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Domain

The MIT domain serves as an adapter for ESCRT-III proteins. It forms an asymmetric three-helix bundle that binds amphipathic MIM (MIT interacting motif) helices along the groove between MIT helices 2 and 3 present in a subset of ESCRT-III proteins thus establishing the canonical MIM-MIT interaction. In an extended conformation along the groove between helices 1 and 3, also binds to a type-2 MIT interacting motif (MIM2).

Function

Involved in late steps of the endosomal multivesicular bodies (MVB) pathway. Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly, possibly in combination with membrane fission (PubMed:18687924). Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. VPS4A/B are required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413).

(Microbial infection) In conjunction with the ESCRT machinery also appears to function in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and enveloped virus budding (HIV-1 and other lentiviruses).

Sequence similarities

Belongs to the AAA ATPase family.

Tissue specificity

Ubiquitously expressed.

Cellular localization

  • Late endosome membrane
  • Peripheral membrane protein
  • Membrane-associated in the prevacuolar endosomal compartment. Localized in HIV-1 particles purified from acutely infected cells.

Alternative names

SKD1, VPS42, MIG1, VPS4B, Vacuolar protein sorting-associated protein 4B, Cell migration-inducing gene 1 protein, Suppressor of K(+) transport growth defect 1, Protein SKD1

Target type

Proteins

Primary research area

Cardiovascular

Molecular weight

49302Da

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Proteins & Peptides

Species of origin