Unc13d unc-13 homolog D [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Unc13dprovided by MGI
Official Full Name: unc-13 homolog Dprovided by MGI
Primary source: MGI:MGI:1917700
See related: Ensembl:ENSMUSG00000057948 AllianceGenome:MGI:1917700
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Jinx; Munc13-4; mFLJ00067; 2610108D09Rik
Summary: Predicted to enable small GTPase binding activity. Involved in platelet dense granule organization; positive regulation of substrate adhesion-dependent cell spreading; and vasculature development. Acts upstream of or within several processes, including defense response to other organism; germinal center formation; and granuloma formation. Predicted to be located in cytosol; lysosome; and secretory vesicle. Used to study familial hemophagocytic lymphohistiocytosis 3. Human ortholog(s) of this gene implicated in familial hemophagocytic lymphohistiocytosis 3. Orthologous to human UNC13D (unc-13 homolog D). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Broad expression in thymus adult (RPKM 20.5), spleen adult (RPKM 18.5) and 15 other tissues See more
Orthologs: human all
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Genomic context

Location:: 11 E2; 11 80.91 cM

Exon count:: 35

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	11	NC_000077.7 (115952921..115969321, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	11	NC_000077.6 (116062095..116078495, complement)

Chromosome 11 - NC_000077.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Defective Zn(2+) homeostasis in mouse and human platelets with alpha- and delta-storage pool diseases.
Title: Defective Zn(2+) homeostasis in mouse and human platelets with α- and δ-storage pool diseases.
we found that platelet-specific Munc13-4 KO mice had a reduction in airway hyper-responsiveness and eosinophilic inflammation. Taken together, our results indicate that Munc13-4-dependent platelet dense granule release plays essential roles in hemostasis, thrombosis and allergic inflammation.
Title: Platelet Munc13-4 regulates hemostasis, thrombosis and airway inflammation.
these results demonstrate that both C2 domains of Munc13-4 play critical roles in Ca(2+)-dependent exocytosis and cytotoxicity by regulating single-granule membrane fusion dynamics in immune cells
Title: C2 Domains of Munc13-4 Are Crucial for Ca(2+)-Dependent Degranulation and Cytotoxicity in NK Cells.
In a model of systemic anaphylaxis, we found no difference between WT and Munc13-2 KO mice, but global and mast cells-specific Munc13-4 KO mice developed less hypothermia. We conclude that although Munc13-2 plays a minor role, Munc13-4 is essential for regulated exocytosis in mast cells
Title: Munc13 proteins control regulated exocytosis in mast cells.
Munc13-4 is a syntaxin 7 binding protein and an important regulator of late endosome maturation.
Title: Munc13-4 interacts with syntaxin 7 and regulates late endosomal maturation, endosomal signaling, and TLR9-initiated cellular responses.
Munc13-4 conveys Ca(2+) sensitivity to platelet SNARE-mediated membrane fusion and reveal a potential mechanism by which Munc13-4 bridges and stabilizes apposing membranes destined for fusion.
Title: Role of Munc13-4 as a Ca2+-dependent tether during platelet secretion.
Data (including data from studies in knockout mice) suggest Munc13-4 binds to Rab11 and regulates trafficking of Rab11-containing vesicles; Munc13-4 appears to regulate final steps of Rab11-positive vesicle docking at plasma membrane in exocytosis.
Title: Munc13-4 Is a Rab11-binding Protein That Regulates Rab11-positive Vesicle Trafficking and Docking at the Plasma Membrane.
Letter: data argue for a critical role of Munc13-4 and therefore also dense granule secretion in infarct progression but not in safeguarding the brain vasculature in acute ischemia.
Title: Munc13-4-mediated secretion is essential for infarct progression but not intracranial hemostasis in acute stroke.
Munc13-4 isoform is functionaly redundant in cytotoxic T lymphocytes.
Title: Different Munc13 isoforms function as priming factors in lytic granule release from murine cytotoxic T lymphocytes.
Data suggest that Rab27a and Rab27b regulate distinct steps in the bone marrow-derived mast cells (BMMC) degranulation pathway, with Rab27a/Mlph/MyoVa regulating cortical actin stability upstream of Rab27a/b/Munc13-4-dependent granule exocytosis.
Title: Distinct and opposing roles for Rab27a/Mlph/MyoVa and Rab27b/Munc13-4 in mast cell secretion.

Submit: New GeneRIF Correction See all GeneRIFs (17)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (1)
Chemically induced (ENU) (1) 1 citation
Endonuclease-mediated (1)

General gene information

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Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables small GTPase binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within defense response to virus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in dense core granule priming	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within establishment of localization in cell	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within exocytosis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within germinal center formation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within granuloma formation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within natural killer cell degranulation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within phagocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of exocytosis	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of regulated secretory pathway	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of substrate adhesion-dependent cell spreading	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of mast cell degranulation	ISO Inferred from Sequence Orthology more info
involved_in secretion	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in Weibel-Palade body	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in endosome	IEA Inferred from Electronic Annotation more info
is_active_in exocytic vesicle	IBA Inferred from Biological aspect of Ancestor more info
located_in exocytic vesicle	ISO Inferred from Sequence Orthology more info
located_in intracellular membrane-bounded organelle	ISO Inferred from Sequence Orthology more info
located_in lysosome	ISO Inferred from Sequence Orthology more info
located_in membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: protein unc-13 homolog D

Names: likely ortholog of H. sapiens unc-13 homolog D (UNC13D)

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001009573.2 → NP_001009573.2 protein unc-13 homolog D

See identical proteins and their annotated locations for NP_001009573.2

Status: VALIDATED

Source sequence(s)

AK220199, BC046519, BG146628, CF164660

Consensus CDS

CCDS25656.1

UniProtKB/Swiss-Prot

B2RUP2

UniProtKB/TrEMBL

Q80UG7

Related

ENSMUSP00000074549.3, ENSMUST00000075036.9

Conserved Domains (3) summary

cd04009
Location:907 → 1042

C2B_Munc13-like; C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins

cd08676
Location:83 → 262

C2A_Munc13-like; C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins

pfam10540
Location:787 → 888

Membr_traf_MHD; Munc13 (mammalian uncoordinated) homology domain

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000077.7 Reference GRCm39 C57BL/6J

Range

115952921..115969321 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006534189.3 → XP_006534252.1 protein unc-13 homolog D isoform X1

See identical proteins and their annotated locations for XP_006534252.1

UniProtKB/Swiss-Prot

A2A856, A3R4M4, A3R4M5, B2RUP2, Q571J0

Related

ENSMUSP00000102059.2, ENSMUST00000106451.8

Conserved Domains (3) summary

cd04009
Location:909 → 1044

C2B_Munc13-like; C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins

cd08676
Location:83 → 262

C2A_Munc13-like; C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins

pfam10540
Location:788 → 890

Membr_traf_MHD; Munc13 (mammalian uncoordinated) homology domain
XM_006534188.3 → XP_006534251.1 protein unc-13 homolog D isoform X1

See identical proteins and their annotated locations for XP_006534251.1

UniProtKB/Swiss-Prot

A2A856, A3R4M4, A3R4M5, B2RUP2, Q571J0

Conserved Domains (3) summary

cd04009
Location:909 → 1044

C2B_Munc13-like; C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins

cd08676
Location:83 → 262

C2A_Munc13-like; C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins

pfam10540
Location:788 → 890

Membr_traf_MHD; Munc13 (mammalian uncoordinated) homology domain
XM_006534190.3 → XP_006534253.1 protein unc-13 homolog D isoform X1

See identical proteins and their annotated locations for XP_006534253.1

UniProtKB/Swiss-Prot

A2A856, A3R4M4, A3R4M5, B2RUP2, Q571J0

Related

ENSMUSP00000102058.2, ENSMUST00000106450.8

Conserved Domains (3) summary

cd04009
Location:909 → 1044

C2B_Munc13-like; C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins

cd08676
Location:83 → 262

C2A_Munc13-like; C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins

pfam10540
Location:788 → 890

Membr_traf_MHD; Munc13 (mammalian uncoordinated) homology domain
XM_006534192.5 → XP_006534255.1 protein unc-13 homolog D isoform X2

Conserved Domains (3) summary

cd04009
Location:898 → 1033

C2B_Munc13-like; C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins

cd08676
Location:72 → 251

C2A_Munc13-like; C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins

pfam10540
Location:777 → 879

Membr_traf_MHD; Munc13 (mammalian uncoordinated) homology domain