Protein-coding gene in the species Homo sapiens
Protein unc-13 homolog D , also known as munc13-4 , is a protein that in humans is encoded by the UNC13D gene .[ 5]
Function
Munc13-4 is a member of the UNC13 family, containing similar domain structure as other family members but lacking an N-terminal phorbol ester-binding C1 domain present in other Munc13 proteins. The protein appears to play a role in vesicle maturation during exocytosis and is involved in regulation of cytolytic granules secretion.
Clinical significance
Mutations in the UNC13D gene are associated with hemophagocytic lymphohistiocytosis type 3.[ 5]
References
Further reading
Marcenaro S, Gallo F, Martini S, et al. (2006). "Analysis of natural killer-cell function in familial hemophagocytic lymphohistiocytosis (FHL): defective CD107a surface expression heralds Munc13-4 defect and discriminates between genetic subtypes of the disease" . Blood . 108 (7): 2316– 23. doi :10.1182/blood-2006-04-015693 PMID 16778144 . Gurgey A, Unal S, Okur H, et al. (2008). "Neonatal primary hemophagocytic lymphohistiocytosis in Turkish children". J. Pediatr. Hematol. Oncol . 30 (12): 871– 6. doi :10.1097/MPH.0b013e31818a9577 . PMID 19131769 . S2CID 25882775 . Saxena SK, Horiuchi H, Fukuda M (2006). "Rab27a regulates epithelial sodium channel (ENaC) activity through synaptotagmin-like protein (SLP-5) and Munc13-4 effector mechanism". Biochem. Biophys. Res. Commun . 344 (2): 651– 7. doi :10.1016/j.bbrc.2006.03.160 . PMID 16630545 . Neeft M, Wieffer M, de Jong AS, et al. (2005). "Munc13-4 is an effector of rab27a and controls secretion of lysosomes in hematopoietic cells" . Mol. Biol. Cell . 16 (2): 731– 41. doi :10.1091/mbc.E04-10-0923 . PMC 545907 PMID 15548590 . Ménager MM, Ménasché G, Romao M, et al. (2007). "Secretory cytotoxic granule maturation and exocytosis require the effector protein hMunc13-4". Nat. Immunol . 8 (3): 257– 67. doi :10.1038/ni1431 . PMID 17237785 . S2CID 25330412 . Santoro A, Cannella S, Trizzino A, et al. (2008). "Mutations affecting mRNA splicing are the most common molecular defect in patients with familial hemophagocytic lymphohistiocytosis type 3" . Haematologica . 93 (7): 1086– 90. doi :10.3324/haematol.12622 PMID 18492689 . Zhang K, Biroschak J, Glass DN, et al. (2008). "Macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis is associated with MUNC13-4 polymorphisms" . Arthritis Rheum . 58 (9): 2892– 6. doi :10.1002/art.23734 . PMC 2779064 PMID 18759271 . Yoon HS, Kim HJ, Yoo KH, et al. (2010). "UNC13D is the predominant causative gene with recurrent splicing mutations in Korean patients with familial hemophagocytic lymphohistiocytosis" . Haematologica . 95 (4): 622– 6. doi :10.3324/haematol.2009.016949 . PMC 2857192 PMID 20015888 . Horne A, Ramme KG, Rudd E, et al. (2008). "Characterization of PRF1, STX11 and UNC13D genotype-phenotype correlations in familial hemophagocytic lymphohistiocytosis" . Br. J. Haematol . 143 (1): 75– 83. doi :10.1111/j.1365-2141.2008.07315.x PMID 18710388 . S2CID 2773353 . Zur Stadt U, Beutel K, Kolberg S, et al. (2006). "Mutation spectrum in children with primary hemophagocytic lymphohistiocytosis: molecular and functional analyses of PRF1, UNC13D, STX11, and RAB27A" . Hum. Mutat . 27 (1): 62– 8. doi :10.1002/humu.20274 PMID 16278825 . S2CID 19226893 . Rudd E, Bryceson YT, Zheng C, et al. (2008). "Spectrum, and clinical and functional implications of UNC13D mutations in familial haemophagocytic lymphohistiocytosis". J. Med. Genet . 45 (3): 134– 41. doi :10.1136/jmg.2007.054288 . PMID 17993578 . S2CID 42503634 . Beutler B (2009). "Microbe sensing, positive feedback loops, and the pathogenesis of inflammatory diseases" . Immunol. Rev . 227 (1): 248– 63. doi :10.1111/j.1600-065X.2008.00733.x . PMC 2713013 PMID 19120489 . Nakao T, Shimizu T, Fukushima T, et al. (2008). "Fatal sibling cases of familial hemophagocytic lymphohistiocytosis (FHL) with MUNC13-4 mutations: case reports". Pediatr Hematol Oncol . 25 (3): 171– 80. doi :10.1080/08880010801938082 . PMID 18432499 . S2CID 205600908 . Donn R, Ellison S, Lamb R, et al. (2008). "Genetic loci contributing to hemophagocytic lymphohistiocytosis do not confer susceptibility to systemic-onset juvenile idiopathic arthritis" . Arthritis Rheum . 58 (3): 869– 74. doi :10.1002/art.23270 . PMC 2675009 PMID 18311812 . Hazen MM, Woodward AL, Hofmann I, et al. (2008). "Mutations of the hemophagocytic lymphohistiocytosis-associated gene UNC13D in a patient with systemic juvenile idiopathic arthritis" . Arthritis Rheum . 58 (2): 567– 70. doi :10.1002/art.23199 PMID 18240215 . Santoro A, Cannella S, Bossi G, et al. (2006). "Novel Munc13-4 mutations in children and young adult patients with haemophagocytic lymphohistiocytosis" . J. Med. Genet . 43 (12): 953– 60. doi :10.1136/jmg.2006.041863 . PMC 2563207 PMID 16825436 . Pivot-Pajot C, Varoqueaux F, de Saint Basile G, Bourgoin SG (2008). "Munc13-4 regulates granule secretion in human neutrophils" . J. Immunol . 180 (10): 6786– 97. doi :10.4049/jimmunol.180.10.6786 PMID 18453599 . Wood SM, Meeths M, Chiang SC, et al. (2009). "Different NK cell-activating receptors preferentially recruit Rab27a or Munc13-4 to perforin-containing granules for cytotoxicity" . Blood . 114 (19): 4117– 27. doi :10.1182/blood-2009-06-225359 PMID 19704116 . Zhong N, Radu G, Ju W, Brown WT (2005). "Novel progerin-interactive partner proteins hnRNP E1, EGF, Mel 18, and UBC9 interact with lamin A/C". Biochem. Biophys. Res. Commun . 338 (2): 855– 61. doi :10.1016/j.bbrc.2005.10.020 . PMID 16248985 . Chang TY, Jaffray J, Woda B, et al. (2011). "Hemophagocytic lymphohistiocytosis with MUNC13-4 gene mutation or reduced natural killer cell function prior to onset of childhood leukemia" . Pediatr Blood Cancer . 56 (5): 856– 8. doi :10.1002/pbc.22846 . PMC 3059114 PMID 21370424 .
External links
This article incorporates text from the United States National Library of Medicine , which is in the public domain .
