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Protein

Leucine-rich repeat transmembrane protein FLRT2

Gene

FLRT2

Organism
Homo sapiens (Human)
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. May play a role in the migration of cortical neurons during brain development via its interaction with UNC5D. 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. Plays a role in fibroblast growth factor-mediated signaling cascades. Required for normal organization of the cardiac basement membrane during embryogenesis, and for normal embryonic epicardium and heart morphogenesis.By similarity

GO - Molecular functioni

  • chemorepellent activity Source: Ensembl
  • protein binding, bridging Source: UniProtKB
  • protein kinase inhibitor activity Source: GO_Central
  • receptor signaling protein activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Cell adhesion

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Leucine-rich repeat transmembrane protein FLRT2
Alternative name(s):
Fibronectin-like domain-containing leucine-rich transmembrane protein 2
Gene namesi
Name:FLRT2
Synonyms:KIAA0405
ORF Names:UNQ232/PRO265
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:3761. FLRT2.

Subcellular locationi

  • Cell membrane By similarity; Single-pass membrane protein By similarity
  • Endoplasmic reticulum membrane By similarity
  • Cell junctionfocal adhesion By similarity
  • Secretedextracellular spaceextracellular matrix By similarity
  • Microsome membrane By similarity
  • Secreted By similarity
  • Cell junctionsynapsesynaptosome By similarity

  • Note: Proteolytic cleavage gives rise to a shedded ectodomain.By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini36 – 541506ExtracellularSequence analysisAdd
BLAST
Transmembranei542 – 56221HelicalSequence analysisAdd
BLAST
Topological domaini563 – 66098CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • cell-cell junction Source: UniProtKB
  • cytoplasm Source: GO_Central
  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • extracellular exosome Source: UniProtKB
  • extracellular space Source: Ensembl
  • focal adhesion Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • neuron projection Source: UniProtKB-SubCell
  • plasma membrane Source: Reactome
  • proteinaceous extracellular matrix Source: UniProtKB
  • 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

Organism-specific databases

PharmGKBiPA28178.

Polymorphism and mutation databases

BioMutaiFLRT2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 35351 PublicationAdd
BLAST
Chaini36 – 660625Leucine-rich repeat transmembrane protein FLRT2PRO_0000021279Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi36 ↔ 42By similarity
Disulfide bondi40 ↔ 49By similarity
Glycosylationi202 – 2021N-linked (GlcNAc...)1 Publication
Glycosylationi298 – 2981N-linked (GlcNAc...)Sequence analysis
Disulfide bondi314 ↔ 339By similarity
Disulfide bondi316 ↔ 360By similarity
Glycosylationi433 – 4331N-linked (GlcNAc...)Sequence analysis
Glycosylationi521 – 5211N-linked (GlcNAc...)Sequence analysis

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.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiO43155.
PaxDbiO43155.
PRIDEiO43155.

PTM databases

iPTMnetiO43155.
PhosphoSiteiO43155.

Expressioni

Tissue specificityi

Expressed in pancreas, skeletal muscle, brain, and heart.1 Publication

Gene expression databases

BgeeiO43155.
CleanExiHS_FLRT2.
GenevisibleiO43155. HS.

Interactioni

Subunit structurei

Self-associates (via leucine-rich repeats), giving rise to homooligomers. Interacts with FGFR1. Interacts with FGFR2. Interacts (via extracellular domain) with ADGRL1/LPHN1. Interacts (via extracellular domain) with ADGRL3 (via olfactomedin-like domain). Interacts (via extracellular domain) with UNC5D (via the first Ig-like domain). Can also interact (via extracellular domain) with UNC5B, but with much lower affinity. Interacts (via extracellular domain) with FN1.By similarity

GO - Molecular functioni

  • protein binding, bridging Source: UniProtKB

Protein-protein interaction databases

BioGridi117268. 1 interaction.
IntActiO43155. 3 interactions.
MINTiMINT-1778460.
STRINGi9606.ENSP00000332879.

Structurei

3D structure databases

ProteinModelPortaliO43155.
SMRiO43155. Positions 35-374.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini36 – 6328LRRNTAdd
BLAST
Repeati64 – 8522LRR 1Add
BLAST
Repeati89 – 10921LRR 2Add
BLAST
Repeati110 – 13122LRR 3Add
BLAST
Repeati134 – 15522LRR 4Add
BLAST
Repeati160 – 18122LRR 5Add
BLAST
Repeati182 – 20221LRR 6Add
BLAST
Repeati205 – 22521LRR 7Add
BLAST
Repeati231 – 25222LRR 8Add
BLAST
Repeati253 – 27422LRR 9Add
BLAST
Repeati277 – 29822LRR 10Add
BLAST
Domaini310 – 36253LRRCTAdd
BLAST
Domaini419 – 51799Fibronectin type-IIIPROSITE-ProRule annotationAdd
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

eggNOGiENOG410IHC8. Eukaryota.
ENOG4111ID7. LUCA.
GeneTreeiENSGT00760000118969.
HOGENOMiHOG000290188.
HOVERGENiHBG051629.
InParanoidiO43155.
KOiK16362.
OMAiFPAELHN.
OrthoDBiEOG7RZ5PF.
PhylomeDBiO43155.
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.

O43155-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGLQTTKWPS HGAFFLKSWL IISLGLYSQV 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 AFSNLRKLER LDISNNQLRM LTQGVFDNLS
310 320 330 340 350
NLKQLTARNN PWFCDCSIKW VTEWLKYIPS SLNVRGFMCQ GPEQVRGMAV
360 370 380 390 400
RELNMNLLSC PTTTPGLPLF TPAPSTASPT TQPPTLSIPN PSRSYTPPTP
410 420 430 440 450
TTSKLPTIPD WDGRERVTPP ISERIQLSIH FVNDTSIQVS WLSLFTVMAY
460 470 480 490 500
KLTWVKMGHS LVGGIVQERI VSGEKQHLSL VNLEPRSTYR ICLVPLDAFN
510 520 530 540 550
YRAVEDTICS 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):74,049
Last modified:June 1, 1998 - v1
Checksum:i9B15F283B0D5F778
GO

Sequence cautioni

The sequence BAA23701.2 differs from that shown. Reason: Erroneous initiation. Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti486 – 4861R → Q.1 Publication
Corresponds to variant rs17646457 [ dbSNP | Ensembl ].
VAR_050996

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF169676 mRNA. Translation: AAF28460.1.
AY358287 mRNA. Translation: AAQ88654.1.
AB007865 mRNA. Translation: BAA23701.2. Different initiation.
BC126249 mRNA. Translation: AAI26250.1.
BC130290 mRNA. Translation: AAI30291.1.
BC143936 mRNA. Translation: AAI43937.1.
CCDSiCCDS9877.1.
RefSeqiNP_037363.1. NM_013231.4.
XP_005267547.1. XM_005267490.2.
XP_011534913.1. XM_011536611.1.
UniGeneiHs.533710.
Hs.624735.
Hs.744139.

Genome annotation databases

EnsembliENST00000330753; ENSP00000332879; ENSG00000185070.
ENST00000554746; ENSP00000451050; ENSG00000185070.
GeneIDi23768.
KEGGihsa:23768.
UCSCiuc001xvr.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF169676 mRNA. Translation: AAF28460.1.
AY358287 mRNA. Translation: AAQ88654.1.
AB007865 mRNA. Translation: BAA23701.2. Different initiation.
BC126249 mRNA. Translation: AAI26250.1.
BC130290 mRNA. Translation: AAI30291.1.
BC143936 mRNA. Translation: AAI43937.1.
CCDSiCCDS9877.1.
RefSeqiNP_037363.1. NM_013231.4.
XP_005267547.1. XM_005267490.2.
XP_011534913.1. XM_011536611.1.
UniGeneiHs.533710.
Hs.624735.
Hs.744139.

3D structure databases

ProteinModelPortaliO43155.
SMRiO43155. Positions 35-374.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117268. 1 interaction.
IntActiO43155. 3 interactions.
MINTiMINT-1778460.
STRINGi9606.ENSP00000332879.

PTM databases

iPTMnetiO43155.
PhosphoSiteiO43155.

Polymorphism and mutation databases

BioMutaiFLRT2.

Proteomic databases

EPDiO43155.
PaxDbiO43155.
PRIDEiO43155.

Protocols and materials databases

DNASUi23768.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000330753; ENSP00000332879; ENSG00000185070.
ENST00000554746; ENSP00000451050; ENSG00000185070.
GeneIDi23768.
KEGGihsa:23768.
UCSCiuc001xvr.4. human.

Organism-specific databases

CTDi23768.
GeneCardsiFLRT2.
H-InvDBHIX0172397.
HGNCiHGNC:3761. FLRT2.
MIMi604807. gene.
neXtProtiNX_O43155.
PharmGKBiPA28178.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IHC8. Eukaryota.
ENOG4111ID7. LUCA.
GeneTreeiENSGT00760000118969.
HOGENOMiHOG000290188.
HOVERGENiHBG051629.
InParanoidiO43155.
KOiK16362.
OMAiFPAELHN.
OrthoDBiEOG7RZ5PF.
PhylomeDBiO43155.
TreeFamiTF315838.

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiFLRT2. human.
GeneWikiiFLRT2.
GenomeRNAii23768.
PROiO43155.
SOURCEiSearch...

Gene expression databases

BgeeiO43155.
CleanExiHS_FLRT2.
GenevisibleiO43155. HS.

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...

Publicationsi

« Hide 'large scale' publications
  1. "Identification of FLRT1, FLRT2, and FLRT3: a novel family of transmembrane leucine-rich repeat proteins."
    Lacy S.E., Bonnemann C.G., Buzney E.A., Kunkel L.M.
    Genomics 62:417-426(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, GLYCOSYLATION.
  2. "Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro."
    Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
    DNA Res. 4:307-313(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  4. "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], VARIANT GLN-486.
    Tissue: Brain and Cerebellum.
  5. "Signal peptide prediction based on analysis of experimentally verified cleavage sites."
    Zhang Z., Henzel W.J.
    Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 36-50.
  6. "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
    Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
    J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-202.
    Tissue: Liver.

Entry informationi

Entry nameiFLRT2_HUMAN
AccessioniPrimary (citable) accession number: O43155
Secondary accession number(s): A0AV84, B7ZLP3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: June 1, 1998
Last modified: June 8, 2016
This is version 151 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.