Munc13 proteins constitute a family of three highly homologous molecules
(Munc13-1, Munc13-2 and Munc13-3) with homology to Caenorhabditis elegans
unc-13p. Munc13 proteins contain a phorbol ester-binding C1 domain (see
<PDOC00379>) and two C2 domains, which are Ca2+/phospholipid binding domains
(see <PDOC00380>). Sequence analyses have uncovered two regions called Munc13
homology domains 1 (MHD1) and 2 (MHD2) that are arranged between two flanking
C2 domains. MHD1 and MHD2 domains are present in a wide variety of proteins
from Arabidopsis thaliana, C. elegans, Drosophila melanogaster, mouse, rat and
human, some of which may function in a Munc13-like manner to regulate membrane
The MHD1 and MHD2 domains are predicted to be α-helical .
Some proteins known to contain MHD1 and MHD2 domains are listed below:
Mammalian Munc13-1. It is specifically targeted to presynaptic active zones
and has a central priming function in synaptic vesicle exocytosis from
Mammalian Munc13-2. It plays a role in vesicle maturation during exocytosis
as a target of the diacylglycerol second messenger pathway.
Mammalian Munc13-3. It probably plays a role in vesicle maturation during
exocytosis as a target of the diacylglycerol second messenger pathway.
Mammalian Munc13-4. It is predominantly expressed in lung where it is
localized to goblet cells of the bronchial epithelium and to alveolar type
II cells, both of which are cell types with secretory function.
Caenorhabditis elegans unc-13p. It may form part of a signal transduction
pathway, transducing the signal from diacylglycerol to effector functions.
Mammalian BAI1-associated protein 3 (BAP3) which exhibit the typical
Munc13-like domain structure with two C2 domains flanking the MHD1 and MHD2
domains, but which lack the long N-terminus with the C1 domain.
Animal calcium-dependent activator proteins for secretion (CAPSs),
regulators of large dense-core vesicle secretion. They contain only a MHD1
domain and are otherwise unrelated to Munc13 proteins.
Arabidopsis thaliana hypothetical proteins with MHD1 and MHD2 domains but
without C1 and C2 domains.
Yeast uncharacterized protein YOR296W, where MHD1 and MHD2 enclose a
central C2 domain. YOR296W is presumably involved in bud formation.
Fission yeast hypothetical protein C11E3.02c in chromosome I, where MHD1
and MHD2 enclose a central C2 domain.
The profile we developed covers the entire MHD1 and MHD2 domains.
October 2006 / First entry.
PROSITE methods (with tools and information) covered by this documentation:
Koch H. Hofmann K. Brose N.
Definition of Munc13-homology-domains and characterization of a novel ubiquitously expressed Munc13 isoform.
PROSITE is copyright. It is produced by the SIB Swiss Institute
Bioinformatics. There are no restrictions on its use by non-profit
institutions as long as its content is in no way modified. Usage by and
for commercial entities requires a license agreement. For information
about the licensing scheme send an email to
or see: prosite_license.html.