ID LGI1_HUMAN Reviewed; 557 AA. AC O95970; A8K0Z1; B4E1S0; Q5W001; Q5W002; Q8NI23; Q96LF5; DT 03-JUL-2003, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1999, sequence version 1. DT 13-FEB-2019, entry version 166. DE RecName: Full=Leucine-rich glioma-inactivated protein 1; DE AltName: Full=Epitempin-1; DE Flags: Precursor; GN Name=LGI1; Synonyms=EPT; ORFNames=UNQ775/PRO1569; 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] (ISOFORM 1). RC TISSUE=Fetal brain; RX PubMed=9879993; DOI=10.1038/sj.onc.1202481; RA Chernova O.B., Somerville R.P., Cowell J.K.; RT "A novel gene, LGI1, from 10q24 is rearranged and downregulated in RT malignant brain tumors."; RL Oncogene 17:2873-2881(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND DISEASE. RX PubMed=11978770; DOI=10.1093/hmg/11.9.1119; RA Morante-Redolat J.M., Gorostidi-Pagola A., Piquer-Sirerol S., RA Saenz A., Poza J.J., Galan J., Gesk S., Sarafidou T., Mautner V.F., RA Binelli S., Staub E., Hinzmann B., French L., Prud'homme J.-F., RA Passarelli D., Scannapieco P., Tassinari C.A., Avanzini G., RA Marti-Masso J.F., Kluwe L., Deloukas P., Moschonas N.K., RA Michelucci R., Siebert R., Nobile C., Perez-Tur J., RA Lopez de Munain A.; RT "Mutations in the LGI1/Epitempin gene on 10q24 cause autosomal RT dominant lateral temporal epilepsy."; RL Hum. Mol. Genet. 11:1119-1128(2002). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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] (ISOFORMS 1 AND 3). RC TISSUE=Brain, and Trachea; 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP FUNCTION. RX PubMed=15047712; DOI=10.1074/jbc.M314192200; RA Kunapuli P., Kasyapa C.S., Hawthorn L., Cowell J.K.; RT "LGI1, a putative tumor metastasis suppressor gene, controls in vitro RT invasiveness and expression of matrix metalloproteinases in glioma RT cells through the ERK1/2 pathway."; RL J. Biol. Chem. 279:23151-23157(2004). RN [9] RP ERRATUM. RA Kunapuli P., Kasyapa C.S., Hawthorn L., Cowell J.K.; RL J. Biol. Chem. 282:2752-2752(2007). RN [10] RP SUBCELLULAR LOCATION, GLYCOSYLATION, MUTAGENESIS OF ASN-192; ASN-277 RP AND ASN-422, AND CHARACTERIZATION OF VARIANTS ETL1 ARG-46; ARG-145; RP ARG-200; CYS-318 AND ALA-383. RX PubMed=17067999; DOI=10.1093/hmg/ddl421; RA Sirerol-Piquer M.S., Ayerdi-Izquierdo A., Morante-Redolat J.M., RA Herranz-Perez V., Favell K., Barker P.A., Perez-Tur J.; RT "The epilepsy gene LGI1 encodes a secreted glycoprotein that binds to RT the cell surface."; RL Hum. Mol. Genet. 15:3436-3445(2006). RN [11] RP FUNCTION, INDUCTION, AND TISSUE SPECIFICITY. RX PubMed=16518856; DOI=10.1002/jcp.20627; RA Gabellini N., Masola V., Quartesan S., Oselladore B., Nobile C., RA Michelucci R., Curtarello M., Parolin C., Palu G.; RT "Increased expression of LGI1 gene triggers growth inhibition and RT apoptosis of neuroblastoma cells."; RL J. Cell. Physiol. 207:711-721(2006). RN [12] RP SUBCELLULAR LOCATION, ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY. RX PubMed=16787412; DOI=10.1111/j.1471-4159.2006.03939.x; RA Furlan S., Roncaroli F., Forner F., Vitiello L., Calabria E., RA Piquer-Sirerol S., Valle G., Perez-Tur J., Michelucci R., Nobile C.; RT "The LGI1/epitempin gene encodes two protein isoforms differentially RT expressed in human brain."; RL J. Neurochem. 98:985-991(2006). RN [13] RP SUBCELLULAR LOCATION, VARIANT ETL1 PRO-232, AND CHARACTERIZATION OF RP VARIANTS ETL1 PRO-232 AND ALA-383. RX PubMed=17296837; DOI=10.1001/archneur.64.2.217; RA Chabrol E., Popescu C., Gourfinkel-An I., Trouillard O., Depienne C., RA Senechal K., Baulac M., LeGuern E., Baulac S.; RT "Two novel epilepsy-linked mutations leading to a loss of function of RT LGI1."; RL Arch. Neurol. 64:217-222(2007). RN [14] RP REVIEW ON VARIANTS. RX PubMed=19191227; DOI=10.1002/humu.20925; RA Nobile C., Michelucci R., Andreazza S., Pasini E., Tosatto S.C., RA Striano P.; RT "LGI1 mutations in autosomal dominant and sporadic lateral temporal RT epilepsy."; RL Hum. Mutat. 30:530-536(2009). RN [15] RP INTERACTION WITH ADAM22. RX PubMed=27066583; DOI=10.1212/NXG.0000000000000046; RA Muona M., Fukata Y., Anttonen A.K., Laari A., Palotie A., Pihko H., RA Loennqvist T., Valanne L., Somer M., Fukata M., Lehesjoki A.E.; RT "Dysfunctional ADAM22 implicated in progressive encephalopathy with RT cortical atrophy and epilepsy."; RL Neurol. Genet. 2:E46-E46(2016). RN [16] RP VARIANT ETL1 ALA-383. RX PubMed=11810107; DOI=10.1038/ng832; RA Kalachikov S., Evgrafov O., Ross B., Winawer M., Barker-Cummings C., RA Boneschi F.M., Choi C., Morozov P., Das K., Teplitskaya E., Yu A., RA Cayanis E., Penchaszadeh G., Kottmann A.H., Pedley T.A., Hauser W.A., RA Ottman R., Gilliam T.C.; RT "Mutations in LGI1 cause autosomal-dominant partial epilepsy with RT auditory features."; RL Nat. Genet. 30:335-341(2002). RN [17] RP VARIANT ETL1 ARG-46. RX PubMed=12205652; DOI=10.1002/ana.10280; RA Gu W., Brodtkorb E., Steinlein O.K.; RT "LGI1 is mutated in familial temporal lobe epilepsy characterized by RT aphasic seizures."; RL Ann. Neurol. 52:364-367(2002). RN [18] RP VARIANT ETL1 ARG-26. RX PubMed=12601709; DOI=10.1002/ana.10492; RA Pizzuti A., Flex E., Di Bonaventura C., Dottorini T., Egeo G., RA Manfredi M., Dallapiccola B., Giallonardo A.T.; RT "Epilepsy with auditory features: a LGI1 gene mutation suggests a RT loss-of-function mechanism."; RL Ann. Neurol. 53:396-399(2003). RN [19] RP VARIANT ETL1 CYS-318. RX PubMed=12771268; DOI=10.1212/01.WNL.0000063324.39980.4A; RA Fertig E., Lincoln A., Martinuzzi A., Mattson R.H., Hisama F.M.; RT "Novel LGI1 mutation in a family with autosomal dominant partial RT epilepsy with auditory features."; RL Neurology 60:1687-1690(2003). RN [20] RP VARIANTS ETL1 GLY-42 AND LEU-473. RX PubMed=15079010; DOI=10.1212/01.WNL.0000118213.94650.81; RA Berkovic S.F., Izzillo P., McMahon J.M., Harkin L.A., McIntosh A.M., RA Phillips H.A., Briellmann R.S., Wallace R.H., Mazarib A., RA Neufeld M.Y., Korczyn A.D., Scheffer I.E., Mulley J.C.; RT "LGI1 mutations in temporal lobe epilepsies."; RL Neurology 62:1115-1119(2004). RN [21] RP VARIANT ETL1 TRP-136. RX PubMed=17562837; DOI=10.1212/01.wnl.0000264932.44153.3c; RA Michelucci R., Mecarelli O., Bovo G., Bisulli F., Testoni S., RA Striano P., Striano S., Tinuper P., Nobile C.; RT "A de novo LGI1 mutation causing idiopathic partial epilepsy with RT telephone-induced seizures."; RL Neurology 68:2150-2151(2007). RN [22] RP VARIANT ETL1 LYS-122. RX PubMed=18625862; DOI=10.1001/archneur.65.7.939; RA Striano P., de Falco A., Diani E., Bovo G., Furlan S., Vitiello L., RA Pinardi F., Striano S., Michelucci R., de Falco F.A., Nobile C.; RT "A novel loss-of-function LGI1 mutation linked to autosomal dominant RT lateral temporal epilepsy."; RL Arch. Neurol. 65:939-942(2008). RN [23] RP VARIANT ETL1 LYS-123. RX PubMed=19552651; DOI=10.1111/j.1528-1167.2009.02181.x; RA Bonaventura C.D., Carni M., Diani E., Fattouch J., Vaudano E.A., RA Egeo G., Pantano P., Maraviglia B., Bozzao L., Manfredi M., RA Prencipe M., Giallonardo T.A., Nobile C.; RT "Drug resistant ADLTE and recurrent partial status epilepticus with RT dysphasic features in a family with a novel LGI1mutation: RT electroclinical, genetic, and EEG/fMRI findings."; RL Epilepsia 50:2481-2486(2009). CC -!- FUNCTION: Regulates voltage-gated potassium channels assembled CC from KCNA1, KCNA4 and KCNAB1. It slows down channel inactivation CC by precluding channel closure mediated by the KCNAB1 subunit. CC Ligand for ADAM22 that positively regulates synaptic transmission CC mediated by AMPA-type glutamate receptors (By similarity). Plays a CC role in suppressing the production of MMP1/3 through the CC phosphatidylinositol 3-kinase/ERK pathway. May play a role in the CC control of neuroblastoma cell survival. {ECO:0000250, CC ECO:0000269|PubMed:15047712, ECO:0000269|PubMed:16518856}. CC -!- SUBUNIT: Oligomer. Interacts with KCNA1 within a complex CC containing KCNA1, KCNA4 and KCNAB1. Part of a complex containing CC ADAM22, DLG4/PSD95 and CACNG2/Stargazin (PubMed:27066583). Can CC bind to ADAM11 and ADAM23. {ECO:0000250, CC ECO:0000269|PubMed:27066583}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16787412, CC ECO:0000269|PubMed:17067999, ECO:0000269|PubMed:17296837}. Cell CC junction, synapse {ECO:0000250}. Note=Isoform 1 but not isoform 2 CC is secreted. Isoform 1 is enriched in the Golgi apparatus while CC isoform 2 accumulates in the endoplasmic reticulum. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=O95970-1; Sequence=Displayed; CC Name=2; CC IsoId=O95970-2; Sequence=VSP_007678, VSP_007679; CC Name=3; CC IsoId=O95970-3; Sequence=VSP_038234; CC -!- TISSUE SPECIFICITY: Predominantly expressed in neural tissues, CC especially in brain. Expression is reduced in low-grade brain CC tumors and significantly reduced or absent in malignant gliomas. CC Isoform 1 is absent in the cerebellum and is detectable in the CC occipital cortex and hippocampus; higher amounts are observed in CC the parietal and frontal cortices, putamen, and, particularly, in CC the temporal neocortex, where it is 3.5 times more abundant than CC in the hippocampus (at protein level). Isoform 3 shows the highest CC expression in the occipital cortex and the lowest in the CC hippocampus (at protein level). {ECO:0000269|PubMed:16518856, CC ECO:0000269|PubMed:16787412}. CC -!- INDUCTION: Down-regulated in neuroblastoma cells. CC {ECO:0000269|PubMed:16518856}. CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:17067999}. CC -!- DISEASE: Epilepsy, familial temporal lobe, 1 (ETL1) [MIM:600512]: CC A focal form of epilepsy characterized by recurrent seizures that CC arise from foci within the temporal lobe. Seizures are usually CC accompanied by sensory symptoms, most often auditory in nature. CC {ECO:0000269|PubMed:11810107, ECO:0000269|PubMed:12205652, CC ECO:0000269|PubMed:12601709, ECO:0000269|PubMed:12771268, CC ECO:0000269|PubMed:15079010, ECO:0000269|PubMed:17067999, CC ECO:0000269|PubMed:17296837, ECO:0000269|PubMed:17562837, CC ECO:0000269|PubMed:18625862, ECO:0000269|PubMed:19552651}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/LGI1ID311ch10q23.html"; 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; AF055636; AAC99316.1; -; mRNA. DR EMBL; AF473548; AAM22074.1; -; mRNA. DR EMBL; AY358885; AAQ89244.1; -; mRNA. DR EMBL; AK289706; BAF82395.1; -; mRNA. DR EMBL; AK303956; BAG64882.1; -; mRNA. DR EMBL; AL157396; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL358154; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471066; EAW50052.1; -; Genomic_DNA. DR EMBL; BC022500; AAH22500.1; -; mRNA. DR CCDS; CCDS7431.1; -. [O95970-1] DR CCDS; CCDS76325.1; -. [O95970-2] DR CCDS; CCDS81490.1; -. [O95970-3] DR RefSeq; NP_001295204.1; NM_001308275.1. [O95970-2] DR RefSeq; NP_001295205.1; NM_001308276.1. [O95970-3] DR RefSeq; NP_005088.1; NM_005097.3. [O95970-1] DR UniGene; Hs.533670; -. DR PDB; 5Y2Z; X-ray; 2.67 A; B/D/F/H/J/L=224-557. DR PDB; 5Y30; X-ray; 1.78 A; A=37-223. DR PDB; 5Y31; X-ray; 7.12 A; B/D=37-557. DR PDBsum; 5Y2Z; -. DR PDBsum; 5Y30; -. DR PDBsum; 5Y31; -. DR ProteinModelPortal; O95970; -. DR SMR; O95970; -. DR BioGrid; 114645; 2. DR CORUM; O95970; -. DR STRING; 9606.ENSP00000360472; -. DR iPTMnet; O95970; -. DR PhosphoSitePlus; O95970; -. DR BioMuta; LGI1; -. DR EPD; O95970; -. DR jPOST; O95970; -. DR PaxDb; O95970; -. DR PeptideAtlas; O95970; -. DR PRIDE; O95970; -. DR ProteomicsDB; 51151; -. DR ProteomicsDB; 51152; -. [O95970-2] DR ProteomicsDB; 51153; -. [O95970-3] DR TopDownProteomics; O95970-3; -. [O95970-3] DR DNASU; 9211; -. DR Ensembl; ENST00000371413; ENSP00000360467; ENSG00000108231. [O95970-2] DR Ensembl; ENST00000371418; ENSP00000360472; ENSG00000108231. [O95970-1] DR Ensembl; ENST00000630047; ENSP00000485917; ENSG00000108231. [O95970-3] DR GeneID; 9211; -. DR KEGG; hsa:9211; -. DR UCSC; uc001kjc.5; human. [O95970-1] DR CTD; 9211; -. DR DisGeNET; 9211; -. DR EuPathDB; HostDB:ENSG00000108231.11; -. DR GeneCards; LGI1; -. DR GeneReviews; LGI1; -. DR HGNC; HGNC:6572; LGI1. DR MalaCards; LGI1; -. DR MIM; 600512; phenotype. DR MIM; 604619; gene. DR neXtProt; NX_O95970; -. DR OpenTargets; ENSG00000108231; -. DR Orphanet; 101046; Autosomal dominant epilepsy with auditory features. DR PharmGKB; PA30349; -. DR eggNOG; ENOG410IIXR; Eukaryota. DR eggNOG; ENOG410XSZV; LUCA. DR GeneTree; ENSGT00940000159793; -. DR HOVERGEN; HBG036744; -. DR InParanoid; O95970; -. DR OMA; IYQWNKG; -. DR OrthoDB; 365688at2759; -. DR PhylomeDB; O95970; -. DR TreeFam; TF333155; -. DR Reactome; R-HSA-5682910; LGI-ADAM interactions. DR ChiTaRS; LGI1; human. DR GeneWiki; LGI1; -. DR GenomeRNAi; 9211; -. DR PRO; PR:O95970; -. DR Proteomes; UP000005640; Chromosome 10. DR Bgee; ENSG00000108231; Expressed in 133 organ(s), highest expression level in caudate nucleus. DR ExpressionAtlas; O95970; baseline and differential. DR Genevisible; O95970; HS. DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0016020; C:membrane; IEA:GOC. DR GO; GO:0043083; C:synaptic cleft; IEA:Ensembl. DR GO; GO:0005102; F:signaling receptor binding; IPI:DFLAT. DR GO; GO:0007411; P:axon guidance; IMP:DFLAT. DR GO; GO:0008283; P:cell population proliferation; TAS:ProtInc. DR GO; GO:0007399; P:nervous system development; TAS:ProtInc. DR GO; GO:0031175; P:neuron projection development; IMP:DFLAT. DR GO; GO:0099645; P:neurotransmitter receptor localization to postsynaptic specialization membrane; IEA:Ensembl. DR GO; GO:0030307; P:positive regulation of cell growth; IMP:DFLAT. DR GO; GO:0050806; P:positive regulation of synaptic transmission; ISS:UniProtKB. DR GO; GO:0051260; P:protein homooligomerization; IEA:Ensembl. DR Gene3D; 3.80.10.10; -; 1. DR InterPro; IPR000483; Cys-rich_flank_reg_C. DR InterPro; IPR009039; EAR. DR InterPro; IPR005492; EPTP. DR InterPro; IPR001611; Leu-rich_rpt. DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp. DR InterPro; IPR032675; LRR_dom_sf. DR Pfam; PF03736; EPTP; 7. DR Pfam; PF13855; LRR_8; 1. DR SMART; SM00369; LRR_TYP; 3. DR SMART; SM00082; LRRCT; 1. DR PROSITE; PS50912; EAR; 7. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell junction; Complete proteome; KW Disease mutation; Epilepsy; Glycoprotein; Leucine-rich repeat; KW Reference proteome; Repeat; Secreted; Signal; Synapse. FT SIGNAL 1 34 {ECO:0000255}. FT CHAIN 35 557 Leucine-rich glioma-inactivated protein FT 1. FT /FTId=PRO_0000017705. FT DOMAIN 35 72 LRRNT. FT REPEAT 92 113 LRR 1. FT REPEAT 116 137 LRR 2. FT REPEAT 140 161 LRR 3. FT DOMAIN 173 223 LRRCT. FT REPEAT 225 267 EAR 1. {ECO:0000255|PROSITE- FT ProRule:PRU00075}. FT REPEAT 271 313 EAR 2. {ECO:0000255|PROSITE- FT ProRule:PRU00075}. FT REPEAT 317 364 EAR 3. {ECO:0000255|PROSITE- FT ProRule:PRU00075}. FT REPEAT 366 415 EAR 4. {ECO:0000255|PROSITE- FT ProRule:PRU00075}. FT REPEAT 419 462 EAR 5. {ECO:0000255|PROSITE- FT ProRule:PRU00075}. FT REPEAT 464 506 EAR 6. {ECO:0000255|PROSITE- FT ProRule:PRU00075}. FT REPEAT 510 552 EAR 7. {ECO:0000255|PROSITE- FT ProRule:PRU00075}. FT CARBOHYD 192 192 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 277 277 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 422 422 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT VAR_SEQ 96 143 Missing (in isoform 3). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_038234. FT VAR_SEQ 280 291 GTSTVVCKPIVI -> VLREIHRFTNMS (in isoform FT 2). {ECO:0000303|PubMed:11978770}. FT /FTId=VSP_007678. FT VAR_SEQ 292 557 Missing (in isoform 2). FT {ECO:0000303|PubMed:11978770}. FT /FTId=VSP_007679. FT VARIANT 26 26 L -> R (in ETL1; probably affects signal FT sequence processing and secretion). FT {ECO:0000269|PubMed:12601709}. FT /FTId=VAR_015771. FT VARIANT 42 42 C -> G (in ETL1; dbSNP:rs797044996). FT {ECO:0000269|PubMed:15079010}. FT /FTId=VAR_023008. FT VARIANT 42 42 C -> R (in ETL1; dbSNP:rs797044996). FT /FTId=VAR_058538. FT VARIANT 46 46 C -> R (in ETL1; loss of protein FT secretion; does not affect glycosylation FT status of the protein; FT dbSNP:rs104894166). FT {ECO:0000269|PubMed:12205652, FT ECO:0000269|PubMed:17067999}. FT /FTId=VAR_015772. FT VARIANT 110 110 A -> D (in ETL1). FT /FTId=VAR_058539. FT VARIANT 122 122 I -> K (in ETL1; dbSNP:rs119488100). FT {ECO:0000269|PubMed:18625862}. FT /FTId=VAR_058540. FT VARIANT 123 123 E -> K (in ETL1). FT {ECO:0000269|PubMed:19552651}. FT /FTId=VAR_058541. FT VARIANT 136 136 R -> W (in ETL1; dbSNP:rs119488099). FT {ECO:0000269|PubMed:17562837}. FT /FTId=VAR_058542. FT VARIANT 145 145 S -> R (in ETL1; loss of protein FT secretion; does not affect glycosylation FT status of the protein). FT {ECO:0000269|PubMed:17067999}. FT /FTId=VAR_058543. FT VARIANT 154 154 L -> P (in ETL1). FT /FTId=VAR_058544. FT VARIANT 200 200 C -> R (in ETL1; loss of protein FT secretion; does not affect glycosylation FT status of the protein). FT {ECO:0000269|PubMed:17067999}. FT /FTId=VAR_058545. FT VARIANT 232 232 L -> P (in ETL1; loss of protein FT secretion; dbSNP:rs104894167). FT {ECO:0000269|PubMed:17296837}. FT /FTId=VAR_058546. FT VARIANT 298 298 I -> T (in ETL1). FT /FTId=VAR_058547. FT VARIANT 318 318 F -> C (in ETL1; loss of protein FT secretion; protein is retained in the FT endoplasmic reticulum; does not affect FT glycosylation status of the protein; FT dbSNP:rs28939075). FT {ECO:0000269|PubMed:12771268, FT ECO:0000269|PubMed:17067999}. FT /FTId=VAR_015774. FT VARIANT 383 383 E -> A (in ETL1; loss of protein FT secretion; protein is retained in the FT endoplasmic reticulum; does not affect FT glycosylation status of the protein; FT dbSNP:rs28937874). FT {ECO:0000269|PubMed:11810107, FT ECO:0000269|PubMed:17067999, FT ECO:0000269|PubMed:17296837}. FT /FTId=VAR_015773. FT VARIANT 432 432 V -> E (in ETL1). FT /FTId=VAR_058548. FT VARIANT 473 473 S -> L (in ETL1; dbSNP:rs797044999). FT {ECO:0000269|PubMed:15079010}. FT /FTId=VAR_023009. FT MUTAGEN 192 192 N->Q: Affects glycosylation; when FT associated with Q-277 and Q-422. Loss of FT protein secretion; when associated with FT Q-277 and Q-422. FT {ECO:0000269|PubMed:17067999}. FT MUTAGEN 277 277 N->Q: Affects glycosylation; when FT associated with Q-192 and Q-422. Loss of FT protein secretion; when associated with FT Q-192 and Q-422. FT {ECO:0000269|PubMed:17067999}. FT MUTAGEN 422 422 N->Q: Affects glycosylation; when FT associated with Q-192 and Q-277. Loss of FT protein secretion; when associated with FT Q-192 and Q-277. FT {ECO:0000269|PubMed:17067999}. FT STRAND 46 48 {ECO:0000244|PDB:5Y30}. FT STRAND 50 57 {ECO:0000244|PDB:5Y30}. FT STRAND 70 76 {ECO:0000244|PDB:5Y30}. FT TURN 84 89 {ECO:0000244|PDB:5Y30}. FT STRAND 94 100 {ECO:0000244|PDB:5Y30}. FT STRAND 102 106 {ECO:0000244|PDB:5Y30}. FT TURN 108 113 {ECO:0000244|PDB:5Y30}. FT STRAND 119 124 {ECO:0000244|PDB:5Y30}. FT STRAND 126 128 {ECO:0000244|PDB:5Y30}. FT TURN 132 137 {ECO:0000244|PDB:5Y30}. FT STRAND 143 145 {ECO:0000244|PDB:5Y30}. FT TURN 156 161 {ECO:0000244|PDB:5Y30}. FT STRAND 167 169 {ECO:0000244|PDB:5Y30}. FT HELIX 179 181 {ECO:0000244|PDB:5Y30}. FT HELIX 182 190 {ECO:0000244|PDB:5Y30}. FT STRAND 193 195 {ECO:0000244|PDB:5Y30}. FT HELIX 204 206 {ECO:0000244|PDB:5Y30}. FT HELIX 211 213 {ECO:0000244|PDB:5Y30}. FT HELIX 216 218 {ECO:0000244|PDB:5Y30}. FT STRAND 225 234 {ECO:0000244|PDB:5Y2Z}. FT STRAND 239 244 {ECO:0000244|PDB:5Y2Z}. FT STRAND 247 253 {ECO:0000244|PDB:5Y2Z}. FT TURN 255 257 {ECO:0000244|PDB:5Y2Z}. FT STRAND 259 266 {ECO:0000244|PDB:5Y2Z}. FT TURN 267 270 {ECO:0000244|PDB:5Y2Z}. FT STRAND 271 279 {ECO:0000244|PDB:5Y2Z}. FT STRAND 283 291 {ECO:0000244|PDB:5Y2Z}. FT STRAND 294 304 {ECO:0000244|PDB:5Y2Z}. FT STRAND 307 312 {ECO:0000244|PDB:5Y2Z}. FT TURN 313 316 {ECO:0000244|PDB:5Y2Z}. FT STRAND 317 323 {ECO:0000244|PDB:5Y2Z}. FT TURN 326 328 {ECO:0000244|PDB:5Y2Z}. FT STRAND 331 340 {ECO:0000244|PDB:5Y2Z}. FT STRAND 343 350 {ECO:0000244|PDB:5Y2Z}. FT STRAND 352 355 {ECO:0000244|PDB:5Y2Z}. FT STRAND 357 362 {ECO:0000244|PDB:5Y2Z}. FT STRAND 367 374 {ECO:0000244|PDB:5Y2Z}. FT STRAND 379 387 {ECO:0000244|PDB:5Y2Z}. FT STRAND 396 403 {ECO:0000244|PDB:5Y2Z}. FT STRAND 409 414 {ECO:0000244|PDB:5Y2Z}. FT TURN 415 418 {ECO:0000244|PDB:5Y2Z}. FT STRAND 419 425 {ECO:0000244|PDB:5Y2Z}. FT STRAND 434 440 {ECO:0000244|PDB:5Y2Z}. FT STRAND 443 449 {ECO:0000244|PDB:5Y2Z}. FT STRAND 451 461 {ECO:0000244|PDB:5Y2Z}. FT STRAND 464 475 {ECO:0000244|PDB:5Y2Z}. FT STRAND 479 484 {ECO:0000244|PDB:5Y2Z}. FT STRAND 487 492 {ECO:0000244|PDB:5Y2Z}. FT STRAND 495 497 {ECO:0000244|PDB:5Y2Z}. FT STRAND 499 505 {ECO:0000244|PDB:5Y2Z}. FT TURN 506 509 {ECO:0000244|PDB:5Y2Z}. FT STRAND 510 517 {ECO:0000244|PDB:5Y2Z}. FT STRAND 520 530 {ECO:0000244|PDB:5Y2Z}. FT STRAND 533 543 {ECO:0000244|PDB:5Y2Z}. FT STRAND 545 551 {ECO:0000244|PDB:5Y2Z}. SQ SEQUENCE 557 AA; 63818 MW; 890EEDA08D95C854 CRC64; MESERSKRMG NACIPLKRIA YFLCLLSALL LTEGKKPAKP KCPAVCTCTK DNALCENARS IPRTVPPDVI SLSFVRSGFT EISEGSFLFT PSLQLLLFTS NSFDVISDDA FIGLPHLEYL FIENNNIKSI SRHTFRGLKS LIHLSLANNN LQTLPKDIFK GLDSLTNVDL RGNSFNCDCK LKWLVEWLGH TNATVEDIYC EGPPEYKKRK INSLSSKDFD CIITEFAKSQ DLPYQSLSID TFSYLNDEYV VIAQPFTGKC IFLEWDHVEK TFRNYDNITG TSTVVCKPIV IETQLYVIVA QLFGGSHIYK RDSFANKFIK IQDIEILKIR KPNDIETFKI ENNWYFVVAD SSKAGFTTIY KWNGNGFYSH QSLHAWYRDT DVEYLEIVRT PQTLRTPHLI LSSSSQRPVI YQWNKATQLF TNQTDIPNME DVYAVKHFSV KGDVYICLTR FIGDSKVMKW GGSSFQDIQR MPSRGSMVFQ PLQINNYQYA ILGSDYSFTQ VYNWDAEKAK FVKFQELNVQ APRSFTHVSI NKRNFLFASS FKGNTQIYKH VIVDLSA //