

• SLIL3
• SLIL3
• Slit-2

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
protein domain	1
PubMedID	0.98
molecular function	0.91
histone modification site profile	0.78

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Target Illumination GWAS Analytics (TIGA)

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 159.46   (req: < 5)

Gene RIFs: 111   (req: <= 3)

Antibodies: 297   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 159.46   (req: >= 5)

Gene RIFs: 111   (req: > 3)

Antibodies: 297   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 46

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

GWAS Traits (4)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
body mass index	EFO_0004340	2	2	2		61.9
smoking status measurement	EFO_0006527	1	1	1		35
type II diabetes mellitus	EFO_0001360	2	2	2		26.1
serum metabolite measurement	EFO_0005653	1	1	1		4.9

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
body mass index	EFO_0004340	2		61.9
smoking status measurement	EFO_0006527	1		35
type II diabetes mellitus	EFO_0001360	2		26.1
serum metabolite measurement	EFO_0005653	1		4.9

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Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	slit guidance ligand 2	VGNC:738	461137
Macaque	slit guidance ligand 2		715470
Mouse	slit guidance ligand 2	MGI:1315205	20563
Dog	slit guidance ligand 2	VGNC:46504	595148
Horse	slit guidance ligand 2	VGNC:51322	100068338

Species	Name	OMA	EggNOG	Inparanoid
Chimp	slit guidance ligand 2
Macaque	slit guidance ligand 2
Mouse	slit guidance ligand 2
Dog	slit guidance ligand 2
Horse	slit guidance ligand 2

Protein Structure (4 Structures, 1 AlphaFold Model)

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Representation

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Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

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More information can be found at RCSB PDB

AF-O94813-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 4 of 4

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (15)

Reactome (10)

KEGG (1)

PathwayCommons (2)

WikiPathways (2)

Activation of RAC1 (R-HSA-428540)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Activation of RAC1	13 targets	R-HSA-428540
Reactome	Axon guidance	533 targets	R-HSA-422475
Reactome	Developmental Biology	1055 targets	R-HSA-1266738
Reactome	Inactivation of CDC42 and RAC1	8 targets	R-HSA-428543
Reactome	Netrin-1 signaling	49 targets	R-HSA-373752

Name	Explore in Pharos	Explore in Source
Activation of RAC1	13 targets	R-HSA-428540
Axon guidance	533 targets	R-HSA-422475
Developmental Biology	1055 targets	R-HSA-1266738
Inactivation of CDC42 and RAC1	8 targets	R-HSA-428543
Netrin-1 signaling	49 targets	R-HSA-373752

Gene Ontology Terms (53)

Functions (8)

Components (7)

Processes (38)

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1 – 8 of 8

GO Term	Evidence	Assigned by
GTPase inhibitor activity	Inferred from Direct Assay (IDA)	UniProtKB
heparin binding	Inferred from Direct Assay (IDA)	UniProtKB
laminin-1 binding	Inferred from Direct Assay (IDA)	UniProtKB
protein homodimerization activity	Inferred from Direct Assay (IDA)	UniProtKB
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
proteoglycan binding	Inferred from Physical Interaction (IPI)	UniProtKB
Roundabout binding	Inferred from Physical Interaction (IPI)	UniProtKB
calcium ion binding	Non-traceable Author Statement (NAS)	UniProtKB

Protein-Protein Interactions (132)

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1 – 10 of 132

• See Interactions on String-DB

ANKRD12

Tbio

Novelty:  0.13114331

p_int:  0.954530617

p_ni:  0.045469383

Score:  0.28

Data Source:  BioPlex,STRINGDB

DEFA1

Tbio

Novelty:  0.01027492

p_int:  0.895342531

p_ni:  0.104657469

Data Source:  BioPlex

MSMB

Tbio

Novelty:  0.00241546

p_int:  0.850952158

p_ni:  0.149047842

Score:  0.214

Data Source:  BioPlex,STRINGDB

PRICKLE3

Tbio

Novelty:  0.26347141

p_int:  0.827077578

p_ni:  0.172922422

Score:  0.263

Data Source:  BioPlex,STRINGDB

PRG3

Tbio

Novelty:  0.09431986

p_int:  0.806917794

p_ni:  0.193082206

Score:  0.181

Data Source:  BioPlex,STRINGDB

ROBO1

Tbio

Novelty:  0.00494884

Score:  0.999

Data Source:  Reactome,STRINGDB

ROBO2

Tbio

Novelty:  0.00757203

Score:  0.996

Data Source:  Reactome,STRINGDB

DCC

Tbio

Novelty:  0.01273911

Score:  0.969

Data Source:  Reactome,STRINGDB

GPC1

Tbio

Novelty:  0.00293087

Score:  0.958

Data Source:  Reactome,STRINGDB

CDC42

Tchem

Family:  Enzyme

Novelty:  0.00032619

Score:  0.951

Data Source:  STRINGDB

Publication Statistics

PubMed Score  159.46

PubMed score by year

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PubTator Score  139.08

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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GWAS Trait Find Similar Targets

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body mass index
serum metabolite measurement
smoking status measurement
type II diabetes mellitus

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cardiovascular system phenotype
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endocrine/exocrine gland phenotype
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integument phenotype
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