FLRT2_HUMAN
ID FLRT2_HUMAN Reviewed; 660 AA.
AC O43155; A0AV84; B7ZLP3;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Leucine-rich repeat transmembrane protein FLRT2;
DE AltName: Full=Fibronectin-like domain-containing leucine-rich transmembrane protein 2;
DE Flags: Precursor;
GN Name=FLRT2; Synonyms=KIAA0405; ORFNames=UNQ232/PRO265;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND GLYCOSYLATION.
RX PubMed=10644439; DOI=10.1006/geno.1999.6033;
RA Lacy S.E., Bonnemann C.G., Buzney E.A., Kunkel L.M.;
RT "Identification of FLRT1, FLRT2, and FLRT3: a novel family of transmembrane
RT leucine-rich repeat proteins.";
RL Genomics 62:417-426(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=9455477; DOI=10.1093/dnares/4.5.307;
RA Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. VIII. 78
RT new cDNA clones from brain which code for large proteins in vitro.";
RL DNA Res. 4:307-313(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLN-486.
RC TISSUE=Brain, and Cerebellum;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 36-50.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [6]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-202.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
CC -!- FUNCTION: Functions in cell-cell adhesion, cell migration and axon
CC guidance. Mediates cell-cell adhesion via its interactions with ADGRL3
CC and probably also other latrophilins that are expressed at the surface
CC of adjacent cells. May play a role in the migration of cortical neurons
CC during brain development via its interaction with UNC5D. Mediates axon
CC growth cone collapse and plays a repulsive role in neuron guidance via
CC its interaction with UNC5D, and possibly also other UNC-5 family
CC members. Plays a role in fibroblast growth factor-mediated signaling
CC cascades. Required for normal organization of the cardiac basement
CC membrane during embryogenesis, and for normal embryonic epicardium and
CC heart morphogenesis. {ECO:0000250|UniProtKB:Q8BLU0}.
CC -!- SUBUNIT: Self-associates (via leucine-rich repeats), giving rise to
CC homooligomers. Interacts with FGFR1. Interacts with FGFR2. Interacts
CC (via extracellular domain) with ADGRL1/LPHN1. Interacts (via
CC extracellular domain) with ADGRL3 (via olfactomedin-like domain).
CC Interacts (via extracellular domain) with UNC5D (via the first Ig-like
CC domain). Can also interact (via extracellular domain) with UNC5B, but
CC with much lower affinity. Interacts (via extracellular domain) with
CC FN1. {ECO:0000250|UniProtKB:Q8BLU0}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8BLU0};
CC Single-pass membrane protein {ECO:0000250|UniProtKB:Q8BLU0}.
CC Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q8BLU0}. Cell
CC junction, focal adhesion {ECO:0000250|UniProtKB:Q8BLU0}. Secreted,
CC extracellular space, extracellular matrix
CC {ECO:0000250|UniProtKB:Q8BLU0}. Microsome membrane
CC {ECO:0000250|UniProtKB:Q8BLU0}. Secreted
CC {ECO:0000250|UniProtKB:Q8BLU0}. Synapse, synaptosome
CC {ECO:0000250|UniProtKB:D3ZTV3}. Note=Proteolytic cleavage gives rise to
CC a shedded ectodomain. {ECO:0000250|UniProtKB:Q8BLU0}.
CC -!- TISSUE SPECIFICITY: Expressed in pancreas, skeletal muscle, brain, and
CC heart. {ECO:0000269|PubMed:10644439}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:10644439,
CC ECO:0000269|PubMed:19159218}.
CC -!- PTM: Proteolytic cleavage in the juxtamembrane region gives rise to a
CC soluble ectodomain. Cleavage is probably effected by a metalloprotease.
CC {ECO:0000250|UniProtKB:Q8BLU0}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA23701.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF169676; AAF28460.1; -; mRNA.
DR EMBL; AY358287; AAQ88654.1; -; mRNA.
DR EMBL; AB007865; BAA23701.2; ALT_INIT; mRNA.
DR EMBL; BC126249; AAI26250.1; -; mRNA.
DR EMBL; BC130290; AAI30291.1; -; mRNA.
DR EMBL; BC143936; AAI43937.1; -; mRNA.
DR CCDS; CCDS9877.1; -.
DR RefSeq; NP_001333072.1; NM_001346143.1.
DR RefSeq; NP_001333073.1; NM_001346144.1.
DR RefSeq; NP_001333074.1; NM_001346145.1.
DR RefSeq; NP_001333075.1; NM_001346146.1.
DR RefSeq; NP_037363.1; NM_013231.5.
DR RefSeq; XP_005267547.1; XM_005267490.3.
DR RefSeq; XP_011534913.1; XM_011536611.2.
DR RefSeq; XP_016876618.1; XM_017021129.1.
DR RefSeq; XP_016876619.1; XM_017021130.1.
DR RefSeq; XP_016876620.1; XM_017021131.1.
DR RefSeq; XP_016876621.1; XM_017021132.1.
DR RefSeq; XP_016876622.1; XM_017021133.1.
DR RefSeq; XP_016876623.1; XM_017021134.1.
DR RefSeq; XP_016876624.1; XM_017021135.1.
DR AlphaFoldDB; O43155; -.
DR SMR; O43155; -.
DR BioGRID; 117268; 19.
DR IntAct; O43155; 4.
DR MINT; O43155; -.
DR STRING; 9606.ENSP00000332879; -.
DR GlyGen; O43155; 5 sites, 1 O-linked glycan (1 site).
DR iPTMnet; O43155; -.
DR PhosphoSitePlus; O43155; -.
DR BioMuta; FLRT2; -.
DR EPD; O43155; -.
DR jPOST; O43155; -.
DR MassIVE; O43155; -.
DR PaxDb; O43155; -.
DR PeptideAtlas; O43155; -.
DR PRIDE; O43155; -.
DR ProteomicsDB; 48775; -.
DR Antibodypedia; 55194; 73 antibodies from 16 providers.
DR DNASU; 23768; -.
DR Ensembl; ENST00000330753.6; ENSP00000332879.4; ENSG00000185070.12.
DR Ensembl; ENST00000554746.1; ENSP00000451050.1; ENSG00000185070.12.
DR Ensembl; ENST00000682132.1; ENSP00000507088.1; ENSG00000185070.12.
DR Ensembl; ENST00000683129.1; ENSP00000507815.1; ENSG00000185070.12.
DR GeneID; 23768; -.
DR KEGG; hsa:23768; -.
DR MANE-Select; ENST00000330753.6; ENSP00000332879.4; NM_013231.6; NP_037363.1.
DR UCSC; uc001xvr.4; human.
DR CTD; 23768; -.
DR DisGeNET; 23768; -.
DR GeneCards; FLRT2; -.
DR HGNC; HGNC:3761; FLRT2.
DR HPA; ENSG00000185070; Tissue enhanced (ovary, pancreas).
DR MIM; 604807; gene.
DR neXtProt; NX_O43155; -.
DR OpenTargets; ENSG00000185070; -.
DR PharmGKB; PA28178; -.
DR VEuPathDB; HostDB:ENSG00000185070; -.
DR eggNOG; ENOG502QSJU; Eukaryota.
DR GeneTree; ENSGT00940000158937; -.
DR HOGENOM; CLU_027624_0_0_1; -.
DR InParanoid; O43155; -.
DR OMA; PTVPDWD; -.
DR OrthoDB; 826997at2759; -.
DR PhylomeDB; O43155; -.
DR TreeFam; TF315838; -.
DR PathwayCommons; O43155; -.
DR Reactome; R-HSA-5654687; Downstream signaling of activated FGFR1.
DR SignaLink; O43155; -.
DR BioGRID-ORCS; 23768; 11 hits in 1070 CRISPR screens.
DR ChiTaRS; FLRT2; human.
DR GeneWiki; FLRT2; -.
DR GenomeRNAi; 23768; -.
DR Pharos; O43155; Tbio.
DR PRO; PR:O43155; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; O43155; protein.
DR Bgee; ENSG00000185070; Expressed in germinal epithelium of ovary and 195 other tissues.
DR Genevisible; O43155; HS.
DR GO; GO:0005911; C:cell-cell junction; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; NAS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
DR GO; GO:0045499; F:chemorepellent activity; IEA:Ensembl.
DR GO; GO:0005104; F:fibroblast growth factor receptor binding; IEA:Ensembl.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; NAS:UniProtKB.
DR GO; GO:0007411; P:axon guidance; IEA:Ensembl.
DR GO; GO:0071711; P:basement membrane organization; ISS:UniProtKB.
DR GO; GO:0061343; P:cell adhesion involved in heart morphogenesis; ISS:UniProtKB.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0003007; P:heart morphogenesis; ISS:UniProtKB.
DR GO; GO:0051965; P:positive regulation of synapse assembly; IEA:Ensembl.
DR GO; GO:2001222; P:regulation of neuron migration; IEA:Ensembl.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR000483; Cys-rich_flank_reg_C.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR000372; LRRNT.
DR Pfam; PF13855; LRR_8; 3.
DR Pfam; PF01463; LRRCT; 1.
DR SMART; SM00369; LRR_TYP; 7.
DR SMART; SM00082; LRRCT; 1.
DR SMART; SM00013; LRRNT; 1.
DR SUPFAM; SSF49265; SSF49265; 1.
DR PROSITE; PS50853; FN3; 1.
PE 1: Evidence at protein level;
KW Cell adhesion; Cell junction; Cell membrane; Developmental protein;
KW Direct protein sequencing; Disulfide bond; Endoplasmic reticulum;
KW Extracellular matrix; Glycoprotein; Leucine-rich repeat; Membrane;
KW Microsome; Reference proteome; Repeat; Secreted; Signal; Synapse;
KW Synaptosome; Transmembrane; Transmembrane helix.
FT SIGNAL 1..35
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 36..660
FT /note="Leucine-rich repeat transmembrane protein FLRT2"
FT /id="PRO_0000021279"
FT TOPO_DOM 36..541
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 542..562
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 563..660
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 36..63
FT /note="LRRNT"
FT REPEAT 64..85
FT /note="LRR 1"
FT REPEAT 89..109
FT /note="LRR 2"
FT REPEAT 110..131
FT /note="LRR 3"
FT REPEAT 134..155
FT /note="LRR 4"
FT REPEAT 160..181
FT /note="LRR 5"
FT REPEAT 182..202
FT /note="LRR 6"
FT REPEAT 205..225
FT /note="LRR 7"
FT REPEAT 231..252
FT /note="LRR 8"
FT REPEAT 253..274
FT /note="LRR 9"
FT REPEAT 277..298
FT /note="LRR 10"
FT DOMAIN 310..362
FT /note="LRRCT"
FT DOMAIN 419..517
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 373..413
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 202
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 298
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 433
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 521
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 36..42
FT /evidence="ECO:0000250|UniProtKB:Q8BGT1"
FT DISULFID 40..49
FT /evidence="ECO:0000250|UniProtKB:Q8BGT1"
FT DISULFID 314..339
FT /evidence="ECO:0000250|UniProtKB:Q8BGT1"
FT DISULFID 316..360
FT /evidence="ECO:0000250|UniProtKB:Q8BLU0"
FT VARIANT 486
FT /note="R -> Q (in dbSNP:rs17646457)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_050996"
SQ SEQUENCE 660 AA; 74049 MW; 9B15F283B0D5F778 CRC64;
MGLQTTKWPS HGAFFLKSWL IISLGLYSQV SKLLACPSVC RCDRNFVYCN ERSLTSVPLG
IPEGVTVLYL HNNQINNAGF PAELHNVQSV HTVYLYGNQL DEFPMNLPKN VRVLHLQENN
IQTISRAALA QLLKLEELHL DDNSISTVGV EDGAFREAIS LKLLFLSKNH LSSVPVGLPV
DLQELRVDEN RIAVISDMAF QNLTSLERLI VDGNLLTNKG IAEGTFSHLT KLKEFSIVRN
SLSHPPPDLP GTHLIRLYLQ DNQINHIPLT AFSNLRKLER LDISNNQLRM LTQGVFDNLS
NLKQLTARNN PWFCDCSIKW VTEWLKYIPS SLNVRGFMCQ GPEQVRGMAV RELNMNLLSC
PTTTPGLPLF TPAPSTASPT TQPPTLSIPN PSRSYTPPTP TTSKLPTIPD WDGRERVTPP
ISERIQLSIH FVNDTSIQVS WLSLFTVMAY KLTWVKMGHS LVGGIVQERI VSGEKQHLSL
VNLEPRSTYR ICLVPLDAFN YRAVEDTICS EATTHASYLN NGSNTASSHE QTTSHSMGSP
FLLAGLIGGA VIFVLVVLLS VFCWHMHKKG RYTSQKWKYN RGRRKDDYCE AGTKKDNSIL
EMTETSFQIV SLNNDQLLKG DFRLQPIYTP NGGINYTDCH IPNNMRYCNS SVPDLEHCHT
