Reviewed, UniProtKB/Swiss-Prot O95970 (LGI1_HUMAN)

Names and origin

Protein names

Recommended name:
    Leucine-rich glioma-inactivated protein 1
Alternative name(s):
    Epitempin-1

Gene names

Name:	LGI1
Synonyms:	EPT
ORF Names:	UNQ775/PRO1569

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	557 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Subcellular location	Secreted Potential.
Tissue specificity	Predominantly expressed in neural tissues, especially in brain. Expression is reduced in low-grade brain tumors and significantly reduced or absent in malignant gliomas.
Involvement in disease	Defects in LGI1 are the cause of lateral temporal lobe epilepsy autosomal dominant (ADLTE) [MIM:600512]; also known as autosomal dominant partial epilepsy with auditory features (ADPEAF). ADLTE is a form of epilepsy characterized by partial seizures, usually preceded by auditory signs. Ref.2 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10
Sequence similarities	Contains 7 EAR repeats. Contains 3 LRR (leucine-rich) repeats.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Epilepsy
Domain	Leucine-rich repeat Repeat Signal
PTM	Glycoprotein
Gene Ontology (GO)
Biological process	cell proliferation Ref.1 Traceable author statement. Source: ProtInc nervous system development Ref.1 Traceable author statement. Source: ProtInc
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O95970-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O95970-2)

The sequence of this isoform differs from the canonical sequence as follows:
     280-291: GTSTVVCKPIVI → VLREIHRFTNMS
     292-557: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 34	34	Potential
	Chain	35 – 557	523	Leucine-rich glioma-inactivated protein 1		PRO_0000017705
Regions
	Repeat	90 – 113	24	LRR 1
	Repeat	114 – 137	24	LRR 2
	Repeat	138 – 161	24	LRR 3
	Repeat	224 – 267	44	EAR 1
	Repeat	270 – 313	44	EAR 2
	Repeat	316 – 364	49	EAR 3
	Repeat	365 – 415	51	EAR 4
	Repeat	418 – 462	45	EAR 5
	Repeat	463 – 506	44	EAR 6
	Repeat	509 – 552	44	EAR 7
Amino acid modifications
	Glycosylation	192	1	N-linked (GlcNAc...) Potential
	Glycosylation	277	1	N-linked (GlcNAc...) Potential
	Glycosylation	422	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	280 – 291	12	GTSTV…KPIVI → VLREIHRFTNMS in isoform 2.		VSP_007678
	Alternative sequence	292 – 557	266	Missing in isoform 2.		VSP_007679
	Natural variant	26	1	L → R in ADLTE; probably affects signal sequence processing and secretion. Ref.8		VAR_015771
	Natural variant	42	1	C → G in ADLTE. Ref.10		VAR_023008
	Natural variant	46	1	C → R in ADLTE. Ref.7		VAR_015772
	Natural variant	318	1	F → C in ADLTE. Ref.9		VAR_015774
	Natural variant	383	1	E → A in ADLTE. Ref.6		VAR_015773
	Natural variant	473	1	S → L in ADLTE. Ref.10		VAR_023009

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: 890EEDA08D95C854	FASTA	557	63,818
	10 20 30 40 50 60 MESERSKRMG NACIPLKRIA YFLCLLSALL LTEGKKPAKP KCPAVCTCTK DNALCENARS 70 80 90 100 110 120 IPRTVPPDVI SLSFVRSGFT EISEGSFLFT PSLQLLLFTS NSFDVISDDA FIGLPHLEYL 130 140 150 160 170 180 FIENNNIKSI SRHTFRGLKS LIHLSLANNN LQTLPKDIFK GLDSLTNVDL RGNSFNCDCK 190 200 210 220 230 240 LKWLVEWLGH TNATVEDIYC EGPPEYKKRK INSLSSKDFD CIITEFAKSQ DLPYQSLSID 250 260 270 280 290 300 TFSYLNDEYV VIAQPFTGKC IFLEWDHVEK TFRNYDNITG TSTVVCKPIV IETQLYVIVA 310 320 330 340 350 360 QLFGGSHIYK RDSFANKFIK IQDIEILKIR KPNDIETFKI ENNWYFVVAD SSKAGFTTIY 370 380 390 400 410 420 KWNGNGFYSH QSLHAWYRDT DVEYLEIVRT PQTLRTPHLI LSSSSQRPVI YQWNKATQLF 430 440 450 460 470 480 TNQTDIPNME DVYAVKHFSV KGDVYICLTR FIGDSKVMKW GGSSFQDIQR MPSRGSMVFQ 490 500 510 520 530 540 PLQINNYQYA ILGSDYSFTQ VYNWDAEKAK FVKFQELNVQ APRSFTHVSI NKRNFLFASS 550 FKGNTQIYKH VIVDLSA
	Isoform 2. Checksum: BC10E3E110E016D0	FASTA	291	33,121
	10 20 30 40 50 60 MESERSKRMG NACIPLKRIA YFLCLLSALL LTEGKKPAKP KCPAVCTCTK DNALCENARS 70 80 90 100 110 120 IPRTVPPDVI SLSFVRSGFT EISEGSFLFT PSLQLLLFTS NSFDVISDDA FIGLPHLEYL 130 140 150 160 170 180 FIENNNIKSI SRHTFRGLKS LIHLSLANNN LQTLPKDIFK GLDSLTNVDL RGNSFNCDCK 190 200 210 220 230 240 LKWLVEWLGH TNATVEDIYC EGPPEYKKRK INSLSSKDFD CIITEFAKSQ DLPYQSLSID 250 260 270 280 290 TFSYLNDEYV VIAQPFTGKC IFLEWDHVEK TFRNYDNITV LREIHRFTNM S

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel gene, LGI1, from 10q24 is rearranged and downregulated in malignant brain tumors." Chernova O.B., Somerville R.P., Cowell J.K. Oncogene 17:2873-2881(1998) [PubMed: 9879993] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Fetal brain.
[2]	"Mutations in the LGI1/Epitempin gene on 10q24 cause autosomal dominant lateral temporal epilepsy." Morante-Redolat J.M., Gorostidi-Pagola A., Piquer-Sirerol S., Saenz A., Poza J.J., Galan J., Gesk S., Sarafidou T., Mautner V.F., Binelli S., Staub E., Hinzmann B., French L., Prud'homme J.-F., Passarelli D., Scannapieco P., Tassinari C.A., Avanzini G. , Marti-Masso J.F., Kluwe L., Deloukas P., Moschonas N.K., Michelucci R., Siebert R., Nobile C., Perez-Tur J., Lopez de Munain A. Hum. Mol. Genet. 11:1119-1128(2002) [PubMed: 11978770] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), DISEASE.
[3]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[6]	"Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features." Kalachikov S., Evgrafov O., Ross B., Winawer M., Barker-Cummings C., Boneschi F.M., Choi C., Morozov P., Das K., Teplitskaya E., Yu A., Cayanis E., Penchaszadeh G., Kottmann A.H., Pedley T.A., Hauser W.A., Ottman R., Gilliam T.C. Nat. Genet. 30:335-341(2002) [PubMed: 11810107] [Abstract] Cited for: VARIANT ADLTE ALA-383.
[7]	"LGI1 is mutated in familial temporal lobe epilepsy characterized by aphasic seizures." Gu W., Brodtkorb E., Steinlein O.K. Ann. Neurol. 52:364-367(2002) [PubMed: 12205652] [Abstract] Cited for: VARIANT ADLTE ARG-46.
[8]	"Epilepsy with auditory features: a LGI1 gene mutation suggests a loss-of-function mechanism." Pizzuti A., Flex E., Di Bonaventura C., Dottorini T., Egeo G., Manfredi M., Dallapiccola B., Giallonardo A.T. Ann. Neurol. 53:396-399(2003) [PubMed: 12601709] [Abstract] Cited for: VARIANT ADLTE ARG-26.
[9]	"Novel LGI1 mutation in a family with autosomal dominant partial epilepsy with auditory features." Fertig E., Lincoln A., Martinuzzi A., Mattson R.H., Hisama F.M. Neurology 60:1687-1690(2003) [PubMed: 12771268] [Abstract] Cited for: VARIANT ADLTE CYS-318.
[10]	"LGI1 mutations in temporal lobe epilepsies." Berkovic S.F., Izzillo P., McMahon J.M., Harkin L.A., McIntosh A.M., Phillips H.A., Briellmann R.S., Wallace R.H., Mazarib A., Neufeld M.Y., Korczyn A.D., Scheffer I.E., Mulley J.C. Neurology 62:1115-1119(2004) [PubMed: 15079010] [Abstract] Cited for: VARIANTS ADLTE GLY-42 AND LEU-473.
+	Additional computationally mapped references.

Web resources

GeneReviews

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF055636 mRNA. Translation: AAC99316.1. AF473548 mRNA. Translation: AAM22074.1. AY358885 mRNA. Translation: AAQ89244.1. AL157396, AL358154 Genomic DNA. Translation: CAH73837.1. AL157396, AL358154 Genomic DNA. Translation: CAH73838.1. AL358154, AL157396 Genomic DNA. Translation: CAI14981.1. AL358154, AL157396 Genomic DNA. Translation: CAI14982.1. BC022500 mRNA. Translation: AAH22500.1.
IPI	IPI00021091. IPI00334395.
RefSeq	NP_005088.1.
UniGene	Hs.533670
3D structure databases
ModBase	Search...
Proteomic databases
PRIDE	O95970.
Genome annotation databases
Ensembl	ENSG00000108231. Homo sapiens. [Contig view]
GeneID	9211.
KEGG	hsa:9211.
Organism-specific databases
GeneCards	GC10P095507.
H-InvDB	HIX0009049.
HGNC	HGNC:6572. LGI1.
MIM	600512. phenotype. 604619. gene.
Orphanet	101046. Epilepsy, lateral temporal lobe, autosomal dominant.
PharmGKB	PA30349.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O95970.
HOVERGEN	O95970.
OMA	O95970. SHTNATV.
Gene expression databases
ArrayExpress	O95970.
Bgee	O95970.
CleanEx	HS_LGI1.
GermOnline	ENSG00000108231. Homo sapiens.
Family and domain databases
InterPro	IPR009039. EAR. IPR005492. EPTP. IPR001611. Leu-rich_rpt. IPR000372. Leu-rich_rpt_Cys-rich-reg_N. IPR003591. Leu-rich_rpt_typical-subtyp. IPR000483. LRR_C. [Graphical view]
Pfam	PF03736. EPTP. 7 hits. PF00560. LRR_1. 2 hits. [Graphical view]
SMART	SM00369. LRR_TYP. 2 hits. SM00082. LRRCT. 1 hit. SM00013. LRRNT. 1 hit. [Graphical view]
PROSITE	PS50912. EAR. 7 hits. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	34531.
SOURCE	Search...

Entry information

Entry name

LGI1_HUMAN

Accession

Primary (citable) accession number: O95970
Secondary accession number(s): Q5W001 , Q5W002, Q8NI23, Q96LF5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 3, 2003
Last sequence update:	May 1, 1999
Last modified:	June 16, 2009
This is version 78 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)