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LRRC15
Identifiers
Aliases	LRRC15, LIB, Leucine rich repeat containing 15
External IDs	MGI: 1921738; HomoloGene: 26080; GeneCards: LRRC15; OMA:LRRC15 - orthologs
Gene location (Human) Chr. Chromosome 3 (human) Band 3q29 Start 194,355,249 bp End 194,369,743 bp
Gene location (Mouse) Chr. Chromosome 16 (mouse) Band 16|16 B2 Start 30,088,120 bp End 30,102,074 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in periodontal fiber tendon of biceps brachii hair follicle decidua tibia skin of hip skin of thigh cartilage tissue skin of arm mucosa of paranasal sinus Top expressed in lip body of femur calvaria skin of abdomen hair follicle molar skin of back conjunctival fornix fossa morula More reference expression data BioGPS n/a
Gene ontology Molecular function fibronectin binding protein kinase inhibitor activity laminin binding collagen binding Cellular component cytoplasm integral component of membrane extracellular exosome membrane extracellular space extracellular matrix collagen-containing extracellular matrix Biological process negative regulation of protein kinase activity cytokine-mediated signaling pathway negative regulation of receptor signaling pathway via JAK-STAT positive regulation of cell migration negative regulation of protein localization to plasma membrane Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 131578 74488 Ensembl ENSG00000172061 ENSMUSG00000052316 UniProt Q8TF66 Q80X72 RefSeq (mRNA) NM_130830 NM_001135057 NM_028973 RefSeq (protein) NP_001128529 NP_570843 NP_083249 Location (UCSC) Chr 3: 194.36 – 194.37 Mb Chr 16: 30.09 – 30.1 Mb PubMed search
Wikidata
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Leucine rich repeat containing 15 is a cell membrane-expressed protein. In humans it is encoded by the LRRC15 gene. It is located on chromosome 3 at 3q29. It belongs to the LRR superfamily, which is involved in cell–cell and cell–ECM interactions.

Preliminary evidence indicates that expression may be related to the severity of COVID-19 and that it is an inhibitory accessory factor for SARS-CoV-2 cell entry.

LRRC15 lacks obvious intracellular domains. LRRC15 displays a highly restricted expression pattern, but is expressed in areas that make up innate immune barriers such as the placenta, skin, activated fibroblasts in wounds, and lymphoid tissues such as the spleen.

LRRC15 may play some role in innate immunity.

LRRC15 is aberrantly expressed in cancer. It is highly expressed in CAFs within the stroma of numerous solid tumors and directly expressed in mesenchymal tumors such as glioblastoma, sarcomas, and melanoma.

See also

• Leucine-rich repeat
• ACE2

References

1. ^ GRCh38: Ensembl release 89: ENSG00000172061 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000052316 – 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. Reynolds, Paul A.; Smolen, Gromoslaw A.; Palmer, Rachel E.; Sgroi, Dennis; Yajnik, Vijay; Gerald, William L.; Haber, Daniel A. (2003-09-01). "Identification of a DNA-binding site and transcriptional target for the EWS–WT1(+KTS) oncoprotein". Genes & Development. 17 (17): 2094–2107. doi:10.1101/gad.1110703. ISSN 0890-9369. PMC 196452. PMID 12923058.
6. "Entrez Gene: Leucine rich repeat containing 15".
7. Gisby JS, Buang NB, Papadaki A, Clarke CL, Malik TH, Medjeral-Thomas N, Pinheiro D, Mortimer PM, Lewis S, Sandhu E, McAdoo SP, Prendecki MF, Willicombe M, Pickering MC, Botto M, Thomas DC, Peters JE (2022). "Multi-omics identify LRRC15 as a COVID-19 severity predictor and persistent pro-1 thrombotic signals in convalescence". medRxiv 10.1101/2022.04.29.22274267v1.
8. Shilts J, Crozier TM, Teixeira-Silva A, Gabaev I, Greenwood ED, Watson SJ, Ortmann BM, Gawden-Bone CM, Pauzaite T, Hoffmann M, Nathan JA, Pöhlmann S, Lehner PJ, Wright GJ (2021). "LRRC15 mediates an accessory interaction with the SARS-CoV-2 spike protein". bioRxiv 10.1101/2021.09.25.461776.
9. Song J, Chow RD, Pena-Hernandez M, Zhang L, Loeb SA, So E, Liang OD, Wilen CB, Lee S. "LRRC15 is an inhibitory receptor blocking SARS-CoV-2 spike-mediated entry in trans". bioRxiv 10.1101/2021.11.23.469714.
10. "Scientists discover receptor that blocks COVID-19 infection". The University of Sydney.
11. Loo L, Waller MA, Moreno CL, Cole AJ, Stella AO, Pop OT, et al. (February 2023). "Fibroblast-expressed LRRC15 is a receptor for SARS-CoV-2 spike and controls antiviral and antifibrotic transcriptional programs". PLOS Biology. 21 (2): e3001967. doi:10.1371/journal.pbio.3001967. PMC 9910744. PMID 36757924.

Further reading

• Reynolds PA, Smolen GA, Palmer RE, Sgroi D, Yajnik V, Gerald WL, Haber DA (September 2003). "Identification of a DNA-binding site and transcriptional target for the EWS-WT1(+KTS) oncoprotein". Genes & Development. 17 (17): 2094–107. doi:10.1101/gad.1110703. PMC 196452. PMID 12923058.
• Dominguez CX, Müller S, Keerthivasan S, Koeppen H, Hung J, Gierke S, Breart B, Foreman O, Bainbridge TW, Castiglioni A, Senbabaoglu Y, Modrusan Z, Liang Y, Junttila MR, Klijn C, Bourgon R, Turley SJ (February 2020). "Single-Cell RNA Sequencing Reveals Stromal Evolution into LRRC15+ Myofibroblasts as a Determinant of Patient Response to Cancer Immunotherapy". Cancer Discovery. 10 (2): 232–253. doi:10.1158/2159-8290.CD-19-0644. PMID 31699795. S2CID 207948443.
• Krishnamurty AT, Shyer JA, Thai M, Gandham V, Buechler MB, Yang YA, Pradhan RN, Wang AW, Sanchez PL, Qu Y, Breart B, Chalouni C, Dunlap D, Ziai J, Elstrott J, Zacharias N, Mao W, Rowntree RK, Sadowsky J, Lewis GD, Pillow TH, Nabet BY, Banchereau R, Tam L, Caothien R, Bacarro N, Roose-Girma M, Modrusan Z, Mariathasan S, Müller S, Turley SJ (September 2022). "LRRC15+ myofibroblasts dictate the stromal setpoint to suppress tumour immunity". Nature. 611 (7934): 148–154. doi:10.1038/s41586-022-05272-1. PMC 9630141. PMID 36171287.
• Foster DS, Januszyk M, Delitto D, Yost KE, Griffin M, Guo J, Guardino N, Delitto AE, Chinta M, Burcham AR, Nguyen AT, Bauer-Rowe KE, Titan AL, Salhotra A, Jones RE, da Silva O, Lindsay HG, Berry CE, Chen K, Henn D, Mascharak S, Talbott HE, Kim A, Nosrati F, Sivaraj D, Ransom RC, Matthews M, Khan A, Wagh D, Coller J, Gurtner GC, Wan DC, Wapnir IL, Chang HY, Norton JA, Longaker MT (November 2022). "Multiomic analysis reveals conservation of cancer-associated fibroblast phenotypes across species and tissue of origin". Cancer Cell. 40 (11): 1392–1406. doi:10.1016/j.ccell.2022.09.015. PMC 9669239. PMID 36270275.
• Buechler MB, Pradhan RN, Krishnamurty AT, Cox C, Calviello AK, Wang AW, Yang YA, Tam L, Caothien R, Roose-Girma M, Modrusan Z, Arron JR, Bourgon R, Müller S, Turley SJ (May 2021). "Cross-tissue organization of the fibroblast lineage". Nature. 593 (7860): 575–579. Bibcode:2021Natur.593..575B. doi:10.1038/s41586-021-03549-5. PMID 33981032.
• Wang Y, Liu Y, Zhang M, Lv L, Zhang X, Zhang P, Zhou Y (March 2018). "LRRC15 promotes osteogenic differentiation of mesenchymal stem cells by modulating p65 cytoplasmic/nuclear translocation". Stem Cell Res Ther. 9 (1): 65. doi:10.1186/s13287-018-0809-1. PMC 5845373. PMID 29523191.
• Cui J, Dean D, Wei R, Hornicek FJ, Ulmert D, Duan Z (September 2020). "Expression and Clinical Implications of Leucine-Rich Repeat Containing 15 (LRRC15) in Osteosarcoma". J Orthop Res. 38 (11): 2362–2372. doi:10.1002/jor.24848. PMID 32902907. S2CID 221573227.
• O'Prey J, Wilkinson S, Ryan KM (June 2008). "Tumor antigen LRRC15 impedes adenoviral infection: implications for virus-based cancer therapy". Journal of Virology. 82 (12): 5933–9. doi:10.1128/JVI.02273-07. PMC 2395123. PMID 18385238.
• Satoh K, Hata M, Yokota H (January 2002). "A novel member of the leucine-rich repeat superfamily induced in rat astrocytes by beta-amyloid". Biochemical and Biophysical Research Communications. 290 (2): 756–62. doi:10.1006/bbrc.2001.6272. PMID 11785964.
• Satoh K, Hata M, Shimizu T, Yokota H, Akatsu H, Yamamoto T, Kosaka K, Yamada T (September 2005). "Lib, transcriptionally induced in senile plaque-associated astrocytes, promotes glial migration through extracellular matrix". Biochemical and Biophysical Research Communications. 335 (2): 631–6. doi:10.1016/j.bbrc.2005.07.117. PMID 16098915.

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