LRIG3 (Leucine-Rich Repeats And Immunoglobulin-Like Domains 3)

2014-05-01 Dongsheng Guo , Feng Mao , Ting Lei Affiliation

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

Identity

HGNC

LRIG3

LOCATION

12q14.1

LOCUSID

121227

ALIAS

LIG3

FUSION GENES

Show Gene Fusions

Abstract

LRIG3 is a member of mammalian LRIG family and less is known about the functions of LRIG3. Accumulating evidences showed that LRIG3 may also function as a tumor suppressor like LRIG1. LRIG3 can inhibit tumor cell proliferation, survival, adhesion and invasion in many types of human cancer cells based on cell experiments. Perinuclear staining of LRIG3 correlated with better survival in astrocytic tumors. Decreased LRIG3 was identified as one of 12 promising serum biomarkers for early stage non-small-cell lung cancer. LRIG3 may play a role in inner ear morphogenesis and neural crest formation.

DNA/RNA

Description

According to Entrez-Gene, LRIG3 gene maps to NC_000012.12 in the region between 58872155 and 58920538 and spans across 48.3 kilobases. LRIG3 gene is encoded on the reverse strand.

Transcription

Homo sapiens leucine-rich repeats and immunoglobulin-like domains 3 has at least two transcript variants. The pre-mRNAs comprise 19 exons. The coding sequence of transcript variant 1 (NM_001136051.2) and 2 (NM_153377.4) is 3691bp and 4110bp respectively.

Proteins

LRIG3 protein. SP: signal peptide; NF: N-terminal cysteine-rich flanking domain; LRRs: 15 leucine-rich repeats; CF: C-terminal cysteinerich flanking domain; Ig C2: C2-type immunoglobulin-like domains; TM: transmembrane domain; Cyto: cytoplasmic domain.

Description

LRIG3 is a transmembrane cell-surface protein consisting of 1059 or 1119 amino acids. LRIG3 contains a signal peptide, 15 tandem LRR with cysteine rich N- and C-flanking domains, three immunoglobulin-like domains, a transmembrane domain, and a cytoplasmic tail.

Expression

LRIG3 is ubiquitously expressed in human organs. The highest expression of LRIG3 is in stomach, thyroid, and skin.

Localisation

Differential subcellular expression in a cell type-sepcific manner.

Function

LRIG3 may function as a tumor suppressor.

Mutations

Note

Mutations in LRIG3 are rare, according to the TCGA data set.

Implicated in

Entity name

Ependymoma

Note

Perinuclear staining of LRIG3 was significantly lower in posterior fossa ependymomas than in supratentorial ependymomas (Yi et al., 2009).

Entity name

Pituitary adenoma

Note

The expression of LRIG 3 in HP75 cell line was lower compared to normal pituitary glands (Guo et al., 2007).

Entity name

Astrocytic tumors

Note

Perinuclear expression of LRIG3 in astrocytic tumors has been associated with better patient survival (Guo et al., 2006). Down-regulation of LRIG3 expression in glioblastoma cell lines resulted in increased proliferation and invasion, decreased apoptosis, and increased EGFR expression (Cai et al., 2009).

Entity name

Cervical adenocarcinoma

Note

High fraction of LRIG3-positive cells were significantly associated with patient survival, and LRIG3 staining intensity was positively correlated with HPV status (Muller et al., 2013).

Entity name

Non-small-cell lung cancer

Note

LRIG3 downregulation was identified as one of 12 promising serum biomarkers for early stage non-small-cell lung cancer (Ostroff et al., 2010).

Fusion protein

The LRIG3-ROS1 fusion has been identified in non-small-cell lung cancer (Cai et al., 2013).

Entity name

Psoriasis

Note

The expression pattern of LRIG3 protein was altered in psoriatic lesions compared to normal skin (Karlsson et al., 2008).

Entity name

Inner ear morphogenesis

Note

During inner ear development, Lrig3 acts to repress Netrin transcription and Lrig3 loss led to defects in inner ear morphogenesis (Abraira et al., 2008).

Entity name

Neural crest formation

Note

LRIG3 is required for neural crest formation in developing Xenopus embryos by regulating the Wnt and Fgf signaling pathways (Zhao et al., 2008).

Bibliography

Pubmed ID	Last Year	Title	Authors
20126551	2010	Vertebrate Lrig3-ErbB interactions occur in vitro but are unlikely to play a role in Lrig3-dependent inner ear morphogenesis.	Abraira VE et al
19200647	2009	Inhibition of LRIG3 gene expression via RNA interference modulates the proliferation, cell cycle, cell apoptosis, adhesion and invasion of glioblastoma cell (GL15).	Cai M et al
19224171	2009	Effects of RNAi-mediated gene silencing of LRIG3 expression on cell cycle and survival of glioma cells.	Cai M et al
23514723	2013	ROS1 fusions in Chinese patients with non-small-cell lung cancer.	Cai W et al
24086156	2013	In vivo analysis of Lrig genes reveals redundant and independent functions in the inner ear.	Del Rio T et al
22484910	2012	Immunohistochemical analysis of LRIG proteins in meningiomas: correlation between estrogen receptor status and LRIG expression.	Ghasimi 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
18037903	2008	Redistribution of LRIG proteins in psoriasis.	Karlsson T et al
23165628	2013	Expression of LRIG1 and LRIG3 correlates with human papillomavirus status and patient survival in cervical adenocarcinoma.	Muller S et al
21170350	2010	Unlocking biomarker discovery: large scale application of aptamer proteomic technology for early detection of lung cancer.	Ostroff RM et al
23392718	2013	Over-expression of LRIG3 suppresses growth and invasion of bladder cancer cells.	Qi Y et al
23723069	2013	Leucine-rich repeat and immunoglobulin domain-containing protein-1 (Lrig1) negative regulatory action toward ErbB receptor tyrosine kinases is opposed by leucine-rich repeat and immunoglobulin domain-containing protein 3 (Lrig3).	Rafidi H et al
22893457	2012	Activin and BMP4 synergistically promote formation of definitive endoderm in human embryonic stem cells.	Teo AK et al
23558895	2013	LRIG1 is a triple threat: ERBB negative regulator, intestinal stem cell marker and tumour suppressor.	Wang Y et al
21417672	2012	Expression of EGFR and LRIG proteins in oesophageal carcinoma with emphasis on patient survival and cellular chemosensitivity.	Wu X et al
22038358	2011	Effect of over-expressed LRIG3 on cell cycle and survival of glioma cells.	Yang H 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
21505989	2011	Effect of silencing LRIG3 gene on the proliferation and apoptosis of bladder cancer T24 cells.	Yuan X et al
18287203	2008	Lrig3 regulates neural crest formation in Xenopus by modulating Fgf and Wnt signaling pathways.	Zhao H et al

Other Information

Locus ID:

NCBI: 121227
MIM: 608870
HGNC: 30991
Ensembl: ENSG00000139263

Variants:

dbSNP: 121227
ClinVar: 121227
TCGA: ENSG00000139263
COSMIC: LRIG3

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000139263	ENST00000320743	Q6UXM1
ENSG00000139263	ENST00000379141	Q6UXM1
ENSG00000139263	ENST00000433272	C9K080
ENSG00000139263	ENST00000550825	H0YID8
ENSG00000139263	ENST00000552267	F8VYZ5

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
20445134	2010	Association of genome-wide variation with the risk of incident heart failure in adults of European and African ancestry: a prospective meta-analysis from the cohorts for heart and aging research in genomic epidemiology (CHARGE) consortium.	73
20379614	2010	Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.	62
20446891	2010	A comprehensive study of the association between the EGFR and ERBB2 genes and glioma risk.	31
16532360	2006	Perinuclear leucine-rich repeats and immunoglobulin-like domain proteins (LRIG1-3) as prognostic indicators in astrocytic tumors.	22
23165628	2013	Expression of LRIG1 and LRIG3 correlates with human papillomavirus status and patient survival in cervical adenocarcinoma.	15
23723069	2013	Leucine-rich repeat and immunoglobulin domain-containing protein-1 (Lrig1) negative regulatory action toward ErbB receptor tyrosine kinases is opposed by leucine-rich repeat and immunoglobulin domain-containing protein 3 (Lrig3).	13
19200647	2009	Inhibition of LRIG3 gene expression via RNA interference modulates the proliferation, cell cycle, cell apoptosis, adhesion and invasion of glioblastoma cell (GL15).	10
18037903	2008	Redistribution of LRIG proteins in psoriasis.	9
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.	5
24998916	2014	Immunohistochemical LRIG3 expression in cervical intraepithelial neoplasia and invasive squamous cell cervical cancer: association with expression of tumor markers, hormones, high-risk HPV-infection, smoking and patient outcome.	4

Citation

Dongsheng Guo ; Feng Mao ; Ting Lei

LRIG3 (Leucine-Rich Repeats And Immunoglobulin-Like Domains 3)

Atlas Genet Cytogenet Oncol Haematol. 2014-05-01

Online version: http://atlasgeneticsoncology.org/gene/47529/lrig3