SMART: Pfam domain ADAM17

The domain within your query sequence starts at position 600 and ends at position 661; the E-value for the ADAM17_MPD domain shown below is 1e-23.

FCKREQELESCACVDTDNSCKVCCRNLSGPCVPYVDAEQKNLFLRKGKPCTVGFCDMNGK
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ADAM17_MPD

PFAM accession number:	PF16698
Interpro abstract (IPR032029):	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 [ (PUBMED:23521534) ].

PFAM accession number:

PF16698

Interpro abstract (IPR032029):

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 [ (PUBMED:23521534) ].

This is a PFAM domain. For full annotation and more information, please see the PFAM entry ADAM17_MPD