ID LGI3_MOUSE Reviewed; 548 AA.
AC Q8K406;
DT 03-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 24-JAN-2024, entry version 151.
DE RecName: Full=Leucine-rich repeat LGI family member 3;
DE AltName: Full=Leubrin;
DE AltName: Full=Leucine-rich glioma-inactivated protein 3;
DE Flags: Precursor;
GN Name=Lgi3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Brain;
RA Yun H.-Y., Lee S.E.;
RL Submitted (NOV-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Hippocampus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; 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 [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH STX1A.
RX PubMed=18760330; DOI=10.1016/j.neulet.2008.08.044;
RA Park W.-J., Lee S.E., Kwon N.S., Baek K.J., Kim D.-S., Yun H.-Y.;
RT "Leucine-rich glioma inactivated 3 associates with syntaxin 1.";
RL Neurosci. Lett. 444:240-244(2008).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=19833108; DOI=10.1016/j.brainres.2009.10.013;
RA Herranz-Perez V., Olucha-Bordonau F.E., Morante-Redolat J.M., Perez-Tur J.;
RT "Regional distribution of the leucine-rich glioma inactivated (LGI) gene
RT family transcripts in the adult mouse brain.";
RL Brain Res. 1307:177-194(2010).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=35948005; DOI=10.1016/j.ajhg.2022.07.006;
RA Marafi D., Kozar N., Duan R., Bradley S., Yokochi K., Al Mutairi F.,
RA Saadi N.W., Whalen S., Brunet T., Kotzaeridou U., Choukair D., Keren B.,
RA Nava C., Kato M., Arai H., Froukh T., Faqeih E.A., Al Asmari A.M.,
RA Saleh M.M., Pinto Vairo F., Pichurin P.N., Klee E.W., Schmitz C.T.,
RA Grochowski C.M., Mitani T., Herman I., Calame D.G., Fatih J.M., Du H.,
RA Coban-Akdemir Z., Pehlivan D., Jhangiani S.N., Gibbs R.A., Miyatake S.,
RA Matsumoto N., Wagstaff L.J., Posey J.E., Lupski J.R., Meijer D., Wagner M.;
RT "A reverse genetics and genomics approach to gene paralog function and
RT disease: Myokymia and the juxtaparanode.";
RL Am. J. Hum. Genet. 109:1713-1723(2022).
CC -!- FUNCTION: May participate in the regulation of neuronal exocytosis.
CC {ECO:0000269|PubMed:18760330}.
CC -!- SUBUNIT: Interacts with STX1A. {ECO:0000269|PubMed:18760330}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q8N145}.
CC Cytoplasmic vesicle, secretory vesicle, synaptic vesicle
CC {ECO:0000269|PubMed:18760330}. Synapse, synaptosome
CC {ECO:0000269|PubMed:18760330}. Cell projection, axon
CC {ECO:0000269|PubMed:35948005}. Note=Found in the synaptosomal membrane
CC fraction. Within peripheral myelinated axons, LGI3 is highly expressed
CC at the juxtaparanodal membrane and colocalizes with the voltage-gated
CC potassium channels Kv1.1 (KCNA1) and Kv1.2 (KCNA2), and CNTNAP2, DLG4,
CC ADAM22 and ADAM23 (PubMed:35948005). {ECO:0000269|PubMed:35948005}.
CC -!- TISSUE SPECIFICITY: Brain. {ECO:0000269|PubMed:19833108}.
CC -!- DISRUPTION PHENOTYPE: LGI3-null mice are fertile, have a normal
CC lifespan, and do not show obvious behavioral abnormalities. They show
CC strongly reduced expression and mislocalization of Kv1 channel
CC complexes that infringe on the paranodal domain. Kv1 channel complexes
CC mislocalization is further exacerbated following nerve injury, as Kv1
CC complexes are confined to the paranodal domain in remyelinated axons.
CC {ECO:0000269|PubMed:35948005}.
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DR EMBL; AF515590; AAM55219.1; -; mRNA.
DR EMBL; AY174077; AAO19739.1; -; mRNA.
DR EMBL; AK049831; BAC33943.1; -; mRNA.
DR EMBL; BC055315; AAH55315.1; -; mRNA.
DR EMBL; BC061460; AAH61460.1; -; mRNA.
DR CCDS; CCDS27255.1; -.
DR RefSeq; NP_660254.1; NM_145219.4.
DR AlphaFoldDB; Q8K406; -.
DR SMR; Q8K406; -.
DR STRING; 10090.ENSMUSP00000046705; -.
DR GlyCosmos; Q8K406; 2 sites, No reported glycans.
DR GlyGen; Q8K406; 3 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q8K406; -.
DR PhosphoSitePlus; Q8K406; -.
DR SwissPalm; Q8K406; -.
DR MaxQB; Q8K406; -.
DR PaxDb; 10090-ENSMUSP00000046705; -.
DR ProteomicsDB; 286189; -.
DR Antibodypedia; 22532; 157 antibodies from 25 providers.
DR DNASU; 213469; -.
DR Ensembl; ENSMUST00000047331.8; ENSMUSP00000046705.7; ENSMUSG00000033595.8.
DR GeneID; 213469; -.
DR KEGG; mmu:213469; -.
DR UCSC; uc007uoh.2; mouse.
DR AGR; MGI:2182619; -.
DR CTD; 203190; -.
DR MGI; MGI:2182619; Lgi3.
DR VEuPathDB; HostDB:ENSMUSG00000033595; -.
DR eggNOG; ENOG502QSAR; Eukaryota.
DR GeneTree; ENSGT00940000160296; -.
DR HOGENOM; CLU_036403_0_0_1; -.
DR InParanoid; Q8K406; -.
DR OMA; EGDWFFA; -.
DR OrthoDB; 4083661at2759; -.
DR PhylomeDB; Q8K406; -.
DR TreeFam; TF333155; -.
DR Reactome; R-MMU-5682910; LGI-ADAM interactions.
DR BioGRID-ORCS; 213469; 2 hits in 76 CRISPR screens.
DR PRO; PR:Q8K406; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q8K406; Protein.
DR Bgee; ENSMUSG00000033595; Expressed in primary visual cortex and 164 other cell types or tissues.
DR ExpressionAtlas; Q8K406; baseline and differential.
DR Genevisible; Q8K406; MM.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0044224; C:juxtaparanode region of axon; IDA:UniProtKB.
DR GO; GO:0008021; C:synaptic vesicle; IDA:UniProtKB.
DR GO; GO:0006887; P:exocytosis; IEA:UniProtKB-KW.
DR GO; GO:0017157; P:regulation of exocytosis; IDA:UniProtKB.
DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 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 InterPro; IPR011041; Quinoprot_gluc/sorb_DH.
DR PANTHER; PTHR24367:SF10; LEUCINE-RICH REPEAT LGI FAMILY MEMBER 3; 1.
DR PANTHER; PTHR24367; LEUCINE-RICH REPEAT-CONTAINING PROTEIN; 1.
DR Pfam; PF03736; EPTP; 7.
DR Pfam; PF13855; LRR_8; 1.
DR SMART; SM00369; LRR_TYP; 3.
DR SMART; SM00082; LRRCT; 1.
DR SUPFAM; SSF52058; L domain-like; 1.
DR SUPFAM; SSF50952; Soluble quinoprotein glucose dehydrogenase; 1.
DR PROSITE; PS50912; EAR; 7.
DR PROSITE; PS51450; LRR; 3.
PE 1: Evidence at protein level;
KW Cell projection; Cytoplasmic vesicle; Exocytosis; Glycoprotein;
KW Leucine-rich repeat; Reference proteome; Repeat; Secreted; Signal; Synapse;
KW Synaptosome.
FT SIGNAL 1..30
FT /evidence="ECO:0000255"
FT CHAIN 31..548
FT /note="Leucine-rich repeat LGI family member 3"
FT /id="PRO_0000017711"
FT DOMAIN 31..64
FT /note="LRRNT"
FT REPEAT 89..110
FT /note="LRR 1"
FT REPEAT 113..134
FT /note="LRR 2"
FT REPEAT 137..158
FT /note="LRR 3"
FT DOMAIN 170..220
FT /note="LRRCT"
FT REPEAT 222..264
FT /note="EAR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00075"
FT REPEAT 268..310
FT /note="EAR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00075"
FT REPEAT 314..361
FT /note="EAR 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00075"
FT REPEAT 363..406
FT /note="EAR 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00075"
FT REPEAT 410..453
FT /note="EAR 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00075"
FT REPEAT 455..497
FT /note="EAR 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00075"
FT REPEAT 501..543
FT /note="EAR 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00075"
FT CARBOHYD 189
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 311
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 548 AA; 61818 MW; 2DB303936354B958 CRC64;
MAGLRARRGP GRRLLVLSTL GFCLMLQVSA KRPPKTPPCP PSCSCTRDTA FCVDSKSVPK
NLPSEVISLT LVNAAFSEIQ DGAFSHLPLL QFLLLNSNKF TLIGDNAFIG LSHLQYLFIE
NNDIWALSKF TFRGLKSLTH LSLANNNLQT LPRDIFRPLD ILSDLDLRGN ALNCDCKVKW
LVEWLAHTNT TVAPIYCASP PRFQEHKVQD LPLREFDCIT TDFVLYQTLS FPAVSAEPFL
YSSDLYLALA QPGASACTIL KWDYVERQLR DYDRIPAPSA VHCKPMVVDG QLYVVVAQLF
GGSYIYHWDP NTTRFTKLQD IDPQRVRKPN DLEAFRIDGD WFFAVADSSK AGATSLYRWH
QNGFYSHQAL HAWHRDTDLE FVDGEGKPRL IVSSSSQAPV IYQWSRSQKQ FVAQGEVTQV
PDAQAVKHFR AGRDSYLCLS RYIGDSKILR WEGTRFSEVQ ALPSRGSLAL QPFLVGGHRY
LALGSDFSFT QIYQWDEGRQ KFVRFQELAV QAPRAFCYMP AGDAQLLLAP SFKGQTLVYR
HVVVDLSA
//
