Human Gene SLIT2 (ENST00000504154.6) from GENCODE V44
  Description: Homo sapiens slit guidance ligand 2 (SLIT2), transcript variant 1, mRNA. (from RefSeq NM_004787)
RefSeq Summary (NM_004787): 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].
Gencode Transcript: ENST00000504154.6
Gencode Gene: ENSG00000145147.20
Transcript (Including UTRs)
   Position: hg38 chr4:20,251,905-20,620,561 Size: 368,657 Total Exon Count: 37 Strand: +
Coding Region
   Position: hg38 chr4:20,253,816-20,619,009 Size: 365,194 Coding Exon Count: 37 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr4:20,251,905-20,620,561)mRNA (may differ from genome)Protein (1529 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCHPRDLynxMalacardsMGImyGene2
neXtProtOMIMPubMedReactomeUniProtKBWikipedia
BioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: SLIT2_HUMAN
DESCRIPTION: RecName: Full=Slit homolog 2 protein; Short=Slit-2; Contains: RecName: Full=Slit homolog 2 protein N-product; Contains: RecName: Full=Slit homolog 2 protein C-product; Flags: Precursor;
FUNCTION: 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.
SUBUNIT: Interacts with GREM1 (By similarity). Homodimer. Binds ROBO1 and ROBO2 with high affinity.
SUBCELLULAR LOCATION: Secreted. Note=The C-terminal cleavage protein is more diffusible than the larger N-terminal protein that is more tightly cell associated.
TISSUE SPECIFICITY: Fetal lung and kidney, and adult spinal cord. Weak expression in adult adrenal gland, thyroid, trachea and other tissues examined.
DOMAIN: The leucine-rich repeat domain is sufficient for guiding both axon projection and neuronal migration, in vitro.
SIMILARITY: Contains 1 CTCK (C-terminal cystine knot-like) domain.
SIMILARITY: Contains 7 EGF-like domains.
SIMILARITY: Contains 1 laminin G-like domain.
SIMILARITY: Contains 20 LRR (leucine-rich) repeats.
SIMILARITY: Contains 4 LRRCT domains.
SIMILARITY: Contains 4 LRRNT domains.

-  Primer design for this transcript
 

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Click here to load the transcript sequence and exon structure into Primer3Plus

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-  MalaCards Disease Associations
  MalaCards Gene Search: SLIT2
Diseases sorted by gene-association score: crohn's colitis (13), brain glioma (7), corneal neovascularization (5)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 23.81 RPKM in Lung
Total median expression: 265.91 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -844.401911-0.442 Picture PostScript Text
3' UTR -387.201552-0.249 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR008985 - ConA-like_lec_gl_sf
IPR013320 - ConA-like_subgrp
IPR000483 - Cys-rich_flank_reg_C
IPR006207 - Cys_knot_C
IPR000742 - EG-like_dom
IPR001881 - EGF-like_Ca-bd
IPR013032 - EGF-like_CS
IPR000152 - EGF-type_Asp/Asn_hydroxyl_site
IPR018097 - EGF_Ca-bd_CS
IPR003645 - Fol_N
IPR001791 - Laminin_G
IPR001611 - Leu-rich_rpt
IPR003591 - Leu-rich_rpt_typical-subtyp
IPR000372 - LRR-contain_N

Pfam Domains:
PF00008 - EGF-like domain
PF02210 - Laminin G domain
PF00560 - Leucine Rich Repeat
PF01463 - Leucine rich repeat C-terminal domain
PF01462 - Leucine rich repeat N-terminal domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2V70 - X-ray MuPIT 2V9S - X-ray MuPIT 2V9T - X-ray MuPIT 2WFH - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on O94813
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005095 GTPase inhibitor activity
GO:0005509 calcium ion binding
GO:0005515 protein binding
GO:0008201 heparin binding
GO:0042802 identical protein binding
GO:0042803 protein homodimerization activity
GO:0043237 laminin-1 binding
GO:0043394 proteoglycan binding
GO:0048495 Roundabout binding

Biological Process:
GO:0001657 ureteric bud development
GO:0001933 negative regulation of protein phosphorylation
GO:0002042 cell migration involved in sprouting angiogenesis
GO:0002689 negative regulation of leukocyte chemotaxis
GO:0006935 chemotaxis
GO:0007275 multicellular organism development
GO:0007399 nervous system development
GO:0007411 axon guidance
GO:0008045 motor neuron axon guidance
GO:0010593 negative regulation of lamellipodium assembly
GO:0010596 negative regulation of endothelial cell migration
GO:0014912 negative regulation of smooth muscle cell migration
GO:0021836 chemorepulsion involved in postnatal olfactory bulb interneuron migration
GO:0021972 corticospinal neuron axon guidance through spinal cord
GO:0030154 cell differentiation
GO:0030308 negative regulation of cell growth
GO:0030336 negative regulation of cell migration
GO:0030837 negative regulation of actin filament polymerization
GO:0031290 retinal ganglion cell axon guidance
GO:0032870 cellular response to hormone stimulus
GO:0034260 negative regulation of GTPase activity
GO:0035385 Roundabout signaling pathway
GO:0043065 positive regulation of apoptotic process
GO:0043116 negative regulation of vascular permeability
GO:0048754 branching morphogenesis of an epithelial tube
GO:0048846 axon extension involved in axon guidance
GO:0050772 positive regulation of axonogenesis
GO:0050919 negative chemotaxis
GO:0050929 induction of negative chemotaxis
GO:0051058 negative regulation of small GTPase mediated signal transduction
GO:0051414 response to cortisol
GO:0061364 apoptotic process involved in luteolysis
GO:0070100 negative regulation of chemokine-mediated signaling pathway
GO:0071504 cellular response to heparin
GO:0071672 negative regulation of smooth muscle cell chemotaxis
GO:0071676 negative regulation of mononuclear cell migration
GO:0090024 negative regulation of neutrophil chemotaxis
GO:0090027 negative regulation of monocyte chemotaxis
GO:0090260 negative regulation of retinal ganglion cell axon guidance
GO:0090288 negative regulation of cellular response to growth factor stimulus
GO:0021834 chemorepulsion involved in embryonic olfactory bulb interneuron precursor migration

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005737 cytoplasm
GO:0005886 plasma membrane
GO:0009986 cell surface
GO:0016020 membrane
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  AF055585 - Homo sapiens neurogenic extracellular slit protein Slit2 mRNA, complete cds.
AB017168 - Homo sapiens mRNA for Slit-2 protein, complete cds.
BC117190 - Homo sapiens slit homolog 2 (Drosophila), mRNA (cDNA clone MGC:150799 IMAGE:40125741), complete cds.
BC143978 - Homo sapiens slit homolog 2 (Drosophila), mRNA (cDNA clone MGC:177513 IMAGE:9052496), complete cds.
AF133270 - Homo sapiens SLIT2 (SLIL2) mRNA, complete cds.
AK308444 - Homo sapiens cDNA, FLJ98392.
AK027326 - Homo sapiens cDNA FLJ14420 fis, clone HEMBA1005581, highly similar to Slit homolog 2 protein precursor.
JD103888 - Sequence 84912 from Patent EP1572962.
JD078033 - Sequence 59057 from Patent EP1572962.
JD181163 - Sequence 162187 from Patent EP1572962.
JD417822 - Sequence 398846 from Patent EP1572962.
AK126459 - Homo sapiens cDNA FLJ44495 fis, clone UTERU2035908, highly similar to Homo sapiens mRNA for Slit-2 protein.
JD240303 - Sequence 221327 from Patent EP1572962.
JD490019 - Sequence 471043 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04360 - Axon guidance

Reactome (by CSHL, EBI, and GO)

Protein O94813 (Reactome details) participates in the following event(s):

R-HSA-204364 ROBO1 binds SLIT2
R-HSA-376149 Proteolytic processing of SLIT
R-HSA-9010872 SLIT2 binds Dystroglycan
R-HSA-9010898 ROBO2 binds SLIT2
R-HSA-376140 Ena/VASP proteins bind ROBO1:SLIT2 complex
R-HSA-376141 Interaction of ABL with ROBO1:SLIT2
R-HSA-376145 SRGAP binds ROBO1:SLIT2
R-HSA-428511 NCK binds ROBO1:SLIT2
R-HSA-428536 ARHGAP39 (Vilse) binds ROBO1:SLIT2
R-HSA-8985591 SLIT2-bound ROBO1 binds MYO9B
R-HSA-8986258 SLIT2:ROBO1 binds CXCR4
R-NUL-428517 SrGAP binds Robo:Slit
R-HSA-9010815 SLITs bind keratan sulfate
R-HSA-428518 Glypican-1 (GPC1) binds SLIT2
R-HSA-428534 Recruitment of Profilin by Ena/VASP proteins
R-HSA-428515 Recruitment of SOS to plasma membrane
R-HSA-428531 Recruitment of PAK to NCK
R-HSA-428883 Recruitment of CAP to ABL
R-HSA-428885 Activation of CLASP
R-HSA-428888 Phosphorylation of ROBO1 by ABL kinase
R-HSA-373715 DCC interaction with ROBO1
R-NUL-9010914 Robo2 binds SLIT2
R-HSA-428533 Inactivation of CDC42
R-HSA-428522 Inactivation of RAC1
R-NUL-428519 Inactivation of Cdc42
R-HSA-428535 Activation of RAC1 by SOS
R-HSA-376176 Signaling by ROBO receptors
R-HSA-9010553 Regulation of expression of SLITs and ROBOs
R-HSA-428890 Role of ABL in ROBO-SLIT signaling
R-HSA-428543 Inactivation of CDC42 and RAC1
R-HSA-428540 Activation of RAC1
R-HSA-8985586 SLIT2:ROBO1 increases RHOA activity
R-HSA-422475 Axon guidance
R-HSA-373752 Netrin-1 signaling
R-HSA-428542 Regulation of commissural axon pathfinding by SLIT and ROBO
R-HSA-1266738 Developmental Biology

-  Other Names for This Gene
  Alternate Gene Symbols: B7ZLR5, ENST00000504154.1, ENST00000504154.2, ENST00000504154.3, ENST00000504154.4, ENST00000504154.5, NM_004787, O94813, O95710, Q17RU3, Q9Y5Q7, SLIL3, SLIT2_HUMAN, uc003gpr.1, uc003gpr.2, uc003gpr.3, uc003gpr.4
UCSC ID: ENST00000504154.6
RefSeq Accession: NM_004787
Protein: O94813 (aka SLIT2_HUMAN or SLT2_HUMAN)
CCDS: CCDS3426.1, CCDS75110.1, CCDS75111.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.