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SLIT2 slit guidance ligand 2 [ Homo sapiens (human) ]

Gene ID: 9353, updated on 3-Apr-2024

Summary

Official Symbol
SLIT2provided by HGNC
Official Full Name
slit guidance ligand 2provided by HGNC
Primary source
HGNC:HGNC:11086
See related
Ensembl:ENSG00000145147 MIM:603746; AllianceGenome:HGNC:11086
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
SLIL3; Slit-2
Summary
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]
Expression
Broad expression in lung (RPKM 13.1), adrenal (RPKM 9.9) and 21 other tissues See more
Orthologs
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Genomic context

Location:
4p15.31
Exon count:
40
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (20251905..20620561)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (20234597..20602238)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (20253528..20622184)

Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105374513 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr4:20029655-20030854 Neighboring gene uncharacterized LOC105374514 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:20254644-20255442 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:20255443-20256241 Neighboring gene NANOG hESC enhancer GRCh37_chr4:20284545-20285162 Neighboring gene NANOG hESC enhancer GRCh37_chr4:20353162-20353707 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21362 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21363 Neighboring gene Sharpr-MPRA regulatory region 13128 Neighboring gene SLIT2 intronic transcript 1 Neighboring gene ReSE screen-validated silencer GRCh37_chr4:20525613-20525800 Neighboring gene NANOG hESC enhancer GRCh37_chr4:20590873-20591475 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:20618190-20618690 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:20631231-20631937 Neighboring gene microRNA 218-1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:20634775-20635276 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:20635277-20635776 Neighboring gene uncharacterized LOC105374515 Neighboring gene ReSE screen-validated silencer GRCh37_chr4:20675647-20675822 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21365 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_77676 Neighboring gene parkin coregulated like Neighboring gene potassium voltage-gated channel interacting protein 4

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

EBI GWAS Catalog

Description
Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study.
EBI GWAS Catalog

HIV-1 interactions

Replication interactions

Interaction Pubs
HIV-1 dendritic cell-to-T cell transmission is inhibited by the presence of recombinant, extracellular Slit2N PubMed

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env The N-terminal leucine-rich repeat fragment of Slit2 inhibits HIV-1 gp120-induced ROBO1-actin association PubMed
env The N-terminal leucine-rich repeat fragment of Slit2 inhibits HIV-1 gp120-induced actin polymerization in T cells PubMed
env The N-terminal leucine-rich repeat fragment of Slit2 inhibits HIV-1 gp120-induced phosphorylation of both LIMK1 and cofilin PubMed
env SLIT2N, an active fragment of SLIT2, inhibits M-tropic HIV-1 gp120-induced Src signaling and activation of its downstream targets Pyk2, CDC42, Rac1, and paxillin in immature monocyte-derived dendritic cells PubMed
env Inhibition of M-tropic HIV-1 gp120-induced transendothelial migration by SLIT2N involves SLIT2N-mediated enhancement of co-localization of Robo1 with WASp and LSP1 in immature monocyte-derived dendritic cells PubMed
env SLIT2N, an active fragment of SLIT2, inhibits M-tropic HIV-1 gp120-induced association of LSP1, Wiskott-Aldrich Syndrome protein (WASp), Actin-Related Protein 2/3 (Arp2/3), and beta-actin in immature monocyte-derived dendritic cells PubMed
env SLIT2N, an active fragment of SLIT2, inhibits M-tropic HIV-1 gp120-induces transendothelial migration and podosome formation in immature monocyte-derived dendritic cells PubMed
env SLIT2 inhibits HIV-1-induced lymphatic hyperpermeability by blocking the interaction between Robo4 and integrin alpha5beta1 in human lymphatic endothelial cells PubMed
env SLIT2 significantly inhibits HIV-1 gp120-induced phosphorylation of c-Src in human lymphatic endothelial cells PubMed
env HIV-1 gp120 modulates the expression of SLIT2 in human lymphatic endothelial cells PubMed
Vif vif HIV-1 Vif upregulates the expression of slit homolog 2 (SLIT2) in Vif-expression T cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Clone Names

  • FLJ14420

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables GTPase inhibitor activity IDA
Inferred from Direct Assay
more info
PubMed 
enables Roundabout binding IBA
Inferred from Biological aspect of Ancestor
more info
 
enables Roundabout binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables calcium ion binding NAS
Non-traceable Author Statement
more info
PubMed 
enables heparin binding IBA
Inferred from Biological aspect of Ancestor
more info
 
enables heparin binding IDA
Inferred from Direct Assay
more info
PubMed 
enables identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables laminin-1 binding IDA
Inferred from Direct Assay
more info
PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables protein homodimerization activity IDA
Inferred from Direct Assay
more info
PubMed 
enables proteoglycan binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
involved_in Roundabout signaling pathway IC
Inferred by Curator
more info
PubMed 
involved_in Roundabout signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in aortic valve morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in apoptotic process involved in luteolysis IEP
Inferred from Expression Pattern
more info
PubMed 
involved_in axon extension involved in axon guidance IDA
Inferred from Direct Assay
more info
PubMed 
involved_in axon guidance IDA
Inferred from Direct Assay
more info
PubMed 
involved_in branching morphogenesis of an epithelial tube IDA
Inferred from Direct Assay
more info
PubMed 
involved_in branching morphogenesis of an epithelial tube IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in cell migration involved in sprouting angiogenesis IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in cellular response to heparin IDA
Inferred from Direct Assay
more info
PubMed 
involved_in cellular response to hormone stimulus IEP
Inferred from Expression Pattern
more info
PubMed 
NOT involved_in chemorepulsion involved in embryonic olfactory bulb interneuron precursor migration IDA
Inferred from Direct Assay
more info
PubMed 
involved_in chemorepulsion involved in postnatal olfactory bulb interneuron migration IDA
Inferred from Direct Assay
more info
PubMed 
involved_in corticospinal neuron axon guidance through spinal cord IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in induction of negative chemotaxis IDA
Inferred from Direct Assay
more info
PubMed 
involved_in motor neuron axon guidance IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative chemotaxis IBA
Inferred from Biological aspect of Ancestor
more info
 
involved_in negative chemotaxis IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative chemotaxis IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in negative regulation of actin filament polymerization IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative regulation of cell growth IBA
Inferred from Biological aspect of Ancestor
more info
 
involved_in negative regulation of cell growth IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in negative regulation of cell migration IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative regulation of cell migration IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in negative regulation of cellular response to growth factor stimulus IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative regulation of chemokine-mediated signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in negative regulation of endothelial cell migration IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative regulation of lamellipodium assembly IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative regulation of leukocyte chemotaxis IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative regulation of monocyte chemotaxis ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in negative regulation of mononuclear cell migration IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative regulation of neutrophil chemotaxis IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative regulation of protein phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative regulation of retinal ganglion cell axon guidance IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative regulation of small GTPase mediated signal transduction IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative regulation of smooth muscle cell chemotaxis IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative regulation of smooth muscle cell migration IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative regulation of vascular permeability IDA
Inferred from Direct Assay
more info
PubMed 
involved_in positive regulation of apoptotic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in positive regulation of axonogenesis TAS
Traceable Author Statement
more info
PubMed 
involved_in pulmonary valve morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in response to cortisol IEP
Inferred from Expression Pattern
more info
PubMed 
involved_in retinal ganglion cell axon guidance IBA
Inferred from Biological aspect of Ancestor
more info
 
involved_in retinal ganglion cell axon guidance IDA
Inferred from Direct Assay
more info
PubMed 
involved_in ureteric bud development IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in ventricular septum morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
Component Evidence Code Pubs
located_in cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
located_in extracellular exosome HDA PubMed 
located_in extracellular region TAS
Traceable Author Statement
more info
 
located_in extracellular space IDA
Inferred from Direct Assay
more info
PubMed 
located_in membrane NAS
Non-traceable Author Statement
more info
PubMed 

NCBI Reference Sequences (RefSeq)

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_047105.1 RefSeqGene

    Range
    4981..373637
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001289135.3NP_001276064.1  slit homolog 2 protein isoform 2 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) contains one alternate in-frame exon and lacks one alternate in-frame exon in the 5' coding region compared to variant 1. It encodes isoform 2, which is shorter than isoform 1.
    Source sequence(s)
    AA489463, AC021118, AC096718, AF133270, AK126459, BC143978, BF112143, BI494498, BM474839, CV370469, DA721496, DB207352
    Consensus CDS
    CCDS75110.1
    UniProtKB/TrEMBL
    X6R3P0
    Related
    ENSP00000422261.1, ENST00000503837.5
    Conserved Domains (8) summary
    TIGR00864
    Location:8281009
    PCC; polycystin cation channel protein
    smart00013
    Location:2758
    LRRNT; Leucine rich repeat N-terminal domain
    smart00282
    Location:11791312
    LamG; Laminin G domain
    cd00054
    Location:10721108
    EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...
    sd00031
    Location:847859
    LRR_1; leucine-rich repeat [structural motif]
    sd00033
    Location:3856
    LRR_RI; leucine-rich repeat [structural motif]
    NF033189
    Location:553850
    internalin_A; class 1 internalin InlA
    pfam13855
    Location:774833
    LRR_8; Leucine rich repeat
  2. NM_001289136.3NP_001276065.1  slit homolog 2 protein isoform 3 precursor

    See identical proteins and their annotated locations for NP_001276065.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1. It encodes isoform 3, which is shorter than isoform 1.
    Source sequence(s)
    AA489463, AC021118, AC096718, AK126459, BC143978, BF112143, BI494498, BM474839, CV370469, DA721496, DB207352
    Consensus CDS
    CCDS75111.1
    UniProtKB/TrEMBL
    X6R3P0
    Related
    ENSP00000427548.1, ENST00000503823.5
    Conserved Domains (8) summary
    TIGR00864
    Location:8241005
    PCC; polycystin cation channel protein
    smart00013
    Location:2758
    LRRNT; Leucine rich repeat N-terminal domain
    smart00282
    Location:11751308
    LamG; Laminin G domain
    cd00054
    Location:10681104
    EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...
    sd00031
    Location:843855
    LRR_1; leucine-rich repeat [structural motif]
    sd00033
    Location:3856
    LRR_RI; leucine-rich repeat [structural motif]
    NF033189
    Location:549846
    internalin_A; class 1 internalin InlA
    pfam13855
    Location:770829
    LRR_8; Leucine rich repeat
  3. NM_004787.4NP_004778.1  slit homolog 2 protein isoform 1 precursor

    See identical proteins and their annotated locations for NP_004778.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AA489463, AC021118, AC096718, AK126459, BC117190, BF112143, BI494498, BM474839, CV370469, DA721496, DB207352
    Consensus CDS
    CCDS3426.1
    UniProtKB/Swiss-Prot
    A0A0A6YYB8, B7ZLR5, O94813, O95710, Q17RU3, Q9Y5Q7
    UniProtKB/TrEMBL
    X6R3P0
    Related
    ENSP00000422591.1, ENST00000504154.6
    Conserved Domains (8) summary
    TIGR00864
    Location:8321013
    PCC; polycystin cation channel protein
    smart00013
    Location:2758
    LRRNT; Leucine rich repeat N-terminal domain
    smart00282
    Location:11831316
    LamG; Laminin G domain
    cd00054
    Location:10761112
    EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...
    sd00031
    Location:851863
    LRR_1; leucine-rich repeat [structural motif]
    sd00033
    Location:3856
    LRR_RI; leucine-rich repeat [structural motif]
    NF033189
    Location:557854
    internalin_A; class 1 internalin InlA
    pfam13855
    Location:778837
    LRR_8; Leucine rich repeat

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000004.12 Reference GRCh38.p14 Primary Assembly

    Range
    20251905..20620561
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005248211.3XP_005248268.1  slit homolog 2 protein isoform X1

    UniProtKB/TrEMBL
    X6R3P0
    Related
    ENSP00000273739.5, ENST00000273739.9
    Conserved Domains (9) summary
    TIGR00864
    Location:8361017
    PCC; polycystin cation channel protein
    smart00013
    Location:2758
    LRRNT; Leucine rich repeat N-terminal domain
    smart00282
    Location:11871320
    LamG; Laminin G domain
    cd00054
    Location:10801116
    EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...
    sd00031
    Location:855867
    LRR_1; leucine-rich repeat [structural motif]
    sd00033
    Location:3856
    LRR_RI; leucine-rich repeat [structural motif]
    NF033189
    Location:561858
    internalin_A; class 1 internalin InlA
    pfam12661
    Location:11341155
    hEGF; Human growth factor-like EGF
    pfam13855
    Location:782841
    LRR_8; Leucine rich repeat
  2. XM_006713986.3XP_006714049.1  slit homolog 2 protein isoform X2

    UniProtKB/TrEMBL
    X6R3P0
    Conserved Domains (7) summary
    TIGR00864
    Location:812993
    PCC; polycystin cation channel protein
    smart00013
    Location:2758
    LRRNT; Leucine rich repeat N-terminal domain
    smart00282
    Location:11631296
    LamG; Laminin G domain
    cd00054
    Location:10561092
    EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...
    sd00033
    Location:3856
    LRR_RI; leucine-rich repeat [structural motif]
    NF033189
    Location:73434
    internalin_A; class 1 internalin InlA
    pfam13855
    Location:55115
    LRR_8; Leucine rich repeat
  3. XM_011513909.3XP_011512211.1  slit homolog 2 protein isoform X3

    UniProtKB/TrEMBL
    X6R3P0
    Conserved Domains (10) summary
    smart00013
    Location:697728
    LRRNT; Leucine rich repeat N-terminal domain
    smart00082
    Location:829878
    LRRCT; Leucine rich repeat C-terminal domain
    smart00282
    Location:11531286
    LamG; Laminin G domain
    cd00054
    Location:10461082
    EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...
    cd00116
    Location:47180
    LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...
    sd00031
    Location:821833
    LRR_1; leucine-rich repeat [structural motif]
    sd00033
    Location:2746
    LRR_RI; leucine-rich repeat [structural motif]
    pfam12799
    Location:294334
    LRR_4; Leucine Rich repeats (2 copies)
    pfam13855
    Location:747807
    LRR_8; Leucine rich repeat
    cl15307
    Location:634683
    TPKR_C2; Tyrosine-protein kinase receptor C2 Ig-like domain
  4. XM_017008845.2XP_016864334.1  slit homolog 2 protein isoform X4

    UniProtKB/TrEMBL
    X6R3P0
    Related
    ENSP00000482129.1, ENST00000622093.4
  5. XM_011513910.2XP_011512212.2  slit homolog 2 protein isoform X5

    Conserved Domains (7) summary
    TIGR00864
    Location:462643
    PCC; polycystin cation channel protein
    smart00013
    Location:135165
    LRRNT; Leucine rich repeat N-terminal domain
    smart00282
    Location:813946
    LamG; Laminin G domain
    cd00054
    Location:706742
    EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...
    sd00031
    Location:481493
    LRR_1; leucine-rich repeat [structural motif]
    sd00033
    Location:167189
    LRR_RI; leucine-rich repeat [structural motif]
    NF033189
    Location:187484
    internalin_A; class 1 internalin InlA

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060928.1 Alternate T2T-CHM13v2.0

    Range
    20234597..20602238
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054351262.1XP_054207237.1  slit homolog 2 protein isoform X1

  2. XM_054351263.1XP_054207238.1  slit homolog 2 protein isoform X2

  3. XM_054351264.1XP_054207239.1  slit homolog 2 protein isoform X3

  4. XM_054351265.1XP_054207240.1  slit homolog 2 protein isoform X4

  5. XM_054351266.1XP_054207241.1  slit homolog 2 protein isoform X5