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FLASH GENE

Symbol

UNC13D

contributors: mct/npt - updated : 19-09-2015

HGNC name	unc-13 homolog D (C. elegans)
HGNC id	23147

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	HPLH3 hemophagocytic lymphohistiocytosis, familial, 3
Location	17q25.1      Physical location : 73.823.309 - 73.840.798
Synonym symbol(s)	Munc13-4, FLJ00067, FHL3, HLH3, HPLH3

DNA

TYPE	functioning gene
STRUCTURE	17.49 kb     32 Exon(s)

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_199242 32 - 4406 NP_954712 123.3 1090 - Donn (2008)

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive stomach       highly Lymphoid/Immune lymph node       highly Nervous brain diencephalon epithalamus pineal gland   Reproductive female system uterus cervix

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular exocrine

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N- and C-terminal C2 domains (C2A and C2B) predicted to bind Ca(2+)
	one MH (MUNC13 homology) domain

HOMOLOGY

interspecies	ortholog to murine Unc13d
	ortholog to rattus Unc13d

Homologene

FAMILY	phospholipid binding domain containing protein family
	CAPS/Munc13 protein family

CATEGORY

immunity/defense

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endosome
	intracellular,cytoplasm,organelle,lysosome
text	colocalizes with cytotoxic granules at the plasma membrane

basic FUNCTION	required for the regulated secretion of cytotoxic granules at the priming stage of the exocytic pathway
	involved in Ca(2+)-dependent secretory lysosome exocytosis in mast cells (Higashio 2008)
	importance of UNC13D in platelets, indicating that it is a limiting factor required for platelet secretion and hemostasis
	restricts motility of RAB27A-expressing vesicles to facilitate lipopolysaccharide-induced priming of exocytosis in neutrophils
	essential in intracellular trafficking and exocytosis of lytic granules
	possible function as a Ca(2+) sensor at rate-limiting priming steps in granule exocytosis
	novel functions in the innate immune response of the neutrophil and have direct implications for the understanding of immunodeficiencies in patients with UNC13D deficiency
	involved in perforin secretion and FHL development
	regulates the late endocytic machinery and late endosomal-associated innate immune cellular functions

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

exocytosis transport

PATHWAY

metabolism

signaling

a component

DOC2A-UNC13D system regulates Ca(2+)-dependent secretory lysosome exocytosis in mast cells (Higashio 2008)

INTERACTION

DNA

RNA

small molecule

protein	exhibited Ca(2+)-stimulated SNARE interactions dependent on C2A and Ca(2+)-dependent membrane binding dependent on C2B
	RAB27A effector that coordinates exocytosis in hematopoietic cell
	UNC13D binding to STX7 was significantly increased by calcium

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

HPLH3

Susceptibility

to autoimmune lymphoproliferative syndrome (ALPS)

Variant & Polymorphism other	rare loss-of-function variations of UND13D are risk factors for ALPS development

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS