FLRT3_HUMAN
ID FLRT3_HUMAN Reviewed; 649 AA.
AC Q9NZU0; D3DW20; Q542Z9; Q96K39; Q96K42; Q96KB1; Q9P259;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=Leucine-rich repeat transmembrane protein FLRT3;
DE AltName: Full=Fibronectin-like domain-containing leucine-rich transmembrane protein 3;
DE Flags: Precursor;
GN Name=FLRT3; Synonyms=KIAA1469; ORFNames=UNQ856/PRO1865;
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], AND TISSUE SPECIFICITY.
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=10819331; DOI=10.1093/dnares/7.2.143;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:143-150(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLN-400.
RC TISSUE=Embryo, and Teratocarcinoma;
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 MRNA], AND VARIANT GLN-400.
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLN-400.
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=14706654; DOI=10.1016/j.bbrc.2003.12.047;
RA Tsuji L., Yamashita T., Kubo T., Madura T., Tanaka H., Hosokawa K.,
RA Tohyama M.;
RT "FLRT3, a cell surface molecule containing LRR repeats and a FNIII domain,
RT promotes neurite outgrowth.";
RL Biochem. Biophys. Res. Commun. 313:1086-1091(2004).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 29-357 IN COMPLEX WITH ADGRL3,
RP SUBUNIT, INTERACTION WITH ADGRL3; UNC5B AND UNC5D, SUBCELLULAR LOCATION,
RP DISULFIDE BOND, GLYCOSYLATION AT ASN-226, AND MUTAGENESIS OF ASP-38;
RP TYR-43; ASN-45; ARG-47; TYR-64; TYR-89; TYR-91; ARG-181 AND ASP-183.
RX PubMed=26235030; DOI=10.1016/j.str.2015.06.024;
RA Lu Y.C., Nazarko O.V., Sando R. III, Salzman G.S., Suedhof T.C., Arac D.;
RT "Structural basis of latrophilin-FLRT-UNC5 interaction in cell adhesion.";
RL Structure 23:1678-1691(2015).
RN [12]
RP VARIANT VAL-452.
RX PubMed=21248752; DOI=10.1038/nature09639;
RA Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H.,
RA Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J.,
RA Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M.,
RA Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L.,
RA Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J.,
RA Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A.,
RA Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K.,
RA Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.;
RT "Exome sequencing identifies frequent mutation of the SWI/SNF complex gene
RT PBRM1 in renal carcinoma.";
RL Nature 469:539-542(2011).
RN [13]
RP VARIANTS HH21 LYS-69; GLY-97; ILE-144 AND ARG-339.
RX PubMed=23643382; DOI=10.1016/j.ajhg.2013.04.008;
RA Miraoui H., Dwyer A.A., Sykiotis G.P., Plummer L., Chung W., Feng B.,
RA Beenken A., Clarke J., Pers T.H., Dworzynski P., Keefe K., Niedziela M.,
RA Raivio T., Crowley W.F. Jr., Seminara S.B., Quinton R., Hughes V.A.,
RA Kumanov P., Young J., Yialamas M.A., Hall J.E., Van Vliet G.,
RA Chanoine J.P., Rubenstein J., Mohammadi M., Tsai P.S., Sidis Y., Lage K.,
RA Pitteloud N.;
RT "Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in
RT individuals with congenital hypogonadotropic hypogonadism.";
RL Am. J. Hum. Genet. 92:725-743(2013).
CC -!- FUNCTION: Functions in cell-cell adhesion, cell migration and axon
CC guidance, exerting an attractive or repulsive role depending on its
CC interaction partners. Plays a role in the spatial organization of brain
CC neurons. Plays a role in vascular development in the retina (By
CC similarity). Plays a role in cell-cell adhesion via its interaction
CC with ADGRL3 and probably also other latrophilins that are expressed at
CC the surface of adjacent cells (PubMed:26235030). Interaction with the
CC intracellular domain of ROBO1 mediates axon attraction towards cells
CC expressing NTN1. Mediates axon growth cone collapse and plays a
CC repulsive role in neuron guidance via its interaction with UNC5B, and
CC possibly also other UNC-5 family members (By similarity). Promotes
CC neurite outgrowth (in vitro) (PubMed:14706654). Mediates cell-cell
CC contacts that promote an increase both in neurite number and in neurite
CC length. Plays a role in the regulation of the density of glutamaergic
CC synapses. Plays a role in fibroblast growth factor-mediated signaling
CC cascades. Required for normal morphogenesis during embryonic
CC development, but not for normal embryonic patterning. Required for
CC normal ventral closure, headfold fusion and definitive endoderm
CC migration during embryonic development. Required for the formation of a
CC normal basement membrane and the maintenance of a normal anterior
CC visceral endoderm during embryonic development (By similarity).
CC {ECO:0000250|UniProtKB:B1H234, ECO:0000250|UniProtKB:Q8BGT1,
CC ECO:0000269|PubMed:14706654, ECO:0000269|PubMed:26235030}.
CC -!- SUBUNIT: Monomer and homodimer. Self-associates (via leucine-rich
CC repeats), giving rise to homooligomers (PubMed:26235030). Interacts
CC with FGFR1. Interacts (via extracellular domain) with ADGRL1/LPHN1 and
CC LPHN2 (via olfactomedin-like domain) (By similarity). Interacts (via
CC extracellular domain) with ADGRL3 (via olfactomedin-like domain); the
CC interaction is direct (PubMed:26235030). Interacts (via extracellular
CC domain) with UNC5B and UNC5D (via extracellular domain); the
CC interaction is direct (PubMed:26235030). Identified in complexes
CC composed of FLRT3, ADGRL3 and UNC5B, respectively FLRT3, ADGRL3 and
CC UNC5D (PubMed:26235030). May also interact (via extracellular domain)
CC with UNC5A and UNC5C. Interacts (via cytoplasmic domain) with ROBO1 (By
CC similarity). {ECO:0000250|UniProtKB:Q8BGT1,
CC ECO:0000269|PubMed:26235030}.
CC -!- INTERACTION:
CC Q9NZU0; Q9HAR2: ADGRL3; NbExp=4; IntAct=EBI-1057092, EBI-2689295;
CC Q9NZU0; P05067-4: APP; NbExp=3; IntAct=EBI-1057092, EBI-302641;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8BGT1};
CC Single-pass membrane protein {ECO:0000250|UniProtKB:Q8BGT1}.
CC Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q8BGT1}. Cell
CC junction, focal adhesion {ECO:0000250|UniProtKB:Q8BGT1}. Secreted
CC {ECO:0000250|UniProtKB:Q8BGT1}. Cell projection, axon
CC {ECO:0000250|UniProtKB:Q8BGT1}. Cell projection, growth cone membrane
CC {ECO:0000250|UniProtKB:Q8BGT1}. Note=Detected on dendritic punctae that
CC colocalize in part with glutamaergic synapses, but not with GABAergic
CC synapses. Proteolytic cleavage in the juxtamembrane region gives rise
CC to a shedded ectodomain. {ECO:0000250|UniProtKB:B1H234,
CC ECO:0000250|UniProtKB:Q8BGT1}.
CC -!- TISSUE SPECIFICITY: Expressed in kidney, brain, pancreas, skeletal
CC muscle, lung, liver, placenta, and heart.
CC {ECO:0000269|PubMed:10644439}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q8BGT1}.
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:Q8BGT1}.
CC -!- DISEASE: Hypogonadotropic hypogonadism 21 with or without anosmia
CC (HH21) [MIM:615271]: A disorder characterized by absent or incomplete
CC sexual maturation by the age of 18 years, in conjunction with low
CC levels of circulating gonadotropins and testosterone and no other
CC abnormalities of the hypothalamic-pituitary axis. In some cases, it is
CC associated with non-reproductive phenotypes, such as anosmia, cleft
CC palate, and sensorineural hearing loss. Anosmia or hyposmia is related
CC to the absence or hypoplasia of the olfactory bulbs and tracts.
CC Hypogonadism is due to deficiency in gonadotropin-releasing hormone and
CC probably results from a failure of embryonic migration of gonadotropin-
CC releasing hormone-synthesizing neurons. In the presence of anosmia,
CC idiopathic hypogonadotropic hypogonadism is referred to as Kallmann
CC syndrome, whereas in the presence of a normal sense of smell, it has
CC been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).
CC {ECO:0000269|PubMed:23643382}. Note=The disease is caused by variants
CC affecting distinct genetic loci, including the gene represented in this
CC entry. Some patients carrying mutations in FLRT3 also have a mutation
CC in another HH-associated gene including FGFR1, HS6ST1 and FGF17
CC (PubMed:23643382). {ECO:0000269|PubMed:23643382}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA95993.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB55282.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB55303.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF169677; AAF28461.1; -; mRNA.
DR EMBL; AB040902; BAA95993.1; ALT_INIT; mRNA.
DR EMBL; AK027297; BAB55023.1; -; mRNA.
DR EMBL; AK027670; BAB55282.1; ALT_INIT; mRNA.
DR EMBL; AK027694; BAB55303.1; ALT_INIT; mRNA.
DR EMBL; AY358319; AAQ88685.1; -; mRNA.
DR EMBL; AK074909; BAC11284.1; -; mRNA.
DR EMBL; AL132826; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471133; EAX10300.1; -; Genomic_DNA.
DR EMBL; CH471133; EAX10301.1; -; Genomic_DNA.
DR EMBL; BC020870; AAH20870.1; -; mRNA.
DR CCDS; CCDS13121.1; -.
DR RefSeq; NP_037413.1; NM_013281.3.
DR RefSeq; NP_938205.1; NM_198391.2.
DR RefSeq; XP_005260739.1; XM_005260682.4.
DR RefSeq; XP_011527506.1; XM_011529204.2.
DR RefSeq; XP_011527507.1; XM_011529205.2.
DR PDB; 5CMN; X-ray; 3.61 A; A/B/C/D=29-357.
DR PDB; 5CMP; X-ray; 2.60 A; A/B/C/D=29-357.
DR PDB; 6JBU; X-ray; 1.85 A; B=29-358.
DR PDBsum; 5CMN; -.
DR PDBsum; 5CMP; -.
DR PDBsum; 6JBU; -.
DR AlphaFoldDB; Q9NZU0; -.
DR SMR; Q9NZU0; -.
DR BioGRID; 117267; 18.
DR CORUM; Q9NZU0; -.
DR DIP; DIP-50407N; -.
DR IntAct; Q9NZU0; 10.
DR STRING; 9606.ENSP00000367292; -.
DR TCDB; 8.A.43.1.27; the neat-domain containing methaemoglobin heme sequestration (n-mhs) family.
DR GlyConnect; 1454; 2 N-Linked glycans (1 site).
DR GlyGen; Q9NZU0; 3 sites, 2 N-linked glycans (1 site).
DR iPTMnet; Q9NZU0; -.
DR PhosphoSitePlus; Q9NZU0; -.
DR BioMuta; FLRT3; -.
DR DMDM; 20138400; -.
DR EPD; Q9NZU0; -.
DR jPOST; Q9NZU0; -.
DR MassIVE; Q9NZU0; -.
DR MaxQB; Q9NZU0; -.
DR PaxDb; Q9NZU0; -.
DR PeptideAtlas; Q9NZU0; -.
DR PRIDE; Q9NZU0; -.
DR ProteomicsDB; 83509; -.
DR Antibodypedia; 24361; 114 antibodies from 24 providers.
DR DNASU; 23767; -.
DR Ensembl; ENST00000341420.5; ENSP00000339912.4; ENSG00000125848.10.
DR Ensembl; ENST00000378053.3; ENSP00000367292.3; ENSG00000125848.10.
DR GeneID; 23767; -.
DR KEGG; hsa:23767; -.
DR MANE-Select; ENST00000341420.5; ENSP00000339912.4; NM_198391.3; NP_938205.1.
DR UCSC; uc002wov.3; human.
DR CTD; 23767; -.
DR DisGeNET; 23767; -.
DR GeneCards; FLRT3; -.
DR GeneReviews; FLRT3; -.
DR HGNC; HGNC:3762; FLRT3.
DR HPA; ENSG00000125848; Tissue enhanced (kidney).
DR MalaCards; FLRT3; -.
DR MIM; 604808; gene.
DR MIM; 615271; phenotype.
DR neXtProt; NX_Q9NZU0; -.
DR OpenTargets; ENSG00000125848; -.
DR Orphanet; 478; Kallmann syndrome.
DR PharmGKB; PA28179; -.
DR VEuPathDB; HostDB:ENSG00000125848; -.
DR eggNOG; ENOG502QQBZ; Eukaryota.
DR GeneTree; ENSGT00940000159704; -.
DR HOGENOM; CLU_027624_0_0_1; -.
DR InParanoid; Q9NZU0; -.
DR OMA; LIWTKIG; -.
DR OrthoDB; 826997at2759; -.
DR PhylomeDB; Q9NZU0; -.
DR TreeFam; TF331598; -.
DR PathwayCommons; Q9NZU0; -.
DR Reactome; R-HSA-376176; Signaling by ROBO receptors.
DR Reactome; R-HSA-5654687; Downstream signaling of activated FGFR1.
DR SignaLink; Q9NZU0; -.
DR BioGRID-ORCS; 23767; 5 hits in 1059 CRISPR screens.
DR GeneWiki; FLRT3; -.
DR GenomeRNAi; 23767; -.
DR Pharos; Q9NZU0; Tbio.
DR PRO; PR:Q9NZU0; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9NZU0; protein.
DR Bgee; ENSG00000125848; Expressed in endothelial cell and 180 other tissues.
DR Genevisible; Q9NZU0; HS.
DR GO; GO:0043679; C:axon terminus; ISS:UniProtKB.
DR GO; GO:0044295; C:axonal growth cone; ISS:UniProtKB.
DR GO; GO:0030054; C:cell junction; IDA:HPA.
DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
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:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0032584; C:growth cone membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0097060; C:synaptic membrane; ISS:UniProtKB.
DR GO; GO:0045499; F:chemorepellent activity; IEA:Ensembl.
DR GO; GO:0005104; F:fibroblast growth factor receptor binding; IEA:Ensembl.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; NAS:UniProtKB.
DR GO; GO:0007411; P:axon guidance; IEA:Ensembl.
DR GO; GO:0098742; P:cell-cell adhesion via plasma-membrane adhesion molecules; IDA:UniProtKB.
DR GO; GO:0048598; P:embryonic morphogenesis; ISS:UniProtKB.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0060322; P:head development; ISS:UniProtKB.
DR GO; GO:0007507; P:heart development; ISS:UniProtKB.
DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR GO; GO:1990138; P:neuron projection extension; IMP:UniProtKB.
DR GO; GO:0051965; P:positive regulation of synapse assembly; IEA:Ensembl.
DR GO; GO:0003345; P:proepicardium cell migration involved in pericardium morphogenesis; ISS:UniProtKB.
DR GO; GO:0048678; P:response to axon injury; ISS:UniProtKB.
DR GO; GO:0007416; P:synapse assembly; ISS:UniProtKB.
DR GO; GO:0099560; P:synaptic membrane adhesion; 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; 2.
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.
DR PROSITE; PS51450; LRR; 8.
PE 1: Evidence at protein level;
KW 3D-structure; Cell adhesion; Cell junction; Cell membrane; Cell projection;
KW Developmental protein; Disease variant; Disulfide bond;
KW Endoplasmic reticulum; Glycoprotein; Hypogonadotropic hypogonadism;
KW Kallmann syndrome; Leucine-rich repeat; Membrane; Reference proteome;
KW Repeat; Secreted; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..649
FT /note="Leucine-rich repeat transmembrane protein FLRT3"
FT /id="PRO_0000021280"
FT TOPO_DOM 29..528
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 529..549
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 550..649
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 29..58
FT /note="LRRNT"
FT /evidence="ECO:0000255"
FT REPEAT 59..80
FT /note="LRR 1"
FT /evidence="ECO:0000255"
FT REPEAT 84..104
FT /note="LRR 2"
FT /evidence="ECO:0000255"
FT REPEAT 105..126
FT /note="LRR 3"
FT /evidence="ECO:0000255"
FT REPEAT 129..150
FT /note="LRR 4"
FT /evidence="ECO:0000255"
FT REPEAT 155..175
FT /note="LRR 5"
FT /evidence="ECO:0000255"
FT REPEAT 176..197
FT /note="LRR 6"
FT /evidence="ECO:0000255"
FT REPEAT 200..220
FT /note="LRR 7"
FT /evidence="ECO:0000255"
FT REPEAT 226..247
FT /note="LRR 8"
FT /evidence="ECO:0000255"
FT REPEAT 248..269
FT /note="LRR 9"
FT /evidence="ECO:0000255"
FT REPEAT 272..293
FT /note="LRR 10"
FT /evidence="ECO:0000255"
FT DOMAIN 305..357
FT /note="LRRCT"
FT /evidence="ECO:0000255"
FT DOMAIN 409..504
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 38..67
FT /note="Interaction with ADGRL3"
FT /evidence="ECO:0000269|PubMed:26235030"
FT REGION 387..407
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 622..649
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 622..638
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 226
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:26235030"
FT CARBOHYD 282
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 296
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 31..37
FT /evidence="ECO:0000269|PubMed:26235030"
FT DISULFID 35..44
FT /evidence="ECO:0000269|PubMed:26235030"
FT DISULFID 309..334
FT /evidence="ECO:0000269|PubMed:26235030"
FT VARIANT 69
FT /note="Q -> K (in HH21; rare variant associated with
FT susceptibility to disease; the patient has a second
FT mutation in the HH-associated gene FGFR1;
FT dbSNP:rs398124653)"
FT /evidence="ECO:0000269|PubMed:23643382"
FT /id="VAR_069950"
FT VARIANT 97
FT /note="E -> G (in HH21; rare variant associated with
FT susceptibility to disease; patients have a second mutation
FT in another HH-associated gene including FGFR1, HS6ST1 and
FT FGF17; dbSNP:rs398124651)"
FT /evidence="ECO:0000269|PubMed:23643382"
FT /id="VAR_069951"
FT VARIANT 144
FT /note="S -> I (in HH21; rare variant associated with
FT susceptibility to disease; patients have a second mutation
FT in another HH-associated gene including FGFR1, HS6ST1 and
FT FGF17; dbSNP:rs398124652)"
FT /evidence="ECO:0000269|PubMed:23643382"
FT /id="VAR_069952"
FT VARIANT 339
FT /note="K -> R (in HH21; dbSNP:rs398124654)"
FT /evidence="ECO:0000269|PubMed:23643382"
FT /id="VAR_069953"
FT VARIANT 377
FT /note="A -> T (in dbSNP:rs8120693)"
FT /id="VAR_050997"
FT VARIANT 400
FT /note="H -> Q (in dbSNP:rs6079391)"
FT /evidence="ECO:0000269|PubMed:12975309,
FT ECO:0000269|PubMed:14702039, ECO:0000269|Ref.7"
FT /id="VAR_017152"
FT VARIANT 452
FT /note="I -> V (found in a renal cell carcinoma case;
FT somatic mutation; dbSNP:rs1393315241)"
FT /evidence="ECO:0000269|PubMed:21248752"
FT /id="VAR_064714"
FT VARIANT 460
FT /note="E -> D (in dbSNP:rs35253731)"
FT /id="VAR_050998"
FT MUTAGEN 38
FT /note="D->A: Abolishes ADGRL3 binding; when associated with
FT A-43; A-45 and A-47."
FT /evidence="ECO:0000269|PubMed:26235030"
FT MUTAGEN 43
FT /note="Y->A: Abolishes ADGRL3 binding; when associated with
FT A-64. Abolishes ADGRL3 binding; when associated with A-38;
FT A-43 and A-47."
FT /evidence="ECO:0000269|PubMed:26235030"
FT MUTAGEN 45
FT /note="N->A: Abolishes ADGRL3 binding; when associated with
FT A-38; A-43 and A-47."
FT /evidence="ECO:0000269|PubMed:26235030"
FT MUTAGEN 47
FT /note="R->A: Abolishes ADGRL3 binding; when associated with
FT A-38; A-43 and A-45."
FT /evidence="ECO:0000269|PubMed:26235030"
FT MUTAGEN 64
FT /note="Y->A: Abolishes ADGRL3 binding; when associated with
FT A-43."
FT /evidence="ECO:0000269|PubMed:26235030"
FT MUTAGEN 89
FT /note="Y->A: Abolishes ADGRL3 binding; when associated with
FT A-91."
FT /evidence="ECO:0000269|PubMed:26235030"
FT MUTAGEN 91
FT /note="Y->A: Abolishes ADGRL3 binding; when associated with
FT A-89."
FT /evidence="ECO:0000269|PubMed:26235030"
FT MUTAGEN 181
FT /note="R->A: No effect on homodimerization; when associated
FT with A-183."
FT /evidence="ECO:0000269|PubMed:26235030"
FT MUTAGEN 181
FT /note="R->N: Adds a glycosylation site that strongly
FT reduces homodimerization; when associated with T-183."
FT /evidence="ECO:0000269|PubMed:26235030"
FT MUTAGEN 183
FT /note="D->A: No effect on homodimerization; when associated
FT with A-181."
FT /evidence="ECO:0000269|PubMed:26235030"
FT MUTAGEN 183
FT /note="D->T: Adds a glycosylation site that strongly
FT reduces homodimerization; when associated with T-183."
FT /evidence="ECO:0000269|PubMed:26235030"
FT CONFLICT 198
FT /note="L -> P (in Ref. 3; BAB55282)"
FT /evidence="ECO:0000305"
FT CONFLICT 307
FT /note="W -> R (in Ref. 3; BAB55282)"
FT /evidence="ECO:0000305"
FT CONFLICT 519
FT /note="K -> Q (in Ref. 3; BAB55023)"
FT /evidence="ECO:0000305"
FT CONFLICT 638
FT /note="D -> G (in Ref. 3; BAB55282)"
FT /evidence="ECO:0000305"
FT STRAND 35..38
FT /evidence="ECO:0007829|PDB:6JBU"
FT STRAND 41..43
FT /evidence="ECO:0007829|PDB:6JBU"
FT STRAND 62..64
FT /evidence="ECO:0007829|PDB:6JBU"
FT HELIX 72..74
FT /evidence="ECO:0007829|PDB:6JBU"
FT HELIX 77..81
FT /evidence="ECO:0007829|PDB:6JBU"
FT STRAND 87..89
FT /evidence="ECO:0007829|PDB:6JBU"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:6JBU"
FT HELIX 121..125
FT /evidence="ECO:0007829|PDB:6JBU"
FT STRAND 132..134
FT /evidence="ECO:0007829|PDB:6JBU"
FT TURN 142..144
FT /evidence="ECO:0007829|PDB:6JBU"
FT TURN 147..152
FT /evidence="ECO:0007829|PDB:6JBU"
FT STRAND 158..160
FT /evidence="ECO:0007829|PDB:6JBU"
FT STRAND 178..181
FT /evidence="ECO:0007829|PDB:6JBU"
FT HELIX 192..195
FT /evidence="ECO:0007829|PDB:6JBU"
FT STRAND 203..205
FT /evidence="ECO:0007829|PDB:6JBU"
FT TURN 213..215
FT /evidence="ECO:0007829|PDB:6JBU"
FT TURN 218..223
FT /evidence="ECO:0007829|PDB:6JBU"
FT STRAND 229..231
FT /evidence="ECO:0007829|PDB:6JBU"
FT STRAND 251..253
FT /evidence="ECO:0007829|PDB:6JBU"
FT TURN 264..269
FT /evidence="ECO:0007829|PDB:6JBU"
FT STRAND 275..277
FT /evidence="ECO:0007829|PDB:6JBU"
FT TURN 288..293
FT /evidence="ECO:0007829|PDB:6JBU"
FT STRAND 299..301
FT /evidence="ECO:0007829|PDB:6JBU"
FT HELIX 311..313
FT /evidence="ECO:0007829|PDB:6JBU"
FT HELIX 314..321
FT /evidence="ECO:0007829|PDB:6JBU"
FT STRAND 328..330
FT /evidence="ECO:0007829|PDB:6JBU"
FT STRAND 333..338
FT /evidence="ECO:0007829|PDB:6JBU"
FT TURN 339..342
FT /evidence="ECO:0007829|PDB:6JBU"
FT HELIX 345..347
FT /evidence="ECO:0007829|PDB:6JBU"
SQ SEQUENCE 649 AA; 73004 MW; 9EFF666C46181F08 CRC64;
MISAAWSIFL IGTKIGLFLQ VAPLSVMAKS CPSVCRCDAG FIYCNDRFLT SIPTGIPEDA
TTLYLQNNQI NNAGIPSDLK NLLKVERIYL YHNSLDEFPT NLPKYVKELH LQENNIRTIT
YDSLSKIPYL EELHLDDNSV SAVSIEEGAF RDSNYLRLLF LSRNHLSTIP WGLPRTIEEL
RLDDNRISTI SSPSLQGLTS LKRLVLDGNL LNNHGLGDKV FFNLVNLTEL SLVRNSLTAA
PVNLPGTNLR KLYLQDNHIN RVPPNAFSYL RQLYRLDMSN NNLSNLPQGI FDDLDNITQL
ILRNNPWYCG CKMKWVRDWL QSLPVKVNVR GLMCQAPEKV RGMAIKDLNA ELFDCKDSGI
VSTIQITTAI PNTVYPAQGQ WPAPVTKQPD IKNPKLTKDH QTTGSPSRKT ITITVKSVTS
DTIHISWKLA LPMTALRLSW LKLGHSPAFG SITETIVTGE RSEYLVTALE PDSPYKVCMV
PMETSNLYLF DETPVCIETE TAPLRMYNPT TTLNREQEKE PYKNPNLPLA AIIGGAVALV
TIALLALVCW YVHRNGSLFS RNCAYSKGRR RKDDYAEAGT KKDNSILEIR ETSFQMLPIS
NEPISKEEFV IHTIFPPNGM NLYKNNHSES SSNRSYRDSG IPDSDHSHS
