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 13-FEB-2019, entry version 171. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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 RT transmembrane 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. RT 78 new cDNA clones from brain which code for large proteins in RT 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., RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., RA Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale RT effort to identify novel human secreted and transmembrane proteins: a RT bioinformatics 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 RT project: 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 RT verified 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 RT multiple 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 CC ADGRL3 and probably also other latrophilins that are expressed at CC the surface of adjacent cells. May play a role in the migration of CC cortical neurons during brain development via its interaction with CC UNC5D. Mediates axon growth cone collapse and plays a repulsive CC role in neuron guidance via its interaction with UNC5D, and CC possibly also other UNC-5 family members. Plays a role in CC fibroblast growth factor-mediated signaling cascades. Required for CC normal organization of the cardiac basement membrane during CC embryogenesis, and for normal embryonic epicardium and heart CC morphogenesis. {ECO:0000250|UniProtKB:Q8BLU0}. CC -!- SUBUNIT: Self-associates (via leucine-rich repeats), giving rise CC to homooligomers. Interacts with FGFR1. Interacts with FGFR2. CC Interacts (via extracellular domain) with ADGRL1/LPHN1. Interacts CC (via extracellular domain) with ADGRL3 (via olfactomedin-like CC domain). Interacts (via extracellular domain) with UNC5D (via the CC first Ig-like domain). Can also interact (via extracellular CC domain) with UNC5B, but with much lower affinity. Interacts (via CC extracellular domain) with FN1. {ECO:0000250|UniProtKB:Q8BLU0}. CC -!- SUBCELLULAR LOCATION: Cell membrane CC {ECO:0000250|UniProtKB:Q8BLU0}; Single-pass membrane protein CC {ECO:0000250|UniProtKB:Q8BLU0}. Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:Q8BLU0}. Cell junction, focal adhesion CC {ECO:0000250|UniProtKB:Q8BLU0}. Secreted, extracellular space, CC extracellular matrix {ECO:0000250|UniProtKB:Q8BLU0}. Microsome CC membrane {ECO:0000250|UniProtKB:Q8BLU0}. Secreted CC {ECO:0000250|UniProtKB:Q8BLU0}. Cell junction, synapse, CC synaptosome {ECO:0000250|UniProtKB:D3ZTV3}. Note=Proteolytic CC cleavage gives rise to a shedded ectodomain. CC {ECO:0000250|UniProtKB:Q8BLU0}. CC -!- TISSUE SPECIFICITY: Expressed in pancreas, skeletal muscle, brain, CC and 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 CC to a soluble ectodomain. Cleavage is probably effected by a CC metalloprotease. {ECO:0000250|UniProtKB:Q8BLU0}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA23701.2; Type=Erroneous initiation; Evidence={ECO:0000305}; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- 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 UniGene; Hs.533710; -. DR UniGene; Hs.624735; -. DR UniGene; Hs.680351; -. DR UniGene; Hs.729224; -. DR UniGene; Hs.744139; -. DR ProteinModelPortal; O43155; -. DR SMR; O43155; -. DR BioGrid; 117268; 1. DR IntAct; O43155; 3. DR MINT; O43155; -. DR STRING; 9606.ENSP00000332879; -. DR iPTMnet; O43155; -. DR PhosphoSitePlus; O43155; -. DR BioMuta; FLRT2; -. DR EPD; O43155; -. DR jPOST; O43155; -. DR PaxDb; O43155; -. DR PeptideAtlas; O43155; -. DR PRIDE; O43155; -. DR ProteomicsDB; 48775; -. DR DNASU; 23768; -. DR Ensembl; ENST00000330753; ENSP00000332879; ENSG00000185070. DR Ensembl; ENST00000554746; ENSP00000451050; ENSG00000185070. DR GeneID; 23768; -. DR KEGG; hsa:23768; -. DR UCSC; uc001xvr.4; human. DR CTD; 23768; -. DR DisGeNET; 23768; -. DR EuPathDB; HostDB:ENSG00000185070.10; -. DR GeneCards; FLRT2; -. DR H-InvDB; HIX0172397; -. DR HGNC; HGNC:3761; FLRT2. DR MIM; 604807; gene. DR neXtProt; NX_O43155; -. DR OpenTargets; ENSG00000185070; -. DR PharmGKB; PA28178; -. DR eggNOG; ENOG410IHC8; Eukaryota. DR eggNOG; ENOG4111ID7; LUCA. DR GeneTree; ENSGT00940000158937; -. DR HOGENOM; HOG000290188; -. DR HOVERGEN; HBG051629; -. DR InParanoid; O43155; -. DR KO; K16362; -. DR OMA; AYCKSSN; -. DR OrthoDB; 826997at2759; -. DR PhylomeDB; O43155; -. DR TreeFam; TF315838; -. DR Reactome; R-HSA-5654687; Downstream signaling of activated FGFR1. DR ChiTaRS; FLRT2; human. DR GeneWiki; FLRT2; -. DR GenomeRNAi; 23768; -. DR PRO; PR:O43155; -. DR Proteomes; UP000005640; Chromosome 14. DR Bgee; ENSG00000185070; Expressed in 228 organ(s), highest expression level in neocortex. 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: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-SubCell. DR GO; GO:0031090; C:organelle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0045202; C:synapse; IEA:UniProtKB-KW. 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 binding, bridging; 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; Complete proteome; KW Developmental protein; Direct protein sequencing; Disulfide bond; KW Endoplasmic reticulum; Extracellular matrix; Glycoprotein; KW Leucine-rich repeat; Membrane; Microsome; Polymorphism; KW Reference proteome; Repeat; Secreted; Signal; Synapse; Synaptosome; KW Transmembrane; Transmembrane helix. FT SIGNAL 1 35 {ECO:0000269|PubMed:15340161}. FT CHAIN 36 660 Leucine-rich repeat transmembrane protein FT FLRT2. FT /FTId=PRO_0000021279. FT TOPO_DOM 36 541 Extracellular. {ECO:0000255}. FT TRANSMEM 542 562 Helical. {ECO:0000255}. FT TOPO_DOM 563 660 Cytoplasmic. {ECO:0000255}. FT DOMAIN 36 63 LRRNT. FT REPEAT 64 85 LRR 1. FT REPEAT 89 109 LRR 2. FT REPEAT 110 131 LRR 3. FT REPEAT 134 155 LRR 4. FT REPEAT 160 181 LRR 5. FT REPEAT 182 202 LRR 6. FT REPEAT 205 225 LRR 7. FT REPEAT 231 252 LRR 8. FT REPEAT 253 274 LRR 9. FT REPEAT 277 298 LRR 10. FT DOMAIN 310 362 LRRCT. FT DOMAIN 419 517 Fibronectin type-III. FT {ECO:0000255|PROSITE-ProRule:PRU00316}. FT CARBOHYD 202 202 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:19159218}. FT CARBOHYD 298 298 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 433 433 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 521 521 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 36 42 {ECO:0000250|UniProtKB:Q8BGT1}. FT DISULFID 40 49 {ECO:0000250|UniProtKB:Q8BGT1}. FT DISULFID 314 339 {ECO:0000250|UniProtKB:Q8BGT1}. FT DISULFID 316 360 {ECO:0000250|UniProtKB:Q8BLU0}. FT VARIANT 486 486 R -> Q (in dbSNP:rs17646457). FT {ECO:0000269|PubMed:15489334}. FT /FTId=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 //