LRIG1

Leucine-rich repeats and immunoglobulin-like domains 1
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 4U7L​, 4U7M​
Identifiers
Symbols	LRIG1 ; LIG-1; LIG1
External IDs	OMIM: 608868 MGI: 107935 HomoloGene: 7380 GeneCards: LRIG1 Gene
Gene ontology Molecular function • protein binding Cellular component • integral component of membrane Biological process • sensory perception of sound • otolith morphogenesis • innervation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	26018	16206
Ensembl	ENSG00000144749	ENSMUSG00000030029
UniProt	Q96JA1	P70193
RefSeq (mRNA)	NM_015541	NM_008377
RefSeq (protein)	NP_056356	NP_032403
Location (UCSC)	Chr 3: 66.38 – 66.5 Mb	Chr 6: 94.6 – 94.7 Mb
PubMed search

Leucine-rich repeats and immunoglobulin-like domains protein 1 is a protein that in humans is encoded by the LRIG1 gene.^[1][2][3] It encodes a transmembrane protein that has been shown to interact with receptor tyrosine kinases of the EGFR-family^[4] , MET^[5] and RET.^[6]

Model organisms

Lrig1 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Abnormal[7]
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Abnormal[8]
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Abnormal
DEXA	Abnormal[9]
Radiography	Abnormal[10]
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Abnormal[11]
Plasma immunoglobulins	Normal
Haematology	Normal
Micronucleus test	Normal
Heart weight	Normal
Tail epidermis wholemount	Abnormal
Skin Histopathology	Abnormal
Eye Histopathology	Normal
Salmonella infection	Abnormal[12]
Citrobacter infection	Abnormal[13]
All tests and analysis from[14][15]

Model organisms have been used in the study of LRIG1 function. A conditional knockout mouse line, called Lrig1^{tm1a(EUCOMM)Wtsi[16][17]} was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.^[18][19][20]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[14][21] Twenty five tests were carried out on homozygous mutant mice and ten significant abnormalities were observed, including decreased body weight and total body fat, scaly skin, abnormal hair shedding, a moderate degree of hearing impairment, vertebral fusion, abnormal plasma chemistry and an increased susceptibility to bacterial infection (with both Salmonella and Citrobacter).^[14]

References

1. Nilsson J, Vallbo C, Guo D, Golovleva I, Hallberg B, Henriksson R, Hedman H (Jun 2001). "Cloning, characterization, and expression of human LIG1". Biochem Biophys Res Commun 284 (5): 1155–61. doi:10.1006/bbrc.2001.5092. PMID 11414704.
2. Hedman H, Nilsson J, Guo D, Henriksson R (Sep 2002). "Is LRIG1 a tumour suppressor gene at chromosome 3p14.3?". Acta Oncol 41 (4): 352–4. doi:10.1080/028418602760169398. PMID 12234026.
3. "Entrez Gene: LRIG1 leucine-rich repeats and immunoglobulin-like domains 1".
4. Gur G, Rubin C, Katz M, et al. (2005). "LRIG1 restricts growth factor signaling by enhancing receptor ubiquitylation and degradation". EMBO J. 23 (16): 3270–81. doi:10.1038/sj.emboj.7600342. PMC 514515. PMID 15282549.
5. Shattuck DL, Miller JK, Laederich M, et al. (2007). "LRIG1 Is a Novel Negative Regulator of the Met Receptor and Opposes Met and Her2 Synergy". Mol. Cell. Biol. 27 (5): 1934–46. doi:10.1128/MCB.00757-06. PMC 1820466. PMID 17178829.
6. Ledda F, Bieraugel O, Fard SS, Vilar M, Paratcha G. (2008). "Lrig1 is an endogenous inhibitor of Ret receptor tyrosine kinase activation, downstream signaling, and biological responses to GDNF". J Neurosci. . 28 (2): 39–49. doi:10.1523/JNEUROSCI.2196-07.2008. PMID 18171921.
7. "Body weight data for Lrig1". Wellcome Trust Sanger Institute.
8. "Dysmorphology data for Lrig1". Wellcome Trust Sanger Institute.
9. "DEXA data for Lrig1". Wellcome Trust Sanger Institute.
10. "Radiography data for Lrig1". Wellcome Trust Sanger Institute.
11. "Clinical chemistry data for Lrig1". Wellcome Trust Sanger Institute.
12. "Salmonella infection data for Lrig1". Wellcome Trust Sanger Institute.
13. "Citrobacter infection data for Lrig1". Wellcome Trust Sanger Institute.
14. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
15. Mouse Resources Portal, Wellcome Trust Sanger Institute.
16. "International Knockout Mouse Consortium".
17. "Mouse Genome Informatics".
18. Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
19. Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
20. Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
21. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading

• Suzuki Y, Sato N, Tohyama M, et al. (1996). "cDNA cloning of a novel membrane glycoprotein that is expressed specifically in glial cells in the mouse brain. LIG-1, a protein with leucine-rich repeats and immunoglobulin-like domains". J. Biol. Chem. 271 (37): 22522–7. doi:10.1074/jbc.271.37.22522. PMID 8798419.
• Suzuki Y, Miura H, Tanemura A, et al. (2002). "Targeted disruption of LIG-1 gene results in psoriasiform epidermal hyperplasia". FEBS Lett. 521 (1–3): 67–71. doi:10.1016/S0014-5793(02)02824-7. PMID 12067728.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Nilsson J, Starefeldt A, Henriksson R, Hedman H (2004). "LRIG1 protein in human cells and tissues". Cell Tissue Res. 312 (1): 65–71. doi:10.1007/s00441-003-0697-1. PMID 12684867.
• Thomasson M, Hedman H, Guo D, et al. (2003). "LRIG1 and epidermal growth factor receptor in renal cell carcinoma: a quantitative RT–PCR and immunohistochemical analysis". Br. J. Cancer 89 (7): 1285–9. doi:10.1038/sj.bjc.6601208. PMC 2394322. PMID 14520461.
• Gur G, Rubin C, Katz M, et al. (2005). "LRIG1 restricts growth factor signaling by enhancing receptor ubiquitylation and degradation". EMBO J. 23 (16): 3270–81. doi:10.1038/sj.emboj.7600342. PMC 514515. PMID 15282549.
• Laederich MB, Funes-Duran M, Yen L, et al. (2004). "The leucine-rich repeat protein LRIG1 is a negative regulator of ErbB family receptor tyrosine kinases". J. Biol. Chem. 279 (45): 47050–6. doi:10.1074/jbc.M409703200. PMID 15345710.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Ljuslinder I, Malmer B, Golovleva I, et al. (2006). "Increased copy number at 3p14 in breast cancer". Breast Cancer Res. 7 (5): R719–27. doi:10.1186/bcr1279. PMC 1242137. PMID 16168117.
• Jensen KB, Watt FM (2006). "Single-cell expression profiling of human epidermal stem and transit-amplifying cells: Lrig1 is a regulator of stem cell quiescence". Proc. Natl. Acad. Sci. U.S.A. 103 (32): 11958–63. doi:10.1073/pnas.0601886103. PMC 1567680. PMID 16877544.
• Shattuck DL, Miller JK, Laederich M, et al. (2007). "LRIG1 Is a Novel Negative Regulator of the Met Receptor and Opposes Met and Her2 Synergy". Mol. Cell. Biol. 27 (5): 1934–46. doi:10.1128/MCB.00757-06. PMC 1820466. PMID 17178829.