unc-13 Phorbol ester/diacylglycerol-binding protein unc-13;Protein kinase C [Caenorhabditis elegans] - Gene

Summary

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Official Symbol: unc-13
Official Full Name: Phorbol ester/diacylglycerol-binding protein unc-13;Protein kinase C
Primary source: WormBase:WBGene00006752
Locus tag: CELE_ZK524.2
See related: AllianceGenome:WB:WBGene00006752
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Caenorhabditis elegans (strain: Bristol N2)
Lineage: Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida; Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae; Caenorhabditis
Summary: Predicted to enable calmodulin binding activity and syntaxin-1 binding activity. Involved in several processes, including positive regulation of oocyte development; regulation of egg-laying behavior; and regulation of nematode pharyngeal pumping. Located in presynaptic active zone. Is expressed in nervous system. Human ortholog(s) of this gene implicated in amyotrophic lateral sclerosis. Orthologous to several human genes including UNC13C (unc-13 homolog C). [provided by Alliance of Genome Resources, Dec 2024]
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Genomic context

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See unc-13 in Genome Data Viewer

Location:: chromosome: I

Exon count:: 31

Sequence:: Chromosome: I; NC_003279.8 (7422785..7454116)

Chromosome I - NC_003279.8 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:: NC_003279.8

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

C. elegans Clarinet/CLA-1 recruits RIMB-1/RIM-binding protein and UNC-13 to orchestrate presynaptic neurotransmitter release.
Title: C. elegans Clarinet/CLA-1 recruits RIMB-1/RIM-binding protein and UNC-13 to orchestrate presynaptic neurotransmitter release.
The M domain in UNC-13 regulates the probability of neurotransmitter release.
Title: The M domain in UNC-13 regulates the probability of neurotransmitter release.
A unique C2 domain at the C terminus of Munc13 promotes synaptic vesicle priming.
Title: A unique C2 domain at the C terminus of Munc13 promotes synaptic vesicle priming.
A Hyperactive Form of unc-13 Enhances Ca(2+) Sensitivity and Synaptic Vesicle Release Probability in C. elegans.
Title: A Hyperactive Form of unc-13 Enhances Ca(2+) Sensitivity and Synaptic Vesicle Release Probability in C. elegans.
Here the authors show that the C2A domain of UNC-13L, like the corresponding domain in mammalian Munc13-1, displays two conserved binding modes: forming C2A/C2A homodimers, or forming a heterodimer with the zinc finger domain of UNC-10/RIM (C2A/RIM).
Title: Heterodimerization of UNC-13/RIM regulates synaptic vesicle release probability but not priming in C. elegans.
cell-nonautonomous contributions of neuronal KGB-1 (and also in muscle) were effective in driving intestinal gene induction, age-dependent regulation of intestinal DAF-16, and stress resistance, and did not require KGB-1 expression in the target tissue. Additional genetic analyses revealed requirement for UNC-13 in mediating neuronal contributions, indicating involvement of neurotransmission.
Title: Integration of Stress Signaling in Caenorhabditis elegans Through Cell-Nonautonomous Contributions of the JNK Homolog KGB-1.
Thus, our study provides novel mechanistic insights into how Munc18/UNC-18 primes synaptic vesicle release and how this protein interacts functionally with Munc13/UNC-13 and Tomosyn/TOM-1.
Title: UNC-18 and Tomosyn Antagonistically Control Synaptic Vesicle Priming Downstream of UNC-13 in Caenorhabditis elegans.
C1-C2B exerts a basal inhibition on Munc13 in the primed state, permitting calcium- and lipid-dependent control of C1-C2B to modulate synaptic strength
Title: A C1-C2 Module in Munc13 Inhibits Calcium-Dependent Neurotransmitter Release.
Synaptic UNC13A protein variant causes increased neurotransmission and dyskinetic movement disorder
Title: Synaptic UNC13A protein variant causes increased neurotransmission and dyskinetic movement disorder.
results suggest that UNC-13L, UNC-13S, and Tomosyn form a molecular code that dictates the timing of neurotransmitter release
Title: UNC-13L, UNC-13S, and Tomosyn form a protein code for fast and slow neurotransmitter release in Caenorhabditis elegans.

Submit: New GeneRIF Correction See all GeneRIFs (17)

Pathways from PubChem

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

STS1-115 (e-PCR)
- UniSTS:241600

ZK524.2 (e-PCR)
- UniSTS:317647

Homology

Orthologs from OrthoDB

Gene Ontology Provided by WormBase

Function	Evidence Code	Pubs
enables calmodulin binding	IBA Inferred from Biological aspect of Ancestor more info
enables calmodulin binding	IEA Inferred from Electronic Annotation more info
enables diacylglycerol binding	IEA Inferred from Electronic Annotation more info
enables kinase activity	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables syntaxin-1 binding	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
acts_upstream_of IRE1-mediated unfolded protein response	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of cell-cell signaling	IC Inferred by Curator more info	PubMed
involved_in chemical synaptic transmission	IEA Inferred from Electronic Annotation more info
involved_in dense core granule priming	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of determination of adult lifespan	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of negative regulation of multicellular organismal process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of oocyte development	IGI Inferred from Genetic Interaction more info	PubMed
involved_in presynaptic dense core vesicle exocytosis	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of egg-laying behavior	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation of egg-laying behavior	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of nematode pharyngeal pumping	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation of nematode pharyngeal pumping	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in spermatogenesis	IGI Inferred from Genetic Interaction more info	PubMed
involved_in synaptic transmission, glutamatergic	IBA Inferred from Biological aspect of Ancestor more info
involved_in synaptic vesicle docking	IBA Inferred from Biological aspect of Ancestor more info
involved_in synaptic vesicle exocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in synaptic vesicle priming	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
is_active_in neuromuscular junction	IBA Inferred from Biological aspect of Ancestor more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in presynapse	IEA Inferred from Electronic Annotation more info
located_in presynaptic active zone	IDA Inferred from Direct Assay more info	PubMed
is_active_in presynaptic active zone cytoplasmic component	IBA Inferred from Biological aspect of Ancestor more info
is_active_in presynaptic membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in synapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in synaptic vesicle membrane	IBA Inferred from Biological aspect of Ancestor more info
is_active_in terminal bouton	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: Phorbol ester/diacylglycerol-binding protein unc-13;Protein kinase C

NP_001021871.1

Confirmed by transcript evidence

NP_001021873.1

Partially confirmed by transcript evidence

NP_001021874.1

Partially confirmed by transcript evidence

NP_001250502.1

Partially confirmed by transcript evidence

NP_001293153.1

Partially confirmed by transcript evidence

NP_001317863.1

Confirmed by transcript evidence

NP_001317864.1

Confirmed by transcript evidence

NP_001317865.1

Confirmed by transcript evidence

NP_001317866.1

Confirmed by transcript evidence

NP_001317867.1

Confirmed by transcript evidence

NP_001367037.1

Partially confirmed by transcript evidence

NCBI Reference Sequences (RefSeq)

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Genome Annotation

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

Reference assembly

Genomic

NC_003279.8 Reference assembly

Range

7422785..7454116

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001026700.2 → NP_001021871.1 Phorbol ester/diacylglycerol-binding protein unc-13 [Caenorhabditis elegans]

See identical proteins and their annotated locations for NP_001021871.1

Status: REVIEWED

UniProtKB/Swiss-Prot

P27715

Conserved Domains (6) summary

cd04027
Location:815 → 941

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

cd08394
Location:18 → 144

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

cd08395
Location:1647 → 1767

C2C_Munc13; C2 domain third repeat in Munc13 (mammalian uncoordinated) proteins

cd00029
Location:693 → 742

C1; Protein kinase C conserved region 1 (C1) . Cysteine-rich zinc binding domain. Some members of this domain family bind phorbol esters and diacylglycerol, some are reported to bind RasGTP. May occur in tandem arrangement. Diacylglycerol (DAG) is a second ...

pfam06292
Location:1130 → 1219

DUF1041; Domain of Unknown Function (DUF1041)

pfam10540
Location:1458 → 1608

Membr_traf_MHD; Munc13 (mammalian uncoordinated) homology domain
NM_001263573.3 → NP_001250502.1 Phorbol ester/diacylglycerol-binding protein unc-13 [Caenorhabditis elegans]

See identical proteins and their annotated locations for NP_001250502.1

Status: REVIEWED

UniProtKB/TrEMBL

G5EDN9

Conserved Domains (6) summary

cd04027
Location:821 → 947

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

cd08394
Location:18 → 144

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

cd08395
Location:1653 → 1773

C2C_Munc13; C2 domain third repeat in Munc13 (mammalian uncoordinated) proteins

cd00029
Location:699 → 748

C1; Protein kinase C conserved region 1 (C1) . Cysteine-rich zinc binding domain. Some members of this domain family bind phorbol esters and diacylglycerol, some are reported to bind RasGTP. May occur in tandem arrangement. Diacylglycerol (DAG) is a second ...

pfam06292
Location:1136 → 1225

DUF1041; Domain of Unknown Function (DUF1041)

pfam10540
Location:1464 → 1614

Membr_traf_MHD; Munc13 (mammalian uncoordinated) homology domain
NM_001330927.3 → NP_001317864.1 Phorbol ester/diacylglycerol-binding protein unc-13 [Caenorhabditis elegans]

Status: REVIEWED

UniProtKB/TrEMBL

A0A1C3NSN5
NM_001026702.3 → NP_001021873.1 Phorbol ester/diacylglycerol-binding protein unc-13 [Caenorhabditis elegans]

See identical proteins and their annotated locations for NP_001021873.1

Status: REVIEWED

UniProtKB/Swiss-Prot

O17665, P27715, Q23512, Q7YSR2, Q867Z2, Q8I095

Conserved Domains (6) summary

cd04027
Location:1157 → 1283

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

cd08394
Location:18 → 144

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

cd08395
Location:1989 → 2109

C2C_Munc13; C2 domain third repeat in Munc13 (mammalian uncoordinated) proteins

cd00029
Location:1035 → 1084

C1; Protein kinase C conserved region 1 (C1) . Cysteine-rich zinc binding domain. Some members of this domain family bind phorbol esters and diacylglycerol, some are reported to bind RasGTP. May occur in tandem arrangement. Diacylglycerol (DAG) is a second ...

pfam06292
Location:1472 → 1561

DUF1041; Domain of Unknown Function (DUF1041)

pfam10540
Location:1800 → 1950

Membr_traf_MHD; Munc13 (mammalian uncoordinated) homology domain
NM_001026703.4 → NP_001021874.1 Phorbol ester/diacylglycerol-binding protein unc-13 [Caenorhabditis elegans]

See identical proteins and their annotated locations for NP_001021874.1

Status: REVIEWED

UniProtKB/Swiss-Prot

P27715

Conserved Domains (6) summary

cd04027
Location:818 → 944

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

cd08394
Location:18 → 144

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

cd08395
Location:1650 → 1770

C2C_Munc13; C2 domain third repeat in Munc13 (mammalian uncoordinated) proteins

cd00029
Location:696 → 745

C1; Protein kinase C conserved region 1 (C1) . Cysteine-rich zinc binding domain. Some members of this domain family bind phorbol esters and diacylglycerol, some are reported to bind RasGTP. May occur in tandem arrangement. Diacylglycerol (DAG) is a second ...

pfam06292
Location:1133 → 1222

DUF1041; Domain of Unknown Function (DUF1041)

pfam10540
Location:1461 → 1611

Membr_traf_MHD; Munc13 (mammalian uncoordinated) homology domain
NM_001330928.3 → NP_001317865.1 Phorbol ester/diacylglycerol-binding protein unc-13 [Caenorhabditis elegans]

Status: REVIEWED

UniProtKB/TrEMBL

A0A1C3NSH2
NM_001330929.3 → NP_001317866.1 Phorbol ester/diacylglycerol-binding protein unc-13 [Caenorhabditis elegans]

Status: REVIEWED

UniProtKB/TrEMBL

A0A1C3NSL4
NM_001380703.1 → NP_001367037.1 Phorbol ester/diacylglycerol-binding protein unc-13 [Caenorhabditis elegans]

Status: REVIEWED

Conserved Domains (5) summary

cd04027
Location:477 → 603

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

cd08395
Location:1309 → 1429

C2C_Munc13; C2 domain third repeat in Munc13 (mammalian uncoordinated) proteins

pfam06292
Location:792 → 881

DUF1041; Domain of Unknown Function (DUF1041)

pfam10540
Location:1119 → 1270

Membr_traf_MHD; Munc13 (mammalian uncoordinated) homology domain

cl00040
Location:336 → 416

C1; protein kinase C conserved region 1 (C1 domain) superfamily
NM_001330930.3 → NP_001317863.1 Phorbol ester/diacylglycerol-binding protein unc-13 [Caenorhabditis elegans]

Status: REVIEWED

UniProtKB/TrEMBL

A0A1C3NSI0
NM_001306224.3 → NP_001293153.1 Phorbol ester/diacylglycerol-binding protein unc-13 [Caenorhabditis elegans]

See identical proteins and their annotated locations for NP_001293153.1

Status: REVIEWED

Conserved Domains (5) summary

cd04027
Location:470 → 596

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

cd08395
Location:1302 → 1422

C2C_Munc13; C2 domain third repeat in Munc13 (mammalian uncoordinated) proteins

pfam00130
Location:348 → 397

C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)

pfam06292
Location:785 → 874

DUF1041; Domain of Unknown Function (DUF1041)

pfam10540
Location:1113 → 1263

Membr_traf_MHD; Munc13 (mammalian uncoordinated) homology domain
NM_001330931.3 → NP_001317867.1 Protein kinase C [Caenorhabditis elegans]

Status: REVIEWED

UniProtKB/TrEMBL

A0A1C3NSJ3