LRIG1 (leucine-rich repeats and immunoglobulin-like domains 1)
2010-12-01 Dongsheng Guo , Baofeng Wang AffiliationDept of Neurosurgery, Tongji Hospital, Huazhong University of Science, Technology, Wuhan, Hubei, 430030, Peoples Republic of China
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.
Coding sequence: 4812 bp.
Proteins
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.
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.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 16847455 | 2007 | A soluble ectodomain of LRIG1 inhibits cancer cell growth by attenuating basal and ligand-dependent EGFR activity. | Goldoni S et al |
| 17393120 | 2007 | Down-regulation of leucine-rich repeats and immunoglobulin-like domain proteins (LRIG1-3) in HP75 pituitary adenoma cell line. | Guo D et al |
| 15203213 | 2004 | The LRIG gene family has three vertebrate paralogs widely expressed in human and mouse tissues and a homolog in Ascidiacea. | Guo D et al |
| 16532360 | 2006 | Perinuclear leucine-rich repeats and immunoglobulin-like domain proteins (LRIG1-3) as prognostic indicators in astrocytic tumors. | Guo D et al |
| 15282549 | 2004 | LRIG1 restricts growth factor signaling by enhancing receptor ubiquitylation and degradation. | Gur G et al |
| 17239582 | 2007 | LRIG inhibitors of growth factor signalling - double-edged swords in human cancer? | Hedman H et al |
| 16877544 | 2006 | Single-cell expression profiling of human epidermal stem and transit-amplifying cells: Lrig1 is a regulator of stem cell quiescence. | Jensen KB et al |
| 18037903 | 2008 | Redistribution of LRIG proteins in psoriasis. | Karlsson T et al |
| 15345710 | 2004 | The leucine-rich repeat protein LRIG1 is a negative regulator of ErbB family receptor tyrosine kinases. | Laederich MB et al |
| 18171921 | 2008 | Lrig1 is an endogenous inhibitor of Ret receptor tyrosine kinase activation, downstream signaling, and biological responses to GDNF. | Ledda F et al |
| 17624990 | 2008 | LRIG1 and squamous epithelial uterine cervical cancer: correlation to prognosis, other tumor markers, sex steroid hormones, and smoking. | Lindström AK et al |
| 17851870 | 2007 | LRIG1 expression in colorectal cancer. | Ljuslinder I et al |
| 18922900 | 2008 | Suppression of the negative regulator LRIG1 contributes to ErbB2 overexpression in breast cancer. | Miller JK et al |
| 12684867 | 2003 | LRIG1 protein in human cells and tissues. | Nilsson J et al |
| 11414704 | 2001 | Cloning, characterization, and expression of human LIG1. | Nilsson J et al |
| 17178829 | 2007 | LRIG1 is a novel negative regulator of the Met receptor and opposes Met and Her2 synergy. | Shattuck DL et al |
| 18542056 | 2008 | LRIG1 negatively regulates the oncogenic EGF receptor mutant EGFRvIII. | Stutz MA et al |
| 15871317 | 2005 | LRIG-1 provides a novel prognostic predictor in squamous cell carcinoma of the skin: immunohistochemical analysis for 38 cases. | Tanemura A et al |
| 21128282 | 2011 | LRIG1 and the liar paradox in prostate cancer: a study of the expression and clinical significance of LRIG1 in prostate cancer. | Thomasson M et al |
| 16978290 | 2006 | LRIG1, a candidate tumour-suppressor gene in human bladder cancer cell line BIU87. | Yang WM et al |
| 15473925 | 2004 | [Molecular mechanism of LRIG1 cDNA-induced apoptosis in human glioma cell line H4]. | Ye F et al |
| 19216216 | 2009 | 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 et al |
| 21087604 | 2011 | Paracrine 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 ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000144749 | ENST00000273261 | Q96JA1 |
| ENSG00000144749 | ENST00000383703 | Q96JA1 |
Expression (GTEx)
Pathways
| Pathway | Source | External ID |
|---|---|---|
| Signal Transduction | REACTOME | R-HSA-162582 |
| Signaling by EGFR | REACTOME | R-HSA-177929 |
| Signaling by MET | REACTOME | R-HSA-6806834 |
| Negative regulation of MET activity | REACTOME | R-HSA-6807004 |
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38454507 | 2024 | Dysregulation and antimetastatic function of circLRIG1 modulated by miR-214-3p/LRIG1 axis in bladder carcinoma. | 0 |
| 38454507 | 2024 | Dysregulation and antimetastatic function of circLRIG1 modulated by miR-214-3p/LRIG1 axis in bladder carcinoma. | 0 |
| 38376291 | 2023 | Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is downregulated in Invasive ductal carcinoma and potential prognostic marker of breast cancer. | 0 |
| 38376291 | 2023 | Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is downregulated in Invasive ductal carcinoma and potential prognostic marker of breast cancer. | 0 |
| 35440669 | 2022 | Aberrant promoter methylation contributes to LRIG1 silencing in basal/triple-negative breast cancer. | 6 |
| 35440669 | 2022 | Aberrant promoter methylation contributes to LRIG1 silencing in basal/triple-negative breast cancer. | 6 |
| 33469151 | 2021 | LRIG proteins regulate lipid metabolism via BMP signaling and affect the risk of type 2 diabetes. | 9 |
| 33786987 | 2021 | The transmembrane protein LRIG1 triggers melanocytic tumor development following chemically induced skin carcinogenesis. | 2 |
| 33893245 | 2021 | microRNA-1246-containing extracellular vesicles from acute myeloid leukemia cells promote the survival of leukemia stem cells via the LRIG1-meditated STAT3 pathway. | 12 |
| 33947959 | 2021 | LRIG1 is a conserved EGFR regulator involved in melanoma development, survival and treatment resistance. | 5 |
| 34151794 | 2021 | Potential Novel Genes for Late-Onset Alzheimer's Disease in East-Asian Descent Identified by APOE-Stratified Genome-Wide Association Study. | 17 |
| 34331569 | 2021 | LRIG1 is a positive prognostic marker in Merkel cell carcinoma and Merkel cell carcinoma expresses epithelial stem cell markers. | 5 |
| 34576152 | 2021 | Aryl Hydrocarbon Receptor Defect Attenuates Mitogen-Activated Signaling through Leucine-Rich Repeats and Immunoglobulin-like Domains 1 (LRIG1)-Dependent EGFR Degradation. | 1 |
| 33469151 | 2021 | LRIG proteins regulate lipid metabolism via BMP signaling and affect the risk of type 2 diabetes. | 9 |
| 33786987 | 2021 | The transmembrane protein LRIG1 triggers melanocytic tumor development following chemically induced skin carcinogenesis. | 2 |
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-(leucine-rich-repeats-and-immunoglobulin-like-domains-1)
