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FLASH GENE

Symbol

LRIG1

contributors: mct - updated : 08-01-2020

HGNC name	leucine-rich repeats and immunoglobulin-like domains 1
HGNC id	17360

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_015541 19 - 4812 NP_056356 119 1093 - 2003 12684867

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Nervous brain       predominantly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular         Homo sapiens Nervous central

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text

kidney

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	leucine-rich repeats
	Ig-like domains in its extracellular region

conjugated

GlycoP

HOMOLOGY

interspecies	homolog to murine Lig-1
	homolog to Drosophila Kekkon-1

Homologene

FAMILY

leucine-rich repeat and the immunoglobulin superfamily

CATEGORY

receptor membrane

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane

basic FUNCTION	playing a role as a growth and tumor suppressor
	functioning as a cell type-specific adhesion molecule or receptor at the glial cell surface
	playing a role in the nervous system in neuroglial differentiation, development, and/or maintenance of neural functions where it is expressed
	plays an essential role in Met degradation
	suppressor of Met function, serving to regulate cellular receptor levels by promoting Met degradation in a ligand- and cbl-independent manner
	acting in a negative feedback loop to regulate the activity of RET receptor tyrosine kinase
	endogenous inhibitor of RET receptor tyrosine kinase activation, downstream signaling, and biological responses to GDNF
	negative regulator of growth factor signaling
	possible role for LRIG1 and LRIG2 proteins in meningioma pathogenesis
	LRIG1 and LRIG3 overlap prominently in the developing vestibular apparatus and simultaneous removal of both genes disrupts inner ear morphogenesis
	LRIG genes appear to act both redundantly and independently, with LRIG2 emerging as the most functionally distinct family member
	LRIG1 is a negative regulator of the STAT3-dependent inflammatory pathway
	is an independent prognostic factor in patients with non-small cell lung cancer that could be important in future decision-making algorithms for adjuvant lung cancer treatment
	important homeostatic role of LRIG1 in skin
	essential role of LRIG1 in regulating morphogenic events that shape the hippocampal circuits
	is a tumor suppressor and a negative regulator of several receptor tyrosine kinases
	LRIG1 functions as a thyroid tumor suppressor
	negatively regulates receptor tyrosine kinases and functions as a tumor suppressor
	participate in the aggressive progression of several tumors, where its expression is frequently decreased
	acts as a critical regulator of melanoma cell invasion, migration, and vasculogenic mimicry upon hypoxia
	tumor suppressor in gastrointestinal tract and epidermis
	represents a pleiotropic AR-regulated feedback tumor suppressor that functions to restrict oncogenic signaling from AR

CELLULAR PROCESS	cell life, differentiation

PHYSIOLOGICAL PROCESS

development

PATHWAY

metabolism

signaling

signal transduction

growth factor receptor

a component

INTERACTION

DNA

RNA

small molecule

protein	negative regulator of EGF receptor and its relatives, ERBB2, ERBB3, and ERBB4, and LRIG1-mediated receptor ubiquitination and degradation may contribute to the suppression of ErbB receptor function
	interacting with MET (LRIG1 destabilizes the Met receptor in a cbl-independent manner)
	capable of physically interacting with RET and LRIG1/RET association inhibits GDNF binding, recruitment of Ret to lipid rafts, receptor autophosphorylation, and mitogen-activated protein kinase (MAPK) activation in response to GDNF
	USP8 is involved in deubiquitination of LRIG1, influencing the efficiency of MET degradation
	LRIG1 physically interacts with NTRK2 and attenuates BDNF signaling
	is a suppressor of various receptor tyrosine kinases, including RET

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   deletion     in various cancers tumoral     --low   in renal cell carcinoma tumoral     --over   destabilizes endogenous Met receptor in breast cancer cells and impairs their ability to respond to hepatocyte growth factor tumoral     --over   suppresses malignant glioma cell growth by attenuating EGFR activity tumoral     --low   in squamous cell carcinoma of the uterine cervix, with high LRIG2 expression identified women with a very poor prognosis tumoral     --over   in prostate cancer

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	prognostic biomarker in non-small cell lung cancer
Therapy target
	System Type Disorder Pubmed cancer brain   feedback negative attenuator of EGFR and could offer a novel therapeutic target to treat patients with malignant gliomas

ANIMAL & CELL MODELS

Lrig1-deficient mice display morphological changes in proximal dendrite arborization and defects in social interaction