Domain

ADAM17, membrane-proximal domain (IPR032029)

Short name: ADAM17_MPD

Domain relationships

None.

Description

This entry represents the membrane-proximal domain (MPD) of disintegrin and metalloproteinase domain-containing protein 17 (ADAM17) from animals. ADAM17 is a major sheddase responsible for the regulation of a wide range of biological processes, such as cellular differentiation, regeneration, and cancer progression.

This MPD region acts as the sheddase switch. PDI (protein-disulfide isomerase) interacts with ADAM17 and down-regulates its enzymatic activity. The interaction is directly with the MPD, the region of dimerisation and substrate recognition, where it catalyses an isomerisation of disulfide bridges within the thioredoxin motif CXXC. This isomerisation results in a major structural change between an active, open state and an inactive, closed state of the MPD. This change is thought to act as a molecular switch, allowing a global reorientation of the extracellular domains in ADAM17 and regulating its shedding activity [PMID: 23521534].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
CDD
Pfam