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Protein

Leucine-rich glioma-inactivated protein 1

Gene

LGI1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Regulates voltage-gated potassium channels assembled from KCNA1, KCNA4 and KCNAB1. It slows down channel inactivation by precluding channel closure mediated by the KCNAB1 subunit. Ligand for ADAM22 that positively regulates synaptic transmission mediated by AMPA-type glutamate receptors (By similarity). Plays a role in suppressing the production of MMP1/3 through the phosphatidylinositol 3-kinase/ERK pathway. May play a role in the control of neuroblastoma cell survival.By similarity2 Publications

GO - Molecular functioni

  • receptor binding Source: DFLAT

GO - Biological processi

  • axon guidance Source: DFLAT
  • cell proliferation Source: ProtInc
  • nervous system development Source: ProtInc
  • neuron projection development Source: DFLAT
  • positive regulation of cell growth Source: DFLAT
  • positive regulation of synaptic transmission Source: UniProtKB
  • protein homooligomerization Source: Ensembl

Enzyme and pathway databases

ReactomeiR-HSA-5682910. LGI-ADAM interactions.

Names & Taxonomyi

Protein namesi
Recommended name:
Leucine-rich glioma-inactivated protein 1
Alternative name(s):
Epitempin-1
Gene namesi
Name:LGI1
Synonyms:EPT
ORF Names:UNQ775/PRO1569
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000108231.11.
HGNCiHGNC:6572. LGI1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Secreted, Synapse

Pathology & Biotechi

Involvement in diseasei

Epilepsy, familial temporal lobe, 1 (ETL1)10 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA focal form of epilepsy characterized by recurrent seizures that arise from foci within the temporal lobe. Seizures are usually accompanied by sensory symptoms, most often auditory in nature.
See also OMIM:600512
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01577126L → R in ETL1; probably affects signal sequence processing and secretion. 1 Publication1
Natural variantiVAR_02300842C → G in ETL1. 1 PublicationCorresponds to variant dbSNP:rs797044996Ensembl.1
Natural variantiVAR_05853842C → R in ETL1. Corresponds to variant dbSNP:rs797044996Ensembl.1
Natural variantiVAR_01577246C → R in ETL1; loss of protein secretion; does not affect glycosylation status of the protein. 2 PublicationsCorresponds to variant dbSNP:rs104894166Ensembl.1
Natural variantiVAR_058539110A → D in ETL1. 1
Natural variantiVAR_058540122I → K in ETL1. 1 PublicationCorresponds to variant dbSNP:rs119488100Ensembl.1
Natural variantiVAR_058541123E → K in ETL1. 1 Publication1
Natural variantiVAR_058542136R → W in ETL1. 1 PublicationCorresponds to variant dbSNP:rs119488099Ensembl.1
Natural variantiVAR_058543145S → R in ETL1; loss of protein secretion; does not affect glycosylation status of the protein. 1 Publication1
Natural variantiVAR_058544154L → P in ETL1. 1
Natural variantiVAR_058545200C → R in ETL1; loss of protein secretion; does not affect glycosylation status of the protein. 1 Publication1
Natural variantiVAR_058546232L → P in ETL1; loss of protein secretion. 1 PublicationCorresponds to variant dbSNP:rs104894167Ensembl.1
Natural variantiVAR_058547298I → T in ETL1. 1
Natural variantiVAR_015774318F → C in ETL1; loss of protein secretion; protein is retained in the endoplasmic reticulum; does not affect glycosylation status of the protein. 2 PublicationsCorresponds to variant dbSNP:rs28939075Ensembl.1
Natural variantiVAR_015773383E → A in ETL1; loss of protein secretion; protein is retained in the endoplasmic reticulum; does not affect glycosylation status of the protein. 3 PublicationsCorresponds to variant dbSNP:rs28937874Ensembl.1
Natural variantiVAR_058548432V → E in ETL1. 1
Natural variantiVAR_023009473S → L in ETL1. 1 PublicationCorresponds to variant dbSNP:rs797044999Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi192N → Q: Affects glycosylation; when associated with Q-277 and Q-422. Loss of protein secretion; when associated with Q-277 and Q-422. 1 Publication1
Mutagenesisi277N → Q: Affects glycosylation; when associated with Q-192 and Q-422. Loss of protein secretion; when associated with Q-192 and Q-422. 1 Publication1
Mutagenesisi422N → Q: Affects glycosylation; when associated with Q-192 and Q-277. Loss of protein secretion; when associated with Q-192 and Q-277. 1 Publication1

Keywords - Diseasei

Disease mutation, Epilepsy

Organism-specific databases

DisGeNETi9211.
GeneReviewsiLGI1.
MalaCardsiLGI1.
MIMi600512. phenotype.
OpenTargetsiENSG00000108231.
Orphaneti101046. Autosomal dominant epilepsy with auditory features.
PharmGKBiPA30349.

Polymorphism and mutation databases

BioMutaiLGI1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 34Sequence analysisAdd BLAST34
ChainiPRO_000001770535 – 557Leucine-rich glioma-inactivated protein 1Add BLAST523

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi192N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi277N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi422N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Glycosylated.1 Publication

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiO95970.
PaxDbiO95970.
PeptideAtlasiO95970.
PRIDEiO95970.
TopDownProteomicsiO95970-3. [O95970-3]

PTM databases

iPTMnetiO95970.
PhosphoSitePlusiO95970.

Expressioni

Tissue specificityi

Predominantly expressed in neural tissues, especially in brain. Expression is reduced in low-grade brain tumors and significantly reduced or absent in malignant gliomas. Isoform 1 is absent in the cerebellum and is detectable in the occipital cortex and hippocampus; higher amounts are observed in the parietal and frontal cortices, putamen, and, particularly, in the temporal neocortex, where it is 3.5 times more abundant than in the hippocampus (at protein level). Isoform 3 shows the highest expression in the occipital cortex and the lowest in the hippocampus (at protein level).2 Publications

Inductioni

Down-regulated in neuroblastoma cells.1 Publication

Gene expression databases

BgeeiENSG00000108231.
CleanExiHS_LGI1.
ExpressionAtlasiO95970. baseline and differential.
GenevisibleiO95970. HS.

Interactioni

Subunit structurei

Oligomer. Interacts with KCNA1 within a complex containing KCNA1, KCNA4 and KCNAB1. Part of a complex containing ADAM22, DLG4/PSD95 and CACNG2 (stargazin). Can bind to ADAM11 and ADAM23.By similarity

GO - Molecular functioni

  • receptor binding Source: DFLAT

Protein-protein interaction databases

BioGridi114645. 2 interactors.
STRINGi9606.ENSP00000360472.

Structurei

3D structure databases

ProteinModelPortaliO95970.
SMRiO95970.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini35 – 72LRRNTAdd BLAST38
Repeati92 – 113LRR 1Add BLAST22
Repeati116 – 137LRR 2Add BLAST22
Repeati140 – 161LRR 3Add BLAST22
Domaini173 – 223LRRCTAdd BLAST51
Repeati224 – 267EAR 1Add BLAST44
Repeati270 – 313EAR 2Add BLAST44
Repeati316 – 364EAR 3Add BLAST49
Repeati365 – 415EAR 4Add BLAST51
Repeati418 – 462EAR 5Add BLAST45
Repeati463 – 506EAR 6Add BLAST44
Repeati509 – 552EAR 7Add BLAST44

Keywords - Domaini

Leucine-rich repeat, Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IIXR. Eukaryota.
ENOG410XSZV. LUCA.
GeneTreeiENSGT00860000133701.
HOVERGENiHBG036744.
InParanoidiO95970.
OMAiFTQVYRW.
OrthoDBiEOG091G03ZX.
PhylomeDBiO95970.
TreeFamiTF333155.

Family and domain databases

Gene3Di3.80.10.10. 2 hits.
InterProiView protein in InterPro
IPR000483. Cys-rich_flank_reg_C.
IPR009039. EAR.
IPR005492. EPTP.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
PfamiView protein in Pfam
PF03736. EPTP. 7 hits.
PF13855. LRR_8. 1 hit.
SMARTiView protein in SMART
SM00369. LRR_TYP. 3 hits.
SM00082. LRRCT. 1 hit.
SUPFAMiSSF52058. SSF52058. 1 hit.
PROSITEiView protein in PROSITE
PS50912. EAR. 7 hits.

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O95970-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MESERSKRMG NACIPLKRIA YFLCLLSALL LTEGKKPAKP KCPAVCTCTK
60 70 80 90 100
DNALCENARS IPRTVPPDVI SLSFVRSGFT EISEGSFLFT PSLQLLLFTS
110 120 130 140 150
NSFDVISDDA FIGLPHLEYL FIENNNIKSI SRHTFRGLKS LIHLSLANNN
160 170 180 190 200
LQTLPKDIFK GLDSLTNVDL RGNSFNCDCK LKWLVEWLGH TNATVEDIYC
210 220 230 240 250
EGPPEYKKRK INSLSSKDFD CIITEFAKSQ DLPYQSLSID TFSYLNDEYV
260 270 280 290 300
VIAQPFTGKC IFLEWDHVEK TFRNYDNITG TSTVVCKPIV IETQLYVIVA
310 320 330 340 350
QLFGGSHIYK RDSFANKFIK IQDIEILKIR KPNDIETFKI ENNWYFVVAD
360 370 380 390 400
SSKAGFTTIY KWNGNGFYSH QSLHAWYRDT DVEYLEIVRT PQTLRTPHLI
410 420 430 440 450
LSSSSQRPVI YQWNKATQLF TNQTDIPNME DVYAVKHFSV KGDVYICLTR
460 470 480 490 500
FIGDSKVMKW GGSSFQDIQR MPSRGSMVFQ PLQINNYQYA ILGSDYSFTQ
510 520 530 540 550
VYNWDAEKAK FVKFQELNVQ APRSFTHVSI NKRNFLFASS FKGNTQIYKH

VIVDLSA
Length:557
Mass (Da):63,818
Last modified:May 1, 1999 - v1
Checksum:i890EEDA08D95C854
GO
Isoform 2 (identifier: O95970-2) [UniParc]FASTAAdd to basket

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

Show »
Length:291
Mass (Da):33,121
Checksum:iBC10E3E110E016D0
GO
Isoform 3 (identifier: O95970-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     96-143: Missing.

Show »
Length:509
Mass (Da):58,302
Checksum:iEA28D9DACAFE97BD
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01577126L → R in ETL1; probably affects signal sequence processing and secretion. 1 Publication1
Natural variantiVAR_02300842C → G in ETL1. 1 PublicationCorresponds to variant dbSNP:rs797044996Ensembl.1
Natural variantiVAR_05853842C → R in ETL1. Corresponds to variant dbSNP:rs797044996Ensembl.1
Natural variantiVAR_01577246C → R in ETL1; loss of protein secretion; does not affect glycosylation status of the protein. 2 PublicationsCorresponds to variant dbSNP:rs104894166Ensembl.1
Natural variantiVAR_058539110A → D in ETL1. 1
Natural variantiVAR_058540122I → K in ETL1. 1 PublicationCorresponds to variant dbSNP:rs119488100Ensembl.1
Natural variantiVAR_058541123E → K in ETL1. 1 Publication1
Natural variantiVAR_058542136R → W in ETL1. 1 PublicationCorresponds to variant dbSNP:rs119488099Ensembl.1
Natural variantiVAR_058543145S → R in ETL1; loss of protein secretion; does not affect glycosylation status of the protein. 1 Publication1
Natural variantiVAR_058544154L → P in ETL1. 1
Natural variantiVAR_058545200C → R in ETL1; loss of protein secretion; does not affect glycosylation status of the protein. 1 Publication1
Natural variantiVAR_058546232L → P in ETL1; loss of protein secretion. 1 PublicationCorresponds to variant dbSNP:rs104894167Ensembl.1
Natural variantiVAR_058547298I → T in ETL1. 1
Natural variantiVAR_015774318F → C in ETL1; loss of protein secretion; protein is retained in the endoplasmic reticulum; does not affect glycosylation status of the protein. 2 PublicationsCorresponds to variant dbSNP:rs28939075Ensembl.1
Natural variantiVAR_015773383E → A in ETL1; loss of protein secretion; protein is retained in the endoplasmic reticulum; does not affect glycosylation status of the protein. 3 PublicationsCorresponds to variant dbSNP:rs28937874Ensembl.1
Natural variantiVAR_058548432V → E in ETL1. 1
Natural variantiVAR_023009473S → L in ETL1. 1 PublicationCorresponds to variant dbSNP:rs797044999Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_03823496 – 143Missing in isoform 3. 1 PublicationAdd BLAST48
Alternative sequenceiVSP_007678280 – 291GTSTV…KPIVI → VLREIHRFTNMS in isoform 2. 1 PublicationAdd BLAST12
Alternative sequenceiVSP_007679292 – 557Missing in isoform 2. 1 PublicationAdd BLAST266

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF055636 mRNA. Translation: AAC99316.1.
AF473548 mRNA. Translation: AAM22074.1.
AY358885 mRNA. Translation: AAQ89244.1.
AK289706 mRNA. Translation: BAF82395.1.
AK303956 mRNA. Translation: BAG64882.1.
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.
CH471066 Genomic DNA. Translation: EAW50052.1.
BC022500 mRNA. Translation: AAH22500.1.
CCDSiCCDS7431.1. [O95970-1]
CCDS76325.1. [O95970-2]
CCDS81490.1. [O95970-3]
RefSeqiNP_001295204.1. NM_001308275.1. [O95970-2]
NP_001295205.1. NM_001308276.1. [O95970-3]
NP_005088.1. NM_005097.3. [O95970-1]
UniGeneiHs.533670.

Genome annotation databases

EnsembliENST00000371413; ENSP00000360467; ENSG00000108231. [O95970-2]
ENST00000371418; ENSP00000360472; ENSG00000108231. [O95970-1]
ENST00000630047; ENSP00000485917; ENSG00000108231. [O95970-3]
GeneIDi9211.
KEGGihsa:9211.
UCSCiuc001kjc.5. human. [O95970-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiLGI1_HUMAN
AccessioniPrimary (citable) accession number: O95970
Secondary accession number(s): A8K0Z1
, B4E1S0, Q5W001, Q5W002, Q8NI23, Q96LF5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 3, 2003
Last sequence update: May 1, 1999
Last modified: September 27, 2017
This is version 155 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot