LGI4_HUMAN
ID LGI4_HUMAN Reviewed; 537 AA.
AC Q8N135; B2RN53; B9EGS7; Q5M8T1;
DT 03-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Leucine-rich repeat LGI family member 4;
DE AltName: Full=LGI1-like protein 3;
DE AltName: Full=Leucine-rich glioma-inactivated protein 4;
DE Flags: Precursor;
GN Name=LGI4; Synonyms=LGIL3; ORFNames=UNQ6515/PRO21485;
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), AND TISSUE SPECIFICITY.
RX PubMed=12023020; DOI=10.1016/s0014-5793(02)02713-8;
RA Gu W., Wevers A., Schroder H., Grzeschik K.H., Derst C., Brodtkorb E.,
RA de Vos R., Steinlein O.K.;
RT "The LGI1 gene involved in lateral temporal lobe epilepsy belongs to a new
RT subfamily of leucine-rich repeat proteins.";
RL FEBS Lett. 519:71-76(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=12095917; DOI=10.1093/hmg/11.15.1757;
RA Scheel H., Tomiuk S., Hofmann K.;
RT "A common protein interaction domain links two recently identified epilepsy
RT genes.";
RL Hum. Mol. Genet. 11:1757-1762(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=12217514; DOI=10.1016/s0968-0004(02)02163-1;
RA Staub E., Perez-Tur J., Siebert R., Nobile C., Moschonas N.K., Deloukas P.,
RA Hinzmann B.;
RT "The novel EPTP repeat defines a superfamily of proteins implicated in
RT epileptic disorders.";
RL Trends Biochem. Sci. 27:441-444(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Testis;
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 [6]
RP SUBCELLULAR LOCATION, INVOLVEMENT IN AMC1, AND VARIANTS AMC1 PRO-258;
RP 288-TRP--ALA-537 DEL AND ASP-434.
RX PubMed=28318499; DOI=10.1016/j.ajhg.2017.02.006;
RA Xue S., Maluenda J., Marguet F., Shboul M., Quevarec L., Bonnard C.,
RA Ng A.Y., Tohari S., Tan T.T., Kong M.K., Monaghan K.G., Cho M.T.,
RA Siskind C.E., Sampson J.B., Rocha C.T., Alkazaleh F., Gonzales M.,
RA Rigonnot L., Whalen S., Gut M., Gut I., Bucourt M., Venkatesh B.,
RA Laquerriere A., Reversade B., Melki J.;
RT "Loss-of-function mutations in LGI4, a secreted ligand involved in schwann
RT cell myelination, are responsible for arthrogryposis multiplex congenita.";
RL Am. J. Hum. Genet. 100:659-665(2017).
CC -!- FUNCTION: Component of Schwann cell signaling pathway(s) that controls
CC axon segregation and myelin formation (By similarity).
CC {ECO:0000250|UniProtKB:Q8K1S1}.
CC -!- SUBUNIT: Can bind to ADAM11, ADAM22 and ADAM23. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8N135-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8N135-2; Sequence=VSP_009230, VSP_009231;
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest expression in brain.
CC {ECO:0000269|PubMed:12023020}.
CC -!- DISEASE: Arthrogryposis multiplex congenita 1, neurogenic, with myelin
CC defect (AMC1) [MIM:617468]: A form of arthrogryposis multiplex
CC congenita, a developmental condition characterized by multiple joint
CC contractures resulting from reduced or absent fetal movements. AMC1 is
CC an autosomal recessive severe form with onset in utero. Most affected
CC individuals die in utero. Those who survive have generalized
CC contractures and hypotonia. The disorder is caused by a neurogenic
CC defect and poor or absent myelin formation around peripheral nerves
CC rather than by a muscular defect. {ECO:0000269|PubMed:28318499}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
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DR EMBL; AF467954; AAM49552.1; -; mRNA.
DR EMBL; AJ487959; CAD32306.1; -; mRNA.
DR EMBL; AJ487519; CAD31787.1; -; mRNA.
DR EMBL; AY358121; AAQ88488.1; -; mRNA.
DR EMBL; BC087848; AAH87848.1; -; mRNA.
DR EMBL; BC136694; AAI36695.1; -; mRNA.
DR EMBL; BC136697; AAI36698.1; -; mRNA.
DR CCDS; CCDS12444.1; -. [Q8N135-1]
DR RefSeq; NP_644813.1; NM_139284.2. [Q8N135-1]
DR AlphaFoldDB; Q8N135; -.
DR SMR; Q8N135; -.
DR BioGRID; 127855; 1.
DR STRING; 9606.ENSP00000312273; -.
DR GlyGen; Q8N135; 2 sites, 2 O-linked glycans (1 site).
DR iPTMnet; Q8N135; -.
DR PhosphoSitePlus; Q8N135; -.
DR BioMuta; LGI4; -.
DR DMDM; 32469741; -.
DR MassIVE; Q8N135; -.
DR PaxDb; Q8N135; -.
DR PeptideAtlas; Q8N135; -.
DR PRIDE; Q8N135; -.
DR ProteomicsDB; 71534; -. [Q8N135-1]
DR ProteomicsDB; 71535; -. [Q8N135-2]
DR Antibodypedia; 29282; 165 antibodies from 25 providers.
DR DNASU; 163175; -.
DR Ensembl; ENST00000310123.8; ENSP00000312273.3; ENSG00000153902.14. [Q8N135-1]
DR Ensembl; ENST00000591633.2; ENSP00000467784.1; ENSG00000153902.14. [Q8N135-2]
DR GeneID; 163175; -.
DR KEGG; hsa:163175; -.
DR MANE-Select; ENST00000310123.8; ENSP00000312273.3; NM_139284.3; NP_644813.1.
DR UCSC; uc002nxx.3; human. [Q8N135-1]
DR CTD; 163175; -.
DR DisGeNET; 163175; -.
DR GeneCards; LGI4; -.
DR HGNC; HGNC:18712; LGI4.
DR HPA; ENSG00000153902; Low tissue specificity.
DR MalaCards; LGI4; -.
DR MIM; 608303; gene.
DR MIM; 617468; phenotype.
DR neXtProt; NX_Q8N135; -.
DR OpenTargets; ENSG00000153902; -.
DR Orphanet; 2680; Hypomyelination neuropathy-arthrogryposis syndrome.
DR PharmGKB; PA38656; -.
DR VEuPathDB; HostDB:ENSG00000153902; -.
DR eggNOG; ENOG502SHYJ; Eukaryota.
DR GeneTree; ENSGT00940000162018; -.
DR HOGENOM; CLU_036403_0_0_1; -.
DR InParanoid; Q8N135; -.
DR OMA; GKCPPRC; -.
DR PhylomeDB; Q8N135; -.
DR TreeFam; TF333155; -.
DR PathwayCommons; Q8N135; -.
DR Reactome; R-HSA-5682910; LGI-ADAM interactions.
DR BioGRID-ORCS; 163175; 12 hits in 1062 CRISPR screens.
DR ChiTaRS; LGI4; human.
DR GenomeRNAi; 163175; -.
DR Pharos; Q8N135; Tbio.
DR PRO; PR:Q8N135; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q8N135; protein.
DR Bgee; ENSG00000153902; Expressed in tibial nerve and 147 other tissues.
DR ExpressionAtlas; Q8N135; baseline and differential.
DR Genevisible; Q8N135; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0008344; P:adult locomotory behavior; IEA:Ensembl.
DR GO; GO:0014009; P:glial cell proliferation; IEA:Ensembl.
DR GO; GO:0022011; P:myelination in peripheral nervous system; IBA:GO_Central.
DR GO; GO:0042551; P:neuron maturation; IBA:GO_Central.
DR GO; GO:0031641; P:regulation of myelination; IMP: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; 3.
DR Pfam; PF13855; LRR_8; 1.
DR SMART; SM00369; LRR_TYP; 3.
DR SMART; SM00082; LRRCT; 1.
DR PROSITE; PS50912; EAR; 7.
DR PROSITE; PS51450; LRR; 3.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Glycoprotein; Leucine-rich repeat;
KW Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..537
FT /note="Leucine-rich repeat LGI family member 4"
FT /id="PRO_0000017712"
FT REPEAT 53..74
FT /note="LRR 1"
FT REPEAT 77..98
FT /note="LRR 2"
FT REPEAT 101..122
FT /note="LRR 3"
FT REPEAT 125..146
FT /note="LRR 4"
FT DOMAIN 158..208
FT /note="LRRCT"
FT REPEAT 210..252
FT /note="EAR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00075"
FT REPEAT 256..298
FT /note="EAR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00075"
FT REPEAT 302..349
FT /note="EAR 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00075"
FT REPEAT 351..394
FT /note="EAR 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00075"
FT REPEAT 396..439
FT /note="EAR 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00075"
FT REPEAT 441..483
FT /note="EAR 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00075"
FT REPEAT 487..532
FT /note="EAR 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00075"
FT CARBOHYD 177
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 210..261
FT /note="ELSWFQTVGESALSVEPFSYQGEPHIVLAQPFAGRCLILSWDYSLQRFRPEE
FT -> GGGLSRWGGRREIWGKGCQGQEARLTPCPAISRSGKTLSKQHCLPEPQFSHL (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:12975309,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_009230"
FT VAR_SEQ 262..537
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12975309,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_009231"
FT VARIANT 258
FT /note="R -> P (in AMC1; dbSNP:rs755500591)"
FT /evidence="ECO:0000269|PubMed:28318499"
FT /id="VAR_080055"
FT VARIANT 288..537
FT /note="Missing (in AMC1)"
FT /evidence="ECO:0000269|PubMed:28318499"
FT /id="VAR_080056"
FT VARIANT 434
FT /note="V -> D (in AMC1; dbSNP:rs1064797094)"
FT /evidence="ECO:0000269|PubMed:28318499"
FT /id="VAR_080057"
SQ SEQUENCE 537 AA; 59141 MW; 47B920C809679926 CRC64;
MGGAGILLLL LAGAGVVVAW RPPKGKCPLR CSCSKDSALC EGSPDLPVSF SPTLLSLSLV
RTGVTQLKAG SFLRIPSLHL LLFTSNSFSV IEDDAFAGLS HLQYLFIEDN EIGSISKNAL
RGLRSLTHLS LANNHLETLP RFLFRGLDTL THVDLRGNPF QCDCRVLWLL QWMPTVNASV
GTGACAGPAS LSHMQLHHLD PKTFKCRAIE LSWFQTVGES ALSVEPFSYQ GEPHIVLAQP
FAGRCLILSW DYSLQRFRPE EELPAASVVS CKPLVLGPSL FVLAARLWGG SQLWARPSPG
LRLAPTQTLA PRRLLRPNDA ELLWLEGQPC FVVADASKAG STTLLCRDGP GFYPHQSLHA
WHRDTDAEAL ELDGRPHLLL ASASQRPVLF HWTGGRFERR TDIPEAEDVY ATRHFQAGGD
VFLCLTRYIG DSMVMRWDGS MFRLLQQLPS RGAHVFQPLL IARDQLAILG SDFAFSQVLR
LEPDKGLLEP LQELGPPALV APRAFAHITM AGRRFLFAAC FKGPTQIYQH HEIDLSA
