Peptidase M13, C-terminal domain
IPR018497
Definition
This entry represents the C-terminal domain of M13 peptidases. This group of metallopeptidases belong to the MEROPS peptidase family M13 (neprilysin family, clan MA(E)). The M13 family includes neprilysin (neutral endopeptidase, NEP, enkephalinase, CD10, CALLA, [ec:3.4.24.11]), endothelin-converting enzyme I (ECE-1, [ec:3.4.24.71]), erythrocyte surface antigen KELL (ECE-3), phosphate-regulating gene on the X chromosome (PHEX), soluble secreted endopeptidase (SEP), and damage-induced neuronal endopeptidase (DINE)/X-converting enzyme (XCE). These proteins consist of a short N-terminal cytoplasmic domain, a single transmembrane helix, and a larger C-terminal extracellular domain containing the active site. The cytoplasmic domain contains a conformationally-restrained octapeptide, which is thought to act as a stop transfer sequence that prevents proteolysis and secretion [[cite:PMID:7674922], [cite:PMID:3555489]]. Proteins in this family fulfill a broad range of physiological roles due to the greater variation in the S2' subsite allowing substrate specificity [[cite:PMID:7674922], [cite:PMID:10849750]]. The protein fold of the peptidase domain for members of this family resembles that of thermolysin, the type example for clan MA and the predicted active site residues for members of this family and thermolysin occur in the motif HEXXH PMID:7674922. M13 peptidases are well-studied proteases found in a wide range of organisms including mammals and bacteria. In mammals they participate in processes such as cardiovascular development, blood-pressure regulation, nervous control of respiration, and regulation of the function of neuropeptides in the central nervous system. In bacteria they may be used for digestion of milk [[cite:PMID:11223883], [cite:PMID:7674922]]. The family includes eukaryotic and prokaryotic oligopeptidases, as well as some of the proteins responsible for the molecular basis of the blood group antigens e.g. Kell PMID:7674922.
8 human proteins with this domain
Each is a reviewed human protein in the Seroatlas serome and a potential autoantibody target; this domain groups them into one antibody-relevant category. Every entry links to its own record.
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