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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)DescriptionActionsGraphical viewLength
Binding sitei103Substrate carboxylBy similarity1
Metal bindingi584Zinc; catalytic1
Active sitei585PROSITE-ProRule annotation1
Metal bindingi588Zinc; catalytic1
Metal bindingi647Zinc; catalyticPROSITE-ProRule annotation1
Active sitei651Proton donorPROSITE-ProRule annotation1

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)DescriptionActionsGraphical viewLength
Topological domaini2 – 28CytoplasmicSequence analysisAdd BLAST27
Transmembranei29 – 51Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST23
Topological domaini52 – 750ExtracellularSequence analysisAdd BLAST699

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3768.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved
ChainiPRO_00000782162 – 750NeprilysinAdd BLAST749

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineBy similarity1
Modified residuei4PhosphoserineBy similarity1
Modified residuei6PhosphoserineBy similarity1
Disulfide bondi57 ↔ 62By similarity
Disulfide bondi80 ↔ 735By similarity
Disulfide bondi88 ↔ 695By similarity
Disulfide bondi143 ↔ 411By similarity
Glycosylationi145N-linked (GlcNAc...)By similarity1
Disulfide bondi234 ↔ 242By similarity
Glycosylationi285N-linked (GlcNAc...)Sequence analysis1
Glycosylationi311N-linked (GlcNAc...)By similarity1
Glycosylationi325N-linked (GlcNAc...)By similarity1
Disulfide bondi621 ↔ 747By similarity
Glycosylationi628N-linked (GlcNAc...)1

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

Proteomic databases

PRIDEiP08049.

Interactioni

Protein-protein interaction databases

STRINGi9986.ENSOCUP00000021723.

Chemistry databases

BindingDBiP08049.

Structurei

Secondary structure

1750
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi60 – 72Combined sources13
Turni79 – 81Combined sources3
Helixi83 – 94Combined sources12
Beta strandi102 – 105Combined sources4
Helixi106 – 122Combined sources17
Helixi131 – 144Combined sources14
Helixi146 – 150Combined sources5
Turni151 – 154Combined sources4
Helixi155 – 160Combined sources6
Helixi161 – 164Combined sources4
Helixi168 – 170Combined sources3
Beta strandi171 – 173Combined sources3
Helixi174 – 177Combined sources4
Turni178 – 181Combined sources4
Helixi184 – 195Combined sources12
Beta strandi200 – 208Combined sources9
Beta strandi211 – 220Combined sources10
Beta strandi225 – 228Combined sources4
Helixi229 – 233Combined sources5
Helixi236 – 238Combined sources3
Helixi239 – 259Combined sources21
Helixi266 – 286Combined sources21
Helixi290 – 293Combined sources4
Helixi296 – 299Combined sources4
Beta strandi302 – 304Combined sources3
Helixi305 – 311Combined sources7
Helixi323 – 331Combined sources9
Helixi332 – 334Combined sources3
Beta strandi343 – 347Combined sources5
Helixi349 – 359Combined sources11
Helixi364 – 376Combined sources13
Turni377 – 379Combined sources3
Helixi380 – 382Combined sources3
Helixi385 – 389Combined sources5
Helixi392 – 399Combined sources8
Helixi407 – 418Combined sources12
Helixi420 – 431Combined sources12
Helixi436 – 454Combined sources19
Turni455 – 457Combined sources3
Helixi463 – 475Combined sources13
Beta strandi477 – 481Combined sources5
Helixi485 – 488Combined sources4
Helixi490 – 496Combined sources7
Turni497 – 499Combined sources3
Helixi507 – 523Combined sources17
Helixi524 – 527Combined sources4
Beta strandi545 – 547Combined sources3
Turni548 – 551Combined sources4
Beta strandi552 – 556Combined sources5
Helixi557 – 559Combined sources3
Turni562 – 564Combined sources3
Helixi571 – 576Combined sources6
Helixi578 – 588Combined sources11
Helixi594 – 596Combined sources3
Helixi609 – 627Combined sources19
Helixi632 – 634Combined sources3
Turni641 – 644Combined sources4
Helixi645 – 669Combined sources25
Helixi682 – 693Combined sources12
Beta strandi696 – 698Combined sources3
Helixi700 – 709Combined sources10
Helixi715 – 724Combined sources10
Helixi727 – 732Combined sources6

3D structure databases

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

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi16 – 23Stop-transfer sequenceSequence analysis8

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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4XBHX-ray2.11A/B55-750[»]
4ZR5X-ray2.80A/B55-750[»]
ProteinModelPortaliP08049.
SMRiP08049.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9986.ENSOCUP00000021723.

Chemistry databases

BindingDBiP08049.
ChEMBLiCHEMBL3768.

Protein family/group databases

MEROPSiM13.001.

Proteomic databases

PRIDEiP08049.

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: November 2, 2016
This is version 132 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.