Reviewed, UniProtKB/Swiss-Prot P08049 (NEP_RABIT)

Names and origin

Protein names

Recommended name:
    Neprilysin
    EC=3.4.24.11
Alternative name(s):
    Neutral endopeptidase 24.11
      Short name=Neutral endopeptidase
      Short name=NEP
    Enkephalinase
    Atriopeptidase
    CD_antigen=CD10

Gene names

Name:

MME

Organism

Oryctolagus cuniculus (Rabbit)

Taxonomic identifier

9986 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › 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. 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	Cell membrane; Single-pass type II membrane protein.
Sequence similarities	Belongs to the peptidase M13 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Domain	Signal-anchor Transmembrane
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Disulfide bond Glycoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
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	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
	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)
	P08049-1 [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: 2440677] [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: 3297057] [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: 3162886] [Abstract] Cited for: MUTAGENESIS.

Cross-references

Sequence databases
EMBLGenBankDDBJ	X05338 mRNA. Translation: CAA28950.1. M16593 mRNA. Translation: AAA53694.1.
PIR	HYRBN. A29451.
RefSeq	NP_001095155.1.
UniGene	Ocu.2011
3D structure databases
HSSP	HSSP built from PDB template 1DMT based on UniProtKB P08473.
SMR	P08049. Positions 55-750.
ModBase	Search...
Protein family/group databases
MEROPS	M13.001.
Genome annotation databases
GeneID	100009251.
Phylogenomic databases
HOVERGEN	P08049.
Enzyme and pathway databases
BRENDA	3.4.24.11. 255.
Family and domain databases
InterPro	IPR006025. Pept_M_Zn_BS. IPR000718. Peptidase_M13. IPR018497. Peptidase_M13_C. IPR008753. Peptidase_M13_N. [Graphical view]
PANTHER	PTHR11733. Peptidase_M13. 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...

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:	June 16, 2009
This is version 81 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)