FLRT1_HUMAN
ID FLRT1_HUMAN Reviewed; 646 AA.
AC Q9NZU1; Q8WVA2;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 3.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Leucine-rich repeat transmembrane protein FLRT1;
DE AltName: Full=Fibronectin-like domain-containing leucine-rich transmembrane protein 1;
DE Flags: Precursor;
GN Name=FLRT1; ORFNames=UNQ752/PRO1483;
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].
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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).
CC -!- FUNCTION: Plays a role in fibroblast growth factor-mediated signaling
CC cascades that lead to the activation of MAP kinases. Promotes neurite
CC outgrowth via FGFR1-mediated activation of downstream MAP kinases.
CC Promotes an increase both in neurite number and in neurite length. May
CC play a role in cell-cell adhesion and cell guidance via its interaction
CC with ADGRL1/LPHN1 and ADGRL3. {ECO:0000250|UniProtKB:Q6RKD8}.
CC -!- SUBUNIT: Interacts with FGFR1. Interacts (via extracellular domain)
CC with ADGRL1/LPHN1 and ADGRL3 (via olfactomedin-like domain).
CC {ECO:0000250|UniProtKB:Q6RKD8}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q6RKD8};
CC Single-pass membrane protein {ECO:0000250|UniProtKB:Q6RKD8}.
CC Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q6RKD8}.
CC Cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:Q6RKD8}. Cytoplasm,
CC perinuclear region {ECO:0000250|UniProtKB:Q6RKD8}. Cell junction, focal
CC adhesion {ECO:0000250|UniProtKB:Q6RKD8}. Secreted
CC {ECO:0000250|UniProtKB:Q6RKD8}. Cell projection, neuron projection
CC {ECO:0000250|UniProtKB:Q6RKD8}. Cell junction
CC {ECO:0000250|UniProtKB:Q6RKD8}. Note=In addition to its location at the
CC cell membrane, colocalizes with FGFR1 in punctate perinuclear
CC cytoplasmic vesicles. Detected along neurites and at contacts between
CC neurite termini and other cells. Proteolytic cleavage gives rise to a
CC shedded ectodomain. {ECO:0000250|UniProtKB:Q6RKD8}.
CC -!- TISSUE SPECIFICITY: Expressed in kidney and brain.
CC {ECO:0000269|PubMed:10644439}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:10644439}.
CC -!- PTM: Phosphorylated in response to FGFR1 signaling, but is not a direct
CC substrate of FGFR1 or SRC. A mutant where the Tyr phosphorylation sites
CC have been replaced by Phe displays constitutive FGFR1-dependent
CC activation of downstream MAP kinases. {ECO:0000250|UniProtKB:Q6RKD8}.
CC -!- PTM: Proteolytic cleavage in the juxtamembrane region gives rise to a
CC soluble ectodomain. {ECO:0000250|UniProtKB:Q6RKD8}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF28459.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAH18370.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAQ88675.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAF82620.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=EAW74194.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF169675; AAF28459.1; ALT_INIT; mRNA.
DR EMBL; AY358308; AAQ88675.1; ALT_INIT; mRNA.
DR EMBL; AK289931; BAF82620.1; ALT_INIT; mRNA.
DR EMBL; AP006333; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471076; EAW74194.1; ALT_INIT; Genomic_DNA.
DR EMBL; BC018370; AAH18370.1; ALT_INIT; mRNA.
DR RefSeq; NP_037412.2; NM_013280.4.
DR RefSeq; XP_005273918.1; XM_005273861.1.
DR RefSeq; XP_011543185.1; XM_011544883.1.
DR AlphaFoldDB; Q9NZU1; -.
DR SMR; Q9NZU1; -.
DR BioGRID; 117269; 43.
DR IntAct; Q9NZU1; 19.
DR MINT; Q9NZU1; -.
DR STRING; 9606.ENSP00000246841; -.
DR GlyGen; Q9NZU1; 2 sites.
DR iPTMnet; Q9NZU1; -.
DR PhosphoSitePlus; Q9NZU1; -.
DR BioMuta; FLRT1; -.
DR DMDM; 215274159; -.
DR MassIVE; Q9NZU1; -.
DR MaxQB; Q9NZU1; -.
DR PaxDb; Q9NZU1; -.
DR PeptideAtlas; Q9NZU1; -.
DR PRIDE; Q9NZU1; -.
DR ProteomicsDB; 83510; -.
DR DNASU; 23769; -.
DR GeneID; 23769; -.
DR KEGG; hsa:23769; -.
DR UCSC; uc001nyi.2; human.
DR CTD; 23769; -.
DR DisGeNET; 23769; -.
DR GeneCards; FLRT1; -.
DR HGNC; HGNC:3760; FLRT1.
DR MalaCards; FLRT1; -.
DR MIM; 604806; gene.
DR neXtProt; NX_Q9NZU1; -.
DR Orphanet; 320406; Spastic paraplegia-optic atrophy-neuropathy syndrome.
DR PharmGKB; PA28177; -.
DR VEuPathDB; HostDB:ENSG00000126500; -.
DR eggNOG; ENOG502QWDS; Eukaryota.
DR HOGENOM; CLU_027624_0_0_1; -.
DR InParanoid; Q9NZU1; -.
DR OrthoDB; 826997at2759; -.
DR PhylomeDB; Q9NZU1; -.
DR TreeFam; TF331598; -.
DR PathwayCommons; Q9NZU1; -.
DR Reactome; R-HSA-5654687; Downstream signaling of activated FGFR1.
DR SignaLink; Q9NZU1; -.
DR BioGRID-ORCS; 23769; 10 hits in 1064 CRISPR screens.
DR GenomeRNAi; 23769; -.
DR Pharos; Q9NZU1; Tdark.
DR PRO; PR:Q9NZU1; -.
DR Proteomes; UP000005640; Unplaced.
DR RNAct; Q9NZU1; protein.
DR Genevisible; Q9NZU1; HS.
DR GO; GO:0005911; C:cell-cell junction; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:UniProtKB.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
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; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0044306; C:neuron projection terminus; ISS:UniProtKB.
DR GO; GO:0032809; C:neuronal cell body membrane; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; NAS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0016358; P:dendrite development; ISS:UniProtKB.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:1990138; P:neuron projection extension; ISS:UniProtKB.
DR CDD; cd00063; FN3; 1.
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; PF01462; LRRNT; 1.
DR SMART; SM00369; LRR_TYP; 8.
DR SMART; SM00082; LRRCT; 1.
DR SMART; SM00013; LRRNT; 1.
DR SUPFAM; SSF49265; SSF49265; 1.
DR PROSITE; PS50853; FN3; 1.
DR PROSITE; PS51450; LRR; 8.
PE 1: Evidence at protein level;
KW Cell adhesion; Cell junction; Cell membrane; Cell projection; Cytoplasm;
KW Cytoplasmic vesicle; Developmental protein; Disulfide bond;
KW Endoplasmic reticulum; Glycoprotein; Leucine-rich repeat; Membrane;
KW Phosphoprotein; Reference proteome; Repeat; Secreted; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..646
FT /note="Leucine-rich repeat transmembrane protein FLRT1"
FT /id="PRO_0000021278"
FT TOPO_DOM 21..524
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 525..545
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 546..646
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 21..53
FT /note="LRRNT"
FT REPEAT 54..75
FT /note="LRR 1"
FT REPEAT 79..99
FT /note="LRR 2"
FT REPEAT 100..121
FT /note="LRR 3"
FT REPEAT 124..145
FT /note="LRR 4"
FT REPEAT 150..171
FT /note="LRR 5"
FT REPEAT 172..192
FT /note="LRR 6"
FT REPEAT 195..218
FT /note="LRR 7"
FT REPEAT 221..241
FT /note="LRR 8"
FT REPEAT 243..264
FT /note="LRR 9"
FT REPEAT 267..288
FT /note="LRR 10"
FT DOMAIN 300..352
FT /note="LRRCT"
FT DOMAIN 409..504
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT CARBOHYD 221
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 277
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 26..32
FT /evidence="ECO:0000250|UniProtKB:Q8BGT1"
FT DISULFID 30..39
FT /evidence="ECO:0000250|UniProtKB:Q8BGT1"
FT DISULFID 304..329
FT /evidence="ECO:0000250|UniProtKB:Q8BGT1"
FT CONFLICT 568
FT /note="K -> E (in Ref. 1; AAF28459)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 646 AA; 71358 MW; 0F81FF7C9CA13129 CRC64;
MDLRDWLFLC YGLIAFLTEV IDSTTCPSVC RCDNGFIYCN DRGLTSIPAD IPDDATTLYL
QNNQINNAGI PQDLKTKVNV QVIYLYENDL DEFPINLPRS LRELHLQDNN VRTIARDSLA
RIPLLEKLHL DDNSVSTVSI EEDAFADSKQ LKLLFLSRNH LSSIPSGLPH TLEELRLDDN
RISTIPLHAF KGLNSLRRLV LDGNLLANQR IADDTFSRLQ NLTELSLVRN SLAAPPLNLP
SAHLQKLYLQ DNAISHIPYN TLAKMRELER LDLSNNNLTT LPRGLFDDLG NLAQLLLRNN
PWFCGCNLMW LRDWVKARAA VVNVRGLMCQ GPEKVRGMAI KDITSEMDEC FETGPQGGVA
NAAAKTTASN HASATTPQGS LFTLKAKRPG LRLPDSNIDY PMATGDGAKT LAIHVKALTA
DSIRITWKAT LPASSFRLSW LRLGHSPAVG SITETLVQGD KTEYLLTALE PKSTYIICMV
TMETSNAYVA DETPVCAKAE TADSYGPTTT LNQEQNAGPM ASLPLAGIIG GAVALVFLFL
VLGAICWYVH QAGELLTRER AYNRGSRKKD DYMESGTKKD NSILEIRGPG LQMLPINPYR
AKEEYVVHTI FPSNGSSLCK ATHTIGYGTT RGYRDGGIPD IDYSYT
