| Binding Partner / Feature | Interaction Region / Domain on MVB12A | Binding Region on Partner | Function of Interaction | Key Citations |
|---|---|---|---|---|
| TSG101 | C-terminal ESCRT-I-binding region within the UMA-containing portion; Morita et al. mapped ESCRT-I binding to residues 192-273, with two adjacent boxes (EBB1 and EBB2), while later structural work localized a minimal human head-binding segment to residues 206-228 (UMA-N) | ESCRT-I head/core region of TSG101; MVB12A contributes an antiparallel β-sheet with TSG101 in the human ESCRT-I head | Core assembly of human ESCRT-I; enables stable incorporation of MVB12A into ESCRT-I and supports ESCRT-I scaffolding in membrane-remodeling pathways including HIV budding and autophagosome closure | (pqac-00000003, pqac-00000015, pqac-00000016) |
| VPS37B | Same C-terminal UMA-containing ESCRT-I-binding region; MVB12A binds stoichiometrically only when TSG101 and VPS37 are present together, indicating composite recognition of the TSG101-VPS37 subcomplex | ESCRT-I head/core, especially VPS37B within the TSG101-VPS37B-VPS28 headpiece | Direct structural integration into the ESCRT-I head; stabilizes the heterotetramer and contributes to higher-order ESCRT-I scaffold formation | (pqac-00000003, pqac-00000015, pqac-00000016) |
| TSG101-VPS37 binary subcomplex | C-terminal UMA region / EBB1-EBB2; MVB12A does not bind isolated TSG101, VPS37B, or VPS28 efficiently, but does bind the TSG101-VPS37B binary complex | Composite binding surface formed by TSG101 and VPS37 | Defines the principal biochemical recruitment route of MVB12A into ESCRT-I; explains why MVB12A is a constitutive ESCRT-I subunit rather than an isolated adaptor | (pqac-00000003, pqac-00000016) |
| VPS28 | No strong independent binding by MVB12A alone; only negligible direct interface in yeast core structure and no stoichiometric binding to VPS28 alone in human assays | N-terminal/head region of VPS28 adjacent to the ESCRT-I headpiece | VPS28 is part of the assembled heterotetramer but is not the primary determinant of MVB12A recruitment; instead VPS28 participates once the full ESCRT-I head is assembled and links ESCRT-I to ESCRT-II | (pqac-00000014, pqac-00000016) |
| VPS37A-D family | UMA-containing C-terminal ESCRT-I-binding region of MVB12A | Conserved ESCRT-I core-forming region (Mod(r) / head-stalk module) of VPS37 paralogs | Human MVB12A can assemble into stable quaternary complexes with TSG101, VPS28, and each of VPS37A, VPS37B, VPS37C, or VPS37D, indicating combinatorial ESCRT-I isoform formation | (pqac-00000003, pqac-00000007) |
| Human ESCRT-I complex stoichiometry | Full-length MVB12A as a constitutive subunit | TSG101, VPS28, and one VPS37 paralog | Soluble human ESCRT-I complexes contain one copy each of TSG101, VPS28, VPS37, and MVB12A, yielding a 1:1:1:1 heterotetramer; this is the core organizational principle for MVB12A function | (pqac-00000000, pqac-00000002, pqac-00000003, pqac-00000012) |
| UMA domain (feature) | UMA (UBAP1-MVB12-associated) domain in the conserved C-terminal region; specifically mediates MVB12A recruitment to ESCRT-I | ESCRT-I core, especially TSG101-VPS37 module | Acts as the ESCRT-I incorporation module for MVB12A-family proteins; explains how metazoan MVB12A/B and UBAP1 join ESCRT-I despite lacking sequence homology to yeast Mvb12 | (pqac-00000000, pqac-00000008) |
| MABP domain (feature) | N-terminal MABP domain of MVB12A | Acidic membranes/liposomes rather than a single protein partner; binds anionic lipids with charge dependence and little headgroup specificity | Membrane-targeting module that helps ESCRT-I associate with acidic membranes; likely contributes to localization on endosomal and related membranes where ESCRT-I acts | (pqac-00000001, pqac-00000008) |
| Acidic phospholipid membranes / late endosomal membranes | MABP domain | Phosphatidylserine-rich and other acidic lipid-containing membranes; puncta correspond largely to Rab7-positive late endosomes in cellular localization assays of MABP fusions | Provides a mechanistic basis for membrane association of MVB12-family proteins and thereby for positioning ESCRT-I at sites of reverse-topology membrane remodeling | (pqac-00000001) |
| ESCRT-I head higher-order assembly | MVB12A UMA-N segment (206-228) embedded in ESCRT-I head | TSG101-VPS28-VPS37B headpiece that can self-assemble into helical arrays | MVB12A is not merely passive cargo in ESCRT-I; in the human head structure containing MVB12A, ESCRT-I can form helical assemblies implicated in scaffolding reverse-topology membrane scission | (pqac-00000000, pqac-00000015) |
| Endosomal cargo sorting function (pathway-level interaction) | MVB12A as an ESCRT-I subunit; no enzymatic active site or classical substrate specificity known | ESCRT-I pathway components, upstream cargo adaptors, downstream ESCRT-II/III machinery | MVB12A functions as a structural/adaptor subunit rather than an enzyme; its role is to help build membrane-associated ESCRT-I assemblies that support ubiquitinated cargo sorting, receptor downregulation, viral budding, and related membrane fission events | (pqac-00000002, pqac-00000004, pqac-00000011, pqac-00000012) |


*Table: This table summarizes the main binding partners, structural modules, and assembly logic of human MVB12A within ESCRT-I. It is useful for quickly linking MVB12A domains to its molecular interactions, membrane association, and functional role in reverse-topology membrane remodeling.*