D
IPR008753

Peptidase M13, N-terminal domain

InterPro entry
Short namePeptidase_M13_N
Overlapping
homologous
superfamilies
 

Description

This entry represents the N-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,
3.4.24.11
), endothelin-converting enzyme I (ECE-1,
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
[2, 3]
. Proteins in this family fulfill a broad range of physiological roles due to the greater variation in the S2' subsite allowing substrate specificity
[2, 4]
. 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
[2]
.

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
[1, 2]
. 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
[2]
.

References

1.The neprilysin (NEP) family of zinc metalloendopeptidases: genomics and function. Turner AJ, Isaac RE, Coates D. Bioessays 23, 261-9, (2001). View articlePMID: 11223883

2.Evolutionary families of metallopeptidases. Rawlings ND, Barrett AJ. Meth. Enzymol. 248, 183-228, (1995). View articlePMID: 7674922

3.Molecular cloning and amino acid sequence of rat enkephalinase. Malfroy B, Schofield PR, Kuang WJ, Seeburg PH, Mason AJ, Henzel WJ. Biochem. Biophys. Res. Commun. 144, 59-66, (1987). View articlePMID: 3555489

4.The neprilysin family in health and disease. Turner AJ, Brown CD, Carson JA, Barnes K. Adv. Exp. Med. Biol. 477, 229-40, (2000). PMID: 10849750

Further reading

5. Substitution of potential metal-coordinating amino acid residues in the zinc-binding site of endopeptidase-24.11. Le Moual H, Roques BP, Crine P, Boileau G. FEBS Lett. 324, 196-200, (1993). View articlePMID: 8099556

GO terms

biological process

molecular function

  • None

cellular component

  • None

Cross References

This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our Privacy Notice and Terms of Use.