PROSITE documentation PDOC51258

Munc13-homology domains 1 and 2 (MHD1 and MHD2) profiles

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 trafficking [1].

The MHD1 and MHD2 domains are predicted to be α-helical [2].

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 glutaminergic synapses.
• 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.