FLRT3_RAT
ID FLRT3_RAT Reviewed; 649 AA.
AC B1H234;
DT 14-OCT-2008, integrated into UniProtKB/Swiss-Prot.
DT 29-APR-2008, sequence version 1.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=Leucine-rich repeat transmembrane protein FLRT3;
DE AltName: Full=Fibronectin-like domain-containing leucine-rich transmembrane protein 3;
DE Flags: Precursor;
GN Name=Flrt3;
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Brown Norway/NHsdMcwi; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=14706654; DOI=10.1016/j.bbrc.2003.12.047;
RA Tsuji L., Yamashita T., Kubo T., Madura T., Tanaka H., Hosokawa K.,
RA Tohyama M.;
RT "FLRT3, a cell surface molecule containing LRR repeats and a FNIII domain,
RT promotes neurite outgrowth.";
RL Biochem. Biophys. Res. Commun. 313:1086-1091(2004).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION BY PERIPHERAL
RP NERVE INJURY, AND DEVELOPMENTAL STAGE.
RX PubMed=15485775; DOI=10.1016/j.mcn.2004.06.008;
RA Robinson M., Parsons Perez M.C., Tebar L., Palmer J., Patel A., Marks D.,
RA Sheasby A., De Felipe C., Coffin R., Livesey F.J., Hunt S.P.;
RT "FLRT3 is expressed in sensory neurons after peripheral nerve injury and
RT regulates neurite outgrowth.";
RL Mol. Cell. Neurosci. 27:202-214(2004).
RN [5]
RP INTERACTION WITH ADGRL1 AND ADGRL3, SUBCELLULAR LOCATION, IDENTIFICATION BY
RP MASS SPECTROMETRY, AND TISSUE SPECIFICITY.
RX PubMed=22405201; DOI=10.1016/j.neuron.2012.01.018;
RA O'Sullivan M.L., de Wit J., Savas J.N., Comoletti D., Otto-Hitt S.,
RA Yates J.R. III, Ghosh A.;
RT "FLRT proteins are endogenous latrophilin ligands and regulate excitatory
RT synapse development.";
RL Neuron 73:903-910(2012).
CC -!- FUNCTION: Functions in cell-cell adhesion, cell migration and axon
CC guidance, exerting an attractive or repulsive role depending on its
CC interaction partners. Plays a role in the spatial organization of brain
CC neurons. Plays a role in vascular development in the retina (By
CC similarity). Plays a role in cell-cell adhesion via its interaction
CC with ADGRL3 and probably also other latrophilins that are expressed at
CC the surface of adjacent cells (By similarity). Interaction with the
CC intracellular domain of ROBO1 mediates axon attraction towards cells
CC expressing NTN1. Mediates axon growth cone collapse and plays a
CC repulsive role in neuron guidance via its interaction with UNC5B, and
CC possibly also other UNC-5 family members (By similarity). Promotes
CC neurite outgrowth (in vitro) (By similarity). Mediates cell-cell
CC contacts that promote an increase both in neurite number and in neurite
CC length (PubMed:15485775). Plays a role in the regulation of the density
CC of glutamaergic synapses (PubMed:22405201). Plays a role in fibroblast
CC growth factor-mediated signaling cascades. Required for normal
CC morphogenesis during embryonic development, but not for normal
CC embryonic patterning. Required for normal ventral closure, headfold
CC fusion and definitive endoderm migration during embryonic development.
CC Required for the formation of a normal basement membrane and the
CC maintenance of a normal anterior visceral endoderm during embryonic
CC development (By similarity). {ECO:0000250|UniProtKB:Q8BGT1,
CC ECO:0000250|UniProtKB:Q9NZU0, ECO:0000269|PubMed:15485775,
CC ECO:0000269|PubMed:22405201}.
CC -!- SUBUNIT: Monomer and homodimer. Self-associates (via leucine-rich
CC repeats), giving rise to homooligomers. Interacts with FGFR1 (By
CC similarity). Interacts (via extracellular domain) with ADGRL1/LPHN1 and
CC ADGRL3 (via olfactomedin-like domain) (PubMed:22405201). Interacts (via
CC extracellular domain) with LPHN2 (via olfactomedin-like domain).
CC Interacts (via extracellular domain) with UNC5B (via Ig domain). May
CC also interact (via extracellular domain) with UNC5A and UNC5C.
CC Interacts (via extracellular domain) with UNC5D (via extracellular
CC domain). Identified in complexes composed of FLRT3, ADGRL3 and UNC5B,
CC respectively FLRT3, ADGRL3 and UNC5D (By similarity). Interacts (via
CC cytoplasmic domain) with ROBO1 (By similarity).
CC {ECO:0000250|UniProtKB:Q8BGT1, ECO:0000250|UniProtKB:Q9NZU0,
CC ECO:0000269|PubMed:22405201}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15485775,
CC ECO:0000269|PubMed:22405201}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:Q8BGT1}. Synapse, synaptosome
CC {ECO:0000269|PubMed:22405201}. Postsynaptic density
CC {ECO:0000269|PubMed:22405201}. Cell projection, dendrite
CC {ECO:0000269|PubMed:22405201}. Synapse {ECO:0000269|PubMed:22405201}.
CC Presynaptic cell membrane {ECO:0000269|PubMed:15485775}. Cell
CC projection, axon {ECO:0000269|PubMed:15485775}. Cell projection, growth
CC cone membrane {ECO:0000269|PubMed:15485775}. Cytoplasmic vesicle
CC {ECO:0000269|PubMed:15485775}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q8BGT1}. Cell junction, focal adhesion
CC {ECO:0000250|UniProtKB:Q8BGT1}. Secreted
CC {ECO:0000250|UniProtKB:Q8BGT1}. Note=Detected on dendritic punctae that
CC colocalize in part with glutamaergic synapses, but not with GABAergic
CC synapses (PubMed:22405201). Proteolytic cleavage in the juxtamembrane
CC region gives rise to a shedded ectodomain (By similarity).
CC {ECO:0000250|UniProtKB:Q8BGT1, ECO:0000269|PubMed:15485775,
CC ECO:0000269|PubMed:22405201}.
CC -!- TISSUE SPECIFICITY: Detected in brain (at protein level)
CC (PubMed:22405201). Detected in brain neurons, especially in basal
CC ganglia, hippocampus dentate gyrus and CA3 region, cerebellum and in
CC olfactory bulb (PubMed:14706654, PubMed:15485775).
CC {ECO:0000269|PubMed:14706654, ECO:0000269|PubMed:15485775,
CC ECO:0000269|PubMed:22405201}.
CC -!- DEVELOPMENTAL STAGE: At 12 dpc, detected in the developing brain, eye,
CC lateral lip of the dermomyotome, somites and branchial arch.
CC {ECO:0000269|PubMed:15485775}.
CC -!- INDUCTION: Up-regulated in neurons in dorsal root ganglia in response
CC to peripheral nerve injury (at protein level) (PubMed:15485775). Up-
CC regulated in neurons in dorsal root ganglia in response to peripheral
CC nerve injury (PubMed:15485775). {ECO:0000269|PubMed:15485775}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q8BGT1}.
CC -!- PTM: Proteolytic cleavage in the juxtamembrane region gives rise to a
CC soluble ectodomain. Cleavage is probably effected by a metalloprotease.
CC {ECO:0000250|UniProtKB:Q8BGT1}.
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DR EMBL; CH473949; EDL80327.1; -; Genomic_DNA.
DR EMBL; BC160843; AAI60843.1; -; mRNA.
DR RefSeq; NP_001119763.1; NM_001126291.1.
DR AlphaFoldDB; B1H234; -.
DR SMR; B1H234; -.
DR STRING; 10116.ENSRNOP00000006454; -.
DR GlyGen; B1H234; 3 sites.
DR iPTMnet; B1H234; -.
DR PhosphoSitePlus; B1H234; -.
DR PaxDb; B1H234; -.
DR PRIDE; B1H234; -.
DR Ensembl; ENSRNOT00000006454; ENSRNOP00000006454; ENSRNOG00000004874.
DR Ensembl; ENSRNOT00000115709; ENSRNOP00000089101; ENSRNOG00000004874.
DR GeneID; 366205; -.
DR KEGG; rno:366205; -.
DR UCSC; RGD:1566005; rat.
DR CTD; 23767; -.
DR RGD; 1566005; Flrt3.
DR eggNOG; ENOG502QQBZ; Eukaryota.
DR GeneTree; ENSGT00940000159704; -.
DR HOGENOM; CLU_027624_0_0_1; -.
DR InParanoid; B1H234; -.
DR OrthoDB; 826997at2759; -.
DR PhylomeDB; B1H234; -.
DR TreeFam; TF331598; -.
DR Reactome; R-RNO-5654687; Downstream signaling of activated FGFR1.
DR PRO; PR:B1H234; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Proteomes; UP000234681; Chromosome 3.
DR Genevisible; B1H234; RN.
DR GO; GO:0043679; C:axon terminus; IDA:UniProtKB.
DR GO; GO:0044295; C:axonal growth cone; ISS:UniProtKB.
DR GO; GO:0005911; C:cell-cell junction; ISO:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; ISO:RGD.
DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:RGD.
DR GO; GO:0032584; C:growth cone membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; IDA:SynGO.
DR GO; GO:0014069; C:postsynaptic density; IDA:SynGO.
DR GO; GO:0042734; C:presynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0097060; C:synaptic membrane; IDA:UniProtKB.
DR GO; GO:0045499; F:chemorepellent activity; ISO:RGD.
DR GO; GO:0005104; F:fibroblast growth factor receptor binding; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0007411; P:axon guidance; IGI:MGI.
DR GO; GO:0098742; P:cell-cell adhesion via plasma-membrane adhesion molecules; ISS:UniProtKB.
DR GO; GO:0048598; P:embryonic morphogenesis; ISS:UniProtKB.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0060322; P:head development; ISS:UniProtKB.
DR GO; GO:0007507; P:heart development; ISS:UniProtKB.
DR GO; GO:0031175; P:neuron projection development; IMP:UniProtKB.
DR GO; GO:1990138; P:neuron projection extension; IMP:UniProtKB.
DR GO; GO:0051965; P:positive regulation of synapse assembly; ISO:RGD.
DR GO; GO:0003345; P:proepicardium cell migration involved in pericardium morphogenesis; ISS:UniProtKB.
DR GO; GO:0048678; P:response to axon injury; IMP:UniProtKB.
DR GO; GO:0007416; P:synapse assembly; ISS:UniProtKB.
DR GO; GO:0050808; P:synapse organization; IMP:SynGO.
DR GO; GO:0099560; P:synaptic membrane adhesion; ISO:RGD.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR000483; Cys-rich_flank_reg_C.
DR InterPro; IPR003961; FN3_dom.
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; 2.
DR SMART; SM00369; LRR_TYP; 7.
DR SMART; SM00082; LRRCT; 1.
DR SMART; SM00013; LRRNT; 1.
DR PROSITE; PS50853; FN3; 1.
DR PROSITE; PS51450; LRR; 8.
PE 1: Evidence at protein level;
KW Cell adhesion; Cell junction; Cell membrane; Cell projection;
KW Cytoplasmic vesicle; Developmental protein; Disulfide bond;
KW Endoplasmic reticulum; Glycoprotein; Leucine-rich repeat; Membrane;
KW Reference proteome; Repeat; Secreted; Signal; Synapse; Synaptosome;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..649
FT /note="Leucine-rich repeat transmembrane protein FLRT3"
FT /id="PRO_0000352675"
FT TOPO_DOM 29..528
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 529..549
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 550..649
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 29..58
FT /note="LRRNT"
FT /evidence="ECO:0000255"
FT REPEAT 59..80
FT /note="LRR 1"
FT /evidence="ECO:0000255"
FT REPEAT 84..104
FT /note="LRR 2"
FT /evidence="ECO:0000255"
FT REPEAT 105..126
FT /note="LRR 3"
FT /evidence="ECO:0000255"
FT REPEAT 129..150
FT /note="LRR 4"
FT /evidence="ECO:0000255"
FT REPEAT 155..176
FT /note="LRR 5"
FT /evidence="ECO:0000255"
FT REPEAT 177..197
FT /note="LRR 6"
FT /evidence="ECO:0000255"
FT REPEAT 200..220
FT /note="LRR 7"
FT /evidence="ECO:0000255"
FT REPEAT 226..247
FT /note="LRR 8"
FT /evidence="ECO:0000255"
FT REPEAT 248..269
FT /note="LRR 9"
FT /evidence="ECO:0000255"
FT REPEAT 272..293
FT /note="LRR 10"
FT /evidence="ECO:0000255"
FT DOMAIN 305..357
FT /note="LRRCT"
FT /evidence="ECO:0000255"
FT DOMAIN 405..504
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 38..67
FT /note="Interaction with ADGRL3"
FT /evidence="ECO:0000250|UniProtKB:Q9NZU0"
FT REGION 378..405
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 629..649
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 226
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 282
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 296
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 31..37
FT /evidence="ECO:0000250|UniProtKB:Q8BGT1"
FT DISULFID 35..44
FT /evidence="ECO:0000250|UniProtKB:Q8BGT1"
FT DISULFID 309..334
FT /evidence="ECO:0000250|UniProtKB:Q8BGT1"
SQ SEQUENCE 649 AA; 72911 MW; 15DF42A55DD1F12C CRC64;
MISPAWSLFL IGTKIGLFFQ VAPLSVMAKS CPSVCRCDAG FIYCNDRSLT SIPVGIPEDA
TTLYLQNNQI NNVGIPSDLK NLLKVQRIYL YHNSLDEFPT NLPKYVKELH LQENNIRTIT
YDSLSKIPYL EELHLDDNSV SAVSIEEGAF RDSNYLRLLF LSRNHLSTIP GGLPRTIEEL
RLDDNRISTI SSPSLHGLTS LKRLVLDGNL LNNHGLGDKV FFNLVNLTEL SLVRNSLTAA
PVNLPGTSLR KLYLQDNHIN RVPPNAFSYL RQLYRLDMSN NNLSNLPQGI FDDLDNITQL
ILRNNPWYCG CKMKWVRDWL QSLPVKVNVR GLMCQAPEKV RGMAIKDLSA ELFDCKDSGI
VSTVQITTAI PNTAYPAQGQ WPAPVTKQPD IKNPKLTKDQ RTTGSPSRKT ILITVKSVTP
DTIHISWRLA LPMTALRLSW LKLGHSPAFG SITETIVTGE RSEYLVTALE PESPYRVCMV
PMETSNLYLF DETPVCIETQ TAPLRMYNPT TTLNREQEKE PYKNPNLPLA AIIGGAVALV
SIALLALVCW YVHRNGSLFS RNCAYSKGRR RKDDYAEAGT KKDNSILEIR ETSFQMLPIS
NEPISKEEFV IHTIFPPNGM NLYKNNLSES SSNRSYRDSG IPDLDHSHS
