GNLY

Granulysin
PDB rendering based on 1l9l.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1L9L​
Identifiers
Symbols	GNLY ; D2S69E; LAG-2; LAG2; NKG5; TLA519
External IDs	OMIM: 188855 HomoloGene: 136805 GeneCards: GNLY Gene
Gene ontology Cellular component • extracellular space Biological process • cellular defense response • killing of cells of other organism • defense response to bacterium • defense response to fungus Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	10578	n/a
Ensembl	ENSG00000115523	n/a
UniProt	P22749	n/a
RefSeq (mRNA)	NM_001302758	n/a
RefSeq (protein)	NP_001289687	n/a
Location (UCSC)	Chr 2: 85.69 – 85.7 Mb	n/a
PubMed search		n/a

Granulysin, also known as GNLY, is a protein which in humans is encoded by the GNLY gene.^[1]

Function

Granulysin is a protein present in cytotoxic granules of cytotoxic T cells and natural killer cells. 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.^[1]

Granulysin is a cytolytic and proinflammatory molecule first identified by a screen for genes expressed “late” (3-5 days) after activation of human peripheral blood mononuclear cells.^[2] 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.^[3] 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.^[4] Mice do not have a granulysin homolog, but transgenic mice expressing human granulysin have been engineered.^[5] Granulysin has been implicated in a myriad of diseases including infection, cancer, transplantation, autoimmunity, skin and reproductive maladies.^[6]

References

1. "Entrez Gene: GNLY granulysin".
2. 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". J. Exp. Med. 165 (3): 601–14. doi:10.1084/jem.165.3.601. PMC 2188281. PMID 2434598.
3. 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.
4. 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". J. Immunol. 174 (9): 5243–8. doi:10.4049/jimmunol.174.9.5243. PMID 15843520.
5. Huang LP, Lyu SC, Clayberger C, Krensky AM (January 2007). "Granulysin-Mediated Tumor Rejection in Transgenic Mice". J. Immunol. 178 (1): 77–84. doi:10.4049/jimmunol.178.1.77. PMC 2664664. PMID 17182542.
6. 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.

Further reading

• Peña SV, Krensky AM (1997). "Granulysin, a new human cytolytic granule-associated protein with possible involvement in cell-mediated cytotoxicity". Semin. Immunol. 9 (2): 117–25. doi:10.1006/smim.1997.0061. PMID 9194222.
• Krensky AM (2000). "Granulysin: a novel antimicrobial peptide of cytolytic T lymphocytes and natural killer cells". Biochem. Pharmacol. 59 (4): 317–20. doi:10.1016/S0006-2952(99)00177-X. PMID 10644038.
• Donlon TA, Krensky AM, Clayberger C (1990). "Localization of the human T lymphocyte activation gene 519 (D2S69E) to chromosome 2p12----q11". Cytogenet. Cell Genet. 53 (4): 230–1. doi:10.1159/000132938. PMID 2209093.
• Yabe T, McSherry C, Bach FH, Houchins JP (1990). "A cDNA clone expressed in natural killer and T cells that likely encodes a secreted protein". J. Exp. Med. 172 (4): 1159–63. doi:10.1084/jem.172.4.1159. PMC 2188624. PMID 2212946.
• Jongstra J, Schall TJ, Dyer BJ; et al. (1987). "The isolation and sequence of a novel gene from a human functional T cell line". J. Exp. Med. 165 (3): 601–14. doi:10.1084/jem.165.3.601. PMC 2188281. PMID 2434598.
• Houchins JP, Kricek F, Chujor CS; et al. (1993). "Genomic structure of NKG5, a human NK and T cell-specific activation gene". Immunogenetics 37 (2): 102–7. doi:10.1007/BF00216832. PMID 8423048.
• Peña SV, Hanson DA, Carr BA; et al. (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.
• Stenger S, Hanson DA, Teitelbaum R; et al. (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.
• Hanson DA, Kaspar AA, Poulain FR, Krensky AM (1999). "Biosynthesis of granulysin, a novel cytolytic molecule". Mol. Immunol. 36 (7): 413–22. doi:10.1016/S0161-5890(99)00063-2. PMID 10449094.
• Kaspar AA, Okada S, Kumar J; et al. (2001). "A distinct pathway of cell-mediated apoptosis initiated by granulysin". J. Immunol. 167 (1): 350–6. doi:10.4049/jimmunol.167.1.350. PMID 11418670.
• Kitamura N, Koshiba M, Horie O, Ryo R (2002). "Expression of granulysin mRNA in the human megakaryoblastic leukemia cell line CMK". Acta Haematol. 108 (1): 13–8. doi:10.1159/000063061. PMID 12145461.
• Ma LL, Spurrell JC, Wang JF; et al. (2003). "CD8 T cell-mediated killing of Cryptococcus neoformans requires granulysin and is dependent on CD4 T cells and IL-15". J. Immunol. 169 (10): 5787–95. doi:10.4049/jimmunol.169.10.5787. PMID 12421959.
• 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.
• Ericson KG, Fadeel B, Andersson M; et al. (2003). "Sequence analysis of the granulysin and granzyme B genes in familial hemophagocytic lymphohistiocytosis". Hum. Genet. 112 (1): 98–9. doi:10.1007/s00439-002-0841-0. PMID 12483306.
• Anderson DH, Sawaya MR, Cascio D; et al. (2003). "Granulysin crystal structure and a structure-derived lytic mechanism". J. Mol. Biol. 325 (2): 355–65. doi:10.1016/S0022-2836(02)01234-2. PMID 12488100.
• Gansert JL, Kiessler V, Engele M; et al. (2003). "Human NKT cells express granulysin and exhibit antimycobacterial activity". J. Immunol. 170 (6): 3154–61. doi:10.4049/jimmunol.170.6.3154. PMID 12626573.
• Ogawa K, Takamori Y, Suzuki K; et al. (2003). "Granulysin in human serum as a marker of cell-mediated immunity". Eur. J. Immunol. 33 (7): 1925–33. doi:10.1002/eji.200323977. PMID 12884856.
• Kotsch K, Mashreghi MF, Bold G; et al. (2004). "Enhanced granulysin mRNA expression in urinary sediment in early and delayed acute renal allograft rejection". Transplantation 77 (12): 1866–75. doi:10.1097/01.TP.0000131157.19937.3F. PMID 15223905.