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Protein

Neprilysin

Gene

MME

Organism
Oryctolagus cuniculus (Rabbit)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Involved in the degradation of atrial natriuretic factor (ANF). Displays UV-inducible elastase activity toward skin preelastic and elastic fibers.By similarity

Catalytic activityi

Preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1'.By similarity

Cofactori

Zn2+Note: Binds 1 zinc ion per subunit.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei103 – 1031Substrate carboxylBy similarity
Metal bindingi584 – 5841Zinc; catalytic
Active sitei585 – 5851PROSITE-ProRule annotation
Metal bindingi588 – 5881Zinc; catalytic
Metal bindingi647 – 6471Zinc; catalyticPROSITE-ProRule annotation
Active sitei651 – 6511Proton donorPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

Protein family/group databases

MEROPSiM13.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Neprilysin (EC:3.4.24.11By similarity)
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 namesi
Name:MME
OrganismiOryctolagus cuniculus (Rabbit)
Taxonomic identifieri9986 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
Proteomesi
  • UP000001811 Componenti: Unplaced

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini2 – 2827CytoplasmicSequence analysisAdd
BLAST
Transmembranei29 – 5123Helical; Signal-anchor for type II membrane proteinSequence analysisAdd
BLAST
Topological domaini52 – 750699ExtracellularSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL3768.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved
Chaini2 – 750749NeprilysinPRO_0000078216Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycineBy similarity
Modified residuei4 – 41PhosphoserineBy similarity
Modified residuei6 – 61PhosphoserineBy similarity
Disulfide bondi57 ↔ 62By similarity
Disulfide bondi80 ↔ 735By similarity
Disulfide bondi88 ↔ 695By similarity
Disulfide bondi143 ↔ 411By similarity
Glycosylationi145 – 1451N-linked (GlcNAc...)By similarity
Disulfide bondi234 ↔ 242By similarity
Glycosylationi285 – 2851N-linked (GlcNAc...)Sequence analysis
Glycosylationi311 – 3111N-linked (GlcNAc...)By similarity
Glycosylationi325 – 3251N-linked (GlcNAc...)By similarity
Disulfide bondi621 ↔ 747By similarity
Glycosylationi628 – 6281N-linked (GlcNAc...)

Post-translational modificationi

Myristoylation is a determinant of membrane targeting.By similarity
Glycosylation at Asn-628 is necessary both for surface expression and neutral endopeptidase activity.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Myristate, Phosphoprotein

Interactioni

Protein-protein interaction databases

STRINGi9986.ENSOCUP00000021723.

Chemistry

BindingDBiP08049.

Structurei

Secondary structure

1
750
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi60 – 7213Combined sources
Turni79 – 813Combined sources
Helixi83 – 9412Combined sources
Beta strandi102 – 1054Combined sources
Helixi106 – 12217Combined sources
Helixi131 – 14414Combined sources
Helixi146 – 1505Combined sources
Turni151 – 1544Combined sources
Helixi155 – 1606Combined sources
Helixi161 – 1644Combined sources
Helixi168 – 1703Combined sources
Beta strandi171 – 1733Combined sources
Helixi174 – 1774Combined sources
Turni178 – 1814Combined sources
Helixi184 – 19512Combined sources
Beta strandi200 – 2089Combined sources
Beta strandi211 – 22010Combined sources
Beta strandi225 – 2284Combined sources
Helixi229 – 2335Combined sources
Helixi236 – 2383Combined sources
Helixi239 – 25921Combined sources
Helixi266 – 28621Combined sources
Helixi290 – 2934Combined sources
Helixi296 – 2994Combined sources
Beta strandi302 – 3043Combined sources
Helixi305 – 3117Combined sources
Helixi323 – 3319Combined sources
Helixi332 – 3343Combined sources
Beta strandi343 – 3475Combined sources
Helixi349 – 35911Combined sources
Helixi364 – 37613Combined sources
Turni377 – 3793Combined sources
Helixi380 – 3823Combined sources
Helixi385 – 3895Combined sources
Helixi392 – 3998Combined sources
Helixi407 – 41812Combined sources
Helixi420 – 43112Combined sources
Helixi436 – 45419Combined sources
Turni455 – 4573Combined sources
Helixi463 – 47513Combined sources
Beta strandi477 – 4815Combined sources
Helixi485 – 4884Combined sources
Helixi490 – 4967Combined sources
Turni497 – 4993Combined sources
Helixi507 – 52317Combined sources
Helixi524 – 5274Combined sources
Beta strandi545 – 5473Combined sources
Turni548 – 5514Combined sources
Beta strandi552 – 5565Combined sources
Helixi557 – 5593Combined sources
Turni562 – 5643Combined sources
Helixi571 – 5766Combined sources
Helixi578 – 58811Combined sources
Helixi594 – 5963Combined sources
Helixi609 – 62719Combined sources
Helixi632 – 6343Combined sources
Turni641 – 6444Combined sources
Helixi645 – 66925Combined sources
Helixi682 – 69312Combined sources
Beta strandi696 – 6983Combined sources
Helixi700 – 70910Combined sources
Helixi715 – 72410Combined sources
Helixi727 – 7326Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4XBHX-ray2.11A/B55-750[»]
4ZR5X-ray2.80A/B55-750[»]
ProteinModelPortaliP08049.
SMRiP08049. Positions 55-750.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi16 – 238Stop-transfer sequenceSequence analysis

Sequence similaritiesi

Belongs to the peptidase M13 family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3624. Eukaryota.
COG3590. LUCA.
HOGENOMiHOG000245574.
HOVERGENiHBG005554.
InParanoidiP08049.
KOiK01389.

Family and domain databases

CDDicd08662. M13. 1 hit.
Gene3Di3.40.390.10. 2 hits.
InterProiIPR024079. MetalloPept_cat_dom.
IPR029727. MME/CD10/NEP.
IPR000718. Peptidase_M13.
IPR018497. Peptidase_M13_C.
IPR008753. Peptidase_M13_N.
[Graphical view]
PANTHERiPTHR11733. PTHR11733. 1 hit.
PTHR11733:SF114. PTHR11733:SF114. 1 hit.
PfamiPF01431. Peptidase_M13. 1 hit.
PF05649. Peptidase_M13_N. 1 hit.
[Graphical view]
PRINTSiPR00786. NEPRILYSIN.
PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P08049-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGRSESQMDI TDINTPKPKK KQRWTPLEIS LSVLVLLLTV IAVTMIALYA
60 70 80 90 100
TYDDGICKSS DCIKSAARLI QNMDATAEPC TDFFKYACGG WLKRNVIPET
110 120 130 140 150
SSRYSNFDIL RDELEVILKD VLQEPKTEDI VAVQKAKTLY RSCVNETAID
160 170 180 190 200
SRGGQPLLKL LPDVYGWPVA TQNWEQTYGT SWSAEKSIAQ LNSNYGKKVL
210 220 230 240 250
INFFVGTDDK NSMNHIIHID QPRLGLPSRD YYECTGIYKE ACTAYVDFMI
260 270 280 290 300
AVAKLIRQEE GLPIDENQIS VEMNKVMELE KEIANATTKS EDRNDPMLLY
310 320 330 340 350
NKMTLAQIQN NFSLEINGKP FSWSNFTNEI MSTVNINIPN EEDVVVYAPE
360 370 380 390 400
YLIKLKPILT KYFPRDFQNL FSWRFIMDLV SSLSRTYKDS RNAFRKALYG
410 420 430 440 450
TTSESATWRR CANYVNGNME NAVGRLYVEA AFAGESKHVV EDLIAQIREV
460 470 480 490 500
FIQTLDDLTW MDAETKKKAE EKALAIKERI GYPDDIVSND NKLNNEYLEL
510 520 530 540 550
NYKEDEYFEN IIQNLKFSQS KQLKKLREKV DKDEWITGAA IVNAFYSSGR
560 570 580 590 600
NQIVFPAGIL QPPFFSAQQS NSLNYGGIGM VIGHEITHGF DDNGRNFNKD
610 620 630 640 650
GDLVDWWTQQ SANNFKEQSQ CMVYQYGNFS WDLAGGQHLN GINTLGENIA
660 670 680 690 700
DNGGIGQAYR AYQNYVKKNG EEKLLPGIDL NHKQLFFLNF AQVWCGTYRP
710 720 730 740 750
EYAVNSIKTD VHSPGNFRII GSLQNSVEFS EAFQCPKNSY MNPEKKCRVW
Length:750
Mass (Da):85,582
Last modified:January 23, 2007 - v2
Checksum:i0F26AF7316BB9D12
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X05338 mRNA. Translation: CAA28950.1.
M16593 mRNA. Translation: AAA53694.1.
PIRiA29451. HYRBN.
RefSeqiNP_001095155.1. NM_001101685.1.
UniGeneiOcu.2011.

Genome annotation databases

GeneIDi100009251.
KEGGiocu:100009251.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X05338 mRNA. Translation: CAA28950.1.
M16593 mRNA. Translation: AAA53694.1.
PIRiA29451. HYRBN.
RefSeqiNP_001095155.1. NM_001101685.1.
UniGeneiOcu.2011.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4XBHX-ray2.11A/B55-750[»]
4ZR5X-ray2.80A/B55-750[»]
ProteinModelPortaliP08049.
SMRiP08049. Positions 55-750.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9986.ENSOCUP00000021723.

Chemistry

BindingDBiP08049.
ChEMBLiCHEMBL3768.

Protein family/group databases

MEROPSiM13.001.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100009251.
KEGGiocu:100009251.

Organism-specific databases

CTDi4311.

Phylogenomic databases

eggNOGiKOG3624. Eukaryota.
COG3590. LUCA.
HOGENOMiHOG000245574.
HOVERGENiHBG005554.
InParanoidiP08049.
KOiK01389.

Miscellaneous databases

PROiP08049.

Family and domain databases

CDDicd08662. M13. 1 hit.
Gene3Di3.40.390.10. 2 hits.
InterProiIPR024079. MetalloPept_cat_dom.
IPR029727. MME/CD10/NEP.
IPR000718. Peptidase_M13.
IPR018497. Peptidase_M13_C.
IPR008753. Peptidase_M13_N.
[Graphical view]
PANTHERiPTHR11733. PTHR11733. 1 hit.
PTHR11733:SF114. PTHR11733:SF114. 1 hit.
PfamiPF01431. Peptidase_M13. 1 hit.
PF05649. Peptidase_M13_N. 1 hit.
[Graphical view]
PRINTSiPR00786. NEPRILYSIN.
PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNEP_RABIT
AccessioniPrimary (citable) accession number: P08049
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: January 23, 2007
Last modified: September 7, 2016
This is version 130 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.