UNC13D

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Unc-13 homolog D (C. elegans)
Identifiers
Symbols UNC13D ; FHL3; HLH3; HPLH3; Munc13-4
External IDs OMIM608897 MGI1917700 HomoloGene26714 GeneCards: UNC13D Gene
Orthologs
Species Human Mouse
Entrez 201294 70450
Ensembl ENSG00000092929 ENSMUSG00000057948
UniProt Q70J99 B2RUP2
RefSeq (mRNA) NM_199242 NM_001009573
RefSeq (protein) NP_954712 NP_001009573
Location (UCSC) Chr 17:
73.82 – 73.84 Mb
Chr 11:
116.06 – 116.08 Mb
PubMed search [1] [2]

Protein unc-13 homolog D, also known as munc13-4, is a protein that in humans is encoded by the UNC13D gene.[1]

Function[edit]

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.

Munc13-4 is an is essential protein in the intracellular trafficking and exocytosis of lytic granules. It is targeted to CD63 positive secretory lysosomes. The C-terminal C2 domain of the protein is involved in this process.[2]

Clinical significance[edit]

Mutations in the UNC13D gene are associated with hemophagocytic lymphohistiocytosis type 3.[1]

References[edit]

  1. ^ a b "Entrez Gene: unc-13 homolog D (C. elegans)". 
  2. ^ Elstak ED, Te Loo M, Tesselaar K, van Kerkhof P, Loeffen J, Grivas D, Hennekam E, Boelens JJ, Hoogerbrugge PM, van der Sluijs P, van Gijn ME, van de Corput L (July 2011). "A novel Dutch mutation in UNC13D reveals an essential role of the C2B domain in munc13-4 function". Pediatr Blood Cancer 58 (4): 598–605. doi:10.1002/pbc.23253. PMID 21755595. 

Further reading[edit]

  • 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. 
  • 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. 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. 
  • 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. 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. 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. 
  • 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. 
  • 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. 
  • 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. PMID 19120489. 
  • Nakao T, Shimizu T, Fukushima T, et al.. "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. 
  • 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. 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. 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. 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. PMID 21370424. 

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.