SLIT2_RAT
ID SLIT2_RAT Reviewed; 766 AA.
AC Q9WVC1;
DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2004, sequence version 3.
DT 25-MAY-2022, entry version 133.
DE RecName: Full=Slit homolog 2 protein;
DE Short=Slit-2;
DE Flags: Precursor; Fragment;
GN Name=Slit2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RX PubMed=10364234; DOI=10.1074/jbc.274.25.17885;
RA Liang Y., Annan R.S., Carr S.A., Popp S., Mevissen M., Margolis R.K.,
RA Margolis R.U.;
RT "Mammalian homologues of the Drosophila slit protein are ligands of the
RT heparan sulfate proteoglycan glypican-1 in brain.";
RL J. Biol. Chem. 274:17885-17892(1999).
RN [2]
RP DEVELOPMENTAL STAGE.
RX PubMed=11754167; DOI=10.1002/cne.10068;
RA Marillat V., Cases O., Nguyen-Ba-Charvet K.T., Tessier-Lavigne M.,
RA Sotelo C., Chedotal A.;
RT "Spatiotemporal expression patterns of slit and robo genes in the rat
RT brain.";
RL J. Comp. Neurol. 442:130-155(2002).
RN [3]
RP INTERACTION WITH GREM1.
RX PubMed=15528323; DOI=10.4049/jimmunol.173.10.5914;
RA Chen B., Blair D.G., Plisov S., Vasiliev G., Perantoni A.O., Chen Q.,
RA Athanasiou M., Wu J.Y., Oppenheim J.J., Yang D.;
RT "Bone morphogenetic protein antagonists Drm/Gremlin and Dan interact with
RT Slits and act as negative regulators of monocyte chemotaxis.";
RL J. Immunol. 173:5914-5917(2004).
CC -!- FUNCTION: Thought to act as molecular guidance cue in cellular
CC migration, and function appears to be mediated by interaction with
CC roundabout homolog receptors. During neural development involved in
CC axonal navigation at the ventral midline of the neural tube and
CC projection of axons to different regions. SLIT1 and SLIT2 seem to be
CC essential for midline guidance in the forebrain by acting as repulsive
CC signal preventing inappropriate midline crossing by axons projecting
CC from the olfactory bulb. In spinal cord development may play a role in
CC guiding commissural axons once they reached the floor plate by
CC modulating the response to netrin. In vitro, silences the attractive
CC effect of NTN1 but not its growth-stimulatory effect and silencing
CC requires the formation of a ROBO1-DCC complex. May be implicated in
CC spinal cord midline post-crossing axon repulsion. In vitro, only
CC commissural axons that crossed the midline responded to SLIT2. In the
CC developing visual system appears to function as repellent for retinal
CC ganglion axons by providing a repulsion that directs these axons along
CC their appropriate paths prior to, and after passage through, the optic
CC chiasm. In vitro, collapses and repels retinal ganglion cell growth
CC cones. Seems to play a role in branching and arborization of CNS
CC sensory axons, and in neuronal cell migration. Seems to be involved in
CC regulating leukocyte migration (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. Binds ROBO1 and ROBO2 with high affinity (By
CC similarity). Interacts with GREM1. {ECO:0000250,
CC ECO:0000269|PubMed:15528323}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- DEVELOPMENTAL STAGE: Detected at E20, between P0 and P10, and in adult
CC in anterior olfactory nuclei, in cortex entorhinal region, hippocampal
CC C3 and dentate gyrus, basal telencephalon septum, hypothalamus
CC ventromedial and preoptic nuclei and dorsal thalamus medial habenula.
CC Detected at E20 in cortex cortical plate. Detected between P0 and P10,
CC and in adult basal telencephalon amygdaloid complex, and diencephalon
CC pretectum optic tract nuclei. {ECO:0000269|PubMed:11754167}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD38940.2; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the C-terminal part.; Evidence={ECO:0000305};
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DR EMBL; AF141386; AAD38940.2; ALT_TERM; mRNA.
DR AlphaFoldDB; Q9WVC1; -.
DR SMR; Q9WVC1; -.
DR IntAct; Q9WVC1; 1.
DR STRING; 10116.ENSRNOP00000005477; -.
DR GlyGen; Q9WVC1; 4 sites.
DR PhosphoSitePlus; Q9WVC1; -.
DR PaxDb; Q9WVC1; -.
DR PRIDE; Q9WVC1; -.
DR RGD; 69310; Slit2.
DR eggNOG; KOG4237; Eukaryota.
DR InParanoid; Q9WVC1; -.
DR PhylomeDB; Q9WVC1; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; ISO:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:InterPro.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0045499; F:chemorepellent activity; ISO:RGD.
DR GO; GO:0004963; F:follicle-stimulating hormone receptor activity; IEA:InterPro.
DR GO; GO:0005095; F:GTPase inhibitor activity; ISO:RGD.
DR GO; GO:0043395; F:heparan sulfate proteoglycan binding; IDA:RGD.
DR GO; GO:0008201; F:heparin binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0043237; F:laminin-1 binding; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0043394; F:proteoglycan binding; ISO:RGD.
DR GO; GO:0048495; F:Roundabout binding; ISO:RGD.
DR GO; GO:0003180; P:aortic valve morphogenesis; ISO:RGD.
DR GO; GO:0061364; P:apoptotic process involved in luteolysis; ISO:RGD.
DR GO; GO:0048846; P:axon extension involved in axon guidance; ISO:RGD.
DR GO; GO:0007411; P:axon guidance; ISO:RGD.
DR GO; GO:0007409; P:axonogenesis; ISO:RGD.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; ISO:RGD.
DR GO; GO:0002042; P:cell migration involved in sprouting angiogenesis; ISO:RGD.
DR GO; GO:0098609; P:cell-cell adhesion; ISO:RGD.
DR GO; GO:0071504; P:cellular response to heparin; ISO:RGD.
DR GO; GO:0032870; P:cellular response to hormone stimulus; ISO:RGD.
DR GO; GO:0021836; P:chemorepulsion involved in postnatal olfactory bulb interneuron migration; ISO:RGD.
DR GO; GO:0021972; P:corticospinal neuron axon guidance through spinal cord; ISO:RGD.
DR GO; GO:0033563; P:dorsal/ventral axon guidance; ISO:RGD.
DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD.
DR GO; GO:0050929; P:induction of negative chemotaxis; ISO:RGD.
DR GO; GO:0001822; P:kidney development; ISO:RGD.
DR GO; GO:0060763; P:mammary duct terminal end bud growth; ISO:RGD.
DR GO; GO:0060603; P:mammary gland duct morphogenesis; ISO:RGD.
DR GO; GO:0001656; P:metanephros development; ISO:RGD.
DR GO; GO:0008045; P:motor neuron axon guidance; ISO:RGD.
DR GO; GO:0050919; P:negative chemotaxis; ISO:RGD.
DR GO; GO:0030837; P:negative regulation of actin filament polymerization; ISO:RGD.
DR GO; GO:0030517; P:negative regulation of axon extension; ISO:RGD.
DR GO; GO:0030308; P:negative regulation of cell growth; ISO:RGD.
DR GO; GO:0030336; P:negative regulation of cell migration; ISO:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0090288; P:negative regulation of cellular response to growth factor stimulus; ISO:RGD.
DR GO; GO:0070100; P:negative regulation of chemokine-mediated signaling pathway; ISO:RGD.
DR GO; GO:0010596; P:negative regulation of endothelial cell migration; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IMP:RGD.
DR GO; GO:0010593; P:negative regulation of lamellipodium assembly; ISO:RGD.
DR GO; GO:0002689; P:negative regulation of leukocyte chemotaxis; ISO:RGD.
DR GO; GO:0090027; P:negative regulation of monocyte chemotaxis; IDA:BHF-UCL.
DR GO; GO:0071676; P:negative regulation of mononuclear cell migration; ISO:RGD.
DR GO; GO:0090024; P:negative regulation of neutrophil chemotaxis; ISO:RGD.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0090260; P:negative regulation of retinal ganglion cell axon guidance; ISO:RGD.
DR GO; GO:0051058; P:negative regulation of small GTPase mediated signal transduction; ISO:RGD.
DR GO; GO:0071672; P:negative regulation of smooth muscle cell chemotaxis; ISO:RGD.
DR GO; GO:0014912; P:negative regulation of smooth muscle cell migration; ISO:RGD.
DR GO; GO:0043116; P:negative regulation of vascular permeability; ISO:RGD.
DR GO; GO:0048812; P:neuron projection morphogenesis; ISO:RGD.
DR GO; GO:0021772; P:olfactory bulb development; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR GO; GO:0003184; P:pulmonary valve morphogenesis; ISO:RGD.
DR GO; GO:0051414; P:response to cortisol; ISO:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0031290; P:retinal ganglion cell axon guidance; ISO:RGD.
DR GO; GO:0035385; P:Roundabout signaling pathway; ISO:RGD.
DR GO; GO:0021510; P:spinal cord development; IEP:RGD.
DR GO; GO:0022029; P:telencephalon cell migration; ISO:RGD.
DR GO; GO:0001657; P:ureteric bud development; ISO:RGD.
DR GO; GO:0060412; P:ventricular septum morphogenesis; ISO:RGD.
DR Gene3D; 3.80.10.10; -; 5.
DR InterPro; IPR000483; Cys-rich_flank_reg_C.
DR InterPro; IPR002272; FSH_rcpt.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR000372; LRRNT.
DR Pfam; PF13855; LRR_8; 6.
DR Pfam; PF01463; LRRCT; 3.
DR Pfam; PF01462; LRRNT; 4.
DR PRINTS; PR01143; FSHRECEPTOR.
DR SMART; SM00369; LRR_TYP; 14.
DR SMART; SM00082; LRRCT; 3.
DR SMART; SM00013; LRRNT; 4.
DR PROSITE; PS51450; LRR; 16.
PE 1: Evidence at protein level;
KW Chemotaxis; Developmental protein; Differentiation; Disulfide bond;
KW Glycoprotein; Heparin-binding; Leucine-rich repeat; Neurogenesis;
KW Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..30
FT /evidence="ECO:0000255"
FT CHAIN 31..766
FT /note="Slit homolog 2 protein"
FT /id="PRO_0000007731"
FT DOMAIN 31..55
FT /note="LRRNT"
FT REPEAT 56..77
FT /note="LRR 1"
FT REPEAT 80..101
FT /note="LRR 2"
FT REPEAT 104..125
FT /note="LRR 3"
FT REPEAT 128..149
FT /note="LRR 4"
FT REPEAT 152..173
FT /note="LRR 5"
FT REPEAT 176..197
FT /note="LRR 6"
FT DOMAIN 209..259
FT /note="LRRCT 1"
FT DOMAIN 268..304
FT /note="LRRNT 2"
FT REPEAT 305..326
FT /note="LRR 7"
FT REPEAT 329..350
FT /note="LRR 8"
FT REPEAT 353..374
FT /note="LRR 9"
FT REPEAT 377..398
FT /note="LRR 10"
FT REPEAT 401..422
FT /note="LRR 11"
FT DOMAIN 434..484
FT /note="LRRCT 2"
FT DOMAIN 493..529
FT /note="LRRNT 3"
FT REPEAT 530..551
FT /note="LRR 12"
FT REPEAT 555..576
FT /note="LRR 13"
FT REPEAT 579..600
FT /note="LRR 14"
FT REPEAT 603..624
FT /note="LRR 15"
FT REPEAT 627..648
FT /note="LRR 16"
FT DOMAIN 660..710
FT /note="LRRCT 3"
FT DOMAIN 714..750
FT /note="LRRNT 4"
FT CARBOHYD 66
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 186
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 560
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 619
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 281..290
FT /evidence="ECO:0000250"
FT DISULFID 438..461
FT /evidence="ECO:0000250"
FT DISULFID 440..482
FT /evidence="ECO:0000250"
FT DISULFID 502..508
FT /evidence="ECO:0000250"
FT DISULFID 506..515
FT /evidence="ECO:0000250"
FT DISULFID 664..687
FT /evidence="ECO:0000250"
FT DISULFID 666..708
FT /evidence="ECO:0000250"
FT DISULFID 723..729
FT /evidence="ECO:0000250"
FT DISULFID 727..736
FT /evidence="ECO:0000250"
FT NON_TER 766
SQ SEQUENCE 766 AA; 86049 MW; A380ACCE0A810FE1 CRC64;
MSGIGWQTLS LSLALVLSIL NKVAPHACPA QCSCSGSTVD CHGLALRIVP RNIPRNTERL
DLNGNNITRI TKTDFAGLRH LRILQLMENK ISTIERGAFH DLKELERLRL NRNNLQLFPE
LLFLGTAKLY RLDLSENQIQ AIPRKAFRGA VDIKNLQLDY NQISCIEDGA FRALRDLEVL
TLNNNNITRL SVASFNHMPK LRTFRLHSNN LYCDCHLAWL SDWLRQRPRV GLYTQCMGPS
HLRGHNVAEV QKREFVCSDE EEGHQSFMAP SCSVLHCPIA CTCSNNIVDC RGKGLTEIPT
NLPETITEIR LEQNSIRVIP PGAFSPYKKL RRLDLSNNQI SELAPDAFQG LRSLNSLVLY
GNKITELPKS LFEGLFSLQL LLLNANKINC LRVDAFQDLH NLNLLSLYDN KLQTVAKGTF
SALRAIQTMH LAQNPFICDC HLKWLADYLH TNPIETSGAR CTSPRRLANK RIGQIKSKKF
RCSGTEDYRS KLSGDCFADL ACPEKCRCEG TTVDCSNQKL NKIPDHIPQY TAELRLNNNE
FTVLEATGIF KKLPQLRKIN LSNNKITDIE EGAFEGASGV NEILLTSNRL ENVQHKMFKG
LESLKTLMLR SNRISCVGND SFTGLGSVRL LSLYDNQITT VAPGAFGTLH SLSTLNLLAN
PFNCNCHLAW LGEWLRRKRI VTGNPRCQKP YFLKEIPIQD VAIQDFTCDD GNDDNSCSPL
SRCPSECTCL DTVVRCSNKG LKVLPKGIPR DVTELYLDGN QFTLVP
