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Protein

Leucine-rich repeat transmembrane protein FLRT2

Gene

Flrt2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

GO - Biological processi

  • axon guidance Source: MGI
  • basement membrane organization Source: UniProtKB
  • cell adhesion involved in heart morphogenesis Source: UniProtKB
  • fibroblast growth factor receptor signaling pathway Source: UniProtKB
  • heart morphogenesis Source: UniProtKB
  • positive regulation of synapse assembly Source: MGI
  • regulation of neuron migration Source: MGI

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

Organism-specific databases

MGIiMGI:3603594 Flrt2

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 domaini36 – 540ExtracellularCuratedAdd BLAST505
Transmembranei541 – 561HelicalSequence analysisAdd BLAST21
Topological domaini562 – 660CytoplasmicCuratedAdd BLAST99

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...) asparagineSequence 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

iPTMnetiQ8BLU0
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 Expressed in 250 organ(s), highest expression level in rostral migratory stream
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

Binary interactionsi

WithEntry#Exp.IntActNotes
Adgrl3Q80TS32EBI-16146541,EBI-770665

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-61401N
IntActiQ8BLU0, 1 interactor
STRINGi10090.ENSMUSP00000062171

Structurei

Secondary structure

1660
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Keywords - Domaini

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

Phylogenomic databases

eggNOGiENOG410IHC8 Eukaryota
ENOG4111ID7 LUCA
GeneTreeiENSGT00920000148996
HOGENOMiHOG000290188
HOVERGENiHBG051629
InParanoidiQ8BLU0
KOiK16362
OMAiAYCKSSN
OrthoDBiEOG091G05YU
PhylomeDBiQ8BLU0
TreeFamiTF315838

Family and domain databases

Gene3Di2.60.40.10, 1 hit
3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR000483 Cys-rich_flank_reg_C
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR013783 Ig-like_fold
IPR001611 Leu-rich_rpt
IPR003591 Leu-rich_rpt_typical-subtyp
IPR032675 LRR_dom_sf
IPR000372 LRRNT
PfamiView protein in Pfam
PF00041 fn3, 1 hit
PF13855 LRR_8, 3 hits
PF01463 LRRCT, 1 hit
SMARTiView protein in SMART
SM00369 LRR_TYP, 7 hits
SM00082 LRRCT, 1 hit
SM00013 LRRNT, 1 hit
SUPFAMiSSF49265 SSF49265, 1 hit
PROSITEiView protein in PROSITE
PS50853 FN3, 1 hit

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

Similar proteinsi

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
IntActiQ8BLU0, 1 interactor
STRINGi10090.ENSMUSP00000062171

PTM databases

iPTMnetiQ8BLU0
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
GeneTreeiENSGT00920000148996
HOGENOMiHOG000290188
HOVERGENiHBG051629
InParanoidiQ8BLU0
KOiK16362
OMAiAYCKSSN
OrthoDBiEOG091G05YU
PhylomeDBiQ8BLU0
TreeFamiTF315838

Enzyme and pathway databases

ReactomeiR-MMU-5654687 Downstream signaling of activated FGFR1

Miscellaneous databases

ChiTaRSiFlrt2 mouse
PROiPR:Q8BLU0
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000047414 Expressed in 250 organ(s), highest expression level in rostral migratory stream
GenevisibleiQ8BLU0 MM

Family and domain databases

Gene3Di2.60.40.10, 1 hit
3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR000483 Cys-rich_flank_reg_C
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR013783 Ig-like_fold
IPR001611 Leu-rich_rpt
IPR003591 Leu-rich_rpt_typical-subtyp
IPR032675 LRR_dom_sf
IPR000372 LRRNT
PfamiView protein in Pfam
PF00041 fn3, 1 hit
PF13855 LRR_8, 3 hits
PF01463 LRRCT, 1 hit
SMARTiView protein in SMART
SM00369 LRR_TYP, 7 hits
SM00082 LRRCT, 1 hit
SM00013 LRRNT, 1 hit
SUPFAMiSSF49265 SSF49265, 1 hit
PROSITEiView protein in PROSITE
PS50853 FN3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiFLRT2_MOUSE
AccessioniPrimary (citable) accession number: Q8BLU0
Secondary accession number(s): Q6A073
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 14, 2015
Last sequence update: March 1, 2003
Last modified: November 7, 2018
This is version 147 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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