LGI1_HUMAN
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 03-AUG-2022, entry version 185.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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., Saenz A.,
RA Poza J.J., Galan J., Gesk S., Sarafidou T., Mautner V.F., Binelli S.,
RA Staub E., Hinzmann B., French L., Prud'homme J.-F., Passarelli D.,
RA Scannapieco P., Tassinari C.A., Avanzini G., Marti-Masso J.F., Kluwe L.,
RA Deloukas P., Moschonas N.K., Michelucci R., Siebert R., Nobile C.,
RA Perez-Tur J., Lopez de Munain A.;
RT "Mutations in the LGI1/Epitempin gene on 10q24 cause autosomal dominant
RT 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., 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] (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., 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 [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., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., 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., 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 [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 project:
RT 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 cells
RT through the ERK1/2 pathway.";
RL J. Biol. Chem. 279:23151-23157(2004).
RN [9]
RP ERRATUM OF PUBMED:15047712.
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 AND
RP ASN-422, AND CHARACTERIZATION OF VARIANTS ETL1 ARG-46; ARG-145; ARG-200;
RP 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 the
RT 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 apoptosis
RT 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 auditory
RT 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., Manfredi M.,
RA Dallapiccola B., Giallonardo A.T.;
RT "Epilepsy with auditory features: a LGI1 gene mutation suggests a loss-of-
RT 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 epilepsy
RT 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., Neufeld M.Y.,
RA 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., Striano P.,
RA 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., Egeo G.,
RA Pantano P., Maraviglia B., Bozzao L., Manfredi M., Prencipe M.,
RA 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: electroclinical,
RT genetic, and EEG/fMRI findings.";
RL Epilepsia 50:2481-2486(2009).
CC -!- FUNCTION: Regulates voltage-gated potassium channels assembled from
CC KCNA1, KCNA4 and KCNAB1. It slows down channel inactivation by
CC precluding channel closure mediated by the KCNAB1 subunit. Ligand for
CC ADAM22 that positively regulates synaptic transmission mediated by
CC AMPA-type glutamate receptors (By similarity). Plays a role in
CC suppressing the production of MMP1/3 through the phosphatidylinositol
CC 3-kinase/ERK pathway. May play a role in the control of neuroblastoma
CC cell survival. {ECO:0000250, ECO:0000269|PubMed:15047712,
CC ECO:0000269|PubMed:16518856}.
CC -!- SUBUNIT: Oligomer. Interacts with KCNA1 within a complex containing
CC KCNA1, KCNA4 and KCNAB1. Part of a complex containing ADAM22,
CC DLG4/PSD95 and CACNG2/Stargazin (PubMed:27066583). Can bind to ADAM11
CC and ADAM23. {ECO:0000250, ECO:0000269|PubMed:27066583}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16787412,
CC ECO:0000269|PubMed:17067999, ECO:0000269|PubMed:17296837}. Synapse
CC {ECO:0000250}. Note=Isoform 1 but not isoform 2 is secreted. Isoform 1
CC is enriched in the Golgi apparatus while isoform 2 accumulates in the
CC 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 tumors
CC and significantly reduced or absent in malignant gliomas. Isoform 1 is
CC absent in the cerebellum and is detectable in the occipital cortex and
CC hippocampus; higher amounts are observed in the parietal and frontal
CC cortices, putamen, and, particularly, in the temporal neocortex, where
CC it is 3.5 times more abundant than in the hippocampus (at protein
CC level). Isoform 3 shows the highest expression in the occipital cortex
CC and the lowest in the hippocampus (at protein level).
CC {ECO:0000269|PubMed:16518856, 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]: A
CC focal form of epilepsy characterized by recurrent seizures that arise
CC from foci within the temporal lobe. Seizures are usually accompanied by
CC 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}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/LGI1ID311ch10q23.html";
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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 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 AlphaFoldDB; O95970; -.
DR SMR; O95970; -.
DR BioGRID; 114645; 65.
DR CORUM; O95970; -.
DR STRING; 9606.ENSP00000360472; -.
DR GlyGen; O95970; 4 sites.
DR iPTMnet; O95970; -.
DR PhosphoSitePlus; O95970; -.
DR BioMuta; LGI1; -.
DR EPD; O95970; -.
DR jPOST; O95970; -.
DR MassIVE; O95970; -.
DR PaxDb; O95970; -.
DR PeptideAtlas; O95970; -.
DR PRIDE; O95970; -.
DR ProteomicsDB; 51151; -. [O95970-1]
DR ProteomicsDB; 51152; -. [O95970-2]
DR ProteomicsDB; 51153; -. [O95970-3]
DR TopDownProteomics; O95970-3; -. [O95970-3]
DR ABCD; O95970; 1 sequenced antibody.
DR Antibodypedia; 30497; 279 antibodies from 34 providers.
DR DNASU; 9211; -.
DR Ensembl; ENST00000371413.4; ENSP00000360467.3; ENSG00000108231.14. [O95970-2]
DR Ensembl; ENST00000371418.9; ENSP00000360472.4; ENSG00000108231.14. [O95970-1]
DR Ensembl; ENST00000630047.2; ENSP00000485917.1; ENSG00000108231.14. [O95970-3]
DR GeneID; 9211; -.
DR KEGG; hsa:9211; -.
DR MANE-Select; ENST00000371418.9; ENSP00000360472.4; NM_005097.4; NP_005088.1.
DR UCSC; uc001kjc.5; human. [O95970-1]
DR CTD; 9211; -.
DR DisGeNET; 9211; -.
DR GeneCards; LGI1; -.
DR GeneReviews; LGI1; -.
DR HGNC; HGNC:6572; LGI1.
DR HPA; ENSG00000108231; Group enriched (brain, choroid plexus).
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 VEuPathDB; HostDB:ENSG00000108231; -.
DR eggNOG; ENOG502REXX; Eukaryota.
DR GeneTree; ENSGT00940000159793; -.
DR HOGENOM; CLU_956325_0_0_1; -.
DR InParanoid; O95970; -.
DR OMA; FTVGSWQ; -.
DR PhylomeDB; O95970; -.
DR TreeFam; TF333155; -.
DR PathwayCommons; O95970; -.
DR Reactome; R-HSA-5682910; LGI-ADAM interactions.
DR SignaLink; O95970; -.
DR BioGRID-ORCS; 9211; 45 hits in 1066 CRISPR screens.
DR ChiTaRS; LGI1; human.
DR GeneWiki; LGI1; -.
DR GenomeRNAi; 9211; -.
DR Pharos; O95970; Tbio.
DR PRO; PR:O95970; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; O95970; protein.
DR Bgee; ENSG00000108231; Expressed in pons and 134 other tissues.
DR ExpressionAtlas; O95970; baseline and differential.
DR Genevisible; O95970; HS.
DR GO; GO:0070161; C:anchoring 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: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: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 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; Disease variant; Epilepsy;
KW Glycoprotein; Leucine-rich repeat; Reference proteome; Repeat; Secreted;
KW Signal; Synapse.
FT SIGNAL 1..34
FT /evidence="ECO:0000255"
FT CHAIN 35..557
FT /note="Leucine-rich glioma-inactivated protein 1"
FT /id="PRO_0000017705"
FT DOMAIN 35..72
FT /note="LRRNT"
FT REPEAT 92..113
FT /note="LRR 1"
FT REPEAT 116..137
FT /note="LRR 2"
FT REPEAT 140..161
FT /note="LRR 3"
FT DOMAIN 173..223
FT /note="LRRCT"
FT REPEAT 225..267
FT /note="EAR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00075"
FT REPEAT 271..313
FT /note="EAR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00075"
FT REPEAT 317..364
FT /note="EAR 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00075"
FT REPEAT 366..415
FT /note="EAR 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00075"
FT REPEAT 419..462
FT /note="EAR 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00075"
FT REPEAT 464..506
FT /note="EAR 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00075"
FT REPEAT 510..552
FT /note="EAR 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00075"
FT CARBOHYD 192
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 277
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 422
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 96..143
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_038234"
FT VAR_SEQ 280..291
FT /note="GTSTVVCKPIVI -> VLREIHRFTNMS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11978770"
FT /id="VSP_007678"
FT VAR_SEQ 292..557
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11978770"
FT /id="VSP_007679"
FT VARIANT 26
FT /note="L -> R (in ETL1; probably affects signal sequence
FT processing and secretion)"
FT /evidence="ECO:0000269|PubMed:12601709"
FT /id="VAR_015771"
FT VARIANT 42
FT /note="C -> G (in ETL1; dbSNP:rs797044996)"
FT /evidence="ECO:0000269|PubMed:15079010"
FT /id="VAR_023008"
FT VARIANT 42
FT /note="C -> R (in ETL1; dbSNP:rs797044996)"
FT /id="VAR_058538"
FT VARIANT 46
FT /note="C -> R (in ETL1; loss of protein secretion; does not
FT affect glycosylation status of the protein;
FT dbSNP:rs104894166)"
FT /evidence="ECO:0000269|PubMed:12205652,
FT ECO:0000269|PubMed:17067999"
FT /id="VAR_015772"
FT VARIANT 110
FT /note="A -> D (in ETL1)"
FT /id="VAR_058539"
FT VARIANT 122
FT /note="I -> K (in ETL1; dbSNP:rs119488100)"
FT /evidence="ECO:0000269|PubMed:18625862"
FT /id="VAR_058540"
FT VARIANT 123
FT /note="E -> K (in ETL1)"
FT /evidence="ECO:0000269|PubMed:19552651"
FT /id="VAR_058541"
FT VARIANT 136
FT /note="R -> W (in ETL1; dbSNP:rs119488099)"
FT /evidence="ECO:0000269|PubMed:17562837"
FT /id="VAR_058542"
FT VARIANT 145
FT /note="S -> R (in ETL1; loss of protein secretion; does not
FT affect glycosylation status of the protein)"
FT /evidence="ECO:0000269|PubMed:17067999"
FT /id="VAR_058543"
FT VARIANT 154
FT /note="L -> P (in ETL1)"
FT /id="VAR_058544"
FT VARIANT 200
FT /note="C -> R (in ETL1; loss of protein secretion; does not
FT affect glycosylation status of the protein)"
FT /evidence="ECO:0000269|PubMed:17067999"
FT /id="VAR_058545"
FT VARIANT 232
FT /note="L -> P (in ETL1; loss of protein secretion;
FT dbSNP:rs104894167)"
FT /evidence="ECO:0000269|PubMed:17296837"
FT /id="VAR_058546"
FT VARIANT 298
FT /note="I -> T (in ETL1)"
FT /id="VAR_058547"
FT VARIANT 318
FT /note="F -> C (in ETL1; loss of protein secretion; protein
FT is retained in the endoplasmic reticulum; does not affect
FT glycosylation status of the protein; dbSNP:rs28939075)"
FT /evidence="ECO:0000269|PubMed:12771268,
FT ECO:0000269|PubMed:17067999"
FT /id="VAR_015774"
FT VARIANT 383
FT /note="E -> A (in ETL1; loss of protein secretion; protein
FT is retained in the endoplasmic reticulum; does not affect
FT glycosylation status of the protein; dbSNP:rs28937874)"
FT /evidence="ECO:0000269|PubMed:11810107,
FT ECO:0000269|PubMed:17067999, ECO:0000269|PubMed:17296837"
FT /id="VAR_015773"
FT VARIANT 432
FT /note="V -> E (in ETL1)"
FT /id="VAR_058548"
FT VARIANT 473
FT /note="S -> L (in ETL1; dbSNP:rs797044999)"
FT /evidence="ECO:0000269|PubMed:15079010"
FT /id="VAR_023009"
FT MUTAGEN 192
FT /note="N->Q: Affects glycosylation; when associated with Q-
FT 277 and Q-422. Loss of protein secretion; when associated
FT with Q-277 and Q-422."
FT /evidence="ECO:0000269|PubMed:17067999"
FT MUTAGEN 277
FT /note="N->Q: Affects glycosylation; when associated with Q-
FT 192 and Q-422. Loss of protein secretion; when associated
FT with Q-192 and Q-422."
FT /evidence="ECO:0000269|PubMed:17067999"
FT MUTAGEN 422
FT /note="N->Q: Affects glycosylation; when associated with Q-
FT 192 and Q-277. Loss of protein secretion; when associated
FT with Q-192 and Q-277."
FT /evidence="ECO:0000269|PubMed:17067999"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:5Y30"
FT STRAND 50..57
FT /evidence="ECO:0007829|PDB:5Y30"
FT STRAND 70..76
FT /evidence="ECO:0007829|PDB:5Y30"
FT TURN 84..89
FT /evidence="ECO:0007829|PDB:5Y30"
FT STRAND 94..100
FT /evidence="ECO:0007829|PDB:5Y30"
FT STRAND 102..106
FT /evidence="ECO:0007829|PDB:5Y30"
FT TURN 108..113
FT /evidence="ECO:0007829|PDB:5Y30"
FT STRAND 119..124
FT /evidence="ECO:0007829|PDB:5Y30"
FT STRAND 126..128
FT /evidence="ECO:0007829|PDB:5Y30"
FT TURN 132..137
FT /evidence="ECO:0007829|PDB:5Y30"
FT STRAND 143..145
FT /evidence="ECO:0007829|PDB:5Y30"
FT TURN 156..161
FT /evidence="ECO:0007829|PDB:5Y30"
FT STRAND 167..169
FT /evidence="ECO:0007829|PDB:5Y30"
FT HELIX 179..181
FT /evidence="ECO:0007829|PDB:5Y30"
FT HELIX 182..190
FT /evidence="ECO:0007829|PDB:5Y30"
FT STRAND 193..195
FT /evidence="ECO:0007829|PDB:5Y30"
FT HELIX 204..206
FT /evidence="ECO:0007829|PDB:5Y30"
FT HELIX 211..213
FT /evidence="ECO:0007829|PDB:5Y30"
FT HELIX 216..218
FT /evidence="ECO:0007829|PDB:5Y30"
FT STRAND 225..234
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 239..244
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 247..253
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT TURN 255..257
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 259..266
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT TURN 267..270
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 271..279
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 283..291
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 294..304
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 307..312
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT TURN 313..316
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 317..323
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT TURN 326..328
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 331..340
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 343..350
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 352..355
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 357..362
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 367..374
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 379..387
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 396..403
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 409..414
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT TURN 415..418
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 419..425
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 434..440
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 443..449
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 451..461
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 464..475
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 479..484
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 487..492
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 495..497
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 499..505
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT TURN 506..509
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 510..517
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 520..530
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 533..543
FT /evidence="ECO:0007829|PDB:5Y2Z"
FT STRAND 545..551
FT /evidence="ECO:0007829|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
