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Protein

Leucine-rich repeat transmembrane protein FLRT3

Gene

Flrt3

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. Plays a role in the spatial organization of brain neurons. Plays a role in vascular development in the retina (By similarity). 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 (By similarity). Interaction with the intracellular domain of ROBO1 mediates axon attraction towards cells expressing NTN1. 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 (By similarity). Promotes neurite outgrowth (in vitro) (By similarity). Mediates cell-cell contacts that promote an increase both in neurite number and in neurite length (PubMed:15485775). Plays a role in the regulation of the density of glutamaergic synapses (PubMed:22405201). Plays a role in fibroblast growth factor-mediated signaling cascades. Required for normal morphogenesis during embryonic development, but not for normal embryonic patterning. Required for normal ventral closure, headfold fusion and definitive endoderm migration during embryonic development. Required for the formation of a normal basement membrane and the maintenance of a normal anterior visceral endoderm during embryonic development (By similarity).By similarity2 Publications

GO - Biological processi

  • axon guidance Source: MGI
  • cell-cell adhesion Source: UniProtKB
  • embryonic morphogenesis Source: UniProtKB
  • fibroblast growth factor receptor signaling pathway Source: UniProtKB
  • head development Source: UniProtKB
  • heart development Source: UniProtKB
  • neuron projection development Source: UniProtKB
  • neuron projection extension Source: UniProtKB
  • proepicardium cell migration involved in pericardium morphogenesis Source: UniProtKB
  • response to axon injury Source: UniProtKB
  • synapse assembly Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Cell adhesion

Names & Taxonomyi

Protein namesi
Recommended name:
Leucine-rich repeat transmembrane protein FLRT3
Alternative name(s):
Fibronectin-like domain-containing leucine-rich transmembrane protein 3
Gene namesi
Name:Flrt3
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi1566005. Flrt3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini29 – 528500ExtracellularSequence analysisAdd
BLAST
Transmembranei529 – 54921HelicalSequence analysisAdd
BLAST
Topological domaini550 – 649100CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • axonal growth cone Source: UniProtKB
  • axon terminus Source: UniProtKB
  • cytoplasmic, membrane-bounded vesicle Source: UniProtKB-SubCell
  • dendrite Source: UniProtKB-SubCell
  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • extracellular region Source: UniProtKB-SubCell
  • focal adhesion Source: UniProtKB-SubCell
  • integral component of plasma membrane Source: UniProtKB
  • postsynaptic density Source: UniProtKB-SubCell
  • postsynaptic membrane Source: UniProtKB-KW
  • presynaptic membrane Source: UniProtKB-SubCell
  • synaptic membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasmic vesicle, Endoplasmic reticulum, Membrane, Postsynaptic cell membrane, Secreted, Synapse, Synaptosome

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2828Sequence analysisAdd
BLAST
Chaini29 – 649621Leucine-rich repeat transmembrane protein FLRT3PRO_0000352675Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi31 ↔ 37By similarity
Disulfide bondi35 ↔ 44By similarity
Glycosylationi226 – 2261N-linked (GlcNAc...)Sequence analysis
Glycosylationi282 – 2821N-linked (GlcNAc...)Sequence analysis
Glycosylationi296 – 2961N-linked (GlcNAc...)Sequence analysis
Disulfide bondi309 ↔ 334By similarity

Post-translational modificationi

N-glycosylated.By similarity
Proteolytic cleavage in the juxtamembrane region gives rise to a soluble ectodomain. Cleavage is probably effected by a metalloprotease.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiB1H234.
PRIDEiB1H234.

PTM databases

iPTMnetiB1H234.

Expressioni

Tissue specificityi

Detected in brain (at protein level) (PubMed:22405201). Detected in brain neurons, especially in basal ganglia, hippocampus dentate gyrus and CA3 region, cerebellum and in olfactory bulb (PubMed:14706654, PubMed:15485775).3 Publications

Developmental stagei

At 12 dpc, detected in the developing brain, eye, lateral lip of the dermomyotome, somites and branchial arch.1 Publication

Inductioni

Up-regulated in neurons in dorsal root ganglia in response to peripheral nerve injury (at protein level) (PubMed:15485775). Up-regulated in neurons in dorsal root ganglia in response to peripheral nerve injury (PubMed:15485775).1 Publication

Gene expression databases

GenevisibleiB1H234. RN.

Interactioni

Subunit structurei

Monomer and homodimer. Self-associates (via leucine-rich repeats), giving rise to homooligomers. Interacts with FGFR1 (By similarity). Interacts (via extracellular domain) with ADGRL1/LPHN1 and ADGRL3 (via olfactomedin-like domain) (PubMed:22405201). Interacts (via extracellular domain) with LPHN2 (via olfactomedin-like domain). Interacts (via extracellular domain) with UNC5B (via Ig domain). May also interact (via extracellular domain) with UNC5A and UNC5C. Interacts (via extracellular domain) with UNC5D (via extracellular domain). Identified in complexes composed of FLRT3, ADGRL3 and UNC5B, respectively FLRT3, ADGRL3 and UNC5D (By similarity). Interacts (via cytoplasmic domain) with ROBO1 (By similarity).By similarity1 Publication

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000006454.

Structurei

3D structure databases

ProteinModelPortaliB1H234.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini29 – 5830LRRNTSequence analysisAdd
BLAST
Repeati59 – 8022LRR 1Sequence analysisAdd
BLAST
Repeati84 – 10421LRR 2Sequence analysisAdd
BLAST
Repeati105 – 12622LRR 3Sequence analysisAdd
BLAST
Repeati129 – 15022LRR 4Sequence analysisAdd
BLAST
Repeati155 – 17622LRR 5Sequence analysisAdd
BLAST
Repeati177 – 19721LRR 6Sequence analysisAdd
BLAST
Repeati200 – 22021LRR 7Sequence analysisAdd
BLAST
Repeati226 – 24722LRR 8Sequence analysisAdd
BLAST
Repeati248 – 26922LRR 9Sequence analysisAdd
BLAST
Repeati272 – 29322LRR 10Sequence analysisAdd
BLAST
Domaini305 – 35753LRRCTSequence analysisAdd
BLAST
Domaini405 – 504100Fibronectin type-IIIPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni38 – 6730Interaction with ADGRL3By similarityAdd
BLAST

Sequence similaritiesi

Contains 1 fibronectin type-III domain.PROSITE-ProRule annotation
Contains 10 LRR (leucine-rich) repeats.Curated
Contains 1 LRRCT domain.Curated
Contains 1 LRRNT domain.Curated

Keywords - Domaini

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

Phylogenomic databases

eggNOGiENOG410IIEA. Eukaryota.
COG4886. LUCA.
HOGENOMiHOG000290188.
HOVERGENiHBG051629.
InParanoidiB1H234.
KOiK16362.
OMAiSPYRVCM.
OrthoDBiEOG773XFK.
PhylomeDBiB1H234.
TreeFamiTF331598.

Family and domain databases

Gene3Di3.80.10.10. 3 hits.
InterProiIPR000483. Cys-rich_flank_reg_C.
IPR003961. FN3_dom.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000372. LRRNT.
[Graphical view]
PfamiPF13855. LRR_8. 2 hits.
[Graphical view]
SMARTiSM00369. LRR_TYP. 7 hits.
SM00082. LRRCT. 1 hit.
SM00013. LRRNT. 1 hit.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 2 hits.
PROSITEiPS50853. FN3. 1 hit.
PS51450. LRR. 8 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

B1H234-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MISPAWSLFL IGTKIGLFFQ VAPLSVMAKS 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 VSTVQITTAI PNTAYPAQGQ WPAPVTKQPD IKNPKLTKDQ
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 IPDLDHSHS
Length:649
Mass (Da):72,911
Last modified:April 29, 2008 - v1
Checksum:i15DF42A55DD1F12C
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CH473949 Genomic DNA. Translation: EDL80327.1.
BC160843 mRNA. Translation: AAI60843.1.
RefSeqiNP_001119763.1. NM_001126291.1.
UniGeneiRn.220263.

Genome annotation databases

GeneIDi366205.
KEGGirno:366205.
UCSCiRGD:1566005. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CH473949 Genomic DNA. Translation: EDL80327.1.
BC160843 mRNA. Translation: AAI60843.1.
RefSeqiNP_001119763.1. NM_001126291.1.
UniGeneiRn.220263.

3D structure databases

ProteinModelPortaliB1H234.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000006454.

PTM databases

iPTMnetiB1H234.

Proteomic databases

PaxDbiB1H234.
PRIDEiB1H234.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi366205.
KEGGirno:366205.
UCSCiRGD:1566005. rat.

Organism-specific databases

CTDi23767.
RGDi1566005. Flrt3.

Phylogenomic databases

eggNOGiENOG410IIEA. Eukaryota.
COG4886. LUCA.
HOGENOMiHOG000290188.
HOVERGENiHBG051629.
InParanoidiB1H234.
KOiK16362.
OMAiSPYRVCM.
OrthoDBiEOG773XFK.
PhylomeDBiB1H234.
TreeFamiTF331598.

Miscellaneous databases

PROiB1H234.

Gene expression databases

GenevisibleiB1H234. RN.

Family and domain databases

Gene3Di3.80.10.10. 3 hits.
InterProiIPR000483. Cys-rich_flank_reg_C.
IPR003961. FN3_dom.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000372. LRRNT.
[Graphical view]
PfamiPF13855. LRR_8. 2 hits.
[Graphical view]
SMARTiSM00369. LRR_TYP. 7 hits.
SM00082. LRRCT. 1 hit.
SM00013. LRRNT. 1 hit.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 2 hits.
PROSITEiPS50853. FN3. 1 hit.
PS51450. LRR. 8 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: Brown Norway.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Brown Norway/NHsdMcwi.
    Tissue: Brain.
  3. "FLRT3, a cell surface molecule containing LRR repeats and a FNIII domain, promotes neurite outgrowth."
    Tsuji L., Yamashita T., Kubo T., Madura T., Tanaka H., Hosokawa K., Tohyama M.
    Biochem. Biophys. Res. Commun. 313:1086-1091(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  4. "FLRT3 is expressed in sensory neurons after peripheral nerve injury and regulates neurite outgrowth."
    Robinson M., Parsons Perez M.C., Tebar L., Palmer J., Patel A., Marks D., Sheasby A., De Felipe C., Coffin R., Livesey F.J., Hunt S.P.
    Mol. Cell. Neurosci. 27:202-214(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION BY PERIPHERAL NERVE INJURY, DEVELOPMENTAL STAGE.
  5. "FLRT proteins are endogenous latrophilin ligands and regulate excitatory synapse development."
    O'Sullivan M.L., de Wit J., Savas J.N., Comoletti D., Otto-Hitt S., Yates J.R. III, Ghosh A.
    Neuron 73:903-910(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ADGRL1 AND ADGRL3, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY, TISSUE SPECIFICITY.

Entry informationi

Entry nameiFLRT3_RAT
AccessioniPrimary (citable) accession number: B1H234
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 14, 2008
Last sequence update: April 29, 2008
Last modified: June 8, 2016
This is version 70 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.