Alternative titles; symbolsLIG1HGNC Approved Gene Symbol: LRIG1Cytogenetic location: 3p14.1 Genomic coordinates (GRCh38): 3:66,378,796-66,501,120 (from NCBI)...
Alternative titles; symbols
HGNC Approved Gene Symbol: LRIG1
Cytogenetic location: 3p14.1 Genomic coordinates (GRCh38): 3:66,378,796-66,501,120 (from NCBI)
▼ Cloning and Expression
By searching for proteins similar to mouse Lig1, followed by PCR of a human brain cDNA library, Nilsson et al. (2001) cloned LRIG1, which they designated LIG1. The deduced 1,093-amino acid protein contains an extracellular N-terminal region with 15 leucine-rich repeats and 3 C2-type immunoglobulin-like domains, followed by a transmembrane region and a cytoplasmic tail. LRIG1 has 6 potential N-glycosylation sites. Mouse and human LRIG1 share 83% amino acid identity, with highest conservation in the extracellular, transmembrane, and membrane-proximal regions. Northern blot analysis detected an LRIG1 transcript of about 5.5 kb abundantly expressed in brain, heart, kidney, skeletal muscle, stomach, and testis. Quantitative RT-PCR detected expression in all tissues examined, with highest expression in brain. Lowest expression was in spleen, which showed 240-fold lower expression compared with brain.
By quantitative PCR analysis, Guo et al. (2004) detected ubiquitous but variable expression of LRIG1. Highest expression was in liver, followed by stomach and brain, and lowest expression was in placenta. Analysis of several mouse tissues showed ubiquitous expression, but the pattern of expression differed from that in human tissues.
▼ Gene Function
By single-cell expression profiling, Jensen and Watt (2006) found LRIG1 expressed in groups of basal cells in the stem cell-rich human interfollicular epidermis. Overexpression of LRIG1 decreased keratinocyte proliferation but did not affect the proportion of stem and transit amplifying cells. Downregulation of LRIG1 by siRNA increased cell-surface EGF receptor (131550) levels, enhanced activation of downstream pathways, and stimulated proliferation. LRIG1 acted in part by negatively regulating the MYC (190080) promoter. Jensen and Watt (2006) proposed that LRIG1 maintains epidermal stem cells in a quiescent nondividing stage and that LRIG1 downregulation triggers proliferation.
▼ Gene Structure
Nilsson et al. (2001) determined that the LRIG1 gene contains 19 exons and spans 225 kb.
By FISH, Nilsson et al. (2001) mapped the LRIG1 gene to chromosome 3p14. Guo et al. (2004) mapped the mouse Lrig1 gene to a region of chromosome 6D2 that shows homology of synteny to human chromosome 3p14.