LRIG1

LRIG1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4U7L, 4U7M
Identifiers
Aliases	LRIG1 , LIG-1, LIG1, leucine-rich repeats and immunoglobulin like domains 1, leucine rich repeats and immunoglobulin like domains 1
External IDs	OMIM: 608868 MGI: 107935 HomoloGene: 7380 GeneCards: LRIG1
Gene location (Human) Chr. Chromosome 3 (human) [1] Band 3p14.1 Start 66,378,797 bp [1] End 66,501,263 bp [1]
Gene location (Mouse) Chr. Chromosome 6 (mouse) [2] Band 6 D2|6 43.15 cM Start 94,581,510 bp [2] End 94,677,139 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in secondary oocyte bronchial epithelial cell body of pancreas cardia gastric mucosa pylorus internal globus pallidus lactiferous duct external globus pallidus body of stomach Top expressed in lip cerebellar cortex secondary oocyte superior frontal gyrus esophagus main bronchus spermatid yolk sac thymus neural tube More reference expression data BioGPS More reference expression data
Orthologs Species Human Mouse Entrez 26018 16206 Ensembl ENSG00000144749 ENSMUSG00000030029 UniProt Q96JA1 P70193 RefSeq (mRNA) NM_015541 NM_008377 NM_001355269 RefSeq (protein) NP_056356 NP_001364273 NP_001364274 NP_001364275 NP_001364276 NP_001364277 NP_001364278 NP_032403 NP_001342198 Location (UCSC) Chr 3: 66.38 – 66.5 Mb Chr 6: 94.58 – 94.68 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Leucine-rich repeats and immunoglobulin-like domains protein 1 is a protein that in humans is encoded by the LRIG1 gene. ^{[5] [6] [7]} It encodes a transmembrane protein that has been shown to interact with receptor tyrosine kinases of the EGFR family ^[8] and with MET ^[9] and RET. ^[10]

Model organisms

Lrig1 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Abnormal [11]
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Abnormal [12]
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Abnormal
DEXA	Abnormal [13]
Radiography	Abnormal [14]
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Abnormal [15]
Plasma immunoglobulins	Normal
Haematology	Normal
Micronucleus test	Normal
Heart weight	Normal
Tail epidermis wholemount	Abnormal
Skin Histopathology	Abnormal
Eye Histopathology	Normal
Salmonella infection	Abnormal [16]
Citrobacter infection	Abnormal [17]
All tests and analysis from [18] [19]

Model organisms have been used in the study of LRIG1 function. A conditional knockout mouse line, called Lrig1^{tm1a(EUCOMM)Wtsi [20] [21]} 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. ^{[22] [23] [24]}

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. ^{[18] [25]} 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). ^[18]

References

1. GRCh38: Ensembl release 89: ENSG00000144749 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000030029 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. 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. S2CID   34357648.
7. "Entrez Gene: LRIG1 leucine-rich repeats and immunoglobulin-like domains 1".
8. 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.
9. 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.
10. 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 . PMC   6671136 . PMID   18171921.
11. "Body weight data for Lrig1". Wellcome Trust Sanger Institute.
12. "Dysmorphology data for Lrig1". Wellcome Trust Sanger Institute.
13. "DEXA data for Lrig1". Wellcome Trust Sanger Institute.
14. "Radiography data for Lrig1". Wellcome Trust Sanger Institute.
15. "Clinical chemistry data for Lrig1". Wellcome Trust Sanger Institute.
16. "Salmonella infection data for Lrig1". Wellcome Trust Sanger Institute.
17. "Citrobacter infection data for Lrig1". Wellcome Trust Sanger Institute.
18. 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. S2CID   85911512.
19. Mouse Resources Portal, Wellcome Trust Sanger Institute.
20. "International Knockout Mouse Consortium".^{[ permanent dead link ]}
21. "Mouse Genome Informatics".
22. 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.
23. Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi: 10.1038/474262a . PMID   21677718.
24. 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. S2CID   18872015.
25. 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. S2CID   5634836.
• 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. Bibcode:2002PNAS...9916899M. 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. S2CID   7060595.
• 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. Bibcode:2006PNAS..10311958J. 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.