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Protein

Leucine-rich repeat transmembrane protein FLRT3

Gene

Flrt3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Functions in cell-cell adhesion, cell migration and axon guidance, exerting an attractive or repulsive role depending on its interaction partners (PubMed:19056886, PubMed:25374360). Plays a role in the spatial organization of brain neurons (PubMed:25374360). Plays a role in vascular development in the retina (PubMed:25374360). Plays a role in cell-cell adhesion via its interaction with ADGRL3 and probably also other latrophilins that are expressed at the surface of adjacent cells (PubMed:22405201, PubMed:25374360). Interaction with the intracellular domain of ROBO1 mediates axon attraction towards cells expressing NTN1 (PubMed:24560577). Mediates axon growth cone collapse and plays a repulsive role in neuron guidance via its interaction with UNC5B, and possibly also other UNC-5 family members (PubMed:21673655, PubMed:25374360). Promotes neurite outgrowth (in vitro) (By similarity). Mediates cell-cell contacts that promote an increase both in neurite number and in neurite length (By similarity). Plays a role in the regulation of the density of glutamaergic synapses (PubMed:22405201). Plays a role in fibroblast growth factor-mediated signaling cascades (PubMed:16872596). Required for normal morphogenesis during embryonic development, but not for normal embryonic patterning (PubMed:19056886). Required for normal ventral closure, headfold fusion and definitive endoderm migration during embryonic development (PubMed:18448090). Required for the formation of a normal basement membrane and the maintenance of a normal anterior visceral endoderm during embryonic development (PubMed:19056886).By similarity7 Publications

GO - Molecular functioni

  • chemorepellent activity Source: MGI
  • fibroblast growth factor receptor binding Source: UniProtKB
  • protein homodimerization activity Source: MGI

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein
Biological processCell adhesion

Enzyme and pathway databases

ReactomeiR-MMU-5654687 Downstream signaling of activated FGFR1

Names & Taxonomyi

Protein namesi
Recommended name:
Leucine-rich repeat transmembrane protein FLRT3Curated
Alternative name(s):
Fibronectin leucine rich transmembrane protein 3Imported
Gene namesi
Name:Flrt3Imported
Synonyms:Kiaa1469Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1918686 Flrt3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini29 – 528ExtracellularCuratedAdd BLAST500
Transmembranei529 – 549HelicalSequence analysisAdd BLAST21
Topological domaini550 – 649CytoplasmicCuratedAdd BLAST100

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Endoplasmic reticulum, Membrane, Secreted

Pathology & Biotechi

Disruption phenotypei

Heterozygous mice are viable and fertile, but homozygous mice display nearly complete embryonic lethality. Most embryos die at about 10.5 dpc (PubMed:18448090, PubMed:19056886). A majority present disruption of the basement membrane and ruptures of the anterior visceral endoderm (PubMed:19056886). About one third display a pronounced defect in the fusion of the lateral edges of the body wall, resulting in cardia bifida. Mutant mice display also a defect in proepicardial cell migration. About one third of the mutants display abnormal morphogenesis of the neuroepithelium and headfold fusion defects. Besides, mutant embryos display defects in definitive endoderm migration, resulting in anterior axis truncations. Each of these phenotypes has partial penetrance, and many mutant embryos present a spectrum of defects. About 3% of the mutants develop into viable and fertile adults (PubMed:18448090, PubMed:19056886).2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi160F → A or N: Abolishes interaction with ADGRL3. 1 Publication1
Mutagenesisi165H → N: Abolishes interaction with UNC5B. 1 Publication1
Mutagenesisi181R → N: Abolishes homooligomerization and FLRT3-mediated cell-cell adhesion; when associated with T-183. 1 Publication1
Mutagenesisi183D → N: Abolishes homooligomerization and FLRT3-mediated cell-cell adhesion; when associated with N-181. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 28Sequence analysisAdd BLAST28
ChainiPRO_000043451729 – 649Leucine-rich repeat transmembrane protein FLRT3Add BLAST621

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi31 ↔ 37Combined sources
Disulfide bondi35 ↔ 44Combined sources
Glycosylationi282N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi309 ↔ 334Combined sources

Post-translational modificationi

N-glycosylated.2 Publications
Proteolytic cleavage in the juxtamembrane region gives rise to a soluble ectodomain. Cleavage is probably effected by a metalloprotease.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ8BGT1
PaxDbiQ8BGT1
PRIDEiQ8BGT1

PTM databases

iPTMnetiQ8BGT1
PhosphoSitePlusiQ8BGT1

Expressioni

Tissue specificityi

Detected in adult brain (PubMed:21350012). Detected in embryonic rostral thalamus neurons (at protein level) (PubMed:24560577). Detected in embryonic rostral thalamus neurons (PubMed:24560577). Detected in neonate eye, in the inner plexiform layer and the outer nuclear layer (PubMed:25374360).2 Publications

Developmental stagei

Detected in embryonic brain at 13 dpc. Levels in brain decrease gradually after 15 dpc, but expression continues after birth (PubMed:21673655). Detected in embryonic myocardium, body wall and pro-epicardial organ at 9.5 dpc. Detected throughout the myocardium at 10.5 dpc, but levels in the epicardial cell layer are strongly decreased. Almost exclusively detected in the neural tube at 14.5 dpc (at protein level) (PubMed:21350012). Detected in the chorion and visceral endoderm between 6 and 8 dpc (PubMed:19056886). Detected in the visceral endoderm at 7 dpc, with a gradient from high expression in the anterior part to low expression at the posterior part (PubMed:19056886). At 8 dpc, detected in definitve endoderm, parts of the neuroectoderm, the headfold and posterior mesoderm (PubMed:19056886). Detected in the developing brain, the proepicardial organ and in somites at 8.5 dpc (PubMed:16872596, PubMed:18448090). At 9.5 and 10.5 dpc, detected in telencephalic vesicles, at the midbrain boundaries with forebrain and hindbrain, the hypothalamic region, in the apical ectodermal ridge, pharyngeal arches, the developing eye, the epithelial structures surrounding the lower region of the developing heart, limb buds and somites (PubMed:16872596, PubMed:18448090). At 10.5 dpc, detected at interlimb somites with loss of expression at limb somites and anterior trunk somites. At 11 dpc, detected in mesoderm in head and branchial arches, migrating germ cells and limbs (PubMed:16872596).4 Publications

Inductioni

Up-regulated by FGF2.1 Publication

Gene expression databases

BgeeiENSMUSG00000051379 Expressed in 272 organ(s), highest expression level in skin of back
GenevisibleiQ8BGT1 MM

Interactioni

Subunit structurei

Monomer and homodimer (By similarity). Self-associates (via leucine-rich repeats), giving rise to homooligomers (PubMed:25374360). Interacts with FGFR1 (PubMed:16872596). Interacts (via extracellular domain) with ADGRL1/LPHN1 and LPHN2 (via olfactomedin-like domain) (PubMed:22405201). Interacts (via extracellular domain) with ADGRL3 (via olfactomedin-like domain) (PubMed:24739570, PubMed:22405201, PubMed:26235031). Interacts (via extracellular domain) with UNC5B (via Ig domain) (PubMed:19492039, PubMed:21673655, PubMed:22405201, PubMed:25374360). May also interact (via extracellular domain) with UNC5A and UNC5C (PubMed:22405201). Interacts (via extracellular domain) with UNC5D (via extracellular domain) (PubMed:19492039). Identified in complexes composed of FLRT3, ADGRL3 and UNC5B, respectively FLRT3, ADGRL3 and UNC5D (By similarity). Interacts (via cytoplasmic domain) with ROBO1 (PubMed:24560577).By similarity7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Adgrl3Q80TS36EBI-16166902,EBI-770665

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-61803N
IntActiQ8BGT1, 1 interactor
STRINGi10090.ENSMUSP00000053399

Structurei

Secondary structure

1649
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ8BGT1
SMRiQ8BGT1
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini30 – 62LRRNTSequence analysisAdd BLAST33
Repeati58 – 82LRR 1Sequence analysisAdd BLAST25
Repeati83 – 105LRR 2Sequence analysisAdd BLAST23
Repeati107 – 126LRR 3Sequence analysisAdd BLAST20
Repeati127 – 152LRR 4Sequence analysisAdd BLAST26
Repeati153 – 176LRR 5Sequence analysisAdd BLAST24
Repeati178 – 197LRR 6Sequence analysisAdd BLAST20
Repeati198 – 223LRR 7Sequence analysisAdd BLAST26
Repeati224 – 246LRR 8Sequence analysisAdd BLAST23
Repeati247 – 269LRR 9Sequence analysisAdd BLAST23
Repeati270 – 293LRR 10Sequence analysisAdd BLAST24
Domaini305 – 356LRRCTSequence analysisAdd BLAST52
Domaini405 – 504Fibronectin type-IIIPROSITE-ProRule annotationAdd BLAST100

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni38 – 67Interaction with ADGRL3By similarityAdd BLAST30

Keywords - Domaini

Leucine-rich repeat, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IIEA Eukaryota
COG4886 LUCA
GeneTreeiENSGT00920000148996
HOGENOMiHOG000290188
HOVERGENiHBG051629
InParanoidiQ8BGT1
KOiK16362
OMAiSPYRVCM
OrthoDBiEOG091G05YU
TreeFamiTF331598

Family and domain databases

Gene3Di3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR000483 Cys-rich_flank_reg_C
IPR003961 FN3_dom
IPR001611 Leu-rich_rpt
IPR003591 Leu-rich_rpt_typical-subtyp
IPR032675 LRR_dom_sf
IPR000372 LRRNT
PfamiView protein in Pfam
PF13855 LRR_8, 2 hits
SMARTiView protein in SMART
SM00369 LRR_TYP, 7 hits
SM00082 LRRCT, 1 hit
SM00013 LRRNT, 1 hit
PROSITEiView protein in PROSITE
PS50853 FN3, 1 hit
PS51450 LRR, 8 hits

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q8BGT1-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MISPAWSLFL IGTKIGLFFQ VAPLSVVAKS CPSVCRCDAG FIYCNDRSLT
60 70 80 90 100
SIPVGIPEDA TTLYLQNNQI NNVGIPSDLK NLLKVQRIYL YHNSLDEFPT
110 120 130 140 150
NLPKYVKELH LQENNIRTIT YDSLSKIPYL EELHLDDNSV SAVSIEEGAF
160 170 180 190 200
RDSNYLRLLF LSRNHLSTIP GGLPRTIEEL RLDDNRISTI SSPSLHGLTS
210 220 230 240 250
LKRLVLDGNL LNNHGLGDKV FFNLVNLTEL SLVRNSLTAA PVNLPGTSLR
260 270 280 290 300
KLYLQDNHIN RVPPNAFSYL RQLYRLDMSN NNLSNLPQGI FDDLDNITQL
310 320 330 340 350
ILRNNPWYCG CKMKWVRDWL QSLPVKVNVR GLMCQAPEKV RGMAIKDLSA
360 370 380 390 400
ELFDCKDSGI VSTIQITTAI PNTAYPAQGQ WPAPVTKQPD IKNPKLIKDQ
410 420 430 440 450
RTTGSPSRKT ILITVKSVTP DTIHISWRLA LPMTALRLSW LKLGHSPAFG
460 470 480 490 500
SITETIVTGE RSEYLVTALE PESPYRVCMV PMETSNLYLF DETPVCIETQ
510 520 530 540 550
TAPLRMYNPT TTLNREQEKE PYKNPNLPLA AIIGGAVALV SIALLALVCW
560 570 580 590 600
YVHRNGSLFS RNCAYSKGRR RKDDYAEAGT KKDNSILEIR ETSFQMLPIS
610 620 630 640
NEPISKEEFV IHTIFPPNGM NLYKNNLSES SSNRSYRDSG IPDSDHSHS
Length:649
Mass (Da):72,879
Last modified:March 1, 2003 - v1
Checksum:i736AC23C5E5BAA41
GO

Sequence cautioni

The sequence BAC98179 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY495670 mRNA Translation: AAR92203.1
AK129369 mRNA Translation: BAC98179.1 Different initiation.
AK028252 mRNA Translation: BAC25843.1
AK031464 mRNA Translation: BAC27417.1
AL928700 Genomic DNA No translation available.
CH466519 Genomic DNA Translation: EDL28416.1
BC052043 mRNA Translation: AAH52043.1
CCDSiCCDS16806.1
RefSeqiNP_001165631.1, NM_001172160.1
NP_848469.1, NM_178382.4
UniGeneiMm.426781

Genome annotation databases

EnsembliENSMUST00000056760; ENSMUSP00000053399; ENSMUSG00000051379
ENSMUST00000110057; ENSMUSP00000105684; ENSMUSG00000051379
GeneIDi71436
KEGGimmu:71436
UCSCiuc012cfb.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY495670 mRNA Translation: AAR92203.1
AK129369 mRNA Translation: BAC98179.1 Different initiation.
AK028252 mRNA Translation: BAC25843.1
AK031464 mRNA Translation: BAC27417.1
AL928700 Genomic DNA No translation available.
CH466519 Genomic DNA Translation: EDL28416.1
BC052043 mRNA Translation: AAH52043.1
CCDSiCCDS16806.1
RefSeqiNP_001165631.1, NM_001172160.1
NP_848469.1, NM_178382.4
UniGeneiMm.426781

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4V2EX-ray2.50A/B29-359[»]
4YEBX-ray3.19B29-386[»]
ProteinModelPortaliQ8BGT1
SMRiQ8BGT1
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-61803N
IntActiQ8BGT1, 1 interactor
STRINGi10090.ENSMUSP00000053399

PTM databases

iPTMnetiQ8BGT1
PhosphoSitePlusiQ8BGT1

Proteomic databases

MaxQBiQ8BGT1
PaxDbiQ8BGT1
PRIDEiQ8BGT1

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000056760; ENSMUSP00000053399; ENSMUSG00000051379
ENSMUST00000110057; ENSMUSP00000105684; ENSMUSG00000051379
GeneIDi71436
KEGGimmu:71436
UCSCiuc012cfb.1 mouse

Organism-specific databases

CTDi23767
MGIiMGI:1918686 Flrt3
RougeiSearch...

Phylogenomic databases

eggNOGiENOG410IIEA Eukaryota
COG4886 LUCA
GeneTreeiENSGT00920000148996
HOGENOMiHOG000290188
HOVERGENiHBG051629
InParanoidiQ8BGT1
KOiK16362
OMAiSPYRVCM
OrthoDBiEOG091G05YU
TreeFamiTF331598

Enzyme and pathway databases

ReactomeiR-MMU-5654687 Downstream signaling of activated FGFR1

Miscellaneous databases

PROiPR:Q8BGT1
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000051379 Expressed in 272 organ(s), highest expression level in skin of back
GenevisibleiQ8BGT1 MM

Family and domain databases

Gene3Di3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR000483 Cys-rich_flank_reg_C
IPR003961 FN3_dom
IPR001611 Leu-rich_rpt
IPR003591 Leu-rich_rpt_typical-subtyp
IPR032675 LRR_dom_sf
IPR000372 LRRNT
PfamiView protein in Pfam
PF13855 LRR_8, 2 hits
SMARTiView protein in SMART
SM00369 LRR_TYP, 7 hits
SM00082 LRRCT, 1 hit
SM00013 LRRNT, 1 hit
PROSITEiView protein in PROSITE
PS50853 FN3, 1 hit
PS51450 LRR, 8 hits
ProtoNetiSearch...

Entry informationi

Entry nameiFLRT3_MOUSE
AccessioniPrimary (citable) accession number: Q8BGT1
Secondary accession number(s): Q6ZPQ1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 14, 2015
Last sequence update: March 1, 2003
Last modified: November 7, 2018
This is version 153 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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