SLIT2

Protein identityUniProt · HPA

UniProt accession

O94813

Gene

SLIT2

Ensembl

ENSG00000145147

Chromosome

4

Canonical length

1529 aa

Protein class

Predicted intracellular proteins, Predicted membrane proteins, Predicted secreted proteins, Transporters

Secretome location

Secreted in other tissues

Quaternary structure

Homodimer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

1529 residues, UniProt reviewed canonical sequence.

>O94813|SLIT2
     1  MRGVGWQMLS LSLGLVLAIL NKVAPQACPA QCSCSGSTVD CHGLALRSVP RNIPRNTERL
    61  DLNGNNITRI TKTDFAGLRH LRVLQLMENK ISTIERGAFQ DLKELERLRL NRNHLQLFPE
   121  LLFLGTAKLY RLDLSENQIQ AIPRKAFRGA VDIKNLQLDY NQISCIEDGA FRALRDLEVL
   181  TLNNNNITRL SVASFNHMPK LRTFRLHSNN LYCDCHLAWL SDWLRQRPRV GLYTQCMGPS
   241  HLRGHNVAEV QKREFVCSGH QSFMAPSCSV LHCPAACTCS NNIVDCRGKG LTEIPTNLPE
   301  TITEIRLEQN TIKVIPPGAF SPYKKLRRID LSNNQISELA PDAFQGLRSL NSLVLYGNKI
   361  TELPKSLFEG LFSLQLLLLN ANKINCLRVD AFQDLHNLNL LSLYDNKLQT IAKGTFSPLR
   421  AIQTMHLAQN PFICDCHLKW LADYLHTNPI ETSGARCTSP RRLANKRIGQ IKSKKFRCSA
   481  KEQYFIPGTE DYRSKLSGDC FADLACPEKC RCEGTTVDCS NQKLNKIPEH IPQYTAELRL
   541  NNNEFTVLEA TGIFKKLPQL RKINFSNNKI TDIEEGAFEG ASGVNEILLT SNRLENVQHK
   601  MFKGLESLKT LMLRSNRITC VGNDSFIGLS SVRLLSLYDN QITTVAPGAF DTLHSLSTLN
   661  LLANPFNCNC YLAWLGEWLR KKRIVTGNPR CQKPYFLKEI PIQDVAIQDF TCDDGNDDNS
   721  CSPLSRCPTE CTCLDTVVRC SNKGLKVLPK GIPRDVTELY LDGNQFTLVP KELSNYKHLT
   781  LIDLSNNRIS TLSNQSFSNM TQLLTLILSY NRLRCIPPRT FDGLKSLRLL SLHGNDISVV
   841  PEGAFNDLSA LSHLAIGANP LYCDCNMQWL SDWVKSEYKE PGIARCAGPG EMADKLLLTT
   901  PSKKFTCQGP VDVNILAKCN PCLSNPCKND GTCNSDPVDF YRCTCPYGFK GQDCDVPIHA
   961  CISNPCKHGG TCHLKEGEED GFWCICADGF EGENCEVNVD DCEDNDCENN STCVDGINNY
  1021  TCLCPPEYTG ELCEEKLDFC AQDLNPCQHD SKCILTPKGF KCDCTPGYVG EHCDIDFDDC
  1081  QDNKCKNGAH CTDAVNGYTC ICPEGYSGLF CEFSPPMVLP RTSPCDNFDC QNGAQCIVRI
  1141  NEPICQCLPG YQGEKCEKLV SVNFINKESY LQIPSAKVRP QTNITLQIAT DEDSGILLYK
  1201  GDKDHIAVEL YRGRVRASYD TGSHPASAIY SVETINDGNF HIVELLALDQ SLSLSVDGGN
  1261  PKIITNLSKQ STLNFDSPLY VGGMPGKSNV ASLRQAPGQN GTSFHGCIRN LYINSELQDF
  1321  QKVPMQTGIL PGCEPCHKKV CAHGTCQPSS QAGFTCECQE GWMGPLCDQR TNDPCLGNKC
  1381  VHGTCLPINA FSYSCKCLEG HGGVLCDEEE DLFNPCQAIK CKHGKCRLSG LGQPYCECSS
  1441  GYTGDSCDRE ISCRGERIRD YYQKQQGYAA CQTTKKVSRL ECRGGCAGGQ CCGPLRSKRR
  1501  KYSFECTDGS SFVDEVEKVV KCGCTRCVS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SLIT2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.32

Highest tissue expression

32 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SLIT2.

Disease | GeneticClinVar

2 pathogenic / likely-pathogenic of 473 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Congenital anomaly of kidney and urinary tract

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.16

gnomAD pLI

1

gnomAD missense Z

2.1

DepMap mean gene effect

0.12

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• aortic valve morphogenesis
• apoptotic process involved in luteolysis
• axon extension involved in axon guidance
• axon guidance
• branching morphogenesis of an epithelial tube
• cell migration involved in sprouting angiogenesis
• cellular response to heparin
• cellular response to hormone stimulus
• chemorepulsion involved in postnatal olfactory bulb interneuron migration
• motor neuron axon guidance
• negative chemotaxis
• negative regulation of actin filament polymerization
• negative regulation of cell growth
• negative regulation of cell migration
• negative regulation of cellular response to growth factor stimulus
• negative regulation of chemokine-mediated signaling pathway
• negative regulation of endothelial cell migration
• negative regulation of lamellipodium assembly
• negative regulation of leukocyte chemotaxis
• negative regulation of monocyte chemotaxis
• negative regulation of mononuclear cell migration
• negative regulation of neutrophil chemotaxis
• negative regulation of protein phosphorylation
• negative regulation of retinal ganglion cell axon guidance
• negative regulation of small GTPase mediated signal transduction
• negative regulation of smooth muscle cell chemotaxis
• negative regulation of smooth muscle cell migration
• negative regulation of vascular permeability
• positive regulation of apoptotic process
• positive regulation of axonogenesis
• pulmonary valve morphogenesis
• response to cortisol
• retinal ganglion cell axon guidance
• Roundabout signaling pathway
• ureteric bud development
• ventricular septum morphogenesis
• corticospinal neuron axon guidance through spinal cord
• induction of negative chemotaxis

Molecular functions

• calcium ion binding
• GTPase inhibitor activity
• heparin binding
• identical protein binding
• laminin-1 binding
• protein homodimerization activity
• proteoglycan binding
• Roundabout binding

Cellular components

• cytoplasm
• extracellular exosome
• extracellular region
• extracellular space
• membrane

Protein domainsUniProt · Pfam · InterPro

• EGF-type aspartate/asparagine hydroxylation site
• Leucine-rich repeat N-terminal domain
• Cysteine-rich flanking region, C-terminal
• EGF-like domain
• Leucine-rich repeat
• Laminin G domain
• EGF-like calcium-binding domain
• Leucine-rich repeat, typical subtype
• Follistatin-like, N-terminal
• Cystine knot, C-terminal
• EGF-like, conserved site
• Concanavalin A-like lectin/glucanase domain superfamily
• EGF-like calcium-binding, conserved site
• Leucine-rich repeat domain superfamily
• Notch and Slit guidance protein
• EGF-like domain
• Laminin G domain
• Leucine Rich Repeat
• Leucine rich repeat N-terminal domain
• Leucine rich repeat C-terminal domain
• Human growth factor-like EGF
• Leucine rich repeat

KeywordsUniProt

• Chemotaxis
• Developmental protein
• Differentiation
• Disulfide bond
• EGF-like domain
• Glycoprotein
• Heparin-binding
• Leucine-rich repeat
• Neurogenesis
• Repeat
• Secreted
• Signal

InteractionsUniProt · HPA

Protein binding partners of SLIT2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• GREM1
• ROBO2
• ROBO1
• ROBO4