The domain within your query sequence starts at position 543 and ends at position 749; the E-value for the Peptidase_M13 domain shown below is 3.3e-67.

NAFYSSGRNQIVFPAGILQPPFFSAQQSNSLNYGGIGMVIGHEITHGFDDNGRNFNKDGD
LVDWWTQQSANNFKDQSQCMVYQYGNFSWDLAGGQHLNGINTLGENIADNGGIGQAYRAY
QNYVKKNGEEKLLPGLDLNHKQLFFLNFAQVWCGTYRPEYAVNSIKTDVHSPGNFRIIGT
LQNSAEFADAFHCRKNSYMNPERKCRV

Peptidase_M13

Peptidase_M13
PFAM accession number:PF01431
Interpro abstract (IPR018497): 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 [(PUBMED:7674922), (PUBMED:3555489)]. Proteins in this family fulfill a broad range of physiological roles due to the greater variation in the S2' subsite allowing substrate specificity [(PUBMED:7674922), (PUBMED: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 [(PUBMED: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 [(PUBMED:11223883), (PUBMED: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 [(PUBMED:7674922)].

Neprilysin (NEP), is expressed in a variety of tissues including kidney and brain, and is involved in many physiological and pathological processes, including blood pressure and inflammatory response. It is a plasma membrane-bound mammalian enzyme that is able to digest biologically-active peptides, including enkephalins [(PUBMED:7674922)], substance P, cholecystokinin, neurotensin and somatostatin. It is an important enzyme in the regulation of amyloid-beta (Abeta) protein that forms amyloid plaques that are associated with Alzeimers disease (AD). The zinc ligands of neprilysin are known and are analogous to those in thermolysin, a related peptidase [(PUBMED:7674922), (PUBMED:8099556)]. Neprilysins, like thermolysin, are inhibited by phosphoramidon, which appears to selectively inhibit this family in mammals. The enzymes are all oligopeptidases, digesting oligo- and polypeptides, but not proteins [(PUBMED:7674922)].

GO process:proteolysis (GO:0006508)
GO function:metalloendopeptidase activity (GO:0004222)

This is a PFAM domain. For full annotation and more information, please see the PFAM entry Peptidase_M13