P08049 (NEP_RABIT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Neprilysin
EC=3.4.24.11

Alternative name(s):
Atriopeptidase
Enkephalinase
Neutral endopeptidase 24.11
Short name=NEP
Short name=Neutral endopeptidase
Skin fibroblast elastase
Short name=SFE
CD_antigen=CD10

Gene names

Name:

MME

Organism

Oryctolagus cuniculus (Rabbit) [Reference proteome]

Taxonomic identifier

9986 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus

Protein attributes

Sequence length	750 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (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. Able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9 By similarity. Involved in the degradation of atrial natriuretic factor (ANF). Displays UV-inducible elastase activity toward skin preelastic and elastic fibers 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	Cell membrane; Single-pass type II membrane protein.
Post-translational modification	Myristoylation is a determinant of membrane targeting By similarity.
Sequence similarities	Belongs to the peptidase M13 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Domain	Signal-anchor Transmembrane Transmembrane helix
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Disulfide bond Glycoprotein Lipoprotein Myristate
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	beta-amyloid metabolic process Inferred from sequence or structural similarity. Source: UniProtKB cellular response to UV-A Inferred from sequence or structural similarity. Source: UniProtKB cellular response to UV-B Inferred from sequence or structural similarity. Source: UniProtKB cellular response to cytokine stimulus Inferred from sequence or structural similarity. Source: UniProtKB creatinine metabolic process Inferred from sequence or structural similarity. Source: UniProtKB kidney development Inferred from sequence or structural similarity. Source: UniProtKB proteolysis Inferred from sequence or structural similarity. Source: UniProtKB replicative senescence Inferred from sequence or structural similarity. Source: UniProtKB sensory perception of pain Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	axon Inferred from sequence or structural similarity. Source: UniProtKB brush border Inferred from sequence or structural similarity. Source: UniProtKB dendrite Inferred from sequence or structural similarity. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW neuron projection terminus Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB synaptic vesicle Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	metalloendopeptidase activity Inferred from sequence or structural similarity. Source: UniProtKB peptide binding Inferred from sequence or structural similarity. Source: UniProtKB zinc ion binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed
	Chain	2 – 750	749	Neprilysin		PRO_0000078216
Regions
	Topological domain	2 – 28	27	Cytoplasmic Potential
	Transmembrane	29 – 51	23	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	52 – 750	699	Extracellular Potential
	Motif	16 – 23	8	Stop-transfer sequence Potential
Sites
	Active site	585	1	By similarity
	Active site	651	1	Proton donor By similarity
	Metal binding	584	1	Zinc; catalytic
	Metal binding	588	1	Zinc; catalytic
	Metal binding	647	1	Zinc; catalytic By similarity
	Binding site	103	1	Substrate carboxyl By similarity
Amino acid modifications
	Lipidation	2	1	N-myristoyl glycine By similarity
	Glycosylation	145	1	N-linked (GlcNAc...) By similarity
	Glycosylation	285	1	N-linked (GlcNAc...) Potential
	Glycosylation	311	1	N-linked (GlcNAc...) By similarity
	Glycosylation	325	1	N-linked (GlcNAc...) By similarity
	Glycosylation	628	1	N-linked (GlcNAc...)
	Disulfide bond	57 ↔ 62		By similarity
	Disulfide bond	80 ↔ 735		By similarity
	Disulfide bond	88 ↔ 695		By similarity
	Disulfide bond	143 ↔ 411		By similarity
	Disulfide bond	234 ↔ 242		By similarity
	Disulfide bond	621 ↔ 747		By similarity

Sequences

	Sequence		Length	Mass (Da)
	P08049 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 0F26AF7316BB9D12	FASTA	750	85,582
	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

References

[1]	"Amino acid sequence of rabbit kidney neutral endopeptidase 24.11 (enkephalinase) deduced from a complementary DNA." 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. 6:1317-1322(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. Tissue: Kidney.
[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]	"An antibody purified with a lambda GT11 fusion protein precipitates enkephalinase activity." Kahn P.H., Powell J.F., Beaumont A., Roques B.P., Mallet J.J. Biochem. Biophys. Res. Commun. 145:488-493(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 206-274.
[4]	"Exploration of the catalytic site of endopeptidase 24.11 by site-directed mutagenesis. Histidine residues 583 and 587 are essential for catalysis." Devault A., Sales V., Nault C., Beaumont A., Roques B., Crine P., Boileau G. FEBS Lett. 231:54-58(1988) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X05338 mRNA. Translation: CAA28950.1. M16593 mRNA. Translation: AAA53694.1.
PIR	HYRBN. A29451.
RefSeq	NP_001095155.1. NM_001101685.1.
UniGene	Ocu.2011.
3D structure databases
ProteinModelPortal	P08049.
SMR	P08049. Positions 55-750.
ModBase	Search...
Protein-protein interaction databases
STRING	9986.ENSOCUP00000021723.
Protein family/group databases
MEROPS	M13.001.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	100009251.
Organism-specific databases
CTD	4311.
Phylogenomic databases
eggNOG	COG3590.
HOGENOM	HOG000245574.
HOVERGEN	HBG005554.
OrthoDB	EOG4XWFXB.
Family and domain databases
Gene3D	3.40.390.10. 2 hits.
InterPro	IPR024079. MetalloPept_cat_dom. IPR000718. Peptidase_M13. IPR018497. Peptidase_M13_C. IPR008753. Peptidase_M13_N. [Graphical view]
PANTHER	PTHR11733. PTHR11733. 1 hit.
Pfam	PF01431. Peptidase_M13. 1 hit. PF05649. Peptidase_M13_N. 1 hit. [Graphical view]
PRINTS	PR00786. NEPRILYSIN.
PROSITE	PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P08049.
ChEMBL	CHEMBL3768.

Entry information

Entry name

NEP_RABIT

Accession

Primary (citable) accession number: P08049

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 111 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program