LRG1

LRG1
Identifiers
Aliases	LRG1 , HMFT1766, LRG, leucine-rich alpha-2-glycoprotein 1, leucine rich alpha-2-glycoprotein 1, LGR-1
External IDs	OMIM: 611289; MGI: 1924155; HomoloGene: 36468; GeneCards: LRG1; OMA:LRG1 - orthologs
Gene location (Human) Chr. Chromosome 19 (human) [1] Band 19p13.3 Start 4,536,402 bp [1] End 4,540,036 bp [1]
Gene location (Mouse) Chr. Chromosome 17 (mouse) [2] Band 17 29.17 cM|17 D Start 56,426,678 bp [2] End 56,429,001 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver pancreatic ductal cell olfactory zone of nasal mucosa nasal epithelium blood body of pancreas palpebral conjunctiva bone marrow gallbladder appendix Top expressed in granulocyte left lobe of liver white adipose tissue lactiferous gland brown adipose tissue subcutaneous adipose tissue ankle joint tibiofemoral joint mesenteric lymph nodes ankle More reference expression data BioGPS n/a
Gene ontology Molecular function transforming growth factor beta receptor binding protein binding molecular function Cellular component extracellular exosome membrane extracellular space specific granule lumen intracellular membrane-bounded organelle tertiary granule lumen ficolin-1-rich granule lumen extracellular region Biological process positive regulation of transforming growth factor beta receptor signaling pathway positive regulation of endothelial cell proliferation positive regulation of angiogenesis brown fat cell differentiation neutrophil degranulation biological process response to bacterium Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 116844 76905 Ensembl ENSG00000171236 ENSMUSG00000037095 UniProt P02750 Q91XL1 RefSeq (mRNA) NM_052972 NM_029796 RefSeq (protein) NP_443204 NP_084072 Location (UCSC) Chr 19: 4.54 – 4.54 Mb Chr 17: 56.43 – 56.43 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Leucine-rich alpha-2-glycoprotein 1 is a protein which in humans is encoded by the gene LRG1. ^[5]

Function

See also: TGF beta signaling pathway and R-SMAD

The leucine-rich repeat (LRR) family of proteins, including LRG1, have been shown to be involved in protein-protein interaction, signal transduction, and cell adhesion and development. LRG1 is expressed during granulocyte differentiation. ^{[5] [6]}

LRG1 has been shown to be involved in promoting neovascularization (new blood vessel growth) through causing a switch in transforming growth factor beta (TGFbeta) signaling in endothelial cells. LRG1 binds to the accessory receptor endoglin and promotes signaling via the ALK1-Smad1/5/8 pathway. ^[7]

Application

Levels of the LRG protein are markedly elevated in acute appendicitis and therefore could be used as a diagnostic aid. ^[8]

LRG1 may be a potential therapeutic target for the treatment of diseases where there is aberrant neovascularization. ^[7]

Circulating LRG1 levels are increased in many cancer patients and may be a useful biomarker. Inhibition of LRG1 normalises the tumor vasculature, improves the efficacy of cytotoxic and immune therapies, ^[9] and restricts metastatic spread. ^[10]

LRG1 has been implicated in the pathogenesis of numerous diseases including cancer, eye disease, neurodegenerative disease, diabetes, lung and kidney disease ^[11]

References

1. GRCh38: Ensembl release 89: ENSG00000171236 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000037095 – 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. "Entrez Gene: LRG1 leucine-rich alpha-2-glycoprotein 1".
6. O'Donnell LC, Druhan LJ, Avalos BR (September 2002). "Molecular characterization and expression analysis of leucine-rich alpha2-glycoprotein, a novel marker of granulocytic differentiation". Journal of Leukocyte Biology. 72 (3): 478–485. doi: 10.1189/jlb.72.3.478 . PMID   12223515. S2CID   967662.
7. Wang X, Abraham S, McKenzie JA, Jeffs N, Swire M, Tripathi VB, et al. (July 2013). "LRG1 promotes angiogenesis by modulating endothelial TGF-β signalling". Nature. 499 (7458): 306–311. Bibcode:2013Natur.499..306W. doi:10.1038/nature12345. PMC   3836402 . PMID   23868260.
8. Vargas IM (2009-06-23). "A urine test for appendicitis?". HarvardScience Press Release. Harvard College. Retrieved 2009-06-25.
9. O'Connor MN, Kallenberg DM, Camilli C, Pilotti C, Dritsoula A, Jackstadt R, et al. (November 2021). "LRG1 destabilizes tumor vessels and restricts immunotherapeutic potency". Med. 2 (11): 1231–1252.e10. doi: 10.1016/j.medj.2021.10.002 . PMC   7614757 . PMID   35590198.
10. Singhal M, Gengenbacher N, Abdul Pari AA, Kamiyama M, Hai L, Kuhn BJ, et al. (September 2021). "Temporal multi-omics identifies LRG1 as a vascular niche instructor of metastasis". Science Translational Medicine. 13 (609) eabe6805. doi:10.1126/scitranslmed.abe6805. PMC   7614902 . PMID   34516824. S2CID   237402143.
11. Camilli C, Hoeh AE, De Rossi G, Moss SE, Greenwood J (January 2022). "LRG1: an emerging player in disease pathogenesis". Journal of Biomedical Science. 29 (1) 6. doi: 10.1186/s12929-022-00790-6 . PMC   8781713 . PMID   35062948.

Further reading

• Li X, Miyajima M, Jiang C, Arai H (February 2007). "Expression of TGF-betas and TGF-beta type II receptor in cerebrospinal fluid of patients with idiopathic normal pressure hydrocephalus". Neuroscience Letters. 413 (2): 141–144. doi:10.1016/j.neulet.2006.11.039. PMID   17194537. S2CID   54324280.
• Ramachandran P, Boontheung P, Xie Y, Sondej M, Wong DT, Loo JA (June 2006). "Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry". Journal of Proteome Research. 5 (6): 1493–1503. doi:10.1021/pr050492k. PMID   16740002.
• Cummings C, Walder J, Treeful A, Jemmerson R (July 2006). "Serum leucine-rich alpha-2-glycoprotein-1 binds cytochrome c and inhibits antibody detection of this apoptotic marker in enzyme-linked immunosorbent assay". Apoptosis. 11 (7): 1121–1129. doi:10.1007/s10495-006-8159-3. PMID   16699948. S2CID   39838086.
• Liu T, Qian WJ, Gritsenko MA, Camp DG, Monroe ME, Moore RJ, Smith RD (2006). "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry". Journal of Proteome Research. 4 (6): 2070–2080. doi:10.1021/pr0502065. PMC   1850943 . PMID   16335952.
• Yamada S, Ohira M, Horie H, Ando K, Takayasu H, Suzuki Y, et al. (August 2004). "Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas". Oncogene. 23 (35): 5901–5911. doi: 10.1038/sj.onc.1207782 . PMID   15221005.
• Bunkenborg J, Pilch BJ, Podtelejnikov AV, Wiśniewski JR (February 2004). "Screening for N-glycosylated proteins by liquid chromatography mass spectrometry". Proteomics. 4 (2): 454–465. doi:10.1002/pmic.200300556. PMID   14760718. S2CID   29261009.
• Anderson NL, Polanski M, Pieper R, Gatlin T, Tirumalai RS, Conrads TP, et al. (April 2004). "The human plasma proteome: a nonredundant list developed by combination of four separate sources". Molecular & Cellular Proteomics. 3 (4): 311–326. doi: 10.1074/mcp.M300127-MCP200 . PMID   14718574.
• O'Donnell LC, Druhan LJ, Avalos BR (September 2002). "Molecular characterization and expression analysis of leucine-rich alpha2-glycoprotein, a novel marker of granulocytic differentiation". Journal of Leukocyte Biology. 72 (3): 478–485. doi: 10.1189/jlb.72.3.478 . PMID   12223515. S2CID   967662.
• Saito K, Tanaka T, Kanda H, Ebisuno Y, Izawa D, Kawamoto S, et al. (February 2002). "Gene expression profiling of mucosal addressin cell adhesion molecule-1+ high endothelial venule cells (HEV) and identification of a leucine-rich HEV glycoprotein as a HEV marker". Journal of Immunology. 168 (3): 1050–1059. doi: 10.4049/jimmunol.168.3.1050 . PMID   11801638.
• Takahashi N, Takahashi Y, Putnam FW (April 1985). "Periodicity of leucine and tandem repetition of a 24-amino acid segment in the primary structure of leucine-rich alpha 2-glycoprotein of human serum". Proceedings of the National Academy of Sciences of the United States of America. 82 (7): 1906–1910. Bibcode:1985PNAS...82.1906T. doi: 10.1073/pnas.82.7.1906 . PMC   397442 . PMID   3856868.
• Andersen JD, Boylan KL, Xue FS, Anderson LB, Witthuhn BA, Markowski TW, et al. (January 2010). "Identification of candidate biomarkers in ovarian cancer serum by depletion of highly abundant proteins and differential in-gel electrophoresis". Electrophoresis. 31 (4): 599–610. doi:10.1002/elps.200900441. PMC   3520508 . PMID   20162585.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.