GNLY

Granulysin, also known as GNLY, is a protein which in humans is encoded by the GNLY gene.[3] It is also known as NK-lysin (NKL) after NK cells;[4] the cattle ortholog is sometimes referred to as Bo-lysin.

GNLY
Available structures
PDBHuman UniProt search: PDBe RCSB
Identifiers
AliasesGNLY, 519, D2S69E, LAG-2, LAG2, NKG5, TLA519, granulysin
External IDsOMIM: 188855 HomoloGene: 136805 GeneCards: GNLY
Gene location (Human)
Chr.Chromosome 2 (human)[1]
Band2p11.2Start85,685,175 bp[1]
End85,698,854 bp[1]
RNA expression pattern


More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

10578

n/a

Ensembl

ENSG00000115523

n/a

UniProt

P22749

n/a

RefSeq (mRNA)

NM_001302758
NM_006433
NM_012483

n/a

RefSeq (protein)

NP_001289687
NP_006424
NP_036615

n/a

Location (UCSC)Chr 2: 85.69 – 85.7 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

Granulysin is released by cytotoxic T cells and NK cells when they are attached to infected body cells. It creates holes in the target cell membrane and destroy it. Granulysin is able to induce apoptosis in target cells and also has antimicrobial action. Granulysin is broadly antimicrobial, killing microbes that cause, for example, tuberculosis and malaria, and can destroy some tumors.[5] A series of peptides generated from the amino acid sequence of granulysin are potential antibiotics.

Function

Granulysin is a protein present in cytolytic granules of cytotoxic T cells (CD8+) and natural killer cells along with perforin and granzymes. Granulysin is a member of the saposin-like protein (SAPLIP) family and is released from cytotoxic T cells upon antigen stimulation. Granulysin has antimicrobial activity against M. tuberculosis and other organisms. Granulysin is alternatively spliced, resulting in the NKG5 and 519 transcripts.[3]

Granulysin is a cytolytic and proinflammatory molecule first identified by a subtractive hybridization screen for genes expressed “late” (3–5 days) after activation of human peripheral blood mononuclear cells.[6] Granulysin is present in cytolytic granules of cytotoxic T lymphocytes (CTL) and natural killer (NK) cells. Granulysin is made as a 15 kD molecule, and a portion of it is cleaved at both the amino and carboxy termini into a 9 kD form. The 9 kD form is released by receptor-mediated granule exocytosis while the 15 kD form is constitutively secreted. Recombinant 9 kD granulysin is broadly cytolytic against tumors and microbes, including gram positive and gram negative bacteria, fungi/yeast and parasites.[7] 9kD granulysin is also a chemoattractant for T lymphocytes, monocytes, and other inflammatory cells and activates the expression of a number of cytokines, including RANTES, MCP-1, MCP-3, MIP-1α, IL-10, IL-1, IL-6 and IFNα.[8] Granulysin has been implicated in a myriad of diseases including infection, cancer, transplantation, autoimmunity, skin and reproductive maladies.[9]

Granulysin has recently been implicated in the development of Stevens–Johnson syndrome.

Evolution

GNLY orthologs have been identified in multiple species, including pigs, chicken, and cattle. Cattle has multiple copies of the gene with functional diversification.[10]

Mice do not have a granulysin homolog, but transgenic mice expressing human granulysin have been engineered.[11]

gollark: Even the PotatOS krist miner could do so, even.
gollark: Which ones, even.
gollark: More mining power basically just means you try random (sequential maybe, but hash functions are meant to be such that it's irrelevant) hashes faster. But which one turns out to work is random.
gollark: No, it's somewhat randomized.
gollark: Guess I'll just deploy a universal network of nanomachine "improvement" stations.

References
  1. GRCh38: Ensembl release 89: ENSG00000115523 - Ensembl, May 2017
  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. "Entrez Gene: GNLY granulysin".
  4. Andersson M, Gunne H, Agerberth B, Boman A, Bergman T, Sillard R, Jörnvall H, Mutt V, Olsson B, Wigzell H (April 1995). "NK-lysin, a novel effector peptide of cytotoxic T and NK cells. Structure and cDNA cloning of the porcine form, induction by interleukin 2, antibacterial and antitumour activity". The EMBO Journal. 14 (8): 1615–25. PMC 398254. PMID 7737114.
  5. Janeway, Charles (2005). Immunobiology: the immune system in health and disease (6th ed.). New York: Garland Science. ISBN 978-0-8153-4101-7.
  6. Jongstra J, Schall TJ, Dyer BJ, Clayberger C, Jorgensen J, Davis MM, Krensky AM (March 1987). "The isolation and sequence of a novel gene from a human functional T cell line". The Journal of Experimental Medicine. 165 (3): 601–14. doi:10.1084/jem.165.3.601. PMC 2188281. PMID 2434598.
  7. Stenger S, Hanson DA, Teitelbaum R, Dewan P, Niazi KR, Froelich CJ, Ganz T, Thoma-Uszynski S, Melián A, Bogdan C, Porcelli SA, Bloom BR, Krensky AM, Modlin RL (October 1998). "An antimicrobial activity of cytolytic T cells mediated by granulysin". Science. 282 (5386): 121–5. doi:10.1126/science.282.5386.121. PMID 9756476.
  8. Deng A, Chen S, Li Q, Lyu SC, Clayberger C, Krensky AM (May 2005). "Granulysin, a cytolytic molecule, is also a chemoattractant and proinflammatory activator". Journal of Immunology. 174 (9): 5243–8. doi:10.4049/jimmunol.174.9.5243. PMID 15843520.
  9. Krensky AM, Clayberger C (March 2009). "Biology and clinical relevance of granulysin". Tissue Antigens. 73 (3): 193–8. doi:10.1111/j.1399-0039.2008.01218.x. PMC 2679253. PMID 19254247.
  10. Chen J, Huddleston J, Buckley RM, Malig M, Lawhon SD, Skow LC, Lee MO, Eichler EE, Andersson L, Womack JE (December 2015). "Bovine NK-lysin: Copy number variation and functional diversification". Proceedings of the National Academy of Sciences of the United States of America. 112 (52): E7223-9. doi:10.1073/pnas.1519374113. PMC 4702975. PMID 26668394.
  11. Huang LP, Lyu SC, Clayberger C, Krensky AM (January 2007). "Granulysin-mediated tumor rejection in transgenic mice". Journal of Immunology. 178 (1): 77–84. doi:10.4049/jimmunol.178.1.77. PMC 2664664. PMID 17182542.
  1. Krista Conger. Grant to fund research into preventing bioterrorism, Stanford Report, November 12, 2003.
  2. Stenger S, Hanson DA, Teitelbaum R, et al. (October 1998). "An antimicrobial activity of cytolytic T cells mediated by granulysin". Science. 282 (5386): 121–5. doi:10.1126/science.282.5386.121. PMID 9756476.
  3. Peña SV, Hanson DA, Carr BA, Goralski TJ, Krensky AM (March 1997). "Processing, subcellular localization, and function of 519 (granulysin), a human late T cell activation molecule with homology to small, lytic, granule proteins". J. Immunol. 158 (6): 2680–8. PMID 9058801.
  4. Krensky AM, Clayberger C (August 2005). "Granulysin: a novel host defense molecule". Am. J. Transplant. 5 (8): 1789–92. doi:10.1111/j.1600-6143.2005.00970.x. PMID 15996224.
  5. Walch, Michael; Dotiwala, Farokh; Mulik, Sachin; Thiery, Jerome; Kirchhausen, Tomas; Clayberger, Carol; Krensky, Alan M.; Martinvalet, Denis; Lieberman, Judy (June 2014). "Cytotoxic Cells Kill Intracellular Bacteria through Granulysin-Mediated Delivery of Granzymes". Cell. 157 (6): 1309–1323. doi:10.1016/j.cell.2014.03.062. PMC 4090916. PMID 24906149.
  6. da Silva AP, Unks D, Lyu SC, et al. (May 2008). "In vitro and in vivo antimicrobial activity of granulysin-derived peptides against Vibrio cholerae". J. Antimicrob. Chemother. 61 (5): 1103–9. doi:10.1093/jac/dkn058. PMC 2664651. PMID 18310138.
  7. Chung WH, Hung SI, Yang JY, Su SC, Huang SP, Wei CY, Chin SW, Chiou CC, Chu SC, Ho HC, Yang CH, Lu CF, Wu JY, Liao YD, Chen YT (Dec 2008). "Granulysin is a key mediator for disseminated keratinocyte death in Stevens–Johnson syndrome and toxic epidermal necrolysis". Nat. Med. 14 (12): 1343–50. doi:10.1038/nm.1884. PMID 19029983.

Further reading


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