[1]	NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE. TISSUE=Kidney; PubMed=2440677 [NCBI, ExPASy, EBI, Israel, Japan] Devault A., Lazure C., Nault C., le Moual H., Seidah N.G., Chretien M., Kahn P., Powell J., Mallet J., Beaumont A., Roques B.P., Crine P., Boileau G.; "Amino acid sequence of rabbit kidney neutral endopeptidase 24.11 (enkephalinase) deduced from a complementary DNA."; EMBO J. 6:1317-1322(1987).
[2]	ERRATUM. Devault A., Lazure C., Nault C., le Moual H., Seidah N.G., Chretien M., Kahn P., Powell J., Mallet J., Beaumont A., Roques B.P., Crine P., Boileau G.; EMBO J. 6:2506-2506(1987).
[3]	NUCLEOTIDE SEQUENCE [MRNA] OF 206-274. DOI=10.1016/0006-291X(87)91347-7; PubMed=3297057 [NCBI, ExPASy, EBI, Israel, Japan] Kahn P.H., Powell J.F., Beaumont A., Roques B.P., Mallet J.J.; "An antibody purified with a lambda GT11 fusion protein precipitates enkephalinase activity."; Biochem. Biophys. Res. Commun. 145:488-493(1987).
[4]	MUTAGENESIS. DOI=10.1016/0014-5793(88)80701-4; PubMed=3162886 [NCBI, ExPASy, EBI, Israel, Japan] Devault A., Sales V., Nault C., Beaumont A., Roques B., Crine P., Boileau G.; "Exploration of the catalytic site of endopeptidase 24.11 by site-directed mutagenesis. Histidine residues 583 and 587 are essential for catalysis."; FEBS Lett. 231:54-58(1988).

Comments

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. Involved in the degradation of atrial natriuretic factor (ANF) (By similarity).
CATALYTIC ACTIVITY: Preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1'.
COFACTOR: Binds 1 zinc ion per subunit.
SUBCELLULAR LOCATION: Membrane; Single-pass type II membrane protein.
SIMILARITY: Belongs to the peptidase M13 family [view classification].

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

X05338; CAA28950.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
M16593; AAA53694.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

A29451; HYRBN.

NP_001095155.1; -.

3D structure databases

HSSP

P08473; 1DMT. [HSSP ENTRY / PDB]

SMR

P08049; 55-750.

ModBase

P08049.

Protein family/group databases

MEROPS

M13.001; -.

Ontologies

GO:0016021;	Cellular component: integral to membrane (inferred from electronic annotation from UniProtKB-KW).
GO:0008270;	Molecular function: zinc ion binding (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.

Family and domain databases

InterPro

IPR006025; Pept_M_Zn_BS.
IPR000718; Peptidase_M13.
IPR008753; Peptidase_M13_N.
Graphical view of domain structure.

PANTHER

PTHR11733; Peptidase_M13; 1.

Pfam

PF01431; Peptidase_M13; 1.
PF05649; Peptidase_M13_N; 1.
Pfam graphical view of domain structure.

PRINTS

PR00786; NEPRILYSIN.

PROSITE

PS00142; ZINC_PROTEASE; 1.

Genome annotation databases

GeneID

100009251; -.

Phylogenomic databases

HOVERGEN

P08049; -.

Other

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Direct protein sequencing; Glycoprotein; Hydrolase; Membrane; Metal-binding; Metalloprotease; Protease; Signal-anchor; Transmembrane; Zinc.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`INIT_MET`	`1 1`		`Removed.`
`CHAIN`	`2 750`	`749`	`Neprilysin.`	`PRO_0000078216`
`TOPO_DOM`	`2 28`	`27`	`Cytoplasmic (Potential).`
`TRANSMEM`	`29 51`	`23`	`Signal-anchor for type II membrane protein (Potential).`
`TOPO_DOM`	`52 750`	`699`	`Extracellular (Potential).`
`MOTIF`	`16 23`	`8`	`Stop-transfer sequence (Potential).`
`ACT_SITE`	`585 585`		`By similarity.`
`ACT_SITE`	`651 651`		`Proton donor (By similarity).`
`METAL`	`584 584`		`Zinc; catalytic.`
`METAL`	`588 588`		`Zinc; catalytic.`
`METAL`	`647 647`		`Zinc; catalytic (By similarity).`
`BINDING`	`103 103`		`Substrate carboxyl (By similarity).`
`CARBOHYD`	`145 145`		`N-linked (GlcNAc...) (By similarity).`
`CARBOHYD`	`285 285`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`311 311`		`N-linked (GlcNAc...) (By similarity).`
`CARBOHYD`	`325 325`		`N-linked (GlcNAc...) (By similarity).`
`CARBOHYD`	`628 628`		`N-linked (GlcNAc...).`
`DISULFID`	`57 62`		`By similarity.`
`DISULFID`	`80 735`		`By similarity.`
`DISULFID`	`88 695`		`By similarity.`
`DISULFID`	`143 411`		`By similarity.`
`DISULFID`	`234 242`		`By similarity.`
`DISULFID`	`621 747`		`By similarity.`

Sequence information

Length: 750 AA [This is the length of the unprocessed precursor]

Molecular weight: 85582 Da [This is the MW of the unprocessed precursor]

CRC64: 0F26AF7316BB9D12 [This is a checksum on the sequence]

        10         20         30         40         50         60 
MGRSESQMDI TDINTPKPKK KQRWTPLEIS LSVLVLLLTV IAVTMIALYA TYDDGICKSS 

        70         80         90        100        110        120 
DCIKSAARLI QNMDATAEPC TDFFKYACGG WLKRNVIPET SSRYSNFDIL RDELEVILKD 

       130        140        150        160        170        180 
VLQEPKTEDI VAVQKAKTLY RSCVNETAID SRGGQPLLKL LPDVYGWPVA TQNWEQTYGT 

       190        200        210        220        230        240 
SWSAEKSIAQ LNSNYGKKVL INFFVGTDDK NSMNHIIHID QPRLGLPSRD YYECTGIYKE 

       250        260        270        280        290        300 
ACTAYVDFMI AVAKLIRQEE GLPIDENQIS VEMNKVMELE KEIANATTKS EDRNDPMLLY 

       310        320        330        340        350        360 
NKMTLAQIQN NFSLEINGKP FSWSNFTNEI MSTVNINIPN EEDVVVYAPE YLIKLKPILT 

       370        380        390        400        410        420 
KYFPRDFQNL FSWRFIMDLV SSLSRTYKDS RNAFRKALYG TTSESATWRR CANYVNGNME 

       430        440        450        460        470        480 
NAVGRLYVEA AFAGESKHVV EDLIAQIREV FIQTLDDLTW MDAETKKKAE EKALAIKERI 

       490        500        510        520        530        540 
GYPDDIVSND NKLNNEYLEL NYKEDEYFEN IIQNLKFSQS KQLKKLREKV DKDEWITGAA 

       550        560        570        580        590        600 
IVNAFYSSGR NQIVFPAGIL QPPFFSAQQS NSLNYGGIGM VIGHEITHGF DDNGRNFNKD 

       610        620        630        640        650        660 
GDLVDWWTQQ SANNFKEQSQ CMVYQYGNFS WDLAGGQHLN GINTLGENIA DNGGIGQAYR 

       670        680        690        700        710        720 
AYQNYVKKNG EEKLLPGIDL NHKQLFFLNF AQVWCGTYRP EYAVNSIKTD VHSPGNFRII 

       730        740        750 
GSLQNSVEFS EAFQCPKNSY MNPEKKCRVW

P08049 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools