Human Gene UNC13D (ENST00000207549.9) from GENCODE V44
Description: Homo sapiens unc-13 homolog D (UNC13D), mRNA. (from RefSeq NM_199242) RefSeq Summary (NM_199242): This gene encodes a protein that 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. Mutations in this gene are associated with familial hemophagocytic lymphohistiocytosis type 3, a genetically heterogeneous, rare autosomal recessive disorder. [provided by RefSeq, Jul 2008]. Sequence Note: The RefSeq transcript and protein were derived from genomic sequence to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on alignments. Gencode Transcript: ENST00000207549.9 Gencode Gene: ENSG00000092929.13 Transcript (Including UTRs) Position: hg38 chr17:75,827,225-75,844,404 Size: 17,180 Total Exon Count: 32 Strand: - Coding Region Position: hg38 chr17:75,827,965-75,844,337 Size: 16,373 Coding Exon Count: 32
ID:UN13D_HUMAN DESCRIPTION: RecName: Full=Protein unc-13 homolog D; AltName: Full=Munc13-4; FUNCTION: Plays a role in cytotoxic granule exocytosis in lymphocytes. Required for both granule maturation and granule docking and priming at the immunologic synapse. Regulates assembly of recycling and late endosomal structures, leading to the formation of an endosomal exocytic compartment that fuses with perforin-containing granules at the immunologic synapse and licences them for exocytosis. Regulates Ca(2+)-dependent secretory lysosome exocytosis in mast cells. SUBUNIT: Interacts with DOC2A (By similarity). Interacts with RAB27A. SUBCELLULAR LOCATION: Cytoplasm. Membrane; Peripheral membrane protein. Late endosome. Recycling endosome. Lysosome. Note=Colocalizes with cytotoxic granules at the plasma membrane. Localizes to endosomal exocytic vesicles. TISSUE SPECIFICITY: Expressed at high levels in spleen, thymus and leukocytes. Also expressed in lung and placenta, and at very low levels in brain, heart, skeletal muscle and kidney. Expressed in cytotoxic T-lymphocytes (CTL) and mast cells. DOMAIN: The MHD1 and MHD2 domains mediate localization on recycling endosomes and lysosome. DISEASE: Defects in UNC13D are the cause of familial hemophagocytic lymphohistiocytosis type 3 (FHL3) [MIM:608898]; also known as HPLH3. Familial hemophagocytic lymphohistiocytosis (FHL) is a genetically heterogeneous, rare autosomal recessive disorder. It is characterized by immune dysregulation with hypercytokinemia and defective natural killer cell function. The clinical features of the disease include fever, hepatosplenomegaly, cytopenia, hypertriglyceridemia, hypofibrinogenemia, and neurological abnormalities ranging from irritability and hypotonia to seizures, cranial nerve deficits, and ataxia. Hemophagocytosis is a prominent feature of the disease, and a non-malignant infiltration of macrophages and activated T-lymphocytes in lymph nodes, spleen, and other organs is also found. SIMILARITY: Belongs to the unc-13 family. SIMILARITY: Contains 2 C2 domains. SIMILARITY: Contains 1 MHD1 (MUNC13 homology domain 1) domain. SIMILARITY: Contains 1 MHD2 (MUNC13 homology domain 2) domain. SEQUENCE CAUTION: Sequence=BAB15764.1; Type=Erroneous initiation; WEB RESOURCE: Name=UNC13Dbase; Note=UNC13D mutation db; URL="http://bioinf.uta.fi/UNC13Dbase/"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/UNC13D";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q70J99
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
