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

2010-12-01   Dongsheng Guo , Baofeng Wang 

Dept of Neurosurgery, Tongji Hospital, Huazhong University of Science, Technology, Wuhan, Hubei, 430030, Peoples Republic of China

Identity

HGNC
LOCATION
3p14.1
LOCUSID
ALIAS
LIG-1,LIG1
FUSION GENES

DNA/RNA

Atlas Image
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.

Proteins

Atlas Image
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

Entity name
Ependymoma
Note
Higher cytoplasmic immunoreactivity of LRIG1 correlates with older patient age and higher LRIG1 nuclear immunoreactivity with lower WHO grade.
Entity name
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 name
Renal cell carcinoma (RCC)
Note
LRIG1 expression is generally downregulated in conventional and papillary RCC but not in chromophobic RCC.
Entity name
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 name
Breast tumor
Note
LRIG1 protein levels are significantly suppressed in the majority of human breast tumors expressing ErbB2.
Entity name
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 name
Astrocytic tumor
Note
Perinuclear staining of LRIG1 is associated with low WHO grade and better survival of the patients.
Entity name
Psoriasis
Note
In psoriasis, LRIG1 is mostly absent from the cell surfaces in the spinous layers.

Bibliography

Pubmed IDLast YearTitleAuthors
168474552007A soluble ectodomain of LRIG1 inhibits cancer cell growth by attenuating basal and ligand-dependent EGFR activity.Goldoni S et al
173931202007Down-regulation of leucine-rich repeats and immunoglobulin-like domain proteins (LRIG1-3) in HP75 pituitary adenoma cell line.Guo D et al
152032132004The LRIG gene family has three vertebrate paralogs widely expressed in human and mouse tissues and a homolog in Ascidiacea.Guo D et al
165323602006Perinuclear leucine-rich repeats and immunoglobulin-like domain proteins (LRIG1-3) as prognostic indicators in astrocytic tumors.Guo D et al
152825492004LRIG1 restricts growth factor signaling by enhancing receptor ubiquitylation and degradation.Gur G et al
172395822007LRIG inhibitors of growth factor signalling - double-edged swords in human cancer?Hedman H et al
168775442006Single-cell expression profiling of human epidermal stem and transit-amplifying cells: Lrig1 is a regulator of stem cell quiescence.Jensen KB et al
180379032008Redistribution of LRIG proteins in psoriasis.Karlsson T et al
153457102004The leucine-rich repeat protein LRIG1 is a negative regulator of ErbB family receptor tyrosine kinases.Laederich MB et al
181719212008Lrig1 is an endogenous inhibitor of Ret receptor tyrosine kinase activation, downstream signaling, and biological responses to GDNF.Ledda F et al
176249902008LRIG1 and squamous epithelial uterine cervical cancer: correlation to prognosis, other tumor markers, sex steroid hormones, and smoking.Lindström AK et al
178518702007LRIG1 expression in colorectal cancer.Ljuslinder I et al
189229002008Suppression of the negative regulator LRIG1 contributes to ErbB2 overexpression in breast cancer.Miller JK et al
126848672003LRIG1 protein in human cells and tissues.Nilsson J et al
114147042001Cloning, characterization, and expression of human LIG1.Nilsson J et al
171788292007LRIG1 is a novel negative regulator of the Met receptor and opposes Met and Her2 synergy.Shattuck DL et al
185420562008LRIG1 negatively regulates the oncogenic EGF receptor mutant EGFRvIII.Stutz MA et al
158713172005LRIG-1 provides a novel prognostic predictor in squamous cell carcinoma of the skin: immunohistochemical analysis for 38 cases.Tanemura A et al
211282822011LRIG1 and the liar paradox in prostate cancer: a study of the expression and clinical significance of LRIG1 in prostate cancer.Thomasson M et al
169782902006LRIG1, a candidate tumour-suppressor gene in human bladder cancer cell line BIU87.Yang WM et al
154739252004[Molecular mechanism of LRIG1 cDNA-induced apoptosis in human glioma cell line H4].Ye F et al
192162162009Expression of leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins in human ependymoma relates to tumor location, WHO grade, and patient age.Yi W et al
210876042011Paracrine regulation of growth factor signaling by shed leucine-rich repeats and immunoglobulin-like domains 1.Yi W et al

Other Information

Locus ID:

NCBI: 26018
MIM: 608868
HGNC: 17360
Ensembl: ENSG00000144749

Variants:

dbSNP: 26018
ClinVar: 26018
TCGA: ENSG00000144749
COSMIC: LRIG1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000144749ENST00000273261Q96JA1
ENSG00000144749ENST00000383703Q96JA1

Expression (GTEx)

0
50
100
150

Pathways

PathwaySourceExternal ID
Signal TransductionREACTOMER-HSA-162582
Signaling by EGFRREACTOMER-HSA-177929
Signaling by METREACTOMER-HSA-6806834
Negative regulation of MET activityREACTOMER-HSA-6807004

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
224643272012The pan-ErbB negative regulator Lrig1 is an intestinal stem cell marker that functions as a tumor suppressor.252
168775442006Single-cell expression profiling of human epidermal stem and transit-amplifying cells: Lrig1 is a regulator of stem cell quiescence.115
152825492004LRIG1 restricts growth factor signaling by enhancing receptor ubiquitylation and degradation.100
153457102004The leucine-rich repeat protein LRIG1 is a negative regulator of ErbB family receptor tyrosine kinases.97
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
171788292007LRIG1 is a novel negative regulator of the Met receptor and opposes Met and Her2 synergy.58
189229002008Suppression of the negative regulator LRIG1 contributes to ErbB2 overexpression in breast cancer.52
122340262002Is LRIG1 a tumour suppressor gene at chromosome 3p14.3?33
218216742011Lrig1 is an estrogen-regulated growth suppressor and correlates with longer relapse-free survival in ERα-positive breast cancer.29
176249902008LRIG1 and squamous epithelial uterine cervical cancer: correlation to prognosis, other tumor markers, sex steroid hormones, and smoking.27

Citation

Dongsheng Guo ; Baofeng Wang

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

Atlas Genet Cytogenet Oncol Haematol. 2010-12-01

Online version: http://atlasgeneticsoncology.org/gene/41198/lrig1