| Feature | Summary | Evidence/Citation |
|---|---|---|
| Approved identity | Human **MVB12B** protein corresponding to UniProt **Q9H7P6**; also called **FAM125B** and **C9orf28** | Primary literature identifies human MVB12B/FAM125B as an ESCRT-I subunit and distinguishes it from the related paralog MVB12A (pqac-00000001, pqac-00000006) |
| Protein family | Member of the **MVB12 family**, one of the metazoan fourth-subunit classes of **ESCRT-I** | Human ESCRT-I contains TSG101, VPS28, VPS37, and a fourth subunit such as MVB12A/MVB12B; UMA-containing proteins are the metazoan MVB12-type subunits (pqac-00000000, pqac-00000003, pqac-00000005) |
| Main molecular role | **Structural/adaptor subunit of ESCRT-I** involved in endosomal cargo sorting and reverse-topology membrane remodeling rather than enzymatic catalysis | ESCRT-I is an upstream complex in multivesicular body biogenesis and other membrane scission events; MVB12 proteins constitute the fourth ESCRT-I subunit class (pqac-00000001, pqac-00000003) |
| Core binding partners | Directly associates with **TSG101** and **VPS37** within the ESCRT-I core; assembled complex also includes **VPS28** | Mapping experiments showed MVB12 proteins bind the **TSG101–VPS37** binary complex, and quaternary complexes contain TSG101, VPS28, VPS37, and MVB12 (pqac-00000006, pqac-00000007) |
| Binding architecture | MVB12-family proteins incorporate into the ESCRT-I head/core through the **UMA region**; human MVB12A structure indicates analogous occupancy of the MVB12 site in human ESCRT-I | Structural work showed UMA-containing human MVB12 proteins integrate into ESCRT-I despite divergence from yeast Mvb12; human ESCRT-I head includes TSG101–VPS28–VPS37B–MVB12A, supporting conserved family organization relevant to MVB12B (pqac-00000000, pqac-00000004, pqac-00000005) |
| Key domains | Contains **UMA** and **MABP** domains; these domains are implicated in ESCRT-I association and membrane-related trafficking functions | Domain analysis of human MVB12A/B identified **UMA** and **MABP** as characteristic features of metazoan MVB12 proteins (pqac-00000005) |
| Complex stoichiometry | ESCRT-I forms a **1:1:1:1 heterotetramer** of **TSG101:VPS28:VPS37:MVB12** | Hydrodynamic and sedimentation analyses showed soluble human ESCRT-I complexes contain one copy of each subunit type; recombinant complex mass matched a monomeric 1:1:1:1 assembly (pqac-00000001, pqac-00000007) |
| Subcellular localization | Predominantly a **cytosolic/endosomal trafficking factor** that is transiently recruited to **endosomal membranes**, especially sites of **multivesicular body (MVB)** / **intraluminal vesicle (ILV)** formation | ESCRT-I is distributed in cytoplasm at steady state but is recruited to membranes during MVB vesicle formation; ESCRT-I functions in endosomal cargo sorting and ILV biogenesis (pqac-00000001, pqac-00000003) |
| Functional cellular compartment | Acts mainly at **early/late endosomal membranes and MVBs** where ubiquitinated cargo is sorted toward lysosomal degradation or exosome release | Reviews describe ESCRT-I as a bridge between cargo-recognition systems and downstream ESCRT machinery during MVB biogenesis and exosome-related pathways (pqac-00000003, pqac-00000011) |
| Post-translational regulation | **TBK1-dependent phosphorylation** of MVB12B, including **S222**, regulates its immune-related EV sorting function | In bacterial infection/DNA-stimulation models, MVB12b was identified as a TBK1 phosphotarget, and the **S222A** mutant impaired the EV-mediated bystander IFN response (pqac-00000002, pqac-00000008) |
| Specialized regulated function | Phosphorylated MVB12B helps sort **DNA into extracellular vesicles/exosomes** for paracrine **cGAS–STING** signaling | MVB12b deficiency or mutation disrupted transfer of IFN-inducing material in EVs from infected or DNA-stimulated donor cells (pqac-00000002, pqac-00000008) |
| Relationship to broader ESCRT functions | Through ESCRT-I, MVB12B contributes to **MVB biogenesis, exosome production, viral budding, cytokinetic abscission, autophagy-linked membrane events, and membrane repair** | ESCRT-I is a core upstream module reused across multiple reverse-topology membrane remodeling pathways (pqac-00000003, pqac-00000009, pqac-00000010) |


*Table: This table summarizes the verified identity, molecular role, domain architecture, binding partners, localization, stoichiometry, and regulatory phosphorylation of human MVB12B. It is useful as a concise evidence-based reference for functional annotation of Q9H7P6.*