{PDOC51258} {PS51258; MHD1} {PS51259; MHD2} {BEGIN} ************************************************************ * 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 ) and two C2 domains, which are Ca2+/phospholipid binding domains (see ). 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 alpha-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. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: October 2006 / First entry. [ 1] Koch H., Hofmann K., Brose N. "Definition of Munc13-homology-domains and characterization of a novel ubiquitously expressed Munc13 isoform." Biochem. J. 349:247-253(2000). PubMed=10861235 [ 2] Basu J., Shen N., Dulubova I., Lu J., Guan R., Guryev O., Grishin N.V., Rosenmund C., Rizo J. "A minimal domain responsible for Munc13 activity." Nat. Struct. Mol. Biol. 12:1017-1018(2005). PubMed=16228007; DOI=10.1038/nsmb1001 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}