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LRIG1 (leucine-rich repeats and immunoglobulin-like domains 1)

Written2010-12Dongsheng Guo, Baofeng Wang
Dept of Neurosurgery, Tongji Hospital, Huazhong University of Science, Technology, Wuhan, Hubei, 430030, People's Republic of China

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)LIG-1
DKFZP586O1624
LIG1
Other aliasDKFZp586O1624
HGNC (Hugo) LRIG1
LocusID (NCBI) 26018
Atlas_Id 41198
Location 3p14.1  [Link to chromosome band 3p14]
Location_base_pair Starts at 66429221 and ends at 66550845 bp from pter ( according to hg19-Feb_2009)  [Mapping LRIG1.png]
Fusion genes
(updated 2016)
LRIG1 (3p14.1) / SLC25A26 (3p14.1)LRIG1 (3p14.1) / SLC26A7 (8q21.3)LRIG1 (3p14.1) / SUCLG2 (3p14.1)
SLC39A6 (18q12.2) / LRIG1 (3p14.1)

DNA/RNA

 
  LRIG1 gene. Exons are represented by red boxes (in scale). Exons 1 to 19 are from the 5' to 3' direction.
Description Genomic DNA encoding LRIG1 spans a region of 122.89 kilobases on chromosome 3, at 3p14. LRIG1 gene is encoded on the reverse strand.
Transcription The pre-mRNA comprises 19 exons.
Coding sequence: 4812 bp.

Protein

 
  LRIG1 protein. SP: signal peptide; NF: N-terminal cysteine-rich flanking domain; LRR: leucine-rich repeat; CF: C-terminal cysteine-rich flanking domain; Ig C2: C2-type immunoglobulin-like domains; TM: transmembrane domain; Cyto: cytoplasmic domain.
Description LRIG1 is a transmembrane cell-surface protein consisting of 1093 amino acids. LRIG1 contains extracellular part containing 15 leucine-rich repeats (LRR) and three C2-type immunoglobulin-like domains, a transmembrane region, and a cytoplasmic tail. LRIG1 can be cut into soluble LRIG1 ectodomain by proteolytic processing, which also is a functional molecule.
Expression LRIG1 is expressed ubiquitously in various epithelial cells, endothelial cells, heart, smooth and striated muscles, and in large neurons.
Localisation Differential subcellular distribution in a cell type-specific manner.
Function LRIG1 acts as a suppressor of receptor tyrosine kinases, such as epidermal growth factor receptor (EGFR) family, MET (hepatocyte growth factor receptor), and RET. The interaction of the extracellular LRR domain and immunoglobulin-like domains of LRIG1 with the extracellular parts of the human EGFR results in recruitment of c-Cbl to the cytoplasmic domains, and induction of EGFR degradation. LRIG1 is involved in signal transduction, cell proliferation, cell apopotosis, cell cycle, cell migration, and cell invasion. LRIG1 as a putative tumor suppressor gene often be down-regulated in various human tumors.
Soluble ectodomain of LRIG1 protein can modulate EGFR signaling and its growth-promoting activity in a paracrine fashion.

Implicated in

Note
  
Entity Ependymoma
Note Higher cytoplasmic immunoreactivity of LRIG1 correlates with older patient age and higher LRIG1 nuclear immunoreactivity with lower WHO grade.
  
  
Entity Prostate cancer
Note High LRIG1 expression is significantly associated with short overall and prostate cancer-specific survival for 256 Swedish patients analysed. In contrast, in the U.S. series, high LRIG1 expression is significantly associated with longer overall survival.
  
  
Entity Renal cell carcinoma (RCC)
Note LRIG1 expression is generally downregulated in conventional and papillary RCC but not in chromophobic RCC.
  
  
Entity Cutaneous squamous cell carcinoma (SCC)
Note LRIG-1 expression is highest in well-differentiated lesions of cutaneous SCC. LRIG-1 expression intensity of tumor cells is significantly correlated with histologic differentiation of SCC. The SCC patients have significant survival benefits in the high LRIG-1 expression groups compared with low LRIG-1 expression groups.
  
  
Entity Breast tumor
Note LRIG1 protein levels are significantly suppressed in the majority of human breast tumors expressing ErbB2.
  
  
Entity Cervical squamous cell carcinoma
Note LRIG1 appears to be a significant prognosis predictor in early-stage cervical cancer, independent of the other tumor markers.
  
  
Entity Astrocytic tumor
Note Perinuclear staining of LRIG1 is associated with low WHO grade and better survival of the patients.
  
  
Entity Psoriasis
Note In psoriasis, LRIG1 is mostly absent from the cell surfaces in the spinous layers.
  

Bibliography

A soluble ectodomain of LRIG1 inhibits cancer cell growth by attenuating basal and ligand-dependent EGFR activity.
Goldoni S, Iozzo RA, Kay P, Campbell S, McQuillan A, Agnew C, Zhu JX, Keene DR, Reed CC, Iozzo RV.
Oncogene. 2007 Jan 18;26(3):368-81. Epub 2006 Jul 17.
PMID 16847455
 
Down-regulation of leucine-rich repeats and immunoglobulin-like domain proteins (LRIG1-3) in HP75 pituitary adenoma cell line.
Guo D, Han L, Shu K, Chen J, Lei T.
J Huazhong Univ Sci Technolog Med Sci. 2007 Feb;27(1):91-4.
PMID 17393120
 
The LRIG gene family has three vertebrate paralogs widely expressed in human and mouse tissues and a homolog in Ascidiacea.
Guo D, Holmlund C, Henriksson R, Hedman H.
Genomics. 2004 Jul;84(1):157-65.
PMID 15203213
 
Perinuclear leucine-rich repeats and immunoglobulin-like domain proteins (LRIG1-3) as prognostic indicators in astrocytic tumors.
Guo D, Nilsson J, Haapasalo H, Raheem O, Bergenheim T, Hedman H, Henriksson R.
Acta Neuropathol. 2006 Mar;111(3):238-46. Epub 2006 Mar 11.
PMID 16532360
 
LRIG1 restricts growth factor signaling by enhancing receptor ubiquitylation and degradation.
Gur G, Rubin C, Katz M, Amit I, Citri A, Nilsson J, Amariglio N, Henriksson R, Rechavi G, Hedman H, Wides R, Yarden Y.
EMBO J. 2004 Aug 18;23(16):3270-81. Epub 2004 Jul 29.
PMID 15282549
 
LRIG inhibitors of growth factor signalling - double-edged swords in human cancer?
Hedman H, Henriksson R.
Eur J Cancer. 2007 Mar;43(4):676-82. Epub 2007 Jan 18. (REVIEW)
PMID 17239582
 
Single-cell expression profiling of human epidermal stem and transit-amplifying cells: Lrig1 is a regulator of stem cell quiescence.
Jensen KB, Watt FM.
Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):11958-63. Epub 2006 Jul 28.
PMID 16877544
 
Redistribution of LRIG proteins in psoriasis.
Karlsson T, Mark EB, Henriksson R, Hedman H.
J Invest Dermatol. 2008 May;128(5):1192-5. Epub 2007 Nov 22.
PMID 18037903
 
The leucine-rich repeat protein LRIG1 is a negative regulator of ErbB family receptor tyrosine kinases.
Laederich MB, Funes-Duran M, Yen L, Ingalla E, Wu X, Carraway KL 3rd, Sweeney C.
J Biol Chem. 2004 Nov 5;279(45):47050-6. Epub 2004 Sep 1.
PMID 15345710
 
Lrig1 is an endogenous inhibitor of Ret receptor tyrosine kinase activation, downstream signaling, and biological responses to GDNF.
Ledda F, Bieraugel O, Fard SS, Vilar M, Paratcha G.
J Neurosci. 2008 Jan 2;28(1):39-49.
PMID 18171921
 
LRIG1 and squamous epithelial uterine cervical cancer: correlation to prognosis, other tumor markers, sex steroid hormones, and smoking.
Lindstrom AK, Ekman K, Stendahl U, Tot T, Henriksson R, Hedman H, Hellberg D.
Int J Gynecol Cancer. 2008 Mar-Apr;18(2):312-7. Epub 2007 Jul 11.
PMID 17624990
 
LRIG1 expression in colorectal cancer.
Ljuslinder I, Golovleva I, Palmqvist R, Oberg A, Stenling R, Jonsson Y, Hedman H, Henriksson R, Malmer B.
Acta Oncol. 2007;46(8):1118-22.
PMID 17851870
 
Suppression of the negative regulator LRIG1 contributes to ErbB2 overexpression in breast cancer.
Miller JK, Shattuck DL, Ingalla EQ, Yen L, Borowsky AD, Young LJ, Cardiff RD, Carraway KL 3rd, Sweeney C.
Cancer Res. 2008 Oct 15;68(20):8286-94.
PMID 18922900
 
LRIG1 protein in human cells and tissues.
Nilsson J, Starefeldt A, Henriksson R, Hedman H.
Cell Tissue Res. 2003 Apr;312(1):65-71. Epub 2003 Mar 18.
PMID 12684867
 
Cloning, characterization, and expression of human LIG1.
Nilsson J, Vallbo C, Guo D, Golovleva I, Hallberg B, Henriksson R, Hedman H.
Biochem Biophys Res Commun. 2001 Jun 29;284(5):1155-61.
PMID 11414704
 
LRIG1 is a novel negative regulator of the Met receptor and opposes Met and Her2 synergy.
Shattuck DL, Miller JK, Laederich M, Funes M, Petersen H, Carraway KL 3rd, Sweeney C.
Mol Cell Biol. 2007 Mar;27(5):1934-46. Epub 2006 Dec 18.
PMID 17178829
 
LRIG1 negatively regulates the oncogenic EGF receptor mutant EGFRvIII.
Stutz MA, Shattuck DL, Laederich MB, Carraway KL 3rd, Sweeney C.
Oncogene. 2008 Sep 25;27(43):5741-52. Epub 2008 Jun 9.
PMID 18542056
 
LRIG-1 provides a novel prognostic predictor in squamous cell carcinoma of the skin: immunohistochemical analysis for 38 cases.
Tanemura A, Nagasawa T, Inui S, Itami S.
Dermatol Surg. 2005 Apr;31(4):423-30.
PMID 15871317
 
LRIG1 and the liar paradox in prostate cancer: A study of the expression and clinical significance of LRIG1 in prostate cancer.
Thomasson M, Wang B, Hammarsten P, Dahlman A, Persson JL, Josefsson A, Stattin P, Granfors T, Egevad L, Henriksson R, Bergh A, Hedman H.
Int J Cancer. 2010 Dec 2. [Epub ahead of print]
PMID 21128282
 
LRIG1, a candidate tumour-suppressor gene in human bladder cancer cell line BIU87.
Yang WM, Yan ZJ, Ye ZQ, Guo DS.
BJU Int. 2006 Oct;98(4):898-902.
PMID 16978290
 
Molecular mechanism of LRIG1 cDNA-induced apoptosis in human glioma cell line H4.
Ye F, Guo DS, Niu HQ, Tao SZ, Ou YB, Lu YP, Lei T.
Ai Zheng. 2004 Oct;23(10):1149-54.
PMID 15473925
 
Expression of leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins in human ependymoma relates to tumor location, WHO grade, and patient age.
Yi W, Haapasalo H, Holmlund C, Jarvela S, Raheem O, Bergenheim AT, Hedman H, Henriksson R.
Clin Neuropathol. 2009 Jan-Feb;28(1):21-7.
PMID 19216216
 
Paracrine regulation of growth factor signaling by shed leucine-rich repeats and immunoglobulin-like domains 1.
Yi W, Holmlund C, Nilsson J, Inui S, Lei T, Itami S, Henriksson R, Hedman H.
Exp Cell Res. 2011 Feb 15;317(4):504-12. Epub 2010 Nov 16.
PMID 21087604
 

Citation

This paper should be referenced as such :
Guo, D ; Wang, B
LRIG1 (leucine-rich repeats, immunoglobulin-like domains 1)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(8):625-627.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/LRIG1ID41198ch3p14.html


External links

Nomenclature
HGNC (Hugo)LRIG1   17360
Cards
AtlasLRIG1ID41198ch3p14
Entrez_Gene (NCBI)LRIG1  26018  leucine-rich repeats and immunoglobulin like domains 1
AliasesLIG-1; LIG1
GeneCards (Weizmann)LRIG1
Ensembl hg19 (Hinxton)ENSG00000144749 [Gene_View]  chr3:66429221-66550845 [Contig_View]  LRIG1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000144749 [Gene_View]  chr3:66429221-66550845 [Contig_View]  LRIG1 [Vega]
ICGC DataPortalENSG00000144749
TCGA cBioPortalLRIG1
AceView (NCBI)LRIG1
Genatlas (Paris)LRIG1
WikiGenes26018
SOURCE (Princeton)LRIG1
Genetics Home Reference (NIH)LRIG1
Genomic and cartography
GoldenPath hg19 (UCSC)LRIG1  -     chr3:66429221-66550845 -  3p14   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)LRIG1  -     3p14   [Description]    (hg38-Dec_2013)
EnsemblLRIG1 - 3p14 [CytoView hg19]  LRIG1 - 3p14 [CytoView hg38]
Mapping of homologs : NCBILRIG1 [Mapview hg19]  LRIG1 [Mapview hg38]
OMIM608868   
Gene and transcription
Genbank (Entrez)AB050468 AF381545 AK126745 AK294984 AK314103
RefSeq transcript (Entrez)NM_015541
RefSeq genomic (Entrez)NC_000003 NC_018914 NT_022517 NW_004929310
Consensus coding sequences : CCDS (NCBI)LRIG1
Cluster EST : UnigeneHs.518055 [ NCBI ]
CGAP (NCI)Hs.518055
Alternative Splicing GalleryENSG00000144749
Gene ExpressionLRIG1 [ NCBI-GEO ]   LRIG1 [ EBI - ARRAY_EXPRESS ]   LRIG1 [ SEEK ]   LRIG1 [ MEM ]
Gene Expression Viewer (FireBrowse)LRIG1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)26018
GTEX Portal (Tissue expression)LRIG1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ96JA1   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ96JA1  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ96JA1
Splice isoforms : SwissVarQ96JA1
PhosPhoSitePlusQ96JA1
Domaine pattern : Prosite (Expaxy)IG_LIKE (PS50835)    LRR (PS51450)   
Domains : Interpro (EBI)Cys-rich_flank_reg_C    Ig-like_dom    Ig-like_fold    Ig_I-set    Ig_sub    Ig_sub2    L_dom-like    Leu-rich_rpt    Leu-rich_rpt_typical-subtyp    LRRNT   
Domain families : Pfam (Sanger)I-set (PF07679)    LRR_8 (PF13855)    LRRCT (PF01463)   
Domain families : Pfam (NCBI)pfam07679    pfam13855    pfam01463   
Domain families : Smart (EMBL)IG (SM00409)  IGc2 (SM00408)  LRR_TYP (SM00369)  LRRCT (SM00082)  LRRNT (SM00013)  
Conserved Domain (NCBI)LRIG1
DMDM Disease mutations26018
Blocks (Seattle)LRIG1
PDB (SRS)4U7L    4U7M   
PDB (PDBSum)4U7L    4U7M   
PDB (IMB)4U7L    4U7M   
PDB (RSDB)4U7L    4U7M   
Structural Biology KnowledgeBase4U7L    4U7M   
SCOP (Structural Classification of Proteins)4U7L    4U7M   
CATH (Classification of proteins structures)4U7L    4U7M   
SuperfamilyQ96JA1
Human Protein AtlasENSG00000144749
Peptide AtlasQ96JA1
HPRD10057
IPIIPI00000775   IPI00470372   IPI00740074   
Protein Interaction databases
DIP (DOE-UCLA)Q96JA1
IntAct (EBI)Q96JA1
FunCoupENSG00000144749
BioGRIDLRIG1
STRING (EMBL)LRIG1
ZODIACLRIG1
Ontologies - Pathways
QuickGOQ96JA1
Ontology : AmiGOsensory perception of sound  integral component of membrane  otolith morphogenesis  innervation  
Ontology : EGO-EBIsensory perception of sound  integral component of membrane  otolith morphogenesis  innervation  
REACTOMEQ96JA1 [protein]
REACTOME Pathways177929 [pathway]   6807004 [pathway]   
NDEx NetworkLRIG1
Atlas of Cancer Signalling NetworkLRIG1
Wikipedia pathwaysLRIG1
Orthology - Evolution
OrthoDB26018
GeneTree (enSembl)ENSG00000144749
Phylogenetic Trees/Animal Genes : TreeFamLRIG1
HOVERGENQ96JA1
HOGENOMQ96JA1
Homologs : HomoloGeneLRIG1
Homology/Alignments : Family Browser (UCSC)LRIG1
Gene fusions - Rearrangements
Fusion : MitelmanLRIG1/SLC25A26 [3p14.1/3p14.1]  
Fusion : MitelmanLRIG1/SLC26A7 [3p14.1/8q21.3]  [t(3;8)(p14;q21)]  
Fusion : MitelmanLRIG1/SUCLG2 [3p14.1/3p14.1]  [t(3;3)(p14;p14)]  
Fusion : MitelmanSLC39A6/LRIG1 [18q12.2/3p14.1]  [t(3;18)(p14;q12)]  
Fusion: TCGALRIG1 3p14.1 SLC26A7 8q21.3 KIRC
Fusion: TCGALRIG1 3p14.1 SUCLG2 3p14.1 PRAD
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerLRIG1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)LRIG1
dbVarLRIG1
ClinVarLRIG1
1000_GenomesLRIG1 
Exome Variant ServerLRIG1
ExAC (Exome Aggregation Consortium)LRIG1 (select the gene name)
Genetic variants : HAPMAP26018
Genomic Variants (DGV)LRIG1 [DGVbeta]
DECIPHER (Syndromes)3:66429221-66550845  ENSG00000144749
CONAN: Copy Number AnalysisLRIG1 
Mutations
ICGC Data PortalLRIG1 
TCGA Data PortalLRIG1 
Broad Tumor PortalLRIG1
OASIS PortalLRIG1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICLRIG1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDLRIG1
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
BioMutasearch LRIG1
DgiDB (Drug Gene Interaction Database)LRIG1
DoCM (Curated mutations)LRIG1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)LRIG1 (select a term)
intoGenLRIG1
NCG5 (London)LRIG1
Cancer3DLRIG1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM608868   
Orphanet
MedgenLRIG1
Genetic Testing Registry LRIG1
NextProtQ96JA1 [Medical]
TSGene26018
GENETestsLRIG1
Huge Navigator LRIG1 [HugePedia]
snp3D : Map Gene to Disease26018
BioCentury BCIQLRIG1
ClinGenLRIG1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD26018
Chemical/Pharm GKB GenePA38450
Clinical trialLRIG1
Miscellaneous
canSAR (ICR)LRIG1 (select the gene name)
Probes
Litterature
PubMed59 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineLRIG1
EVEXLRIG1
GoPubMedLRIG1
iHOPLRIG1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Apr 12 11:34:29 CEST 2017

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