Hmdb loader
Identification
HMDB Protein ID HMDBP02539
Secondary Accession Numbers
  • 8038
Name Neprilysin
Synonyms
  1. Atriopeptidase
  2. CALLA
  3. CD10 antigen
  4. Common acute lymphocytic leukemia antigen
  5. Enkephalinase
  6. NEP
  7. Neutral endopeptidase
  8. Neutral endopeptidase 24.11
Gene Name MME
Protein Type Unknown
Biological Properties
General Function Involved in metalloendopeptidase activity
Specific Function Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids. Biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond. Able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9. Involved in the degradation of atrial natriuretic factor (ANF)
Pathways Not Available
Reactions Not Available
GO Classification
Function
endopeptidase activity
catalytic activity
hydrolase activity
metalloendopeptidase activity
peptidase activity
peptidase activity, acting on l-amino acid peptides
metallopeptidase activity
Process
metabolic process
macromolecule metabolic process
protein metabolic process
proteolysis
Cellular Location
  1. Cell membrane
  2. Single-pass type II membrane protein
Gene Properties
Chromosome Location Chromosome:3
Locus 3q25.1-q25.2
SNPs MME
Gene Sequence
>2253 bp
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
Protein Properties
Number of Residues 750
Molecular Weight 85513.2
Theoretical pI 5.43
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • 29-51
Protein Sequence
>Neprilysin
MGKSESQMDITDINTPKPKKKQRWTPLEISLSVLVLLLTIIAVTMIALYATYDDGICKSS
DCIKSAARLIQNMDATTEPCTDFFKYACGGWLKRNVIPETSSRYGNFDILRDELEVVLKD
VLQEPKTEDIVAVQKAKALYRSCINESAIDSRGGEPLLKLLPDIYGWPVATENWEQKYGA
SWTAEKAIAQLNSKYGKKVLINLFVGTDDKNSVNHVIHIDQPRLGLPSRDYYECTGIYKE
ACTAYVDFMISVARLIRQEERLPIDENQLALEMNKVMELEKEIANATAKPEDRNDPMLLY
NKMTLAQIQNNFSLEINGKPFSWLNFTNEIMSTVNISITNEEDVVVYAPEYLTKLKPILT
KYSARDLQNLMSWRFIMDLVSSLSRTYKESRNAFRKALYGTTSETATWRRCANYVNGNME
NAVGRLYVEAAFAGESKHVVEDLIAQIREVFIQTLDDLTWMDAETKKRAEEKALAIKERI
GYPDDIVSNDNKLNNEYLELNYKEDEYFENIIQNLKFSQSKQLKKLREKVDKDEWISGAA
VVNAFYSSGRNQIVFPAGILQPPFFSAQQSNSLNYGGIGMVIGHEITHGFDDNGRNFNKD
GDLVDWWTQQSASNFKEQSQCMVYQYGNFSWDLAGGQHLNGINTLGENIADNGGLGQAYR
AYQNYIKKNGEEKLLPGLDLNHKQLFFLNFAQVWCGTYRPEYAVNSIKTDVHSPGNFRII
GTLQNSAEFSEAFHCRKNSYMNPEKKCRVW
GenBank ID Protein 29626
UniProtKB/Swiss-Prot ID P08473
UniProtKB/Swiss-Prot Entry Name NEP_HUMAN
PDB IDs
GenBank Gene ID Y00811
GeneCard ID MME
GenAtlas ID MME
HGNC ID HGNC:7154
References
General References
  1. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039 ]
  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. Zhang H, Li XJ, Martin DB, Aebersold R: Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. Nat Biotechnol. 2003 Jun;21(6):660-6. Epub 2003 May 18. [PubMed:12754519 ]
  4. 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. [PubMed:2971756 ]
  5. 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. [PubMed:2968607 ]
  6. 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. [PubMed:2528730 ]
  7. 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. [PubMed:3162217 ]
  8. 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. [PubMed:2531377 ]
  9. 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. [PubMed:8168535 ]
  10. Rice GI, Thomas DA, Grant PJ, Turner AJ, Hooper NM: Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism. Biochem J. 2004 Oct 1;383(Pt 1):45-51. [PubMed:15283675 ]
  11. 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. [PubMed:17101991 ]
  12. Oefner C, D'Arcy A, Hennig M, Winkler FK, Dale GE: Structure of human neutral endopeptidase (Neprilysin) complexed with phosphoramidon. J Mol Biol. 2000 Feb 18;296(2):341-9. [PubMed:10669592 ]
  13. Oefner C, Roques BP, Fournie-Zaluski MC, Dale GE: Structural analysis of neprilysin with various specific and potent inhibitors. Acta Crystallogr D Biol Crystallogr. 2004 Feb;60(Pt 2):392-6. Epub 2004 Jan 23. [PubMed:14747736 ]
  14. Oefner C, Pierau S, Schulz H, Dale GE: Structural studies of a bifunctional inhibitor of neprilysin and DPP-IV. Acta Crystallogr D Biol Crystallogr. 2007 Sep;63(Pt 9):975-81. Epub 2007 Aug 17. [PubMed:17704566 ]