MABP domain
IPR023341
Definition
A key aspect of eukaryotic intracellular trafficking is the sorting of cell-surface proteins into multi-vesicular endosomes or bodies (MVBs), which eventually fuse with the lysosome, where they are degraded by lipases and peptidases. This is the primary mechanism for down-regulation of signaling via transmembrane receptors and removal of misfolded or defective membrane proteins. This process is also utilised by several viruses (e.g. HIV-1) to facilitate budding of their virions from the cell-membrane. Studies in animals and fungi have shown that it depends on an intricate series of interactions, which is initiated via ubiquitination (typically one or more mono-ubiquitinations) of the cytoplasmic tails of membrane proteins by specific E3 ligases. Ubiquitinated membrane proteins are then captured into endosomes by the ESCRT system and prevented from being recycled back to the plasma membrane via the retrograde trafficking system. The ESCRT system also folds the endosomal membranes into invaginations that are concentrated in these ubiquitinated targets and catalyses their abscission into intra-luminal-vesicles inside the endosome. This largely seals the fate of these membrane proteins as targets for lysosomal degradation. The ESCRT system comprises 4 major protein complexes, ESCRT-0 to ESCRT-III, which are successively involved in the above-described steps PMID:20448139. ESCRT-I contains three subunits that are conserved between yeast and animals, namely the inactive E2-ligase protein TSG101/VPS23, VPS28 and VPS37. Additionally, both yeast and metazoan ESCRT-I contain a fourth subunit termed MVB12 (multivesicular body sorting factor of 12 kD); however, the MVB12 subunits from the two lineages do not show significant sequence similarity. The metazoan MVB12 proteins contain two distinct conserved domains that occur independently in various proteins. The N-terminal region of MVB12 forms the MVB12-associated β-prism (MABP), which is also found in DENND4A/B/C from vertebrates, the membrane trafficking regulator Crag from Drosophila, bacterial proteins typified by the MAC/perforin (MACPF)-like protein plu1415 from Photorhabdus luminescens and uncharacterised proteins from choanoflagellates and stamenopiles. It has been suggested that the MABP domain has a membrane-associated function, perhaps even specific interactions with membrane components. It is plausible that the eukaryotic MABP domains are adaptators that help linking other associated domains found in the same polypeptide to vesicular membranes PMID:20448139. The MABP domain has an internal repeat structure of three homologous segments. Consistent with this, the structurally characterised representative Photorhabdus plu1415, showed that this region precisely corresponds to a type-I β-prism domain with an internal three-fold symmetry. Each of the three sub-domains of the β-prism structure is a distinctive three-stranded β-sheet. The MABP domain shares a triradial symmetry with β-sheets parallel to the prism axis. The β-prism fold is associated with membrane interaction. The majority of the eukaryotic MABP domain versions contain a conserved cysteine in the first and third subdomain of the β-prism [[cite:PMID:20448139], [cite:PMID:17717151]].
5 human proteins with this domain
Each is a reviewed human protein in the Seroatlas serome and a potential autoantibody target; this domain groups them into one antibody-relevant category. Every entry links to its own record.
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