Q61391 (NEP_MOUSE) 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

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [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 › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

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. Ref.6
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	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	beta-amyloid metabolic process Inferred from direct assay PubMed 12074840. Source: MGI 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 mutant phenotype PubMed 9751784. Source: UniProtKB
Cellular_component	axon Inferred from direct assay PubMed 12074840. Source: MGI brush border Inferred from sequence or structural similarity. Source: UniProtKB dendrite Inferred from direct assay PubMed 12074840. Source: MGI integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW neuron projection terminus Inferred from direct assay PubMed 12074840. Source: MGI plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB synaptic vesicle Inferred from direct assay PubMed 12074840. Source: MGI
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 By similarity

Chain

2 – 750

749

Neprilysin

PRO_0000078214

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 By similarity

Metal binding

588

1

Zinc; catalytic By similarity

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...) Ref.5

Glycosylation

211

1

N-linked (GlcNAc...) Potential

Glycosylation

285

1

N-linked (GlcNAc...) Ref.5

Glycosylation

311

1

N-linked (GlcNAc...) Ref.5

Glycosylation

317

1

N-linked (GlcNAc...) Ref.5

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

Experimental info

Sequence conflict

230

1

D → G in AAA37386. Ref.1

Secondary structure

1

.

.

.

750

Helix Strand Turn

Details...

Beta strand

9 – 12

4

Sequences

	Sequence		Length	Mass (Da)
	Q61391 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 1FC39A971D98F6FE	FASTA	750	85,702
	10 20 30 40 50 60 MGRSESQMDI TDINAPKPKK KQRWTPLEIS LSVLVLLLTI IAVTMIALYA TYDDGICKSS 70 80 90 100 110 120 DCIKSAARLI QNMDASVEPC TDFFKYACGG WLKRNVIPET SSRYSNFDIL RDELEVILKD 130 140 150 160 170 180 VLQEPKTEDI VAVQKAKTLY RSCINESAID SRGGQPLLKL LPDIYGWPVA SDNWDQTYGT 190 200 210 220 230 240 SWTAEKSIAQ LNSKYGKKVL INFFVGTDDK NSTQHIIHFD QPRLGLPSRD YYECTGIYKE 250 260 270 280 290 300 ACTAYVDFMI SVARLIRQEQ SLPIDENQLS LEMNKVMELE KEIANATTKP EDRNDPMLLY 310 320 330 340 350 360 NKMTLAKLQN NFSLEVNGKS 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 NYREDEYFEN IIQNLKFSQS KQLKKLREKV DKDEWISGAA 550 560 570 580 590 600 VVNAFYSSGR NQIVFPAGIL QPPFFSAQQS NSLNYGGIGM VIGHEITHGF DDNGRNFNKD 610 620 630 640 650 660 GDLVDWWTQQ SANNFKDQSQ CMVYQYGNFS 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]	"Murine common acute lymphoblastic leukemia antigen (CD10 neutral endopeptidase 24.11). Molecular characterization, chromosomal localization, and modeling of the active site." Chen C.Y., Salles G., Seldin M.F., Kister A.E., Reinher E.L., Shipp M.A. J. Immunol. 148:2817-2825(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: BALB/c.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Epididymis and Testis.
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J and FVB/N. Tissue: Embryonic germ cell and Mammary tumor.
[4]	Lubec G., Sunyer B., Chen W.-Q. Submitted (JAN-2009) to UniProtKB Cited for: PROTEIN SEQUENCE OF 473-479, MASS SPECTROMETRY. Strain: OF1. Tissue: Hippocampus.
[5]	"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins." Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D. Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-145; ASN-285; ASN-311 AND ASN-317, MASS SPECTROMETRY.
[6]	"Neprilysin is identical to skin fibroblast elastase: its role in skin aging and UV responses." Morisaki N., Moriwaki S., Sugiyama-Nakagiri Y., Haketa K., Takema Y., Imokawa G. J. Biol. Chem. 285:39819-39827(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION AS SKIN FIBROBLAST ELASTASE, FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M81591 mRNA. Translation: AAA37386.1.
AK031446 mRNA. Translation: BAC27410.1.
AK033824 mRNA. Translation: BAC28487.1.
BC034092 mRNA. Translation: AAH34092.1.
BC066840 mRNA. Translation: AAH66840.1.

IPI

IPI00461861.

RefSeq

NP_032630.2. NM_008604.3.

UniGene

Mm.296022.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2YVC	X-ray	3.20	D/E/F	2-23	[»]

ProteinModelPortal

Q61391.

SMR

Q61391. Positions 55-750.

ModBase

Search...

Protein family/group databases

MEROPS

M13.001.

PTM databases

PhosphoSite

Q61391.

Proteomic databases

PaxDb

Q61391.

PRIDE

Q61391.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000029400; ENSMUSP00000029400; ENSMUSG00000027820.

GeneID

17380.

KEGG

mmu:17380.

UCSC

uc008pjp.1. mouse.

Organism-specific databases

CTD

4311.

MGI

MGI:97004. Mme.

Phylogenomic databases

eggNOG

COG3590.

GeneTree

ENSGT00650000093248.

HOGENOM

HOG000245574.

HOVERGEN

HBG005554.

InParanoid

Q61391.

KO

K01389.

OMA

VWCGTYR.

OrthoDB

EOG4XWFXB.

Gene expression databases

ArrayExpress

Q61391.

Bgee

Q61391.

CleanEx

MM_MME.

Genevestigator

Q61391.

GermOnline

ENSMUSG00000027820. Mus musculus.

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

Q61391.

ChEMBL

CHEMBL2642.

EvolutionaryTrace

Q61391.

NextBio

291980.

SOURCE

Search...

Entry information

Entry name

NEP_MOUSE

Accession

Primary (citable) accession number: Q61391
Secondary accession number(s): Q6NXX5, Q8K251

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 119 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program