Reviewed, UniProtKB/Swiss-Prot P07861 (NEP_RAT)

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

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

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).
Catalytic activity	Preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1'.
Cofactor	Binds 1 zinc ion per subunit.
Enzyme regulation	Inhibited in a dose dependent manner by sialorphin.
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	peptide metabolic process Inferred from mutant phenotype. Source: RGD proteolysis Inferred from direct assay. Source: RGD
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW membrane fraction Inferred from direct assay. Source: RGD plasma membrane Inferred from mutant phenotype. Source: RGD
Molecular function	metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro peptide binding Inferred from direct assay. Source: RGD 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_0000078217
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 By similarity
	Metal binding	588	1	Zinc; catalytic By similarity
	Metal binding	647	1	Zinc; catalytic By similarity
	Binding site	103	1	Substrate carboxyl
Amino acid modifications
	Glycosylation	145	1	N-linked (GlcNAc...) By similarity
	Glycosylation	211	1	N-linked (GlcNAc...) Potential
	Glycosylation	285	1	N-linked (GlcNAc...) Potential
	Glycosylation	311	1	N-linked (GlcNAc...) Ref.1
	Glycosylation	325	1	N-linked (GlcNAc...) By similarity
	Glycosylation	628	1	N-linked (GlcNAc...) By similarity
	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)
	P07861-1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 609D4716C4B15CBC	FASTA	750	85,795
	10 20 30 40 50 60 MGRSESQMDI TDINAPKPKK KQRWTPLEIS LSVLVLLLTI IAVTMIALYA TYDDGICKSS 70 80 90 100 110 120 DCIKSAARLI QNMDASAEPC TDFFKYACGG WLKRNVIPET SSRYSNFDIL RDELEVILKD 130 140 150 160 170 180 VLQEPKTEDI VAVQKAKTLY RSCINESAID SRGGQPLLTL LPDIYGWPVA SQNWEQTYGT 190 200 210 220 230 240 SWTAEKSIAQ LNSKYGKKVL INFFVGTDDK NSTQHIIHFD QPRLGLPSRD YYECTGIYKE 250 260 270 280 290 300 ACTAYVDFMI SVARLIRQEQ RLPIDENQLS LEMNKVMELE KEIANATTKP EDRNDPMLLY 310 320 330 340 350 360 NKMTLAKLQN NFSLEINGKP FSWSNFTNEI MSTVNINIQN EEEVVVYAPE YLTKLKPILT 370 380 390 400 410 420 KYSPRDLQNL MSWRFIMDLV SSLSRNYKES RNAFRKALYG TTSETATWRR CANYVNGNME 430 440 450 460 470 480 NAVGRLYVEA AFAGESKHVV EDLIAQIREV FIQTLDDLTW MDAETKKKAE EKALAIKERI 490 500 510 520 530 540 GYPDDIISNE NKLNNEYLEL NYKEEEYFEN IIQNLKFSQS KQLKKLREKV DKDEWISGAA 550 560 570 580 590 600 VVNAFYSSGR NQIVFPAGIL QPPFFSARQS NSLNYGGIGM VIGHEITHGF DDNGRNFNKD 610 620 630 640 650 660 GDLVDWWTQQ SANNFKDQSQ CMVYQYGNFT WDLAGGQHLN GINTLGENIA DNGGIGQAYR 670 680 690 700 710 720 AYQNYVKKNG EEKLLPGLDL NHKQLFFLNF AQVWCGTYRP EYAVNSIKTD VHSPGNFRII 730 740 750 GTLQNSAEFA DAFHCRKNSY MNPERKCRVW

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and amino acid sequence of rat enkephalinase." Malfroy B., Schofield P.R., Kuang W.-J., Seeburg P.H., Mason A.J., Henzel W.J. Biochem. Biophys. Res. Commun. 144:59-66(1987) [PubMed: 3555489] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Kidney.
[3]	"Identification of the active-site arginine in rat neutral endopeptidase 24.11 (enkephalinase) as arginine 102 and analysis of a glutamine 102 mutant." Bateman R.C. Jr., Jackson D., Slaughter C.A., Unnithan S., Chai Y.G., Moomaw C., Hersh L.B. J. Biol. Chem. 264:6151-6157(1989) [PubMed: 2703483] [Abstract] Cited for: ACTIVE SITE ARG-103.
[4]	"Sialorphin, a natural inhibitor of rat membrane-bound neutral endopeptidase that displays analgesic activity." Rougeot C., Messaoudi M., Hermitte V., Rigault A.G., Blisnick T., Dugave C., Desor D., Rougeon F. Proc. Natl. Acad. Sci. U.S.A. 100:8549-8554(2003) [PubMed: 12835417] [Abstract] Cited for: INHIBITION BY SIALORPHIN.

Cross-references

Sequence databases
EMBLGenBankDDBJ	M15944 mRNA. Translation: AAA41116.1. BC085753 mRNA. Translation: AAH85753.1.
IPI	IPI00231789.
PIR	HYRTN. A29295.
RefSeq	NP_036740.1.
UniGene	Rn.33598
3D structure databases
HSSP	HSSP built from PDB template 1DMT based on UniProtKB P08473.
SMR	P07861. Positions 55-750.
ModBase	Search...
Protein family/group databases
MEROPS	M13.001.
Proteomic databases
PRIDE	P07861.
Genome annotation databases
Ensembl	ENSRNOG00000009514. Rattus norvegicus. [Contig view]
GeneID	24590.
KEGG	rno:24590.
Organism-specific databases
RGD	3098. Mme.
Phylogenomic databases
HOVERGEN	P07861.
OMA	P07861. GRNQIVF.
Enzyme and pathway databases
BRENDA	3.4.24.11. 248.
Gene expression databases
ArrayExpress	P07861.
GermOnline	ENSRNOG00000009514. Rattus norvegicus.
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...
Other Resources
NextBio	603776.

Entry information

Entry name

NEP_RAT

Accession

Primary (citable) accession number: P07861

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 89 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)