{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSyntaxin 11 (STX11) is a specialized SNARE protein that plays a pivotal role in the regulated exocytosis of cytotoxic granules in immune effector cells. In natural killer (NK) cells and cytotoxic T lymphocytes, STX11 orchestrates the membrane fusion events at the immunological synapse by interacting with essential regulatory proteins such as Munc18‐2 (STXBP2) and by forming functional complexes with other SNARE family members. This machinery is necessary for proper degranulation and target cell killing, and mutations in STX11 underlie familial hemophagocytic lymphohistiocytosis (FHL) type 4. Defects in STX11 function disrupt the stability of these protein complexes and compromise granule release, thereby contributing to severe hyperinflammatory syndromes with variable age at onset and ethnic prevalence."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its central role in cytotoxic lymphocytes, STX11 contributes significantly to vesicle fusion events in other hematopoietic cells. In platelets and neutrophils, for instance, STX11 is integral to the formation of SNARE complexes with partners such as SNAP23 and various VAMP proteins, ensuring efficient granule secretion during activation. Critically, posttranslational modifications—most notably S‐acylation—regulate STX11’s membrane association and localization, with altered acylation or reduced protein expression correlating with defective agonist-induced secretion, as observed in neonatal platelets. Detailed subcellular analyses further reveal that dynamic trafficking and compartmentalization of STX11 facilitate its role in mediating regulated exocytosis across distinct cell types."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its established roles in cytotoxicity and platelet function, emerging evidence implicates STX11 in a broader spectrum of cellular processes. Epigenetic mechanisms appear to modulate STX11 expression during development, hinting at age-dependent regulation of its function. Moreover, aberrant STX11 expression or mutation has been associated with tumor suppressor activity in peripheral T-cell lymphomas, while its participation in vesicle trafficking pathways also supports host defense by restricting the intracellular replication of pathogens such as Coxiella burnetii. In addition, STX11 influences CD4 T cell-mediated B cell help, thereby affecting germinal center formation, antibody isotype switching, and overall humoral responses, as well as regulating fatty acid uptake critical for muscle regeneration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "21", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Udo Zur Stadt, Karin Beutel, Susanne Kolberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutation spectrum in children with primary hemophagocytic lymphohistiocytosis: molecular and functional analyses of PRF1, UNC13D, STX11, and RAB27A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.20274"}], "href": "https://doi.org/10.1002/humu.20274"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16278825"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16278825"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yenan T Bryceson, Eva Rudd, Chengyun Zheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Defective cytotoxic lymphocyte degranulation in syntaxin-11 deficient familial hemophagocytic lymphohistiocytosis 4 (FHL4) patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2007-02-074468"}], "href": "https://doi.org/10.1182/blood-2007-02-074468"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17525286"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17525286"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Laura N Arneson, Adipong Brickshawana, Colin M Segovis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cutting edge: syntaxin 11 regulates lymphocyte-mediated secretion and cytotoxicity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.179.6.3397"}], "href": "https://doi.org/10.4049/jimmunol.179.6.3397"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17785771"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17785771"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "AnnaCarin Horne, Kim Göransdotter Ramme, Eva Rudd, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of PRF1, STX11 and UNC13D genotype-phenotype correlations in familial hemophagocytic lymphohistiocytosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Haematol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-2141.2008.07315.x"}], "href": "https://doi.org/10.1111/j.1365-2141.2008.07315.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18710388"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18710388"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Udo zur Stadt, Jan Rohr, Wenke Seifert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Familial hemophagocytic lymphohistiocytosis type 5 (FHL-5) is caused by mutations in Munc18-2 and impaired binding to syntaxin 11."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2009.09.005"}], "href": "https://doi.org/10.1016/j.ajhg.2009.09.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19804848"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19804848"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Silvia Danielian, Natalia Basile, Carlos Rocco, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel syntaxin 11 gene (STX11) mutation in three Argentinean patients with hemophagocytic lymphohistiocytosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Immunol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10875-009-9350-4"}], "href": "https://doi.org/10.1007/s10875-009-9350-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19967551"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19967551"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Rebecca A Marsh, Noriko Satake, Jennifer Biroschak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "STX11 mutations and clinical phenotypes of familial hemophagocytic lymphohistiocytosis in North America."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pediatr Blood Cancer (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/pbc.22499"}], "href": "https://doi.org/10.1002/pbc.22499"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20486178"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20486178"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Christine A Macartney, Sheila Weitzman, Stephanie M Wood, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Unusual functional manifestations of a novel STX11 frameshift mutation in two infants with familial hemophagocytic lymphohistiocytosis type 4 (FHL4)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pediatr Blood Cancer (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/pbc.22676"}], "href": "https://doi.org/10.1002/pbc.22676"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21298754"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21298754"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Fernando E Sepulveda, Franck Debeurme, Gaël Ménasché, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinct severity of HLH in both human and murine mutants with complete loss of cytotoxic effector PRF1, RAB27A, and STX11."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2012-07-440339"}], "href": "https://doi.org/10.1182/blood-2012-07-440339"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23160464"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23160464"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Mahantappa Halimani, Varsha Pattu, Misty R Marshall, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Syntaxin11 serves as a t-SNARE for the fusion of lytic granules in human cytotoxic T lymphocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Immunol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/eji.201344011"}], "href": "https://doi.org/10.1002/eji.201344011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24227526"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24227526"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Aysenur Bahadir, Şebnem Kader, Alper Han Çebi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Familial Hemophagocytic Lymphohistiocytosis With Heterozygous STX11 and Homozygous UNC13D Mutations Diagnosed in the Neonatal Period."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pediatr Hematol Oncol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/MPH.0000000000002449"}], "href": "https://doi.org/10.1097/MPH.0000000000002449"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35293882"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35293882"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Tamara Kögl, Hsin-Fang Chang, Julian Staniek, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Patients and mice with deficiency in the SNARE protein SYNTAXIN-11 have a secondary B cell defect."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20221122"}], "href": "https://doi.org/10.1084/jem.20221122"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38722309"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38722309"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Li-Xin Xie, Janis de la Iglesia-Vicente, Yun-Xiang Fang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression and subcellular localization of syntaxin 11 in human neutrophils."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Inflamm Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00011-009-0006-x"}], "href": "https://doi.org/10.1007/s00011-009-0006-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19259622"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19259622"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Alena Dabrazhynetskaya, Jinxia Ma, Andre Ortlieb Guerreiro-Cacais, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Syntaxin 11 marks a distinct intracellular compartment recruited to the immunological synapse of NK cells to colocalize with cytotoxic granules."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1582-4934.2011.01280.x"}], "href": "https://doi.org/10.1111/j.1582-4934.2011.01280.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21342435"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21342435"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Huang Zhizhuo, Xu Junmei, Shen Yuelin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Screening the PRF1, UNC13D, STX11, SH2D1A, XIAP, and ITK gene mutations in Chinese children with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pediatr Blood Cancer (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/pbc.23216"}], "href": "https://doi.org/10.1002/pbc.23216"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21674762"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21674762"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Shaojing Ye, Zubair A Karim, Rania Al Hawas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Syntaxin-11, but not syntaxin-2 or syntaxin-4, is required for platelet secretion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2012-05-430603"}], "href": "https://doi.org/10.1182/blood-2012-05-430603"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22767500"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22767500"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Andrew L Hellewell, Ombretta Foresti, Nicola Gover, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of familial hemophagocytic lymphohistiocytosis type 4 (FHL-4) mutant proteins reveals that S-acylation is required for the function of syntaxin 11 in natural killer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0098900"}], "href": "https://doi.org/10.1371/journal.pone.0098900"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24910990"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24910990"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Eva Caparrós-Pérez, Raúl Teruel-Montoya, Verónica Palma-Barquero, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Down Regulation of the Munc18b-syntaxin-11 Complex and β1-tubulin Impairs Secretion and Spreading in Neonatal Platelets."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thromb Haemost (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1160/TH17-04-0241"}], "href": "https://doi.org/10.1160/TH17-04-0241"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29044293"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29044293"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Jinchao Zhang, Yunjie Huang, Jing Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dynamic cycling of t-SNARE acylation regulates platelet exocytosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA117.000140"}], "href": "https://doi.org/10.1074/jbc.RA117.000140"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29352103"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29352103"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Phan Thi Xinh, Ho Quoc Chuong, Truong Pham Hong Diem, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Spectrum mutations of PRF1, UNC13D, STX11, and STXBP2 genes in Vietnamese patients with hemophagocytic lymphohistiocytosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Lab Hematol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/ijlh.13674"}], "href": "https://doi.org/10.1111/ijlh.13674"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34339548"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34339548"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Geneviève Marcelin, Catherine Diatloff-Zito, Annie Nicole, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Developmental methylation program and concerted expression of Stx11 in mouse tissues."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mamm Genome (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00335-008-9162-5"}], "href": "https://doi.org/10.1007/s00335-008-9162-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19169743"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19169743"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Noriaki Yoshida, Shinobu Tsuzuki, Kennosuke Karube, et al. "}, {"type": "b", "children": [{"type": "t", "text": "STX11 functions as a novel tumor suppressor gene in peripheral T-cell lymphomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Sci (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cas.12742"}], "href": "https://doi.org/10.1111/cas.12742"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26176172"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26176172"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Sandhya Ganesan, Natalie N Alvarez, Samuel Steiner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Syntaxin 11 Contributes to the Interferon-Inducible Restriction of Coxiella burnetii Intracellular Infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "mBio (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/mbio.03545-22"}], "href": "https://doi.org/10.1128/mbio.03545-22"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36728431"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36728431"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Juan Wang, Dong-Lin Li, Lang-Fan Zheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dynamic palmitoylation of STX11 controls injury-induced fatty acid uptake to promote muscle regeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2023.12.005"}], "href": "https://doi.org/10.1016/j.devcel.2023.12.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38198890"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38198890"}]}]}]}