Neprilysin
Details
- Name
- Neprilysin
- Synonyms
- 3.4.24.11
- Atriopeptidase
- CALLA
- Common acute lymphocytic leukemia antigen
- Enkephalinase
- EPN
- NEP
- Neutral endopeptidase
- Neutral endopeptidase 24.11
- SFE
- Skin fibroblast elastase
- Gene Name
- MME
- UniProtKB Entry
- P08473Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0036982|Neprilysin MGKSESQMDITDINTPKPKKKQRWTPLEISLSVLVLLLTIIAVTMIALYATYDDGICKSS DCIKSAARLIQNMDATTEPCTDFFKYACGGWLKRNVIPETSSRYGNFDILRDELEVVLKD VLQEPKTEDIVAVQKAKALYRSCINESAIDSRGGEPLLKLLPDIYGWPVATENWEQKYGA SWTAEKAIAQLNSKYGKKVLINLFVGTDDKNSVNHVIHIDQPRLGLPSRDYYECTGIYKE ACTAYVDFMISVARLIRQEERLPIDENQLALEMNKVMELEKEIANATAKPEDRNDPMLLY NKMTLAQIQNNFSLEINGKPFSWLNFTNEIMSTVNISITNEEDVVVYAPEYLTKLKPILT KYSARDLQNLMSWRFIMDLVSSLSRTYKESRNAFRKALYGTTSETATWRRCANYVNGNME NAVGRLYVEAAFAGESKHVVEDLIAQIREVFIQTLDDLTWMDAETKKRAEEKALAIKERI GYPDDIVSNDNKLNNEYLELNYKEDEYFENIIQNLKFSQSKQLKKLREKVDKDEWISGAA VVNAFYSSGRNQIVFPAGILQPPFFSAQQSNSLNYGGIGMVIGHEITHGFDDNGRNFNKD GDLVDWWTQQSASNFKEQSQCMVYQYGNFSWDLAGGQHLNGINTLGENIADNGGLGQAYR AYQNYIKKNGEEKLLPGLDLNHKQLFFLNFAQVWCGTYRPEYAVNSIKTDVHSPGNFRII GTLQNSAEFSEAFHCRKNSYMNPEKKCRVW
- Number of residues
- 750
- Molecular Weight
- 85513.225
- Theoretical pI
- 5.43
- GO Classification
- Functionscardiolipin binding / oligopeptidase activity / phosphatidylserine binding / protein homodimerization activityProcessesamyloid-beta clearance / amyloid-beta clearance by cellular catabolic process / amyloid-beta metabolic process / bradykinin catabolic process / hormone catabolic process / learning or memory / lung development / neuropeptide processing / placenta development / positive regulation of long-term synaptic potentiation / positive regulation of neurogenesis / protein catabolic process / protein processing / response to estrogen / substance P catabolic processComponentscell surface / cytoplasmic vesicle / early endosome / membrane / membrane raft / neuronal cell body / presynapse / secretory granule membrane / trans-Golgi network
- General Function
- Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids (PubMed:15283675, PubMed:6208535, PubMed:6349683, PubMed:8168535). Biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond (PubMed:17101991, PubMed:6349683). Catalyzes cleavage of bradykinin, substance P and neurotensin peptides (PubMed:6208535). Able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9 (PubMed:15283675, PubMed:6349683). Involved in the degradation of atrial natriuretic factor (ANF) and brain natriuretic factor (BNP(1-32)) (PubMed:16254193, PubMed:2531377, PubMed:2972276). Displays UV-inducible elastase activity toward skin preelastic and elastic fibers (PubMed:20876573)
- Specific Function
- cardiolipin binding
- Pfam Domain Function
- Signal Regions
- Not Available
- Transmembrane Regions
- 29-51
- Cellular Location
- Cell membrane
- Gene sequence
>lcl|BSEQ0018931|Neprilysin (MME) ATGGGCAAGTCAGAAAGTCAGATGGATATAACTGATATCAACACTCCAAAGCCAAAGAAG AAACAGCGATGGACTCCACTGGAGATCAGCCTCTCGGTCCTTGTCCTGCTCCTCACCATC ATAGCTGTGACAATGATCGCACTCTATGCAACCTACGATGATGGTATTTGCAAGTCATCA GACTGCATAAAATCAGCTGCTCGACTGATCCAAAACATGGATGCCACCACTGAGCCTTGT ACAGACTTTTTCAAATATGCTTGCGGAGGCTGGTTGAAACGTAATGTCATTCCCGAGACC AGCTCCCGTTACGGCAACTTTGACATTTTAAGAGATGAACTAGAAGTCGTTTTGAAAGAT GTCCTTCAAGAACCCAAAACTGAAGATATAGTAGCAGTGCAGAAAGCAAAAGCATTGTAC AGGTCTTGTATAAATGAATCTGCTATTGATAGCAGAGGTGGAGAACCTCTACTCAAACTG TTACCAGACATATATGGGTGGCCAGTAGCAACAGAAAACTGGGAGCAAAAATATGGTGCT TCTTGGACAGCTGAAAAAGCTATTGCACAACTGAATTCTAAATATGGGAAAAAAGTCCTT ATTAATTTGTTTGTTGGCACTGATGATAAGAATTCTGTGAATCATGTAATTCATATTGAC CAACCTCGACTTGGCCTCCCTTCTAGAGATTACTATGAATGCACTGGAATCTATAAAGAG GCTTGTACAGCATATGTGGATTTTATGATTTCTGTGGCCAGATTGATTCGTCAGGAAGAA AGATTGCCCATCGATGAAAACCAGCTTGCTTTGGAAATGAATAAAGTTATGGAATTGGAA AAAGAAATTGCCAATGCTACGGCTAAACCTGAAGATCGAAATGATCCAATGCTTCTGTAT AACAAGATGACATTGGCCCAGATCCAAAATAACTTTTCACTAGAGATCAATGGGAAGCCA TTCAGCTGGTTGAATTTCACAAATGAAATCATGTCAACTGTGAATATTAGTATTACAAAT GAGGAAGATGTGGTTGTTTATGCTCCAGAATATTTAACCAAACTTAAGCCCATTCTTACC AAATATTCTGCCAGAGATCTTCAAAATTTAATGTCCTGGAGATTCATAATGGATCTTGTA AGCAGCCTCAGCCGAACCTACAAGGAGTCCAGAAATGCTTTCCGCAAGGCCCTTTATGGT ACAACCTCAGAAACAGCAACTTGGAGACGTTGTGCAAACTATGTCAATGGGAATATGGAA AATGCTGTGGGGAGGCTTTATGTGGAAGCAGCATTTGCTGGAGAGAGTAAACATGTGGTC GAGGATTTGATTGCACAGATCCGAGAAGTTTTTATTCAGACTTTAGATGACCTCACTTGG ATGGATGCCGAGACAAAAAAGAGAGCTGAAGAAAAGGCCTTAGCAATTAAAGAAAGGATC GGCTATCCTGATGACATTGTTTCAAATGATAACAAACTGAATAATGAGTACCTCGAGTTG AACTACAAAGAAGATGAATACTTCGAGAACATAATTCAAAATTTGAAATTCAGCCAAAGT AAACAACTGAAGAAGCTCCGAGAAAAGGTGGACAAAGATGAGTGGATAAGTGGAGCAGCT GTAGTCAATGCATTTTACTCTTCAGGAAGAAATCAGATAGTCTTCCCAGCCGGCATTCTG CAGCCCCCCTTCTTTAGTGCCCAGCAGTCCAACTCATTGAACTATGGGGGCATCGGCATG GTCATAGGACACGAAATCACCCATGGCTTCGATGACAATGGCAGAAACTTTAACAAAGAT GGAGACCTCGTTGACTGGTGGACTCAACAGTCTGCAAGTAACTTTAAGGAGCAATCCCAG TGCATGGTGTATCAGTATGGAAACTTTTCCTGGGACCTGGCAGGTGGACAGCACCTTAAT GGAATTAATACACTGGGAGAAAACATTGCTGATAATGGAGGTCTTGGTCAAGCATACAGA GCCTATCAGAATTATATTAAAAAGAATGGCGAAGAAAAATTACTTCCTGGACTTGACCTA AATCACAAACAACTATTTTTCTTGAACTTTGCACAGGTGTGGTGTGGAACCTATAGGCCA GAGTATGCGGTTAACTCCATTAAAACAGATGTGCACAGTCCAGGCAATTTCAGGATTATT GGGACTTTGCAGAACTCTGCAGAGTTTTCAGAAGCCTTTCACTGCCGCAAGAATTCATAC ATGAATCCAGAAAAGAAGTGCCGGGTTTGGTGA
- Chromosome Location
- 3
- Locus
- 3q25.2
- External Identifiers
Resource Link UniProtKB ID P08473 UniProtKB Entry Name NEP_HUMAN GenBank Protein ID 34758 GenBank Gene ID X07166 GeneCard ID MME GenAtlas ID MME HGNC ID HGNC:7154 PDB ID(s) 1DMT, 1R1H, 1R1I, 1R1J, 1Y8J, 2QPJ, 2YB9, 4CTH, 5JMY, 6GID, 6SH1, 6SH2, 6SUK, 6SVY, 6THP, 6XVP KEGG ID hsa:4311 IUPHAR/Guide To Pharmacology ID 1611 NCBI Gene ID 4311 - General References
- Letarte M, Vera S, Tran R, Addis JB, Onizuka RJ, Quackenbush EJ, Jongeneel CV, McInnes RR: Common acute lymphocytic leukemia antigen is identical to neutral endopeptidase. J Exp Med. 1988 Oct 1;168(4):1247-53. [Article]
- Shipp MA, Richardson NE, Sayre PH, Brown NR, Masteller EL, Clayton LK, Ritz J, Reinherz EL: Molecular cloning of the common acute lymphoblastic leukemia antigen (CALLA) identifies a type II integral membrane protein. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4819-23. [Article]
- D'Adamio L, Shipp MA, Masteller EL, Reinherz EL: Organization of the gene encoding common acute lymphoblastic leukemia antigen (neutral endopeptidase 24.11): multiple miniexons and separate 5' untranslated regions. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7103-7. [Article]
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- Malfroy B, Kuang WJ, Seeburg PH, Mason AJ, Schofield PR: Molecular cloning and amino acid sequence of human enkephalinase (neutral endopeptidase). FEBS Lett. 1988 Feb 29;229(1):206-10. [Article]
- Vanneste Y, Michel A, Dimaline R, Najdovski T, Deschodt-Lanckman M: Hydrolysis of alpha-human atrial natriuretic peptide in vitro by human kidney membranes and purified endopeptidase-24.11. Evidence for a novel cleavage site. Biochem J. 1988 Sep 1;254(2):531-7. [Article]
- Yandle TG, Brennan SO, Espiner EA, Nicholls MG, Richards AM: Endopeptidase-24.11 in human plasma degrades atrial natriuretic factor (ANF) to ANF(99-105/106-126). Peptides. 1989 Jul-Aug;10(4):891-4. [Article]
- Le Moual H, Dion N, Roques BP, Crine P, Boileau G: Asp650 is crucial for catalytic activity of neutral endopeptidase 24-11. Eur J Biochem. 1994 Apr 1;221(1):475-80. [Article]
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- Wisner A, Dufour E, Messaoudi M, Nejdi A, Marcel A, Ungeheuer MN, Rougeot C: Human Opiorphin, a natural antinociceptive modulator of opioid-dependent pathways. Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17979-84. Epub 2006 Nov 13. [Article]
- Morisaki N, Moriwaki S, Sugiyama-Nakagiri Y, Haketa K, Takema Y, Imokawa G: Neprilysin is identical to skin fibroblast elastase: its role in skin aging and UV responses. J Biol Chem. 2010 Dec 17;285(51):39819-27. doi: 10.1074/jbc.M110.161547. Epub 2010 Sep 28. [Article]
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Associated Data
- Bio-Entities
Bio-Entity Type Neprilysin (Humans) protein primary- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details Candoxatril experimental yes target inhibitor Details Omapatrilat investigational yes target modulator Details N-[3-[(1-Aminoethyl)(Hydroxy)Phosphoryl]-2-(1,1'-Biphenyl-4-Ylmethyl)Propanoyl]Alanine experimental unknown target Details Phosphoramidon experimental yes target inhibitor Details N-(3-Phenyl-2-Sulfanylpropanoyl)Phenylalanylalanine experimental unknown target Details [2(R,S)-2-Sulfanylheptanoyl]-Phe-Ala experimental yes target inhibitor Details Daglutril investigational yes target modulator Details 2-[(1S)-1-BENZYL-2-SULFANYLETHYL]-1H-IMIDAZO[4,5-C]PYRIDIN-5-IUM experimental unknown target Details Thiorphan experimental yes target inhibitor Details Liraglutide approved unknown enzyme substrate Details Sacubitril approved yes target antagonistinhibitor Details Candoxatrilat experimental yes target inhibitor Details Semaglutide approved, investigational no enzyme substrate Details Sacubitrilat experimental yes target inhibitor Details Ilepatril investigational yes target modulator Details Gallopamil investigational yes target inhibitor Details SLV-334 investigational yes target modulator Details