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Protein

Leucine-rich repeat transmembrane protein FLRT2

Gene

Flrt2

Organism
Mus musculus (Mouse)
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. Mediates cell-cell adhesion via its interactions with ADGRL3 and probably also other latrophilins that are expressed at the surface of adjacent cells (PubMed:21350012, PubMed:25728924 PubMed:25374360). May play a role in the migration of cortical neurons during brain development via its interaction with UNC5D (PubMed:21673655). Mediates axon growth cone collapse and plays a repulsive role in neuron guidance via its interaction with UNC5D, and possibly also other UNC-5 family members (PubMed:21673655, PubMed:25728924). Plays a role in fibroblast growth factor-mediated signaling cascades (PubMed:16872596). Required for normal organization of the cardiac basement membrane during embryogenesis, and for normal embryonic epicardium and heart morphogenesis (PubMed:21350012).5 Publications

GO - Molecular functioni

  • chemorepellent activity Source: MGI
  • fibroblast growth factor receptor binding Source: UniProtKB
  • protein kinase inhibitor activity Source: GO_Central

GO - Biological processi

  • axon guidance Source: MGI
  • basement membrane organization Source: UniProtKB
  • cell adhesion involved in heart morphogenesis Source: UniProtKB
  • cytokine-mediated signaling pathway Source: GO_Central
  • fibroblast growth factor receptor signaling pathway Source: UniProtKB
  • heart morphogenesis Source: UniProtKB
  • negative regulation of JAK-STAT cascade Source: GO_Central
  • negative regulation of protein kinase activity Source: GO_Central
  • positive regulation of synapse assembly Source: MGI
  • regulation of neuron migration Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Cell adhesion

Enzyme and pathway databases

ReactomeiR-MMU-5654687. Downstream signaling of activated FGFR1.

Names & Taxonomyi

Protein namesi
Recommended name:
Leucine-rich repeat transmembrane protein FLRT2Curated
Alternative name(s):
Fibronectin leucine rich transmembrane protein 2Imported
Gene namesi
Name:Flrt2Imported
Synonyms:Kiaa04051 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:3603594. Flrt2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini36 – 540ExtracellularCuratedAdd BLAST505
Transmembranei541 – 561HelicalSequence analysisAdd BLAST21
Topological domaini562 – 660CytoplasmicCuratedAdd BLAST99

GO - Cellular componenti

  • cell-cell junction Source: UniProtKB
  • cytoplasm Source: GO_Central
  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • extracellular exosome Source: MGI
  • extracellular space Source: MGI
  • focal adhesion Source: MGI
  • integral component of plasma membrane Source: UniProtKB
  • neuron projection Source: UniProtKB-SubCell
  • organelle membrane Source: UniProtKB-SubCell
  • proteinaceous extracellular matrix Source: UniProtKB-SubCell
  • synapse Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Endoplasmic reticulum, Extracellular matrix, Membrane, Microsome, Secreted, Synapse, Synaptosome

Pathology & Biotechi

Disruption phenotypei

Heterozygous mice are viable and fertile, but homozygous mice display nearly complete embryonic lethality. Most embryos die at about 12.5 dpc, probably due to impaired expansion of the ventricular myocardium during development, reduced endocardial volume and heart insufficiency. Contrary to wild-type, the epicardium appears ruffled and presents numerous holes, due to defective formation of cell-cell adhesions. Still, there is a very small percentage of life-born pups that survive at least up to weaning.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi170H → E or N: Abolishes interaction with UNC5D. 1 Publication1
Mutagenesisi186R → N: Abolishes homooligomerization and FLRT2-mediated cell-cell adhesion; when associated with T-188. 1 Publication1
Mutagenesisi188D → T: Abolishes homooligomerization and FLRT2-mediated cell-cell adhesion; when associated with N-186. 1 Publication1
Mutagenesisi248D → N: No effect on interaction with UNC5D; when associated with T-250. 1 Publication1
Mutagenesisi250P → T: No effect on interaction with UNC5D; when associated with N-248. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 35Sequence analysisAdd BLAST35
ChainiPRO_000043452336 – 660Leucine-rich repeat transmembrane protein FLRT2Add BLAST625

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi36 ↔ 42Combined sources
Disulfide bondi40 ↔ 49Combined sources
Glycosylationi202N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi314 ↔ 339Combined sources
Disulfide bondi316 ↔ 360Combined 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

MaxQBiQ8BLU0.
PaxDbiQ8BLU0.
PRIDEiQ8BLU0.

PTM databases

PhosphoSitePlusiQ8BLU0.

Expressioni

Tissue specificityi

Detected in adult brain (at protein level).1 Publication

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 in the epicardial cell layer and throughout the myocardium at 10.5 dpc. Highly expressed in embryonic and neonate heart, but after that levels decrease strongly, and the protein is barely detectable 3 weeks after birth, with even lower levels after 7 and 15 weeks (at protein level) (PubMed:21350012). Detected in the anterior endoderm at 7.5 dpc. Detected on anterior somites, the allantois and mesenchymal tissue behind the developing heart at 8.5 dpc (PubMed:18448090). Detected in the cephalic mesenchyme and in tissue posterior to the developing heart at 9.5 and 10.5 dpc. Detected in the developing stomach and in a subset of the trunk sclerotome at 10.5 dpc. At 11 dpc, detected also in branchial arches, eyes and limbs (PubMed:16872596, PubMed:18448090).4 Publications

Inductioni

Up-regulated by FGF2.1 Publication

Gene expression databases

BgeeiENSMUSG00000047414.
GenevisibleiQ8BLU0. MM.

Interactioni

Subunit structurei

Self-associates (via leucine-rich repeats), giving rise to homooligomers (PubMed:25374360). Interacts with FGFR1 (PubMed:16872596). Interacts with FGFR2 (PubMed:21765038). Interacts (via extracellular domain) with ADGRL1/LPHN1 (PubMed:22405201). Interacts (via extracellular domain) with ADGRL3 (via olfactomedin-like domain)(PubMed:22405201, PubMed:25728924). Interacts (via extracellular domain) with UNC5D (via the first Ig-like domain) (PubMed:21673655, PubMed:25374360). Can also interact (via extracellular domain) with UNC5B, but with much lower affinity (PubMed:21673655). Interacts (via extracellular domain) with FN1 (PubMed:24585683).7 Publications

GO - Molecular functioni

  • fibroblast growth factor receptor binding Source: UniProtKB

Protein-protein interaction databases

DIPiDIP-61401N.
STRINGi10090.ENSMUSP00000062171.

Structurei

Secondary structure

1660
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi38 – 43Combined sources6
Beta strandi46 – 48Combined sources3
Beta strandi66 – 69Combined sources4
Helixi82 – 84Combined sources3
Beta strandi92 – 94Combined sources3
Beta strandi113 – 115Combined sources3
Helixi126 – 131Combined sources6
Beta strandi137 – 139Combined sources3
Turni147 – 149Combined sources3
Turni152 – 154Combined sources3
Helixi155 – 157Combined sources3
Beta strandi163 – 165Combined sources3
Beta strandi184 – 186Combined sources3
Turni197 – 200Combined sources4
Beta strandi208 – 210Combined sources3
Turni218 – 220Combined sources3
Helixi226 – 228Combined sources3
Beta strandi234 – 236Combined sources3
Beta strandi256 – 258Combined sources3
Turni269 – 271Combined sources3
Turni272 – 274Combined sources3
Beta strandi280 – 282Combined sources3
Beta strandi295 – 298Combined sources4
Beta strandi304 – 306Combined sources3
Helixi316 – 318Combined sources3
Helixi319 – 327Combined sources9
Beta strandi332 – 335Combined sources4
Beta strandi338 – 342Combined sources5
Turni343 – 347Combined sources5
Helixi350 – 352Combined sources3
Turni355 – 359Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4V2CX-ray4.00A/C35-362[»]
4V2DX-ray2.50A36-361[»]
5FTTX-ray3.40B/F35-362[»]
5FTUX-ray6.01B/F/J35-362[»]
ProteinModelPortaliQ8BLU0.
SMRiQ8BLU0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini36 – 63LRRNTSequence analysisAdd BLAST28
Repeati62 – 87LRR 1Sequence analysisAdd BLAST26
Repeati88 – 108LRR 2Sequence analysisAdd BLAST21
Repeati109 – 131LRR 3Sequence analysisAdd BLAST23
Repeati132 – 157LRR 4Sequence analysisAdd BLAST26
Repeati159 – 181LRR 5Sequence analysisAdd BLAST23
Repeati183 – 202LRR 6Sequence analysisAdd BLAST20
Repeati203 – 228LRR 7Sequence analysisAdd BLAST26
Repeati229 – 251LRR 8Sequence analysisAdd BLAST23
Repeati252 – 274LRR 9Sequence analysisAdd BLAST23
Repeati275 – 298LRR 10Sequence analysisAdd BLAST24
Domaini310 – 362LRRCTSequence analysisAdd BLAST53
Domaini419 – 517Fibronectin type-IIIPROSITE-ProRule annotationAdd BLAST99

Sequence similaritiesi

Contains 1 fibronectin type-III domain.PROSITE-ProRule annotation
Contains 10 LRR (leucine-rich) repeats.Sequence analysis1 Publication
Contains 1 LRRCT domain.Sequence analysis
Contains 1 LRRNT domain.Sequence analysis

Keywords - Domaini

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

Phylogenomic databases

eggNOGiENOG410IHC8. Eukaryota.
ENOG4111ID7. LUCA.
GeneTreeiENSGT00760000118969.
HOGENOMiHOG000290188.
HOVERGENiHBG051629.
KOiK16362.
OMAiFPAELHN.
OrthoDBiEOG091G05YU.
PhylomeDBiQ8BLU0.
TreeFamiTF315838.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
3.80.10.10. 3 hits.
InterProiIPR000483. Cys-rich_flank_reg_C.
IPR003961. FN3_dom.
IPR013783. Ig-like_fold.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000372. LRRNT.
[Graphical view]
PfamiPF00041. fn3. 1 hit.
PF13855. LRR_8. 3 hits.
PF01463. LRRCT. 1 hit.
[Graphical view]
SMARTiSM00369. LRR_TYP. 7 hits.
SM00082. LRRCT. 1 hit.
SM00013. LRRNT. 1 hit.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 1 hit.
SSF52058. SSF52058. 1 hit.
PROSITEiPS50853. FN3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q8BLU0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGLQTTKWPG RGAFILKFWL IISLGLYLQV SKLLACPSVC RCDRNFVYCN
60 70 80 90 100
ERSLTSVPLG IPEGVTVLYL HNNQINNAGF PAELHNVQSV HTVYLYGNQL
110 120 130 140 150
DEFPMNLPKN VRVLHLQENN IQTISRAALA QLLKLEELHL DDNSISTVGV
160 170 180 190 200
EDGAFREAIS LKLLFLSKNH LSSVPVGLPV DLQELRVDEN RIAVISDMAF
210 220 230 240 250
QNLTSLERLI VDGNLLTNKG IAEGTFSHLT KLKEFSIVRN SLSHPPPDLP
260 270 280 290 300
GTHLIRLYLQ DNQINHIPLT AFANLRKLER LDISNNQLRM LTQGVFDHLS
310 320 330 340 350
NLKQLTARNN PWFCDCSIKW VTEWLKYIPS SLNVRGFMCQ GPEQVRGMAV
360 370 380 390 400
RELNMNLLSC PTTTPGLPVF TPAPSTVSPT TQSPTLSVPS PSRGSVPPAP
410 420 430 440 450
TPSKLPTIPD WDGRERVTPP ISERIQLSIH FVNDTSIQVS WLSLFTVMAY
460 470 480 490 500
KLTWVKMGHS LVGGIVQERI VSGEKQHLSL VNLEPRSTYR ICLVPLDAFN
510 520 530 540 550
YRTVEDTICS EATTHASYLN NGSNTASSHE QTTSHSMGSP FLLAGLIGGA
560 570 580 590 600
VIFVLVVLLS VFCWHMHKKG RYTSQKWKYN RGRRKDDYCE AGTKKDNSIL
610 620 630 640 650
EMTETSFQIV SLNNDQLLKG DFRLQPIYTP NGGINYTDCH IPNNMRYCNS
660
SVPDLEHCHT
Length:660
Mass (Da):73,948
Last modified:March 1, 2003 - v1
Checksum:i5C1A9BBA3142C020
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY495669 mRNA. Translation: AAR92202.1.
AK041311 mRNA. Translation: BAC30900.1.
AK135149 mRNA. Translation: BAE22441.1.
AC122430 Genomic DNA. No translation available.
AC125487 Genomic DNA. No translation available.
CH466549 Genomic DNA. Translation: EDL18942.1.
BC096471 mRNA. Translation: AAH96471.1.
BC138297 mRNA. Translation: AAI38298.1.
BC138298 mRNA. Translation: AAI38299.1.
AK172945 mRNA. Translation: BAD32223.1.
CCDSiCCDS26094.1.
RefSeqiNP_958926.1. NM_201518.4.
XP_006516118.1. XM_006516055.3.
XP_011242434.1. XM_011244132.2.
UniGeneiMm.341948.

Genome annotation databases

EnsembliENSMUST00000057324; ENSMUSP00000062171; ENSMUSG00000047414.
ENSMUST00000110117; ENSMUSP00000105744; ENSMUSG00000047414.
GeneIDi399558.
KEGGimmu:399558.
UCSCiuc007olc.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY495669 mRNA. Translation: AAR92202.1.
AK041311 mRNA. Translation: BAC30900.1.
AK135149 mRNA. Translation: BAE22441.1.
AC122430 Genomic DNA. No translation available.
AC125487 Genomic DNA. No translation available.
CH466549 Genomic DNA. Translation: EDL18942.1.
BC096471 mRNA. Translation: AAH96471.1.
BC138297 mRNA. Translation: AAI38298.1.
BC138298 mRNA. Translation: AAI38299.1.
AK172945 mRNA. Translation: BAD32223.1.
CCDSiCCDS26094.1.
RefSeqiNP_958926.1. NM_201518.4.
XP_006516118.1. XM_006516055.3.
XP_011242434.1. XM_011244132.2.
UniGeneiMm.341948.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4V2CX-ray4.00A/C35-362[»]
4V2DX-ray2.50A36-361[»]
5FTTX-ray3.40B/F35-362[»]
5FTUX-ray6.01B/F/J35-362[»]
ProteinModelPortaliQ8BLU0.
SMRiQ8BLU0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-61401N.
STRINGi10090.ENSMUSP00000062171.

PTM databases

PhosphoSitePlusiQ8BLU0.

Proteomic databases

MaxQBiQ8BLU0.
PaxDbiQ8BLU0.
PRIDEiQ8BLU0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000057324; ENSMUSP00000062171; ENSMUSG00000047414.
ENSMUST00000110117; ENSMUSP00000105744; ENSMUSG00000047414.
GeneIDi399558.
KEGGimmu:399558.
UCSCiuc007olc.2. mouse.

Organism-specific databases

CTDi23768.
MGIiMGI:3603594. Flrt2.
RougeiSearch...

Phylogenomic databases

eggNOGiENOG410IHC8. Eukaryota.
ENOG4111ID7. LUCA.
GeneTreeiENSGT00760000118969.
HOGENOMiHOG000290188.
HOVERGENiHBG051629.
KOiK16362.
OMAiFPAELHN.
OrthoDBiEOG091G05YU.
PhylomeDBiQ8BLU0.
TreeFamiTF315838.

Enzyme and pathway databases

ReactomeiR-MMU-5654687. Downstream signaling of activated FGFR1.

Miscellaneous databases

ChiTaRSiFlrt2. mouse.
PROiQ8BLU0.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000047414.
GenevisibleiQ8BLU0. MM.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
3.80.10.10. 3 hits.
InterProiIPR000483. Cys-rich_flank_reg_C.
IPR003961. FN3_dom.
IPR013783. Ig-like_fold.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000372. LRRNT.
[Graphical view]
PfamiPF00041. fn3. 1 hit.
PF13855. LRR_8. 3 hits.
PF01463. LRRCT. 1 hit.
[Graphical view]
SMARTiSM00369. LRR_TYP. 7 hits.
SM00082. LRRCT. 1 hit.
SM00013. LRRNT. 1 hit.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 1 hit.
SSF52058. SSF52058. 1 hit.
PROSITEiPS50853. FN3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFLRT2_MOUSE
AccessioniPrimary (citable) accession number: Q8BLU0
Secondary accession number(s): Q6A073
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 14, 2015
Last sequence update: March 1, 2003
Last modified: November 2, 2016
This is version 137 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

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
  3. 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.