UNC13D

UNC13D
Identifiers
Aliases	UNC13D , FHL3, HLH3, HPLH3, Munc13-4, unc-13 homolog D
External IDs	OMIM: 608897; MGI: 1917700; HomoloGene: 26714; GeneCards: UNC13D; OMA:UNC13D - orthologs
Gene location (Human) Chr. Chromosome 17 (human) [1] Band 17q25.1 Start 75,827,225 bp [1] End 75,844,552 bp [1]
Gene location (Mouse) Chr. Chromosome 11 (mouse) [2] Band 11|11 E2 Start 115,952,921 bp [2] End 115,968,787 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte bone marrow cell spleen right lung upper lobe of left lung monocyte sural nerve blood appendix lymph node Top expressed in granulocyte embryo morula blood blastocyst thymus embryo epiblast mesenteric lymph nodes spleen More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding Cellular component cytoplasm Weibel-Palade body recycling endosome endosome late endosome lysosome exocytic vesicle membrane extracellular region cytosol azurophil granule lumen endoplasmic reticulum intracellular membrane-bounded organelle Biological process natural killer cell degranulation regulation of mast cell degranulation germinal center formation positive regulation of exocytosis positive regulation of substrate adhesion-dependent cell spreading defense response to virus granuloma formation positive regulation of regulated secretory pathway phagocytosis exocytosis neutrophil degranulation Sources:Amigo / QuickGO
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: 75.83 – 75.84 Mb Chr 11: 115.95 – 115.97 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

1. GRCh38: Ensembl release 89: ENSG00000092929 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000057948 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: unc-13 homolog D (C. elegans)".

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

• UNC13D+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

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