View source for UNC13D

{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
'''Protein unc-13 homolog D''', also known as '''munc13-4''', is a [[protein]] that in humans is encoded by the ''UNC13D'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: unc-13 homolog D (C. elegans)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=201294| accessdate = }}</ref>
== Function ==
Munc13-4 is a member of the UNC13 family, containing similar domain structure as other family members but lacking an [[N-terminus|N-terminal]] [[phorbol]] ester-binding [[C1 domain]] present in other Munc13 proteins. The protein appears to play a role in [[vesicle (biology)|vesicle]] maturation during [[exocytosis]] and is involved in regulation of [[cytolytic granule]]s secretion.
== Clinical significance ==
Mutations in the UNC13D gene are associated with [[hemophagocytic lymphohistiocytosis]] type 3.<ref name="entrez"/>
==References==
{{reflist}}
==Further reading==
{{refbegin | 2}}
*{{cite journal   |vauthors=Marcenaro S, Gallo F, Martini S, etal |title=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. |journal=Blood |volume=108 |issue= 7 |pages= 2316–23 |year= 2006 |pmid= 16778144 |doi= 10.1182/blood-2006-04-015693 |doi-access= free }}
*{{cite journal   |vauthors=Gurgey A, Unal S, Okur H, etal |title=Neonatal primary hemophagocytic lymphohistiocytosis in Turkish children. |journal=J. Pediatr. Hematol. Oncol. |volume=30 |issue= 12 |pages= 871–6 |year= 2008 |pmid= 19131769 |doi= 10.1097/MPH.0b013e31818a9577 |s2cid=25882775 }}
*{{cite journal  |vauthors=Saxena SK, Horiuchi H, Fukuda M |title=Rab27a regulates epithelial sodium channel (ENaC) activity through synaptotagmin-like protein (SLP-5) and Munc13-4 effector mechanism. |journal=Biochem. Biophys. Res. Commun. |volume=344 |issue= 2 |pages= 651–7 |year= 2006 |pmid= 16630545 |doi= 10.1016/j.bbrc.2006.03.160 }}
*{{cite journal   |vauthors=Neeft M, Wieffer M, de Jong AS, etal |title=Munc13-4 is an effector of rab27a and controls secretion of lysosomes in hematopoietic cells. |journal=Mol. Biol. Cell |volume=16 |issue= 2 |pages= 731–41 |year= 2005 |pmid= 15548590 |doi= 10.1091/mbc.E04-10-0923 |pmc=545907}}
*{{cite journal  |vauthors=Ménager MM, Ménasché G, Romao M |title=Secretory cytotoxic granule maturation and exocytosis require the effector protein hMunc13-4. |journal=Nat. Immunol. |volume=8 |issue= 3 |pages= 257–67 |year= 2007 |pmid= 17237785 |doi= 10.1038/ni1431 |s2cid=25330412 |display-authors=etal}}
*{{cite journal   |vauthors=Santoro A, Cannella S, Trizzino A, etal |title=Mutations affecting mRNA splicing are the most common molecular defect in patients with familial hemophagocytic lymphohistiocytosis type 3. |journal=Haematologica |volume=93 |issue= 7 |pages= 1086–90 |year= 2008 |pmid= 18492689 |doi= 10.3324/haematol.12622 |doi-access= free }}
*{{cite journal   |vauthors=Zhang K, Biroschak J, Glass DN, etal |title=Macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis is associated with MUNC13-4 polymorphisms. |journal=Arthritis Rheum. |volume=58 |issue= 9 |pages= 2892–6 |year= 2008 |pmid= 18759271 |doi= 10.1002/art.23734 |pmc=2779064}}
*{{cite journal   |vauthors=Yoon HS, Kim HJ, Yoo KH, etal |title=UNC13D is the predominant causative gene with recurrent splicing mutations in Korean patients with familial hemophagocytic lymphohistiocytosis. |journal=Haematologica |volume=95 |issue= 4 |pages= 622–6 |year= 2010 |pmid= 20015888 |doi= 10.3324/haematol.2009.016949 |pmc=2857192}}
*{{cite journal   |vauthors=Horne A, Ramme KG, Rudd E, etal |title=Characterization of PRF1, STX11 and UNC13D genotype-phenotype correlations in familial hemophagocytic lymphohistiocytosis. |journal=Br. J. Haematol. |volume=143 |issue= 1 |pages= 75–83 |year= 2008 |pmid= 18710388 |doi= 10.1111/j.1365-2141.2008.07315.x |s2cid=2773353 |doi-access=free }}
*{{cite journal   |vauthors=Zur Stadt U, Beutel K, Kolberg S, etal |title=Mutation spectrum in children with primary hemophagocytic lymphohistiocytosis: molecular and functional analyses of PRF1, UNC13D, STX11, and RAB27A. |journal=Hum. Mutat. |volume=27 |issue= 1 |pages= 62–8 |year= 2006 |pmid= 16278825 |doi= 10.1002/humu.20274 |s2cid=19226893 |doi-access=free }}
*{{cite journal   |vauthors=Rudd E, Bryceson YT, Zheng C, etal |title=Spectrum, and clinical and functional implications of UNC13D mutations in familial haemophagocytic lymphohistiocytosis. |journal=J. Med. Genet. |volume=45 |issue= 3 |pages= 134–41 |year= 2008 |pmid= 17993578 |doi= 10.1136/jmg.2007.054288 |s2cid=42503634 }}
*{{cite journal  |author=Beutler B |title=Microbe sensing, positive feedback loops, and the pathogenesis of inflammatory diseases. |journal=Immunol. Rev. |volume=227 |issue= 1 |pages= 248–63 |year= 2009 |pmid= 19120489 |doi= 10.1111/j.1600-065X.2008.00733.x |pmc=2713013}}
*{{cite journal   |vauthors=Nakao T, Shimizu T, Fukushima T, etal |title=Fatal sibling cases of familial hemophagocytic lymphohistiocytosis (FHL) with MUNC13-4 mutations: case reports. |journal=Pediatr Hematol Oncol |volume=25 |issue= 3 |pages= 171–80 |year=  2008|pmid= 18432499 |doi= 10.1080/08880010801938082 |s2cid=205600908 }}
*{{cite journal   |vauthors=Donn R, Ellison S, Lamb R, etal |title=Genetic loci contributing to hemophagocytic lymphohistiocytosis do not confer susceptibility to systemic-onset juvenile idiopathic arthritis. |journal=Arthritis Rheum. |volume=58 |issue= 3 |pages= 869–74 |year= 2008 |pmid= 18311812 |doi= 10.1002/art.23270 |pmc=2675009}}
*{{cite journal   |vauthors=Hazen MM, Woodward AL, Hofmann I, etal |title=Mutations of the hemophagocytic lymphohistiocytosis-associated gene UNC13D in a patient with systemic juvenile idiopathic arthritis. |journal=Arthritis Rheum. |volume=58 |issue= 2 |pages= 567–70 |year= 2008 |pmid= 18240215 |doi= 10.1002/art.23199 |doi-access= free }}
*{{cite journal   |vauthors=Santoro A, Cannella S, Bossi G, etal |title=Novel Munc13-4 mutations in children and young adult patients with haemophagocytic lymphohistiocytosis. |journal=J. Med. Genet. |volume=43 |issue= 12 |pages= 953–60 |year= 2006 |pmid= 16825436 |doi= 10.1136/jmg.2006.041863 |pmc=2563207}}
*{{cite journal  |vauthors=Pivot-Pajot C, Varoqueaux F, de Saint Basile G, Bourgoin SG |title=Munc13-4 regulates granule secretion in human neutrophils. |journal=J. Immunol. |volume=180 |issue= 10 |pages= 6786–97 |year= 2008 |pmid= 18453599 |doi=  10.4049/jimmunol.180.10.6786|doi-access=free }}
*{{cite journal   |vauthors=Wood SM, Meeths M, Chiang SC, etal |title=Different NK cell-activating receptors preferentially recruit Rab27a or Munc13-4 to perforin-containing granules for cytotoxicity. |journal=Blood |volume=114 |issue= 19 |pages= 4117–27 |year= 2009 |pmid= 19704116 |doi= 10.1182/blood-2009-06-225359 |doi-access= free }}
*{{cite journal  |vauthors=Zhong N, Radu G, Ju W, Brown WT |title=Novel progerin-interactive partner proteins hnRNP E1, EGF, Mel 18, and UBC9 interact with lamin A/C. |journal=Biochem. Biophys. Res. Commun. |volume=338 |issue= 2 |pages= 855–61 |year= 2005 |pmid= 16248985 |doi= 10.1016/j.bbrc.2005.10.020 }}
*{{cite journal   |vauthors=Chang TY, Jaffray J, Woda B, etal |title=Hemophagocytic lymphohistiocytosis with MUNC13-4 gene mutation or reduced natural killer cell function prior to onset of childhood leukemia. |journal=Pediatr Blood Cancer |volume=56 |issue= 5 |pages= 856–8 |year= 2011 |pmid= 21370424 |doi= 10.1002/pbc.22846 |pmc=3059114}}
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==External links==
* {{MeshName|UNC13D+protein,+human}}
{{NLM content}}
{{gene-17-stub}}